FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yang, BW Shi, Y Xia, XD Xi, ML Wang, X Ji, BY Meng, JH AF Yang, Baowei Shi, Ying Xia, Xiaodong Xi, Meili Wang, Xin Ji, Baoyi Meng, Jianghong TI Inactivation of foodborne pathogens in raw milk using high hydrostatic pressure SO FOOD CONTROL LA English DT Article DE High hydrostatic pressure; Pathogens; Inactivation ID ESCHERICHIA-COLI O157-H7; LIQUID WHOLE EGG; STAPHYLOCOCCUS-AUREUS; SALMONELLA; HEAT; HOMOGENIZATION; QUALITY; CHEESE; PRESERVATION; TEMPERATURES AB Plate counting, viability test, pulse field gel electrophoresis (PFGE) and transmission electron microscopy (TEM) were used to investigate the effect of high hydrostatic pressure (HHP) on Salmonella, Escherichia coli, Shigella and Staphyloccocus aureus in raw milk in order to determine the optimal inactivation conditions, and further understand the mechanisms of HHP on pathogens inactivation in food. The results exhibited that 300 Mpa treatment with 30 min duration at 25 degrees C was the optimal condition for Salmonella. E. coli, Shigella and S. aureus inactivation. Damage of the cell wall, cell membrane and cytoplasmic components by high pressure treatment can be observed in TEM micrographs. The injured cells could not be recovered, the growth rate of survivors was much lower than that of the untreated cells. PFGE showed neither corresponding DNA bands with same molecular weight nor DNA bands with same brightness could be found in the lanes between HHP treated pathogens and untreated ones. The results indicated that HHP processing can be applied to inactivate pathogens in food, the inactivation is mainly due to cell membrane damage, cell wall rupture and chromosome DNA degradation. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Yang, Baowei; Shi, Ying; Xia, Xiaodong; Xi, Meili; Wang, Xin; Ji, Baoyi; Meng, Jianghong] NW A&F Univ, Coll Food Sci & Engn, Yangling 712100, Peoples R China. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Meng, JH (reprint author), NW A&F Univ, Coll Food Sci & Engn, 28 Xinong Rd, Yangling 712100, Peoples R China. EM jmeng@umd.edu FU Houji Scholar Program; Principal Fund of Northwest A&F University, Yangling, Shaanxi, China FX The research work was supported in part by the Houji Scholar Program, and the Principal Fund of Northwest A&F University, Yangling, Shaanxi, China. We also appreciate Drs Shuangkui Du and Min Sheng in Northwest A&F University for data analysis by using SPSS software. NR 35 TC 17 Z9 20 U1 6 U2 91 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 EI 1873-7129 J9 FOOD CONTROL JI Food Control PD DEC PY 2012 VL 28 IS 2 BP 273 EP 278 DI 10.1016/j.foodcont.2012.04.030 PG 6 WC Food Science & Technology SC Food Science & Technology GA 991HY UT WOS:000307693300013 ER PT J AU Li, JX Jeske, DR Klein, JA AF Li, Judy X. Jeske, Daniel R. Klein, Jeffrey A. TI Sequential analysis methodology for a Poisson GLMM with applications to multicenter randomized clinical trials SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Sequential hypothesis testing; Nuisance parameters; GLMM; Clinical trials AB Sequential analyses in clinical trials have ethical and economic advantages over fixed sample size methods. The sequential probability ratio test (SPRT) is a hypothesis testing procedure which evaluates data as it is collected. The original SPRT was developed by Wald for one-parameter families of distributions and later extended by Bartlett to handle the case of nuisance parameters. However, Bartlett's SPRT requires independent and identically distributed observations. In this paper we show that Bartlett's SPRT can be applied to generalized linear model (GLM) contexts. Then we propose an SPRT analysis methodology for a Poisson generalized linear mixed model (GLMM) that is suitable for our application to the design of a multicenter randomized clinical trial that compares two preventive treatments for surgical site infections. We validate the methodology with a simulation study that includes a comparison to Neyman-Pearson and Bayesian fixed sample size test designs and the Wald SPRT. (C) 2012 Elsevier B.V. All rights reserved. C1 [Jeske, Daniel R.; Klein, Jeffrey A.] Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. [Li, Judy X.] US FDA, Rockville, MD 20855 USA. RP Jeske, DR (reprint author), Univ Calif Riverside, Dept Stat, 1330 Olmsted Hall,900 Univ Ave, Riverside, CA 92521 USA. EM daniel.jeske@ucr.edu NR 17 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD DEC PY 2012 VL 142 IS 12 BP 3225 EP 3234 DI 10.1016/j.jspi.2012.04.014 PG 10 WC Statistics & Probability SC Mathematics GA 009JW UT WOS:000309023100015 ER PT J AU Wang, YG He, Y Abraham, B Rouhani, FN Brantly, ML Scott, DE Reed, JL AF Wang, Yonggang He, Yong Abraham, Bindu Rouhani, Farshid N. Brantly, Mark L. Scott, Dorothy E. Reed, Jennifer L. TI Cytosolic, Autocrine Alpha-1 Proteinase Inhibitor (A1PI) Inhibits Caspase-1 and Blocks IL-1 beta Dependent Cytokine Release in Monocytes SO PLOS ONE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; ALPHA(1)-ANTITRYPSIN DEFICIENCY; MURAMYL DIPEPTIDE; DOWN-REGULATION; ACTIVATION; MACROPHAGES; INFLAMMASOME; INTERLEUKIN-1-BETA; EMPHYSEMA; PATHWAY AB Rationale: Activation state-dependent secretion of alpha-1 proteinase inhibitor (A1PI) by monocytes and macrophages was first reported in 1985. Since then, monocytes and tissue macrophages have emerged as key sentinels of infection and tissue damage via activation of self-assembling pattern recognition receptors (inflammasomes), which trigger inflammation and cell death in a caspase-1 dependent process. These studies examine the relationship between A1PI expression in primary monocytes and monocytic cell lines, and inflammatory cytokine expression in response to inflammasome directed stimuli. Methods: IL-1 beta expression was examined in lung macrophages expressing wild type A1PI (A1PI-M) or disease-associated Z isoform A1PI (A1PI-Z). Inflammatory cytokine release was evaluated in THP-1 monocytic cells or THP-1 cells lacking the inflammasome adaptor ASC, transfected with expression vectors encoding A1PI-M or A1PI-Z. A1PI-M was localized within monocytes by immunoprecipitation in hypotonic cell fractions. Cell-free titration of A1PI-M was performed against recombinant active caspase-1 in vitro. Results: IL-1 beta expression was elevated in lung macrophages expressing A1PI-Z. Overexpression of A1PI-M in THP-1 monocytes reduced secretion of IL-1 beta and TNF-alpha. In contrast, overexpression of A1PI-Z enhanced IL-1 beta and TNF-alpha secretion in an ASC dependent manner. A1PI-Z-enhanced cytokine release was inhibited by a small molecule caspase-1 inhibitor but not by high levels of exogenous wtA1PI. Cytosolic localization of A1PI-M in monocytes was not diminished with microtubule-inhibiting agents. A1PI-M co-localized with caspase-1 in gel-filtered cytoplasmic THP-1 preparations, and was co-immunoprecipitated with caspase 1 from nigericin-stimulated THP-1 cell lysate. Plasma-derived A1PI inhibited recombinant caspase-1 mediated conversion of a peptide substrate in a dose dependent manner. Conclusions: Our results suggest that monocyte/macrophage-expressed A1PI-M antagonizes IL-1 beta secretion possibly via caspase-1 inhibition, a function which disease-associated A1PI-Z may lack. Therapeutic approaches which limit inflammasome responses in patients with A1PI deficiency, in combination with A1PI augmentation, may provide additional respiratory tissue-sparing benefits. C1 [Wang, Yonggang; He, Yong; Abraham, Bindu; Scott, Dorothy E.; Reed, Jennifer L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Rouhani, Farshid N.; Brantly, Mark L.] Univ Florida, Dept Med, Gainesville, FL USA. RP Reed, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM jennifer.reed@fda.hhs.gov FU US Food and Drug Administration FX This work was supported by US Food and Drug Administration operating funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 5 Z9 6 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 30 PY 2012 VL 7 IS 11 AR e51078 DI 10.1371/journal.pone.0051078 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054WM UT WOS:000312376100279 PM 23226468 ER PT J AU Chua, WJ Hansen, TH AF Chua, Wei-Jen Hansen, Ted H. TI IMMUNOLOGY Vitamins prime immunity SO NATURE LA English DT Editorial Material ID INVARIANT T-CELLS; DISEASE; MR1 C1 [Chua, Wei-Jen] US FDA, Bethesda, MD 20892 USA. [Hansen, Ted H.] Washington Univ, Sch Med, St Louis, MO 63110 USA. RP Chua, WJ (reprint author), US FDA, Bethesda, MD 20892 USA. EM wei-jen.yankelevich@fda.hhs.gov; hansen@wustl.edu OI Yankelevich, Wei-Jen/0000-0002-5234-7845 FU NIAID NIH HHS [R01 AI046553] NR 13 TC 3 Z9 3 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 29 PY 2012 VL 491 IS 7426 BP 680 EP 681 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 044FY UT WOS:000311606000029 PM 23192143 ER PT J AU Adriani, W Koot, S Columba-Cabezas, S Romano, E Travaglini, D van den Bos, R Granstrem, O Ali, SF Laviola, G AF Adriani, Walter Koot, Susanne Columba-Cabezas, Sandra Romano, Emilia Travaglini, Domenica van den Bos, Ruud Granstrem, Oleg Ali, Syed F. Laviola, Giovanni TI Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE Auto-antibodies to neuro-receptors; DAT; Delay of reward; Flexibility of choice behaviour; ADHD; OCD ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; SPONTANEOUSLY HYPERTENSIVE-RAT; GLUTAMATE-RECEPTOR GLUR3; EXON-III POLYMORPHISM; DOPAMINE TRANSPORTER; DORSOMEDIAL STRIATUM; IMPULSIVE BEHAVIOR AB Background: Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural/neurochemical phenotype. Methods: Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec). Results: DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. Conclusions: Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders. C1 [Adriani, Walter; Koot, Susanne; Columba-Cabezas, Sandra; Romano, Emilia; Travaglini, Domenica; Laviola, Giovanni] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Koot, Susanne; van den Bos, Ruud] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, Utrecht, Netherlands. [Granstrem, Oleg] IP Pavlovs State Med Univ, Dept Neurol & Neurosurg, St Petersburg, Russia. [Granstrem, Oleg] Geropharm Ltd, St Petersburg, Russia. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Adriani, W (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM Walter.Adriani@iss.it RI Laviola, Giovanni/K-4392-2016; Columba Cabezas, Sandra/A-6015-2013 OI Laviola, Giovanni/0000-0003-0388-0835; Columba Cabezas, Sandra/0000-0001-7727-6636 FU European Community [278367]; ERARE-EuroRETT (ERAR/6) Networking Grant; European Mind and Metabolism Association; Erasmus Lifelong Learning Programme support FX Research was performed under the project "ADHD-sythe" (young investigator program, years 2009-12), and as partner in the EU project "NeuroGenMRI" (ERAnet "Prio-Med-Child" joint call, years 2011-14), Italian Ministry of Health (to W. A.); partially funded from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 278367 (EMTICS). This paper reflects only the authors' views and the European Union is not liable for any use that may be made of the information contained herein. We also are grateful to the ERARE-EuroRETT (ERAR/6) Networking Grant (to G. L.); an European Mind and Metabolism Association support (to D. T.) and an Erasmus Lifelong Learning Programme support (to S. K.). We'd like to thank Alessandra Berry and Masha Shumilina for practical help, Harry Blom for theoretical advice, Giacomo Dell'Omo for technical support, and Prof. Luciano Saso for precious advice. NR 87 TC 6 Z9 6 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD NOV 28 PY 2012 VL 8 AR 54 DI 10.1186/1744-9081-8-54 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 068AW UT WOS:000313337900001 PM 23192105 ER PT J AU Dashkevich, NM Ovanesov, MV Balandina, AN Karamzin, SS Shestakov, PI Soshitova, NP Tokarev, AA Panteleev, MA Ataullakhanov, FI AF Dashkevich, N. M. Ovanesov, M. V. Balandina, A. N. Karamzin, S. S. Shestakov, P. I. Soshitova, N. P. Tokarev, A. A. Panteleev, M. A. Ataullakhanov, F. I. TI Thrombin Activity Propagates in Space During Blood Coagulation as an Excitation Wave SO BIOPHYSICAL JOURNAL LA English DT Article ID FACTOR-X ACTIVATION; TISSUE FACTOR PATHWAY; PLASMA PROTEASE INHIBITORS; FACTOR-VII ACTIVATION; FACTOR-IXA; SPATIOTEMPORAL DYNAMICS; PROTHROMBINASE COMPLEX; HUMAN-PLATELETS; FACTOR-XIA; THROMBOMODULIN COMPLEX AB Injury-induced bleeding is stopped by a hemostatic plug formation that is controlled by a complex nonlinear and spatially heterogeneous biochemical network of proteolytic enzymes called blood coagulation. We studied spatial dynamics of thrombin, the central enzyme of this network, by developing a fluorogenic substrate-based method for time-and space-resolved imaging of thrombin enzymatic activity. Clotting stimulation by immobilized tissue factor induced localized thrombin activity impulse that propagated in space and possessed all characteristic traits of a traveling excitation wave: constant spatial velocity, constant amplitude, and insensitivity to the initial stimulation once it exceeded activation threshold. The parameters of this traveling wave were controlled by the availability of phospholipids or platelets, and the wave did not form in plasmas from hemophilia A or C patients who lack factors VIII and XI, which are mediators of the two principal positive feedbacks of coagulation. Stimulation of the negative feedback of the protein C pathway with thrombomodulin produced nonstationary patterns of wave formation followed by deceleration and annihilation. This indicates that blood can function as an excitable medium that conducts traveling waves of coagulation. C1 [Dashkevich, N. M.; Balandina, A. N.; Shestakov, P. I.; Panteleev, M. A.; Ataullakhanov, F. I.] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. [Dashkevich, N. M.; Karamzin, S. S.; Shestakov, P. I.; Soshitova, N. P.; Panteleev, M. A.; Ataullakhanov, F. I.] HemaCore Hematol Corp, Moscow, Russia. [Ovanesov, M. V.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Balandina, A. N.; Tokarev, A. A.; Ataullakhanov, F. I.] Fed Res & Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia. [Panteleev, M. A.; Ataullakhanov, F. I.] Moscow MV Lomonosov State Univ, Dept Phys, Moscow, Russia. RP Ataullakhanov, FI (reprint author), Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. EM ataullakhanov.fazly@gmail.com RI Dashkevich, Natalia/A-8373-2014; Ataullakhanov, Fazoil/J-8076-2012; Panteleev, Mikhail/H-5491-2012; OI Panteleev, Mikhail/0000-0002-8128-7757; Tokarev, Alexey/0000-0002-3480-1813; Balandina, Anna/0000-0002-7032-695X FU Russian Foundation for Basic Research [10-01-91055, 11-04-00303, 11-04-12080, 12-04-00652, 12-04-00438, 12-04-32095, 12-04-33055]; Russian Academy of Sciences FX The study was supported by the Russian Foundation for Basic Research grants 10-01-91055, 11-04-00303, 11-04-12080, 12-04-00652, 12-04-00438, 12-04-32095, 12-04-33055 and by the Russian Academy of Sciences Presidium Basic Research Programs Molecular and Cellular Biology, Basic Science for Medicine, Integrative Physiology, and Molecular Mechanisms of Physiologic Functions. NR 74 TC 21 Z9 22 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 21 PY 2012 VL 103 IS 10 BP 2233 EP 2240 DI 10.1016/j.bpj.2012.10.011 PG 8 WC Biophysics SC Biophysics GA 041RN UT WOS:000311419000022 PM 23200057 ER PT J AU Cooper-DeHoff, RM Bird, ST Nichols, GA Delaney, JC Winterstein, AG AF Cooper-DeHoff, Rhonda M. Bird, Steve T. Nichols, Greg A. Delaney, J. C. Winterstein, Almut G. TI Association of Antihypertensive Drug Classes, Alone or in Combination, with Incident Diabetes: A Nested Case-control Study SO CIRCULATION LA English DT Meeting Abstract DE Hypertension; Drug interactions; Glucose; Antihypertensive agents; Pharmacology C1 [Cooper-DeHoff, Rhonda M.; Delaney, J. C.; Winterstein, Almut G.] Univ Florida, Gainesville, FL USA. [Bird, Steve T.] US FDA, DHHS FDA CDER OM CACP, Silver Spring, MD USA. [Nichols, Greg A.] Kaiser Permanente Northwest, Cntr Hlth Rsch, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11073 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001176 ER PT J AU Herz, ND Strauss, DG Ritchey, ME Loring, Z Jacobs, SB Silverman, H Worrall, CM Kelman, J Pina, IL Canos, DA AF Herz, Naomi D. Strauss, David G. Ritchey, Mary E. Loring, Zak Jacobs, Samantha B. Silverman, Henry Worrall, Christopher M. Kelman, Jeffrey Pina, Ileana L. Canos, Daniel A. TI Cardiac Resynchronization Therapy Defibrillators: Pre and Postmarket Experience SO CIRCULATION LA English DT Meeting Abstract DE CRT; Heart failure; FDA; Device; Surveillance C1 [Herz, Naomi D.; Ritchey, Mary E.; Jacobs, Samantha B.; Canos, Daniel A.] US FDA, Off Surveillance & Biometr, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Strauss, David G.; Loring, Zak] US FDA, Off Sci & Engn, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Silverman, Henry] Acumen LLC, SafeRx, Burlingame, CA USA. [Worrall, Christopher M.; Kelman, Jeffrey] Cntrs Medicare & Medicaid Serv, Cntr Medicare, Baltimore, MD USA. [Pina, Ileana L.] US FDA, Off Device Evaluat, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14558 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004264 ER PT J AU Johannesen, L Vicente, J Galeotti, L Loring, Z Florian, JA Garnett, CE Stockbridge, N Strauss, DG AF Johannesen, Lars Vicente, Jose Galeotti, Loriano Loring, Zak Florian, Jeffry A. Garnett, Christine E. Stockbridge, Norman Strauss, David G. TI Normal Limits of Variability of Spatial QRS-T Angle and Ventricular Gradient: Analysis of 20 Thorough-QT Studies SO CIRCULATION LA English DT Meeting Abstract DE Clinical trials; Biomarkers; Ventricular arrhythmia; Qt interval; Drugs C1 [Johannesen, Lars; Florian, Jeffry A.; Garnett, Christine E.] US FDA, Off Translat Sci, Cntr Drug Evaluat & Rsch, Silver Spring, MD USA. [Vicente, Jose; Galeotti, Loriano; Loring, Zak; Strauss, David G.] US FDA, Off Sci & Engn Labs, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Stockbridge, Norman] US FDA, Off New Drugs, Cntr Drug Evaluat & Rsch, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15725 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005297 ER PT J AU Loring, Z Canos, DA Selzman, K Herz, ND Silverman, H MaCurdy, TF Worrall, CM Kelman, J Richey, ME Pina, IL Strauss, DG AF Loring, Zak Canos, Daneil A. Selzman, Kimberly Herz, Naomi D. Silverman, Henry MaCurdy, Thomas F. Worrall, Christopher M. Kelman, Jeffrey Richey, Mary E. Pina, Ileana L. Strauss, David G. TI Left Bundle Branch Block Predicts Better Survival in Women than Men Receiving Cardiac Resynchronization Therapy: Long Term Follow-Up of 145,000 Patients SO CIRCULATION LA English DT Meeting Abstract DE Resynchronization therapy; Device C1 [Loring, Zak; Strauss, David G.] US FDA, Off Sci & Engn Labs, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Canos, Daneil A.; Herz, Naomi D.; Richey, Mary E.] US FDA, Off Surveillance & Biometr, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Selzman, Kimberly; Pina, Ileana L.] US FDA, Off Device Evaluat, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Silverman, Henry; MaCurdy, Thomas F.] Acumen LLC, SafeRx, Burlingame, CA USA. [Worrall, Christopher M.; Kelman, Jeffrey] Cntr Medicare Serv, Cntr Medicare, Baltimore, MD USA. [Worrall, Christopher M.; Kelman, Jeffrey] Cntr Medicaid Serv, Cntr Medicare, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15602 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005254 ER PT J AU Gieseker, CM Mayer, TD Crosby, TC Carson, J Dalsgaard, I Darwish, AM Gaunt, PS Gao, DX Hsu, HM Lin, TL Oaks, JL Pyecroft, M Teitzel, C Somsiri, T Wu, CC AF Gieseker, Charles M. Mayer, Tamara D. Crosby, Tina C. Carson, Jeremy Dalsgaard, Inger Darwish, Ahmed M. Gaunt, Patricia S. Gao, Dana X. Hsu, Hui-Min Lin, Tsang L. Oaks, J. Lindsay Pyecroft, Melissa Teitzel, Charlene Somsiri, Temdoung Wu, Ching C. TI Quality control ranges for testing broth microdilution susceptibility of Flavobacterium columnare and F. psychrophilum to nine antimicrobials SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE Standard methods; Antimicrobial susceptibility testing; Fish; Flavobacteria ID FLEXIBACTER-COLUMNARIS; AQUATIC BACTERIA; FISH; RESISTANCE; STANDARDS; FRANCE AB A multi-laboratory broth microdilution method trial was performed to standardize the specialized test conditions required for the fish pathogens Flavobacterium columnare and F. psychrophilum. Nine laboratories tested the quality control (QC) strains Escherichia colt ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 against 10 antimicrobials (ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine, oxolinic acid, oxytetracycline, and trimethoprim/sulfamethoxazole) in diluted (4 g l(-1)) cation-adjusted Mueller-Hinton broth incubated at 28 and 18 degrees C for 44-48 and 92-96 h, respectively. QC ranges were set for 9 of the 10 antimicrobials. Most of the minimal inhibitory concentration (MIC) distributions (16 of 18, 9 drugs at both temperatures) for A. salmonicida ATCC 33658 were centered on a single median MIC +/- 1 two-fold drug dilution resulting in a QC range that spanned 3 dilutions. More of the E. call ATCC 25922 MIC distributions (7 of 16) were centered between 2 MIC dilutions requiring a QC range that spanned 4 dilutions. A QC range could not be determined for E. colt ATCC 25922 against 2 antimicrobials at the low temperature. These data and their associated QC ranges have been approved by the Clinical and Laboratory Standards Institute (CLSI), and will be included in the next edition of the CLSI M49-A Guideline. This method represents the first standardized reference method for testing fish pathogenic Flavobacterium spp. C1 [Gieseker, Charles M.; Mayer, Tamara D.; Crosby, Tina C.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Carson, Jeremy; Pyecroft, Melissa] Dept Primary Ind, Fish Hlth Unit, Pk Water & Environm, Launceston, Tas 7249, Australia. [Dalsgaard, Inger] Tech Univ Denmark, Natl Vet Inst, DK-1870 Frederiksberg C, Denmark. [Darwish, Ahmed M.] USDA ARS, Harry K Dupree Stuttgart Natl Aquaculture Res Ctr, Stuttgart, AR 72160 USA. [Gaunt, Patricia S.; Gao, Dana X.] Mississippi State Univ, Coll Vet Med, Thad Cochran Natl Warmwater Aquaculture Ctr, Stoneville, MS 38766 USA. [Hsu, Hui-Min] Univ Wisconsin, Wisconsin Vet Diagnost Lab, Madison, WI 53706 USA. [Oaks, J. Lindsay; Teitzel, Charlene] Univ Washington, Washington Anim Dis Diagnost Lab, Pullman, WA 99164 USA. [Somsiri, Temdoung] Kasetsart Univ, Inland Aquat Anim Hlth Res Inst, Bangkok 10900, Thailand. [Lin, Tsang L.; Wu, Ching C.] Purdue Univ, Anim Dis Diagnost Lab, W Lafayette, IN 47907 USA. RP Gieseker, CM (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM charles.gieseker@fda.hhs.gov NR 21 TC 3 Z9 3 U1 0 U2 17 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD NOV 19 PY 2012 VL 101 IS 3 BP 207 EP 215 DI 10.3354/dao02527 PG 9 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 054QC UT WOS:000312357300004 PM 23324417 ER PT J AU Degheidy, HA Branchaw, AL Bauer, LC Bauer, SR AF Degheidy, Heba A. Branchaw, Allison L. Bauer, Lucy C. Bauer, Steven R. TI B Cell Development and the Splenic Microenvironment in Dlk-1 Deficient Mice SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Degheidy, Heba A.; Branchaw, Allison L.; Bauer, Steven R.] US FDA, CBER, Bethesda, MD 20014 USA. [Bauer, Lucy C.] US FDA, CDRH OSEL DB, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1251 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902315 ER PT J AU Howard, TE Drigalenko, E Johnson, MP Cole, SS Kim, B Viel, KR Sauna, ZE Curran, JE Blangero, J Almasy, LA Goring, HH AF Howard, Tom E. Drigalenko, Eugene Johnson, Matthew P. Cole, Shelley S. Kim, Benjamin Viel, Kevin R. Sauna, Zuben E. Curran, Joanne E. Blangero, John Almasy, Laura A. Goering, Harald H. TI Common SNPs within or near Three Immune Response Genes Implicated in the Risk of FVIII Immunogenicity in Hemophilia A Do Not Influence Steady-State Levels of Their Encoded mRNAs SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Drigalenko, Eugene; Johnson, Matthew P.; Cole, Shelley S.; Curran, Joanne E.; Blangero, John; Almasy, Laura A.; Goering, Harald H.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Kim, Benjamin] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Viel, Kevin R.] Histonis Inc, Atlanta, GA USA. [Sauna, Zuben E.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3366 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602318 ER PT J AU Kim, B Sauna, ZE Carless, MA Curran, JE Viel, KR Cole, SS Raja, R Blangero, J Howard, TE AF Kim, Benjamin Sauna, Zuben E. Carless, Melanie A. Curran, Joanne E. Viel, Kevin R. Cole, Shelley S. Raja, Rajalingam Blangero, John Howard, Tom E. TI F8 and HLA-II Haplotypes in the Hispanic Population: Implications for Inhibitor Risk Development in Hispanic Hemophilia A Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kim, Benjamin] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Sauna, Zuben E.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Carless, Melanie A.; Curran, Joanne E.; Cole, Shelley S.; Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Viel, Kevin R.] Histonis Inc, Atlanta, GA USA. [Raja, Rajalingam] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Howard, Tom E.] Vet Affairs Greater Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3365 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602319 ER PT J AU Kumari, N Xu, M Kovlaskyy, D Dhawan, S Nekhai, S AF Kumari, Namita Xu, Min Kovlaskyy, Dmytro Dhawan, Subhash Nekhai, Sergei TI Novel 2-Phenyl-1-Pyridin-2yl-Ethanone (PpY) Based Iron Chelators Increase Expression of IkB alpha and Heme Oxygenase-1 and Inhibit HIV-1 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kumari, Namita; Xu, Min; Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Kovlaskyy, Dmytro] Natl Taras Shevchenko Univ, Kiev, Ukraine. [Dhawan, Subhash] US FDA, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1052 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602021 ER PT J AU Kurasawa, JH Shestopal, SA Karnaukhova, E Struble, EB Lee, TK Sarafanov, AG AF Kurasawa, James H. Shestopal, Svetlana A. Karnaukhova, Elena Struble, Evi B. Lee, Timothy K. Sarafanov, Andrey G. TI Characterization of Molecular Interaction of Blood Coagulation Factor VIII and Its Clearance Receptor, Low-Density Lipoprotein Receptor SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kurasawa, James H.; Shestopal, Svetlana A.; Sarafanov, Andrey G.] US FDA, CDER, Off Blood Res & Review, Rockville, MD 20857 USA. [Karnaukhova, Elena; Struble, Evi B.; Lee, Timothy K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2206 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905230 ER PT J AU Liang, YD Struble, EB Woodle, SA Jha, N Scott, D Lee, TK Ovanesov, MV AF Liang, Yideng Struble, Evi B. Woodle, Samuel A. Jha, Naveen Scott, Dorothy Lee, Timothy K. Ovanesov, Mikhail V. TI Thrombin Generation Responses to Human Factor XIa in Plasma of Animal Species SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Liang, Yideng; Struble, Evi B.; Woodle, Samuel A.; Jha, Naveen; Scott, Dorothy; Lee, Timothy K.; Ovanesov, Mikhail V.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 5142 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605446 ER PT J AU Ovanesov, MV Kurasawa, JH Jha, N Shestopal, SA Lee, TK Sarafanov, AG AF Ovanesov, Mikhail V. Kurasawa, James H. Jha, Naveen Shestopal, Svetlana A. Lee, Timothy K. Sarafanov, Andrey G. TI Inhibitory Effect of an Anti-Factor VIII Antibody Fragment On Factor VIII Activity in Different Functional Assays SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ovanesov, Mikhail V.; Jha, Naveen; Lee, Timothy K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Kurasawa, James H.; Shestopal, Svetlana A.; Sarafanov, Andrey G.] US FDA, CBER, Off Blood Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4387 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605137 ER PT J AU Pawelczyk, E Degheidy, HA Branchaw, AL Holmbeck, K Bauer, SR AF Pawelczyk, Edyta Degheidy, Heba A. Branchaw, Allison L. Holmbeck, Kenn Bauer, Steven R. TI Dlk-1 Regulates B Cell Development Through Altered Bone Marrow Stromal Microenvironment, Not by Affecting Hematopoitic Stem/Progenitor Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pawelczyk, Edyta; Branchaw, Allison L.; Bauer, Steven R.] US FDA, CBER, Bethesda, MD 20014 USA. [Degheidy, Heba A.] US FDA, CDRH, OSEL, DB, Silver Spring, MD USA. [Holmbeck, Kenn] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3465 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604062 ER PT J AU Simhadri, VL Hershko, K Blaisdell, A Wu, A Tseng, S Newell, J Hunt, R Choi, J Sauna, ZE Bram, RJ Komar, AA Kimchi-Sarfaty, C AF Simhadri, Vijaya L. Hershko, Klilah Blaisdell, Adam Wu, Andrew Tseng, Sandy Newell, Jordan Hunt, Ryan Choi, JaeWon Sauna, Zuben E. Bram, Richard J. Komar, Anton A. Kimchi-Sarfaty, Chava TI Secretion and Activity of ADAMTS13 Are Impaired by Cyclosporin A SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Simhadri, Vijaya L.; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD USA. [Hershko, Klilah; Blaisdell, Adam; Wu, Andrew; Tseng, Sandy; Newell, Jordan; Hunt, Ryan; Choi, JaeWon] FDA CBER OBRR DH, Rockville, MD USA. [Bram, Richard J.] Mayoclin Fdn, Rochester, MN USA. [Komar, Anton A.] Cleveland State Univ, Cleveland, OH 44115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3349 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602335 ER PT J AU Xu, F Vostal, J AF Xu, Fei Vostal, Jaroslav TI Vitamin K3 Is a Potential Ultraviolet Photosensitizer for Pathogen Reduction of Human Platelets and Plasma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Xu, Fei; Vostal, Jaroslav] OBRR, CBER, FDA, Lab Cellular Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3434 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604093 ER PT J AU Cho, S Choi, YS Luu, HMD Guo, J AF Cho, Seungil Choi, Yong Soo Luu, Hoan My-Do Guo, Ji TI Determination of total leachable bisphenol A from polysulfone membranes based on multiple consecutive extractions SO TALANTA LA English DT Article DE Bisphenol A; Leachable; Membrane; Polysulfone; Hemodialyzer; Hemoconcentrator AB The paper presents the development of a multiple consecutive extraction method enabling the determination of the total amount of bisphenol A (BPA) released from porous polysulfone (PS) membranes in a hemodialyzer or hemoconcentrator under simulated-use conditions. The levels of BPA were determined using solid phase extraction (SPE) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS). We demonstrated that it was difficult to determine the total amount of BPA released from the PS membranes using a single extraction method with finite solvent volume because of the chemical equilibrium between the extraction solution and the polymer phase. Repeated extractions gave more accurate results than a single extraction for the determination of the total amount of leachables in porous membranes. A general equation was derived to fit the elution profile of BPA released during multiple consecutive extractions. Published by Elsevier B.V. C1 [Cho, Seungil; Choi, Yong Soo; Luu, Hoan My-Do; Guo, Ji] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Cho, S (reprint author), US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM seungil.cho@fda.hhs.gov NR 14 TC 2 Z9 2 U1 0 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD NOV 15 PY 2012 VL 101 BP 537 EP 540 DI 10.1016/j.talanta.2012.09.033 PG 4 WC Chemistry, Analytical SC Chemistry GA 064OH UT WOS:000313084400078 PM 23158360 ER PT J AU Awotwe-Otoo, D Agarabi, C Wu, GK Casey, E Read, E Lute, S Brorson, KA Khan, MA Shah, RB AF Awotwe-Otoo, David Agarabi, Cyrus Wu, Geoffrey K. Casey, Elizabeth Read, Erik Lute, Scott Brorson, Kurt A. Khan, Mansoor A. Shah, Rakhi B. TI Quality by design: Impact of formulation variables and their interactions on quality attributes of a lyophilized monoclonal antibody SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Lyophilization; Monoclonal antibody; IgG3 kappa; Quality by design; Formulation; Design of experiments ID AGGREGATION; TEMPERATURE; STABILITY; THERAPEUTICS; OPTIMIZATION; MOISTURE; PH AB The purpose of this study was to use QbD approaches to evaluate the effect of several variables and their interactions on quality of a challenging model murine IgG3 kappa monoclonal antibody (mAb), and then to obtain an optimized formulation with predefined quality target product profile. This antibody was chosen because it has a propensity to precipitate and thus represents a challenge condition for formulation development. Preliminary experiments were conducted to rule out incompatible buffer systems for the mAb product quality. A fractional factorial experimental design was then applied to screen the effects of buffer type, pH and excipients such as sucrose, sodium chloride (NaCl). lactic acid and Polysorbate 20 on glass transition temperature (T-g'), monoclonal antibody concentration (A(280)), presence of aggregation, unfolding transition temperature (T-m) of the lyophilized product, and particle size of the reconstituted product. A Box-Behnken experimental design was subsequently applied to study the main, interaction, and quadratic effects of these variables on the responses. Pareto ranking analyses showed that the three most important factors affecting the selected responses for this particular antibody were pH, NaCl, and Polysorbate 20. The presence of curvature in the variables' effects on responses indicated interactions. Based on the constraints set on the responses, a design space was identified for this mAb and confirmed with experiments at three different levels of the variables within the design space. The model indicated a combination of high pH (8) and NaCl (50 mM) levels, and a low Polysorbate 20 (0.008 mM) level at which an optimal formulation of the mAb could be achieved. Moisture contents and other analytical procedures such as size exclusion chromatography, protein A analysis and SDS-PAGE of the pre-lyophilized and final reconstituted lyophilized products indicated an intact protein structure with minimal aggregation after formulation and lyophilization. In conclusion, experimental design approach was effective in identifying optimal concentrations of excipients and pH for this challenging monoclonal antibody formulation. Published by Elsevier B.V. C1 [Awotwe-Otoo, David; Agarabi, Cyrus; Khan, Mansoor A.; Shah, Rakhi B.] US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Rockville, MD 20857 USA. [Wu, Geoffrey K.] US FDA, Off Gener Drugs, OPS, CDER, Rockville, MD 20857 USA. [Casey, Elizabeth] Purdue Univ, Dept Agr & Biol Engn, W Lafayette, IN 47907 USA. [Read, Erik; Lute, Scott; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, OPS,CDER, Rockville, MD 20857 USA. RP Shah, RB (reprint author), 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD USA. EM rakhi.shah@fda.hhs.gov NR 32 TC 21 Z9 23 U1 4 U2 43 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD NOV 15 PY 2012 VL 438 IS 1-2 BP 167 EP 175 DI 10.1016/j.ijpharm.2012.08.033 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 033AD UT WOS:000310763700019 PM 22944306 ER PT J AU Weng, ZQ Greenhaw, J Salminen, WF Shi, Q AF Weng, Zuquan Greenhaw, James Salminen, William F. Shi, Qiang TI Mechanisms for epigallocatechin gallate induced inhibition of drug metabolizing enzymes in rat liver microsomes SO TOXICOLOGY LETTERS LA English DT Article DE Epigallocatechin gallate; Cytochrome P450; Rat; Microsome; Covalent-binding; Glutathione ID CATECHOL-O-METHYLTRANSFERASE; GLUTATHIONE-S-TRANSFERASE; GREEN TEA POLYPHENOLS; MEMBRANE-PROTEINS; HERBAL EXTRACTS; CYTOCHROME-P450; ACTIVATION; HEPATOTOXICITY; NITROSYLATION; PURIFICATION AB Epigallocatechin gallate (EGCG) inhibits drug metabolizing enzymes by unknown mechanisms. Here we examined if the inhibition is due to covalent-binding of EGCG to the enzymes or formation of protein aggregates. EGCG was incubated with rat liver microsomes at 1-100 mu M for 30 min. The EGCG-binding proteins were affinity purified using m-aminophenylboronic acid agarose and probed with antibodies against glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin, cytochrome P450 (CYP) 1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A, catechol-O-methyltransferase (COMT) and microsomal glutathione transferase 1 (MGST1). All but actin and soluble COMT were positively detected at >= 1 mu M EGCG, indicating EGCG selectively bound to a subset of proteins including membrane-bound COMT. The binding correlated well with inhibition of CYP activities, except for CYP2E1 whose activity was unaffected despite evident binding. The antioxidant enzyme MGST1, but not cytosolic GSTs, was remarkably inhibited, providing novel evidence supporting the pro-oxidative effects of EGCG. When microsomes incubated with EGCG were probed on Western blots, all but the actin and CYP2E1 antibodies showed a significant reduction in binding at >= 1 mu M EGCG, suggesting that a fraction of the indicated proteins formed aggregates that likely contributed to the inhibitory effects of EGCG but were not recognizable by antibodies against the intact proteins. This raised the possibility that previous reports on EGCG regulating protein expression using GAPDH as a reference should be revisited for accuracy. Remarkable protein aggregate formation in EGCG-treated microsomes was also observed by analyzing Coomassie Blue-stained SDS-PAGE gels. EGCG effects were partially abolished in the presence of 1 mM glutathione, suggesting they are particularly relevant to the in vivo conditions when glutathione is depleted by toxicant insults. Published by Elsevier Ireland Ltd. C1 [Weng, Zuquan; Greenhaw, James; Salminen, William F.; Shi, Qiang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, Q (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Qiang.Shi@fda.hhs.gov RI Qiang, Shi/E-6266-2012 FU Research Participation Program at the National Center for Toxicological Research FX Dr. Zuquan Weng is supported by the Research Participation Program at the National Center for Toxicological Research administrated by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. Disclaimer: This article is not an official guidance or policy statement of the US Food and Drug Administration (FDA). No official support or endorsement by the FDA is intended or should be inferred. NR 44 TC 11 Z9 12 U1 2 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 15 PY 2012 VL 214 IS 3 BP 328 EP 338 DI 10.1016/j.toxlet.2012.09.011 PG 11 WC Toxicology SC Toxicology GA 029YN UT WOS:000310534100014 PM 23010222 ER PT J AU Brookhart, MA Walker, AM Lu, Y Polakowski, L Li, J Paeglow, C Puenpatom, T Izurieta, H Daniel, GW AF Brookhart, M. Alan Walker, Alexander M. Lu, Yun Polakowski, Laura Li, Jie Paeglow, Corrie Puenpatom, Tosmai Izurieta, Hector Daniel, Gregory W. TI Characterizing Vaccine-associated Risks Using Cubic Smoothing Splines SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE nonparametric regression; pharmacoepidemiology; self-controlled design; vaccine safety ID ACTIVE SURVEILLANCE; CASE SERIES; SAFETY; DESIGN AB Estimating risks associated with the use of childhood vaccines is challenging. The authors propose a new approach for studying short-term vaccine-related risks. The method uses a cubic smoothing spline to flexibly estimate the daily risk of an event after vaccination. The predicted incidence rates from the spline regression are then compared with the expected rates under a log-linear trend that excludes the days surrounding vaccination. The 2 models are then used to estimate the excess cumulative incidence attributable to the vaccination during the 42-day period after vaccination. Confidence intervals are obtained using a model-based bootstrap procedure. The method is applied to a study of known effects (positive controls) and expected noneffects (negative controls) of the measles, mumps, and rubella and measles, mumps, rubella, and varicella vaccines among children who are 1 year of age. The splines revealed well-resolved spikes in fever, rash, and adenopathy diagnoses, with the maximum incidence occurring between 9 and 11 days after vaccination. For the negative control outcomes, the spline model yielded a predicted incidence more consistent with the modeled day-specific risks, although there was evidence of increased risk of diagnoses of congenital malformations after vaccination, possibly because of a provider visit effect. The proposed approach may be useful for vaccine safety surveillance. C1 [Brookhart, M. Alan] Univ N Carolina, Dept Epidemiol, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Walker, Alexander M.] World Hlth Informat Sci Consultants, Newton, MA USA. [Lu, Yun; Polakowski, Laura; Izurieta, Hector] US FDA, CBER, Rockville, MD 20857 USA. [Li, Jie; Paeglow, Corrie; Puenpatom, Tosmai; Daniel, Gregory W.] HealthCore, Wilmington, DE USA. RP Brookhart, MA (reprint author), Univ N Carolina, Dept Epidemiol, UNC Gillings Sch Global Publ Hlth, CB 7435, Chapel Hill, NC 27599 USA. EM abrookhart@unc.edu NR 14 TC 1 Z9 1 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2012 VL 176 IS 10 BP 949 EP 957 DI 10.1093/aje/kws158 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 034SH UT WOS:000310892700012 PM 23100246 ER PT J AU Hassenplug, JC AF Hassenplug, John C. TI Patient Access to Medical Devices REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Food & Drug Adm, Silver Spring, MD USA. RP Hassenplug, JC (reprint author), Food & Drug Adm, Silver Spring, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 15 PY 2012 VL 367 IS 20 BP 1964 EP 1965 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 036MB UT WOS:000311029300029 ER PT J AU Jain, M Zhang, LS He, M Patterson, EE Nilubol, N Fojo, AT Joshi, B Puri, R Kebebew, E AF Jain, Meenu Zhang, Lisa He, Mei Patterson, Erin E. Nilubol, Naris Fojo, Antonio T. Joshi, Bharat Puri, Raj Kebebew, Electron TI Interleukin-13 Receptor Alpha2 Is a Novel Therapeutic Target for Human Adrenocortical Carcinoma SO CANCER LA English DT Article DE interleukin-13 receptor alpha2; interleuken-13-Pseudomonas exotoxin; adrenocortical carcinoma; invasion ID CHIMERIC FUSION PROTEINS; SQUAMOUS-CELL CARCINOMA; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMAS; CANCER THERAPY; EXPRESSION; CHAIN; TUMORS; HEAD AB BACKGROUND. Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome-wide expression studies have demonstrated the overexpression of interleukin-13 receptor alpha2 (IL13R alpha 2) in some human malignancies. METHODS. The authors evaluated IL13R alpha 2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 R alpha 2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI-H295R [high IL13R alpha 2 expression] and SW13 [low IL13R alpha 2 expression]) to a highly specific IL-13 conjugated with Pseudomonas exotoxin (IL-13-PE) also was evaluated in both in vitro and in vivo models. RESULTS. IL13R alpha 2 was overexpressed in malignant tumors compared with benign and normal samples (15-fold higher; P < .05). Immunohistochemistry also confirmed higher protein expression in malignant and benign tumors than in normal adrenocortical tissues (P < .05). The half-maximal inhibitory concentration for IL-13-PE was 1.3 ng/mL in the NCI-H295R cell line and 1000 ng/mL in the SW13 cell line. Mice that received intratumoral or intraperitoneal IL-13-PE injection had a significant reduction in tumor size and increased tumor necrosis compared with control groups (P < .05) and also had prolonged survival (P < .05). IL13R alpha 2 protein expression increased in cells that were treated with IL-13 ligand along with cell invasion (P < .05). Direct IL13R alpha 2 knockdown decreased cellular proliferation and invasion (P < .05). CONCLUSIONS. The current results indicated that IL13R alpha 2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13R alpha 2 is a novel therapeutic target for the treatment of human ACC. Cancer 2012;118;5698-708 (C) 2012 American Cancer Society. C1 [Kebebew, Electron] NCI, Endocrine Oncol Branch, CRC Hatfield Clin Res Ctr 10, NIH, Bethesda, MD 20892 USA. [Joshi, Bharat; Puri, Raj] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Fojo, Antonio T.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, CRC Hatfield Clin Res Ctr 10, NIH, Bethesda, MD 20892 USA. EM electron.kebebew@nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health [1ZIABC011286-01, 1ZIABC011275-01] FX This study was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (grants 1ZIABC011286-01 and 1ZIABC011275-01). NR 41 TC 8 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5698 EP 5708 DI 10.1002/cncr.27629 PG 11 WC Oncology SC Oncology GA 029GW UT WOS:000310483800030 PM 22570059 ER PT J AU Prestwich, GD Bhatia, S Breuer, CK Dahl, SLM Mason, C McFarland, R McQuillan, DJ Sackner-Bernstein, J Schox, J Tente, WE Trounson, A Breuer, CK Trounson, A AF Prestwich, Glenn D. Bhatia, Sangeeta Breuer, Christopher K. Dahl, Shannon L. M. Mason, Chris McFarland, Richard McQuillan, David J. Sackner-Bernstein, Jonathan Schox, Jeffrey Tente, William E. Trounson, Alan Breuer, Christopher K. Trounson, Alan TI What Is the Greatest Regulatory Challenge in the Translation of Biomaterials to the Clinic? SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article C1 [Prestwich, Glenn D.] Univ Utah, Dept Med, Salt Lake City, UT 84108 USA. [Bhatia, Sangeeta] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Bhatia, Sangeeta] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Breuer, Christopher K.] Ohio State Univ, Nationwide Childrens Hosp, Ctr Regenerat Med & Cell Based Therapies, Wexner Med Ctr, Columbus, OH 43205 USA. [Dahl, Shannon L. M.; McQuillan, David J.; Tente, William E.] Humacyte, Res Triangle Pk, NC 27709 USA. [Mason, Chris] UCL, Adv Ctr Biochem Engn, London WC1E 6BT, England. [McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Sackner-Bernstein, Jonathan] Neostem, New York, NY 10170 USA. [Schox, Jeffrey] Schox PLC, San Francisco, CA 94107 USA. [Trounson, Alan] Calif Inst Regenerat Med, San Francisco, CA 94107 USA. [Schox, Jeffrey] Stanford Law School, Stanford, CA USA. [Bhatia, Sangeeta] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Prestwich, GD (reprint author), Univ Utah, Dept Med, Salt Lake City, UT 84108 USA. EM glenn.prestwich@pharm.utah.edu; sbhatia@mit.edu; christo-pher.breuer@nationwidechildrens.org; dahl@humacyte.com; chris.mason@ucl.ac.uk; rich-ard.mcfarland@fda.hhs.gov; jsb@neostem.com; jef@schox.com; atrounson@cirm.ca.gov FU Gunze Ltd.; Pall Corporation FX C.K.B. receives grant support from Gunze Ltd. and the Pall Corporation. G.D.P. holds equity in BioTime, Inc.; Carbylan Biosurgery, Inc.; GlycoMira Therapeutics, Inc.; and Organovo, Inc. NR 1 TC 12 Z9 13 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 14 PY 2012 VL 4 IS 160 AR 160cm14 DI 10.1126/scitranslmed.3004915 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 037IQ UT WOS:000311097100002 PM 23152323 ER PT J AU Toh, S Reichman, ME Houstoun, M Southworth, MR Ding, X Hernandez, AF Levenson, M Li, LL McCloskey, C Shoaibi, A Wu, E Zornberg, G Hennessy, S AF Toh, Sengwee Reichman, Marsha E. Houstoun, Monika Southworth, Mary Ross Ding, Xiao Hernandez, Adrian F. Levenson, Mark Li, Lingling McCloskey, Carolyn Shoaibi, Azadeh Wu, Eileen Zornberg, Gwen Hennessy, Sean TI Comparative Risk for Angioedema Associated With the Use of Drugs That Target the Renin-Angiotensin-Aldosterone System SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INHIBITOR-ASSOCIATED ANGIOEDEMA; CONVERTING ENZYME-INHIBITORS; ACE-INHIBITORS; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; CLINICAL-EXPERIENCE; RECEPTOR BLOCKERS; PROPENSITY SCORE; POOLED ANALYSIS; SAFETY AB Background: Although certain drugs that target the renin-angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited to the use of most drugs that target the system. We assessed the risk for angioedema associated with the use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren. Methods: We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313), aliskiren (n = 4867), or a beta-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using beta-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs. Results: A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for beta-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for beta-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for beta-blockers. Compared with the use of beta-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren. Conclusions: Compared with beta-blockers, ACEIs or aliskiren was associated with an approximately 3-fold higher risk for angioedema, although the number of exposed events for aliskiren was small. The risk for angioedema was lower with ARBs than with ACEIs or aliskiren. C1 [Toh, Sengwee; Li, Lingling] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Toh, Sengwee; Li, Lingling] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Reichman, Marsha E.; Houstoun, Monika; McCloskey, Carolyn; Wu, Eileen; Zornberg, Gwen] Ctr Drug Evaluat & Res Food & Drug Adm, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Southworth, Mary Ross] Ctr Drug Evaluat & Res Food & Drug Adm, Off New Drugs, Silver Spring, MD USA. [Ding, Xiao; Levenson, Mark] Ctr Drug Evaluat & Res Food & Drug Adm, Off Translat Sci, Silver Spring, MD USA. [Shoaibi, Azadeh] Ctr Drug Evaluat & Res Food & Drug Adm, Off Med Policy, Silver Spring, MD USA. [Hernandez, Adrian F.] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Hennessy, Sean] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hennessy, Sean] Univ Penn, Ctr Pharmacoepidemiol Res & Training, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Toh, S (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM darrentoh@post.harvard.edu RI Toh, Sengwee/D-7567-2017; Hernandez, Adrian F./A-7818-2016 OI Toh, Sengwee/0000-0002-5160-0810; Hernandez, Adrian F./0000-0003-3387-9616 FU Amylin; AstraZeneca; Corthera; Johnson Johnson; sanofi-aventis; Bristol-Myers Squibb; Food and Drug Administration from the Department of Health and Human Services [HHSF223200910006I] FX Dr Hernandez has received research support or consulting fees from Amylin, AstraZeneca, Corthera, Johnson & Johnson, and sanofi-aventis. Dr Hennessy has received research support from AstraZeneca and Bristol-Myers Squibb and has consulted for Abbott and Novartis, unrelated to the products examined in this study.; The Mini-Sentinel program is funded by the Food and Drug Administration through contract HHSF223200910006I from the Department of Health and Human Services. NR 42 TC 56 Z9 57 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 12 PY 2012 VL 172 IS 20 BP 1582 EP 1589 DI 10.1001/2013.jamainternmed.34 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 035XR UT WOS:000310987300010 PM 23147456 ER PT J AU Wang, SJ Hung, HMJ O'Neill, R AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert TI Paradigms for adaptive statistical information designs: practical experiences and strategies SO STATISTICS IN MEDICINE LA English DT Article DE adaptive design paradigms; Brownian motion; conditional power; exploratory adaptive statistical information design; linear drift; twilight zone ID CLINICAL-TRIAL DESIGN; SAMPLE-SIZE; SECONDARY PREVENTION; TARGETED THERAPY; I ERROR; WIZARD; AZITHROMYCIN; PERSPECTIVES; SUBSET AB In the last decade or so, interest in adaptive design clinical trials has gradually been directed towards their use in regulatory submissions by pharmaceutical drug sponsors to evaluate investigational new drugs. Methodological advances of adaptive designs are abundant in the statistical literature since the 1970s. The adaptive design paradigm has been enthusiastically perceived to increase the efficiency and to be more cost-effective than the fixed design paradigm for drug development. Much interest in adaptive designs is in those studies with two-stages, where stage 1 is exploratory and stage 2 depends upon stage 1 results, but where the data of both stages will be combined to yield statistical evidence for use as that of a pivotal registration trial. It was not until the recent release of the US Food and Drug Administration Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics (2010) that the boundaries of flexibility for adaptive designs were specifically considered for regulatory purposes, including what are exploratory goals, and what are the goals of adequate and well-controlled (A&WC) trials (2002). The guidance carefully described these distinctions in an attempt to minimize the confusion between the goals of preliminary learning phases of drug development, which are inherently substantially uncertain, and the definitive inference-based phases of drug development. In this paper, in addition to discussing some aspects of adaptive designs in a confirmatory study setting, we underscore the value of adaptive designs when used in exploratory trials to improve planning of subsequent A&WC trials. One type of adaptation that is receiving attention is the re-estimation of the sample size during the course of the trial. We refer to this type of adaptation as an adaptive statistical information design. Specifically, a case example is used to illustrate how challenging it is to plan a confirmatory adaptive statistical information design. We highlight the substantial risk of planning the sample size for confirmatory trials when information is very uninformative and stipulate the advantages of adaptive statistical information designs for planning exploratory trials. Practical experiences and strategies as lessons learned from more recent adaptive design proposals will be discussed to pinpoint the improved utilities of adaptive design clinical trials and their potential to increase the chance of a successful drug development. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Wang, Sue-Jane] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS, CDER, Mailstop WO 21,Room 3562 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU RSR, Center for Drug and Evaluation, US Food and Drug Administration [05-02, 5-14] FX The work presented here includes that of our research supported by the RSR funds # 05-02 and # 5-14, Center for Drug and Evaluation, US Food and Drug Administration. The authors thank Dr Joshua Chen for discussing their 2004 paper. The authors are grateful to the reviewers for their insightful comments to help enhancing the presentation of this paper. The professional views presented in this paper are not necessarily those of the US Food and Drug Administration. NR 34 TC 11 Z9 12 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3011 EP 3023 DI 10.1002/sim.5410 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200008 PM 22927234 ER PT J AU Lusk, TS Ottesen, AR White, JR Allard, MW Brown, EW Kase, JA AF Lusk, Tina S. Ottesen, Andrea R. White, James R. Allard, Marc W. Brown, Eric W. Kase, Julie A. TI Characterization of microflora in Latin-style cheeses by next-generation sequencing technology SO BMC MICROBIOLOGY LA English DT Article DE Latin-style cheese; Next Generation Sequencing; Microflora; Bacteria; Exiguobacterium ID LISTERIA-MONOCYTOGENES; BACTERIAL COMMUNITIES; PASTEURIZED MILK; RAW-MILK; SP-NOV; EXIGUOBACTERIUM; DIVERSITY; WATER; OUTBREAK; GROWTH AB Background: Cheese contamination can occur at numerous stages in the manufacturing process including the use of improperly pasteurized or raw milk. Of concern is the potential contamination by Listeria monocytogenes and other pathogenic bacteria that find the high moisture levels and moderate pH of popular Latin-style cheeses like queso fresco a hospitable environment. In the investigation of a foodborne outbreak, samples typically undergo enrichment in broth for 24 hours followed by selective agar plating to isolate bacterial colonies for confirmatory testing. The broth enrichment step may also enable background microflora to proliferate, which can confound subsequent analysis if not inhibited by effective broth or agar additives. We used 16S rRNA gene sequencing to provide a preliminary survey of bacterial species associated with three brands of Latin-style cheeses after 24-hour broth enrichment. Results: Brand A showed a greater diversity than the other two cheese brands (Brands B and C) at nearly every taxonomic level except phylum. Brand B showed the least diversity and was dominated by a single bacterial taxon, Exiguobacterium, not previously reported in cheese. This genus was also found in Brand C, although Lactococcus was prominent, an expected finding since this bacteria belongs to the group of lactic acid bacteria (LAB) commonly found in fermented foods. Conclusions: The contrasting diversity observed in Latin-style cheese was surprising, demonstrating that despite similarity of cheese type, raw materials and cheese making conditions appear to play a critical role in the microflora composition of the final product. The high bacterial diversity associated with Brand A suggests it may have been prepared with raw materials of high bacterial diversity or influenced by the ecology of the processing environment. Additionally, the presence of Exiguobacterium in high proportions (96%) in Brand B and, to a lesser extent, Brand C (46%), may have been influenced by the enrichment process. This study is the first to define Latin-style cheese microflora using Next-Generation Sequencing. These valuable preliminary data will direct selective tailoring of agar formulations to improve culture-based detection of pathogens in Latin-style cheese. C1 [Lusk, Tina S.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37830 USA. [Ottesen, Andrea R.; Allard, Marc W.; Brown, Eric W.; Kase, Julie A.] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, College Pk, MD 20740 USA. [White, James R.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. RP Lusk, TS (reprint author), Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37830 USA. EM tina.lusk@fda.hhs.gov FU Research Participation Program at the Center for Food Safety and Applied Nutrition FX This project was supported in part by an appointment (TSL) to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 52 TC 16 Z9 16 U1 0 U2 44 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD NOV 7 PY 2012 VL 12 AR 254 DI 10.1186/1471-2180-12-254 PG 10 WC Microbiology SC Microbiology GA 045JO UT WOS:000311692200001 PM 23134566 ER PT J AU Hunt, A Bohm, SR Bidol, SA Achen, M Cui, J Denny, L Brandt, E Davis, S Woody, D Reimschuessel, R Tuite, C Rotstein, D Schwensohn, C Behravesh, CB Imanishi, M AF Hunt, April Bohm, Susan R. Bidol, Sally A. Achen, Maya Cui, Jing Denny, Lynn Brandt, Eric Davis, Sam Woody, Dillard Reimschuessel, Renate Tuite, Carla Rotstein, David Schwensohn, Colin Behravesh, Casey Barton Imanishi, Maho CA Public Hlth Agcy Canada TI Notes From the Field: Human Salmonella Infantis Infections Linked to Dry Dog Food-United States and Canada, 2012 (Reprinted from MMWR, vol 23, pg 436, 2012) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Imanishi, Maho] CDC, EIS, Atlanta, GA 30333 USA. [Denny, Lynn; Brandt, Eric] Ohio Dept Hlth, Columbus, OH 43266 USA. [Woody, Dillard; Reimschuessel, Renate] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. [Tuite, Carla; Rotstein, David] US FDA, Coordinated Outbreak Response & Evaluat Network, Rockville, MD 20857 USA. [Schwensohn, Colin; Behravesh, Casey Barton] CDC, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. RP Imanishi, M (reprint author), CDC, EIS, Atlanta, GA 30333 USA. EM hwl2@cdc.gov NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2012 VL 308 IS 17 BP 1736 EP 1736 DI 10.1001/jama.2012.10060 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 032NR UT WOS:000310726500009 ER PT J AU Lo Surdo, J Bauer, SR AF Lo Surdo, Jessica Bauer, Steven R. TI Quantitative Approaches to Detect Donor and Passage Differences in Adipogenic Potential and Clonogenicity in Human Bone Marrow-Derived Mesenchymal Stem Cells SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID MULTIPOTENT STROMAL CELLS; LIMITING DILUTION ASSAYS; OSTEOGENIC DIFFERENTIATION; ADIPOSE-TISSUE; PROGENITOR CELLS; EXPRESSION; POPULATIONS; EXPANSION; CULTURES; PROLIFERATION AB Bone marrow-derived multipotent stromal cells (MSCs), also known as mesenchymal stem cells, have great promise due to their capacity for tri-lineage differentiation and immunosuppressive properties, which allows for their allogeneic use and ultimately may allow for treatment of many diseases. MSCs will require extensive expansion and passaging to obtain cells in sufficient numbers necessary for cell therapies. MSCs from many donors could potentially be used. Because of this, there is a need to understand the role of passaging and donor differences on differentiation capacity using quantitative approaches. Here, we evaluated MSCs from two donors (noted as PCBM1632 and PCBM1641 by the manufacturer) at tissue culture passages 3, 5, and 7. We used a colony forming unit (CFU) assay and limiting dilution to quantify clonogenicity and precursor frequency during adipogenesis, and quantitative real-time-polymerase chain reaction for adipogenic markers to evaluate changes on a gene expression level. Further, we observed changes in cell size, and we sorted small and large populations to evaluate size-related adipogenic potential. While the adipogenic precursor frequency of similar to 1 in 76 cells remained similar through passages for cells from PCBM1641, we found a large decrease in the adipogenic potential of MSCs from PCBM1632, with 1 in 2035 cells being capable of differentiating into an adipocyte at passage 7. MSCs from both donors showed an increase in cell diameter with increasing passage, which correlates with a decrease in clonogenicity by CFU analysis. We also measured adipose lineage gene expression following induction of adipocyte differentiation. Expression of these genes decreased with passage number for MSCs from PCBM1632 and correlated with the decrease in adipogenic potential by passage 7. In contrast, MSCs from PCBM1641 showed increased expression of these genes with increasing passage. We have shown that several quantitative assays can detect differences in MSC differentiation capacity, clonogenicity, and cell size between donors and passages. These quantitative methods are useful to assess the quality of MSCs. C1 [Lo Surdo, Jessica; Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20892 USA. RP Bauer, SR (reprint author), US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, NIH Bldg,29B 2NN10 HFM-740,8800 Rockville Pike, Bethesda, MD 20892 USA. EM steven.bauer@fda.hhs.gov OI Bauer, Steven/0000-0003-2831-846X FU FDA Modernizing Science grant program; BARDA grant; Division of Cell and Gene Therapies; FDA's Office of the Chief Scientist; BARDA; Division of Cellular and Gene Therapies FX This project was supported in part by Jessica Lo Surdo's appointment to the Research Participation Program at CBER administered by the Oak Ridge Institute for Science and Education through US DOE and US FDA. This work was also supported in part by the FDA Modernizing Science grant program, a BARDA grant, and Division of Cell and Gene Therapies. The authors would like to acknowledge Drs. Cheng-Hong Wei and Jeffry Smith for reviewing this article and Howard Mostowski for his assistance in sorting MSC samples. Research support came from FDA's Office of the Chief Scientist, BARDA, and operating funds from the Division of Cellular and Gene Therapies. NR 65 TC 32 Z9 32 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD NOV PY 2012 VL 18 IS 11 BP 877 EP 889 DI 10.1089/ten.tec.2011.0736 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 030MN UT WOS:000310574900006 PM 22563812 ER PT J AU DeMuth, JE Ji, QC Booth, BP Fluhler, EN Greathead, R Ho, S Stubbs, RJ Turk, DJ AF DeMuth, James E. Ji, Qin C. Booth, Brian P. Fluhler, Eric N. Greathead, Roger Ho, Stacy Stubbs, R. John Turk, Douglas J. TI Emerging technology for bioanalysis in the next decade SO BIOANALYSIS LA English DT Editorial Material AB The 13th Annual University of Wisconsin Land O'Lakes Bioanalytical Conference 16-20 July 2012, Merrimac, WI, USA This University of Wisconsin School of Pharmacy bioanalytical conference is presented each year by the Extension Services in Pharmacy, the professional development department within the School. The purpose of this 4-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioarialysis. To increase the interactive nature of the conference, the program was a mixture of lectures, poster sessions, round table discussions and workshops. This article summarizes the presentations at the 13th Annual Conference. C1 [DeMuth, James E.] Univ Wisconsin, Madison, WI 53705 USA. [Booth, Brian P.] US FDA, Ctr Drug Res & Evaluat, Rockville, MD 20857 USA. [Turk, Douglas J.] PRACS Inst, Toronto, ON, Canada. RP DeMuth, JE (reprint author), Univ Wisconsin, 777 Highland Ave, Madison, WI 53705 USA. EM jedemuth@pharmacy.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD NOV PY 2012 VL 4 IS 21 BP 2557 EP 2561 DI 10.4155/BIO.12.227 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 085MZ UT WOS:000314620200008 PM 23173791 ER PT J AU Jaworska, K Krynitsky, AJ Rader, JI AF Jaworska, Karolina Krynitsky, Alexander J. Rader, Jeanne I. TI Simultaneous Analysis of Steviol and Steviol Glycosides by Liquid Chromatography with Ultraviolet Detection on a Mixed-Mode Column: Application to Stevia Plant Material and Stevia-Containing Dietary Supplements SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID POTENTIAL SWEETENING AGENTS; CAPILLARY ELECTROPHORESIS; MASS-SPECTROMETRY; REBAUDIANA; QUANTIFICATION; FLAVONOIDS; DITERPENE; ORIGIN AB Simultaneous separation of steviol and steviol glycosides is challenging because of differences in their polarity and chemical structure. In this study, simultaneous analysis of steviol and steviol glycosides was achieved by LC with UV detection using a mixed-mode RP weak anion exchange chromatography column. Steviol and seven steviol glycosides were analyzed on an Acclaim Mixed-Mode Wax-1 (Dionex) column with a linear gradient of deionized water adjusted to pH 3.00 with phosphoric acid and acetonitrile. The extraction was performed by sonicating dry plant material at 40 degrees C in acetonitrile-water (30 + 70, v/v). LOQ values (mg/g dry weight of plant material) were rebaudioside B, 0.50; steviol, 0.70, dulcoside A, 1.0; steviolbioside, 1.2; stevioside and rebaudioside C, 2.0; rebaudioside D, 3.3; and rebaudioside A, 5.0. The method demonstrated suitable performance for all analytes tested with respect to accuracy (mean recoveries 95-99%), intraday and interday precision for retention times (0.070-0.28% and 0.33-1.0% RSD, respectively), and linearity. The method was used to authenticate steviol glycosides in several samples of Stevia plant material as well as to quantitate steviol glycosides in dietary supplements containing Stevia. C1 [Jaworska, Karolina; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Krynitsky, AJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Alex.Krynitsky@fda.hhs.gov FU U.S. Food and Drug Administration FX Karolina Jaworska is a predoctoral student at the Technische Universitat Berlin, Institute of Food Technology and Food Chemistry, Germany. This project was supported by an appointment of Karolina Jaworska to the Research Fellowship Program of the U.S. Food and Drug Administration administered by the Oak Ridge Institute of Science and Education. We wish to thank Romina Shah, Pierluigi Delmonte, Rahul Pawar, Erich Grundel, and Ali Reza Fardin Kia for helpful discussions. NR 34 TC 5 Z9 6 U1 1 U2 51 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2012 VL 95 IS 6 BP 1588 EP 1596 DI 10.5740/jaoacint.11-435 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 065IU UT WOS:000313142800008 PM 23451373 ER PT J AU Ma, J Krynitsky, AJ Grundel, E Rader, JI AF Ma, Jun Krynitsky, Alexander J. Grundel, Erich Rader, Jeanne I. TI Quantitative Determination of Cucurbitane-Type Triterpenes and Triterpene Glycosides in Dietary Supplements Containing Bitter Melon (Momordica charantia) by HPLC-MS/MS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIGHT-SCATTERING DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; CONSTITUENTS; FRUITS AB Momordica charantia L. (Cucurbitaceae), commonly known as bitter melon, is widely cultivated in many tropical and subtropical areas of the world. It is a common food staple; its fruits, leaves, seeds, stems, and roots also have a long history of use in traditional medicine. In the United States, dietary supplements labeled as containing bitter melon can be purchased over-the-counter and from Internet suppliers. Currently, no quantitative analytical method is available for monitoring the content of cucurbitane-type triterpenes and triterpene glycosides, the major constituents of bitter melon, in such supplements. We investigated the use of HPLC-electrospray ionization (ESI)-MS/MS for the quantitative determination of such compounds in dietary supplements containing bitter melon. Values for each compound obtained from external calibration were compared with those obtained from the method of standard additions to address matrix effects associated with ESI. In addition, the cucurbitane-type triterpene and triterpene glycoside contents of two dietary supplements determined by the HPLC-ESI-MS/MS method with standard additions were compared with those measured by an HPLC method with evaporative light scattering detection, which was recently developed for quantification of such compounds in dried fruits of M. charantia. The contents of five cucurbitane-type triterpenes and triterpene glycosides in 10 dietary supplements were measured using the HPLC-ESI-MS/MS method with standard additions. The total contents of the five compounds ranged from 17 to 3464 mu g/serving. C1 [Ma, Jun; Krynitsky, Alexander J.; Grundel, Erich; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Ma, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jun.ma@fda.hhs.gov NR 29 TC 2 Z9 2 U1 5 U2 18 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2012 VL 95 IS 6 BP 1597 EP 1608 DI 10.5740/jaoacint.11-511 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 065IU UT WOS:000313142800009 PM 23451374 ER PT J AU Bao, L Liang, CZ Trucksess, MW Xu, YL Lv, N Wu, ZX Jing, P Fry, FS AF Bao, Lei Liang, Chengzhu Trucksess, Mary W. Xu, Yanli Lv, Ning Wu, Zhenxing Jing, Ping Fry, Fred S. TI Determination of Aflatoxins B-1, B-2, G(1), and G(2) in Olive Oil, Peanut Oil, and Sesame Oil Using Immunoaffinity Column Cleanup, Postcolumn Derivatization, and Liquid Chromatography/Fluorescence Detection: Collaborative Study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NATURAL OCCURRENCE; OCHRATOXIN-A; PERFORMANCE; PRECISION; PASTE AB The accuracy, repeatability, and reproducibility characteristics of a method using immunoaffinity column (IAC) cleanup with postcolumn derivatization and LC with a fluorescence detector (FLD) for determination of aflatoxins (AFs; sum of AFs B-1, B-2, G(1), and G(2)) in olive oil, peanut oil, and sesame oil have been established in a collaborative study involving 15 laboratories from six countries. Blind duplicate samples of blank, spiked at levels ranging from 0.25 to 20.0 mu g/kg for AF, were analyzed. A naturally contaminated peanut oil sample was also included. Test samples were extracted with methanol-water (55 + 45, v/v). After shaking and centrifuging, the lower layer was filtered, diluted with water, and filtered through glass microfiber filter paper. The filtrate was then passed through an IAC, and the toxins were eluted with methanol. The toxins were then subjected to RPLC-FLD analysis after postcolumn derivatization. Average recoveries of AFs from olive oil, peanut oil, and sesame oil ranged from 84 to 92% (at spiking levels ranging from 2.0 to 20.0 mu g/kg); of AFB(1) from 86 to 93% (at spiking levels ranging from 1.0 to 10.0 mu g/kg); of AFB(2) from 89 to 95% (at spiking levels ranging from 0.25 to 2.5 mu g/kg); of AFG(1) from 85 to 97% (at spiking levels ranging from 0.5 to 5.0 mu g/kg); and of AFG(2) from 76 to 85% (at spiking levels ranging from 0.25 to 2.5 mu g/kg). RSDs for within-laboratory repeatability (RSDr) ranged from 3.4 to 10.2% for AF, from 3.5 to 10.9% for AFB(1), from 3.2 to 9.5% for AFB(2), from 6.5 to 14.9% for AFG(1), and from 4.8 to 14.2% for AFG(2). RSDs for between-laboratory reproducibility (RSDR) ranged from 6.1 to 14.5% for AF, from 7.5 to 15.4% for AFB(1), from 7.1 to 14.6% for AFB(2), from 10.8 to 18.1% for AFG(1), and from 7.6 to 23.7% for AFG(2). Horwitz ratio values were <= 2 for the analytes in the three matrixes. C1 [Bao, Lei; Liang, Chengzhu; Xu, Yanli; Lv, Ning; Wu, Zhenxing; Jing, Ping] Shandong Exit Entry Inspect & Quarantine Bur Chin, Qing Dao 266002, Peoples R China. [Trucksess, Mary W.; Fry, Fred S.] US FDA, College Pk, MD 20740 USA. RP Bao, L (reprint author), Shandong Exit Entry Inspect & Quarantine Bur Chin, Qing Dao 266002, Peoples R China. EM baoleiqd@yahoo.com.cn FU Quality Inspection Public Welfare Research Projects [200910295]; Ministry of Science and Technology, Beijing, China FX This work was partially supported by the Quality Inspection Public Welfare Research Projects (200910295), Ministry of Science and Technology, Beijing, China. NR 25 TC 3 Z9 3 U1 6 U2 34 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2012 VL 95 IS 6 BP 1689 EP 1700 DI 10.5740/jaoacint.12-199 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 065IU UT WOS:000313142800020 PM 23451385 ER PT J AU Ganderup, NC Harvey, W Mortensen, JT Harrouk, W AF Ganderup, Niels Christian Harvey, Warren Mortensen, Jens Thing Harrouk, Wafa TI The Minipig as Nonrodent Species in Toxicology-Where Are We Now? SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE minipig; toxicology; regulatory toxicology ID LEUKOCYTE DIFFERENTIATION ANTIGENS; GOTTINGEN MINIATURE PIGS; O-CRESYL PHOSPHATE; ANIMAL-MODELS; ERUCIC-ACID; CANOLA OIL; IN-VITRO; ACETYLCHOLINESTERASE ACTIVITIES; INTERNATIONAL WORKSHOP; SAFETY PHARMACOLOGY AB Over the past 3 decades minipigs have moved from being an obscure alternative to dogs and nonhuman primates to being a standard animal model in regulatory toxicity studies. This article covers the use of minipigs as a model in the context of nonclinical drug safety and provides an overview of the minipig's developmental history and relates minipigs to other animal species commonly used in toxicology; and the minipig's translational power is supported by 43 case studies of marketed drug products covered. Special focus is given to criteria for selecting minipigs in nonclinical programs supporting the development of new medicines; the use of swine in the assessment of food additives, agrochemicals, and pesticides; as well as a regulatory perspective on the use of minipigs in Food and Drug Administration (FDA)-regulated products. This article presents the main points conveyed at a symposium held at the 2010 American College of Toxicology meeting in Baltimore, Maryland. C1 [Ganderup, Niels Christian] Ellegaard Gottingen Minipigs, DK-4261 Dalmose, Denmark. [Harvey, Warren] Charles River Preclin Serv, Edinburgh, Midlothian, Scotland. [Mortensen, Jens Thing] CiToxLAB, Lille Skensved, Denmark. [Harrouk, Wafa] US FDA, Silver Spring, MD USA. RP Ganderup, NC (reprint author), Ellegaard Gottingen Minipigs, Soroe Landevej 302, DK-4261 Dalmose, Denmark. EM nc@ganderup.dk NR 163 TC 18 Z9 19 U1 0 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD NOV-DEC PY 2012 VL 31 IS 6 BP 507 EP 528 DI 10.1177/1091581812462039 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 063NS UT WOS:000313007300001 PM 23134714 ER PT J AU Marchand, HC Rose, BJ Fine, AM Kremzner, ME AF Marchand, Heidi C. Rose, Brenda J. Fine, Anna M. Kremzner, Mary E. TI The US Food and Drug Administration: Drug Information Resource for Formulary Recommendations SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Article AB BACKGROUND: The U.S. Food and Drug Administration (FDA) is the regulatory agency responsible for approving all pharmaceutical products marketed in the United States. While the FDA does not conduct research for developing pharmaceutical products, the agency does review all of the scientific evidence that a pharmaceutical sponsor submits and ensures that it demonstrates U.S. regulatory standards for the product and meets approval requirements. OBJECTIVES: To provide insights, for the managed care pharmacist, into the agency's decision-making process and into the recommendations for appropriate usage and regulatory recommendations for risk mitigation by pharmaceutical sponsors. METHODS: The FDA website contains a vast amount of clinically useful and meaningful information. This review focused on specific topics within the website that can be useful for the managed care pharmacist, including the following: (a) the FDA's review and evaluation of new drug applications (NDA), supplemental new drug applications (s-NDA), and biological new drug applications (BLA); (b) materials regarding a therapeutic product presented to a public FDA advisory committee meeting; and (c) the postmarket requirements and commitments database that provides information on the studies that a sponsor must conduct to maintain a product's approval for marketing in the United States. RESULTS: This review examined the drug information contained on the FDA's website and summarized the FDA's medical and technical review, analysis and decision processes. Detailed drug information provided to the FDA by the pharmaceutical sponsor demonstrating a product's efficacy and safety is publically available upon the product's approval. CONCLUSION: For the managed care pharmacist involved with formulary review and recommendations, the FDA's website contains information that is available to provide insight into the agency's evaluation process and decision making for marketed pharmaceutical products. Use of these materials and understanding the regulatory context under which medical products are reviewed and approved may assist managed care pharmacists in making informed recommendations for use of the products within the context of their health systems. J Manag Care Pharm. 2012;18(9):713-18 Copyright (c) 2012, Academy of Managed Care Pharmacy. All rights reserved. C1 [Marchand, Heidi C.; Rose, Brenda J.; Fine, Anna M.] US FDA, Hlth Profess Liaison Program, Off Special Hlth Issues, Silver Spring, MD 20903 USA. [Kremzner, Mary E.] US PHS, Silver Spring, MD USA. [Kremzner, Mary E.] US FDA, Div Informat, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Marchand, HC (reprint author), US FDA, Hlth Profess Liaison Program, Off Special Hlth Issues, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Heidi.Marchand@fda.hhs.gov NR 1 TC 3 Z9 3 U1 0 U2 7 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD NOV-DEC PY 2012 VL 18 IS 9 BP 713 EP 718 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 062MN UT WOS:000312924000004 PM 23206214 ER PT J AU Ferguson, SA Law, CD Abshire, JS AF Ferguson, Sherry A. Law, C. Delbert Abshire, Jordan S. TI Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Bisphenol A; Locomotor activity; Learning; Novelty preference; Motor coordination; Startle ID SPRAGUE-DAWLEY RATS; PLACE PREFERENCE BEHAVIOR; ETHINYL ESTRADIOL; PRENATAL EXPOSURE; SEXUAL-DIFFERENTIATION; RESTRAINT STRESS; FEMALE; TOXICITY; ESTROGEN; MEMORY AB Widespread bisphenol A (BPA) exposure necessitates increased knowledge of its potential effects for better risk assessment and regulatory guidance. Here, female Sprague-Dawley rats, reared in low exogenous estrogen environments and bred at adulthood, were gavaged on gestational days 6-21 with vehicle (VEH), 2.5 or 25.0 mu g/kg/day BPA, or 5.0 or 10.0 mu g/kg/day ethinyl estradiol (EE2). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose their dam received. A naive control group (NC) was not gavaged. Post-weaning, one offspring/sex/litter (n = 11-12/sex/group) was assessed for the typical behaviors measured in developmental neurotoxicology studies. At PND 29, novelty preference was unaffected by treatment; however, relative to the VEH group, males and females of both EE2 groups were more active. VEH males appeared somewhat hypoactive in open field assessments at PNDs 40-42 and, as a result, males of the BPA and EE2 groups were significantly more active. Latency to locate the Barnes maze escape box at PNDs 47-50 was increased in males and females of the 5.0 mu g/kg/day EE2 group. Relative to other male groups, VEH males exhibited an increased startle response on the first trial block at PND 54 and thus, males of both BPA groups and the 10.0 mu g/kg/day EE2 group exhibited a significantly decreased startle response. PNDs 43-44 motor coordination and PNDs 75-79 water maze performance were unaffected by treatment. These results indicate few consistent or dose-related effects resulting from developmental treatment with BPA at these doses. Few of these behaviors, however, were sexually dimorphic which may prove more sensitive. Published by Elsevier Inc. C1 [Ferguson, Sherry A.; Law, C. Delbert; Abshire, Jordan S.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov; Charles.Law@fda.hhs.gov; Jordan.Abshire@fda.hhs.gov RI Abshire, James/I-2800-2013 FU National Center for Toxicological Research/Food and Drug Administration [P00706] FX This work was supported by the National Center for Toxicological Research/Food and Drug Administration (Experiment # P00706). NR 64 TC 19 Z9 19 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2012 VL 34 IS 6 BP 598 EP 606 DI 10.1016/j.ntt.2012.09.006 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056VD UT WOS:000312518600008 PM 23041373 ER PT J AU Gwaltney, C Slagle, A Martin, ML Mollon, P AF Gwaltney, C. Slagle, A. Martin, M. L. Mollon, P. TI THE PATIENT'S EXPERIENCE OF NUISANCE BLEEDING AND BRUISING WHILE ON ANTIPLATELET MEDICATIONS FOR ACS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Gwaltney, C.] Invivodata Inc, Westerly, RI USA. [Slagle, A.] FDA CDER OND, Silver Spring, MD USA. [Martin, M. L.] Hlth Res Associates Inc, Seattle, WA USA. [Mollon, P.] Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2012 VL 15 IS 7 BP A379 EP A379 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055JF UT WOS:000312411100542 ER PT J AU Parshikov, IA Netrusov, AI Sutherland, JB AF Parshikov, Igor A. Netrusov, Alexander I. Sutherland, John B. TI Microbial transformation of antimalarial terpenoids SO BIOTECHNOLOGY ADVANCES LA English DT Review DE Artemisinin; Biotransformation; Malaria; Plasmodium; Terpenes ID ASPERGILLUS-NIGER; PLASMODIUM-FALCIPARUM; IN-VITRO; ARTEMISININ DERIVATIVES; CUNNINGHAMELLA-ELEGANS; QINGHAOSU ARTEMISININ; PIMARANE DITERPENES; TRITERPENOID ACIDS; RESISTANT MALARIA; NATURAL-PRODUCTS AB The fungal and bacterial transformation of terpenoids derived from plant essential oils, especially the sesquiterpenoid artemisinin from Artemisia annua, has produced several new candidate drugs for the treatment of malaria. Obtaining new derivatives of terpenoids, including artemisinin derivatives with increased antimalarial activity, is an important goal of research in microbial biotechnology and medicinal chemistry. Published by Elsevier Inc. C1 [Sutherland, John B.] USDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Parshikov, Igor A.] First Moscow State Med Univ IM Sechenov, Moscow, Russia. [Netrusov, Alexander I.] Moscow MV Lomonosov State Univ, Moscow, Russia. RP Sutherland, JB (reprint author), USDA, Natl Ctr Toxicol Res, Jefferson, AR USA. EM john.sutherland@fda.hhs.gov OI netrusov, alexander/0000-0002-2803-3037; Parshikov, Igor/0000-0003-1466-1128 NR 93 TC 16 Z9 18 U1 4 U2 73 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 EI 1873-1899 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD NOV-DEC PY 2012 VL 30 IS 6 BP 1516 EP 1523 DI 10.1016/j.biotechadv.2012.03.010 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 047RQ UT WOS:000311859100028 PM 22484051 ER PT J AU de Claro, RA McGinn, K Kwitkowski, V Bullock, J Khandelwal, A Habtemariam, B Ouyang, YL Saber, H Lee, K Koti, K Rothmann, M Shapiro, M Borrego, F Clouse, K Chen, XH Brown, J Akinsanya, L Kane, R Kaminskas, E Farrell, A Pazdur, R AF de Claro, R. Angelo McGinn, Karen Kwitkowski, Virginia Bullock, Julie Khandelwal, Aakanksha Habtemariam, Bahru Ouyang, Yanli Saber, Haleh Lee, Kyung Koti, Kallappa Rothmann, Mark Shapiro, Marjorie Borrego, Francisco Clouse, Kathleen Chen, Xiao Hong Brown, Janice Akinsanya, Lara Kane, Robert Kaminskas, Edvardas Farrell, Ann Pazdur, Richard TI U.S. Food and Drug Administration Approval Summary: Brentuximab Vedotin for the Treatment of Relapsed Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large-Cell Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II; SGN-35 AB The U.S. Food and Drug Administration (FDA) describes the accelerated approval of brentuximab vedotin for patients with relapsed Hodgkin lymphoma and relapsed systemic anaplastic large-cell lymphoma (sALCL). FDA analyzed the results of two single-arm trials, enrolling 102 patients with Hodgkin lymphoma and 58 patients with sALCL. Both trials had primary endpoints of objective response rate (ORR) and key secondary endpoints of response duration and complete response (CR) rate. For patients with Hodgkin lymphoma, ORR was 73% (95% CI, 65-83%); median response duration was 6.7 months, and CR was 32% (95% CI, 23-42%). For patients with sALCL, ORR was 86% (95% CI, 77-95%), median response duration was 12.6 months, and CR was 57% (95% CI, 44-70%). The most common adverse reactions were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting. FDA granted accelerated approval of brentuximab vedotin for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplantation (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates, and for the treatment of patients with sALCL after failure of at least one prior multiagent chemotherapy regimen. Clin Cancer Res; 18(21); 5845-9. (C) 2012 AACR. C1 [McGinn, Karen] US FDA, Div Hematol Prod, Off Hematol & Oncol Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bullock, Julie; Khandelwal, Aakanksha; Habtemariam, Bahru] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lee, Kyung; Koti, Kallappa; Rothmann, Mark] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shapiro, Marjorie; Borrego, Francisco; Clouse, Kathleen] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Chen, Xiao Hong; Brown, Janice] US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McGinn, K (reprint author), US FDA, Div Hematol Prod, Off Hematol & Oncol Prod, Off New Drugs,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM karen.mcginn@fda.hhs.gov NR 16 TC 75 Z9 75 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 5845 EP 5849 DI 10.1158/1078-0432.CCR-12-1803 PG 5 WC Oncology SC Oncology GA 049YV UT WOS:000312020400004 PM 22962441 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Re: racial disparities in outcomes after appendectomy for acute appendicitis SO AMERICAN JOURNAL OF SURGERY LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2012 VL 204 IS 5 BP 813 EP 813 PG 1 WC Surgery SC Surgery GA 045YZ UT WOS:000311734000055 PM 22658292 ER PT J AU Gonzalez-Escalona, N Brown, EW Zhang, GD AF Gonzalez-Escalona, Narjol Brown, Eric W. Zhang, Guodong TI Development and evaluation of a multiplex real-time PCR (qPCR) assay targeting ttrRSBCA locus and invA gene for accurate detection of Salmonella spp. in fresh produce and eggs (vol 48, pg 202, 2012) SO FOOD RESEARCH INTERNATIONAL LA English DT Correction C1 [Gonzalez-Escalona, Narjol; Brown, Eric W.; Zhang, Guodong] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 1 TC 0 Z9 0 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0963-9969 J9 FOOD RES INT JI Food Res. Int. PD NOV PY 2012 VL 49 IS 1 BP 618 EP 618 PG 1 WC Food Science & Technology SC Food Science & Technology GA 044AT UT WOS:000311592500080 ER PT J AU Ali, MM AF Ali, Mir M. TI Social Learning Theory, Cigarette Taxes and Adolescent Smoking Behavior SO JAHRBUCHER FUR NATIONALOKONOMIE UND STATISTIK LA English DT Article DE Adolescent smoking; stages of smoking; social learning theory ID YOUTH SMOKING; INSTRUMENTAL VARIABLES; ENDOGENEITY; SELECTION; TOBACCO; POLICIES; ALCOHOL; PARENTS; PRICES; MODEL AB In this paper we evaluate the effectiveness of cigarette taxes as a mechanism to reduce smoking rates among adolescents. In our model, we categorize individuals by their smoking frequencies and intensities instead of relying on the widely used dichotomous measure of smoking. Using data of a nationally representative sample of adolescents, we use an endogenity corrected model with school-level fixed effects to obtain our estimates. Moving beyond the conventional definition of smoking to a definition that recognizes the complex nature of addiction by categorizing smoking into various stages and also by controlling for peer and family effects together, we learn that adolescents are not necessarily the most responsive to taxes. Influence from peers and family plays a more significant role in influencing adolescent smoking. C1 US FDA, Off Regulat Policy & Social Sci, College Pk, MD 20740 USA. RP Ali, MM (reprint author), US FDA, Off Regulat Policy & Social Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mir.ali@fda.hhs.gov NR 28 TC 1 Z9 1 U1 3 U2 23 PU LUCIUS LUCIUS VERLAG MBH PI STUTTGART PA GEROKSTR 51, D-70184 STUTTGART, GERMANY SN 0021-4027 J9 JAHRB NATL STAT JI Jahrb. Natl. Okon. Stat. PD NOV PY 2012 VL 232 IS 6 BP 633 EP 651 PG 19 WC Economics; Social Sciences, Mathematical Methods SC Business & Economics; Mathematical Methods In Social Sciences GA 047YM UT WOS:000311877400003 ER PT J AU Hait, J Tallent, S Melka, D Keys, C Bennett, R AF Hait, Jennifer Tallent, Sandra Melka, David Keys, Christine Bennett, Reginald TI STAPHYLOCOCCUS AUREUS OUTBREAK INVESTIGATION OF AN ILLINOIS BAKERY SO JOURNAL OF FOOD SAFETY LA English DT Article ID MULTIPLEX PCR; UNITED-STATES; IDENTIFICATION; ENTEROTOXIN; STRAINS; GENES; ASSAY; MILK AB Over 100 individuals were sickened after ingesting an assortment of desserts linked to four staphylococcal food poisoning outbreaks leading investigators to products manufactured by an Illinois bakery. The investigative team identified substantial deviations from the current Good Manufacturing Practice Regulations, 21 CFR Part 110, during multiple visits to the bakery. A total of 299 environmental swabs and 16 raw ingredients were collected for bacteriological analysis. Staphylococcus aureus isolates recovered from these samples were evaluated using either serological or polymerase chain reaction methods for the identification of staphylococcal enterotoxins SEA-SEE, SEG-SEI, SE-like SElJ-SElU or their respective genes, and for PantonValentine leukocidin cytotoxin. A raw ingredient and 16% of the environmental samples revealed the presence of enterotoxigenic S. aureus capable of producing diverse combinations of toxins. Antimicrobial susceptibility testing found that all S. aureus isolates were resistant to one or more agent(s). Pulsed field gel electrophoresis characterization of the isolates identified six pattern types. C1 [Hait, Jennifer; Tallent, Sandra; Melka, David; Keys, Christine; Bennett, Reginald] US FDA, College Pk, MD 20740 USA. RP Hait, J (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jennifer.hait@fda.hhs.gov FU Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) Program [NRS127, NRS194, NRS113, NRS119, NRS109, NRS111]; NIAID/ NIH [HHSN272200700055C] FX The following isolates were obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) Program supported under NIAID/ NIH, Contract No. HHSN272200700055C. NR 18 TC 6 Z9 6 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD NOV PY 2012 VL 32 IS 4 BP 435 EP 444 DI 10.1111/jfs.12002 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 044II UT WOS:000311612400006 ER PT J AU Gelderman, MP Vostal, JG AF Gelderman, Monique P. Vostal, Jaroslav G. TI In Reply to: "Is the SCID mouse model applicable to human acute lung injury?" reply SO TRANSFUSION LA English DT Letter ID SAFETY; TRIAL C1 [Gelderman, Monique P.; Vostal, Jaroslav G.] US FDA, Ctr Biol Evaluat & Res, OBRR, Lab Cellular Hematol,Div Hematol, Rockville, MD 20857 USA. RP Gelderman, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, OBRR, Lab Cellular Hematol,Div Hematol, Rockville, MD 20857 USA. EM monique.gelderman-fuhrmann@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2012 VL 52 IS 11 BP 2492 EP 2493 DI 10.1111/j.1537-2995.2012.03898.x PG 2 WC Hematology SC Hematology GA 035VB UT WOS:000310977500031 ER PT J AU Pava-Ripoll, M Pearson, REG Miller, AK Ziobro, GC AF Pava-Ripoll, Monica Pearson, Rachel E. Goeriz Miller, Amy K. Ziobro, George C. TI Prevalence and Relative Risk of Cronobacter spp., Salmonella spp., and Listeria monocytogenes Associated with the Body Surfaces and Guts of Individual Filth Flies SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MUSCA-DOMESTICA L.; POWDERED INFANT FORMULA; REGULATORY ACTION CRITERIA; ENTEROBACTER-SAKAZAKII; MILK FORMULA; STOMOXYS-CALCITRANS; FOODBORNE ILLNESS; ESCHERICHIA-COLI; UNITED-STATES; HOUSE-FLY AB Although flies are important vectors of food-borne pathogens, there is little information to accurately assess the food-related health risk of the presence of individual flies, especially in urban areas. This study quantifies the prevalence and the relative risk of food-borne pathogens associated with the body surfaces and guts of individual wild flies. One hundred flies were collected from the dumpsters of 10 randomly selected urban restaurants. Flies were identified using taxonomic keys before being individually dissected. Cronobacter spp., Salmonella spp., and Listeria monocytogenes were detected using the PCR-based BAX system Q7. Positive samples were confirmed by culture on specific media and through PCR amplification and sequencing or ribotyping. Among collected flies were the housefly, Musca domestica (47%), the blowflies, Lucilia cuprina (33%) and Lucilia sericata (14%), and others (6%). Cronobacter species were detected in 14% of flies, including C. sakazakii, C. turicensis, and C. universalis, leading to the proposal of flies as a natural reservoir of this food-borne pathogen. Six percent of flies carried Salmonella enterica, including the serovars Poona, Hadar, Schwarzengrund, Senftenberg, and Brackenridge. L. monocytogenes was detected in 3% of flies. Overall, the prevalence of food-borne pathogens was three times greater in the guts than on the body surfaces of the flies. The relative risk of flies carrying any of the three pathogens was associated with the type of pathogen, the body part of the fly, and the ambient temperature. These data enhance the ability to predict the microbiological risk associated with the presence of individual flies in food and food facilities. C1 [Pava-Ripoll, Monica; Pearson, Rachel E. Goeriz; Miller, Amy K.; Ziobro, George C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Pava-Ripoll, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM Monica.Pava-Ripoll@fda.hhs.gov FU Research Participation Program at the Center of Food Safety and Applied Nutrition FX This project was supported in part by an appointment to the Research Participation Program at the Center of Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 91 TC 15 Z9 19 U1 2 U2 46 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2012 VL 78 IS 22 BP 7891 EP 7902 DI 10.1128/AEM.02195-12 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 028MX UT WOS:000310427500010 PM 22941079 ER PT J AU Shakir, Z Khan, S Sung, KD Khare, S Khan, A Steele, R Nawaz, M AF Shakir, Zakiya Khan, Saeed Sung, Kidon Khare, Sangeeta Khan, Ashraf Steele, Roger Nawaz, Mohamed TI Molecular Characterization of Fluoroquinolone-Resistant Aeromonas spp. Isolated from Imported Shrimp SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PHYLOGENETIC ANALYSIS; QUINOLONE RESISTANCE; ESCHERICHIA-COLI; MUTATIONS; GENES; PSEUDOMONAS; AQUACULTURE; MECHANISMS; HYDROPHILA; SEQUENCES AB Sixty-three nalidixic acid-resistant Aeromonas sp. isolates were obtained from imported shrimp. Phylogenetic analysis of gyrB sequences indicated that 18 were A. enteropelogenes, 26 were A. caviae, and 19 were A. sobria. Double missense mutations in the quinolone resistance-determining region (QRDR) of gyrA at codon 83 (Ser -> Val/Ile) and codon 92 (Leu -> Met) coupled with a point mutation of parC at codon 80 (Ser -> Ile/Phe) conferred high levels of quinolone resistance in the isolates. A majority of A. enteropelogenes and A. caviae strains harbored toxin genes, whereas only a few A. sobria strains harbored these genes. The fluoroquinolone-resistant Aeromonas spp. exhibited higher cytotoxicity than fluoroquinolone-sensitive, virulent Aeromonas spp. to rat epithelial cells. C1 [Khan, Saeed; Sung, Kidon; Khare, Sangeeta; Khan, Ashraf; Steele, Roger; Nawaz, Mohamed] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Shakir, Zakiya] Univ Oklahoma, Norman, OK 73019 USA. RP Nawaz, M (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM mohamed.nawaz@fda.hhs.gov RI Khan, Ashraf/E-8133-2013 FU National Center for Toxicological Research, U.S. Food and Drug Administration FX This work was supported by the National Center for Toxicological Research, U.S. Food and Drug Administration. NR 32 TC 3 Z9 5 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2012 VL 78 IS 22 BP 8137 EP 8141 DI 10.1128/AEM.02081-12 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 028MX UT WOS:000310427500039 PM 22923408 ER PT J AU Arzhantsev, S Vilker, V Kauffman, J AF Arzhantsev, Sergey Vilker, Vincent Kauffman, John TI Deep-Ultraviolet (UV) Resonance Raman Spectroscopy as a Tool for Quality Control of Formulated Therapeutic Proteins SO APPLIED SPECTROSCOPY LA English DT Article DE Deep-ultraviolet resonance Raman spectroscopy; DUVRR; Biopharmaceuticals; Quality control ID SECONDARY STRUCTURE; CONFORMATION; CYCLOHEXANE; EVOLUTION; RESIDUES; INSULIN AB A deep-ultraviolet (UV) Raman spectrometer with excitation source tunable from 193 to 210 nm has been built and characterized. The dispersion of the spectrometer over the entire range was measured and described theoretically. The relative sensitivity of the spectrometer was estimated using the integrated intensity ratio of two Raman bands of cyclohexane. Resonance Raman spectra of three formulated insulin products were measured and compared. A band-targeted entropy minimization algorithm was applied to the collected spectra for mixture analysis of insulin products. We conclude that it is feasible to develop robust qualitative methods for quality control of protein-based formulated drug using DUVRR spectroscopy. C1 [Arzhantsev, Sergey; Kauffman, John] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Vilker, Vincent] US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Arzhantsev, S (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM arzhantsev@fda.hhs.gov FU FDA Center for Drug Evaluation and Research Critical Path Program FX The authors acknowledge Director of Division of Pharmaceutical Analysis Lucinda F. Buhse and Deputy Director of Division of Pharmaceutical Analysis Benjamin J. Westenberger for support of this research and Professor Sanford Asher and his group (University of Pittsburgh) for help with evaluation of the CCD camera. This work was funded by the FDA Center for Drug Evaluation and Research Critical Path Program. NR 30 TC 3 Z9 3 U1 0 U2 27 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD NOV PY 2012 VL 66 IS 11 BP 1262 EP 1268 DI 10.1366/11-06572 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 039TC UT WOS:000311268400002 PM 23146181 ER PT J AU Hong, HX Branham, WS Dial, SL Moland, CL Fang, H Shen, J Perkins, R Sheehan, D Tong, WD AF Hong, Huixiao Branham, William S. Dial, Stacey L. Moland, Carrie L. Fang, Hong Shen, Jie Perkins, Roger Sheehan, Daniel Tong, Weida TI Rat alpha-Fetoprotein Binding Affinities of a Large Set of Structurally Article Diverse Chemicals Elucidated the Relationships between Structures and Binding Affinities SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR; ESTRADIOL BINDING; FATTY-ACIDS; IN-VITRO; ALPHA-1-FETOPROTEIN; PROTEIN; PLASMA; MOUSE; LIGANDS AB Endocrine disrupting chemicals interfere with the endocrine system in animals, including humans, to exert adverse effects. One of the mechanisms of endocrine disruption is through the binding of receptors such as the estrogen receptor (ER) in target cells. The concentration of any chemical in serum is important for its entry into the target cells to bind the receptors. alpha-Fetoprotein (AFP) is a major transport protein in rodent serum that can bind with estrogens and thus change a chemical's availability for entrance into the target cell. Sequestration of an estrogen in the serum can alter the chemical's potential for disrupting estrogen receptor-mediated responses. To better understand endocrine disruption, we developed a competitive binding assay using rat amniotic fluid, which contains very high levels of AFP, and measured the binding to the rat AFP for 125 structurally diverse chemicals, most of which are known to bind ER. Fifty-three chemicals were able to bind the rat AFP in the assay, while 72 chemicals were determined to be nonbinders. Observations from closely examining the relationship between the binding data and structures of the tested chemicals are rationally explained in a manner consistent with proposed binding regions of rat AFP in the literature. The data reported here represent the largest data set of structurally diverse chemicals tested for rat AFP binding. The data assist in elucidating binding interactions and mechanisms between chemicals and rat AFP and, in turn, assist in the evaluation of the endocrine disrupting potential of chemicals. C1 [Hong, Huixiao; Shen, Jie; Perkins, Roger; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Branham, William S.; Moland, Carrie L.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Dial, Stacey L.; Sheehan, Daniel] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fang, Hong] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov; weida.tong@fda.hhs.gov NR 57 TC 16 Z9 16 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2012 VL 25 IS 11 BP 2553 EP 2566 DI 10.1021/tx3003406 PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 038KO UT WOS:000311173800029 PM 23013281 ER PT J AU Goldstein, RER Micallef, SA Gibbs, SG Davis, JA He, X George, A Kleinfelter, LM Schreiber, NA Mukherjee, S Sapkota, A Joseph, SW Sapkota, AR AF Goldstein, Rachel E. Rosenberg Micallef, Shirley A. Gibbs, Shawn G. Davis, Johnnie A. He, Xin George, Ashish Kleinfelter, Lara M. Schreiber, Nicole A. Mukherjee, Sampa Sapkota, Amir Joseph, Sam W. Sapkota, Amy R. TI Methicillin-Resistant Staphylococcus aureus (MRSA) Detected at Four US Wastewater Treatment Plants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antibiotic resistance; community-acquired methicillin-resistant Staphylococcus aureus; methicillin-resistant Staphylococcus aureus; methicillin-susceptible Staphylococcus aureus; MRSA; MSSA; reclaimed wastewater; wastewater; wastewater treatment plant ID MULTIPLEX PCR STRATEGY; UNITED-STATES; RAPID DETECTION; MEC ELEMENT; INFECTIONS; GENE; IDENTIFICATION; STRAINS; ASSAY AB BACKGROUND: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is increasing in the United States, and it is possible that municipal wastewater could be a reservoir of this microorganism. To date, no U.S. studies have evaluated the occurrence of MRSA in wastewater. OBJECTIVE: We examined the occurrence of MRSA and methicillin-susceptible S. aureus (MSSA) at U.S. wastewater treatment plants. METHODS: We collected wastewater samples from two Mid-Atlantic and two Midwest wastewater treatment plants between October 2009 and October 2010. Samples were analyzed for MRSA and MSSA using membrane filtration. Isolates were confirmed using biochemical tests and PCR (polymerase chain reaction). Antimicrobial susceptibility testing was performed by Sensititre* microbroth dilution. Staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine leucocidin (PVL) screening, and pulsed field gel electrophoresis (PFGE) were performed to further characterize the strains. Data were analyzed by two-sample proportion tests and analysis of variance. RESULTS: We detected MRSA (n = 240) and MSSA (n = 119) in 22 of 44 (50%) and 24 of 44 (55%) wastewater samples, respectively. The odds of samples being MRSA-positive decreased as treatment progressed: 10 of 12 (83%) influent samples were MRSA-positive, while only one of 12 (8%) effluent samples was MRSA-positive. Ninety-three percent and 29% of unique MRSA and MSSA isolates, respectively, were multidrug resistant. SCCmec types II and IV, the pvl gene, and USA types 100, 300, and 700 (PFGE strain types commonly found in the United States) were identified among the MRSA isolates. CONCLUSIONS: Our findings raise potential public health concerns for wastewater treatment plant workers and individuals exposed to reclaimed wastewater. Because of increasing use of reclaimed wastewater, further study is needed to evaluate the risk of exposure to antibiotic-resistant bacteria in treated wastewater. C1 [Goldstein, Rachel E. Rosenberg; Micallef, Shirley A.; George, Ashish; Kleinfelter, Lara M.; Schreiber, Nicole A.; Sapkota, Amir; Joseph, Sam W.; Sapkota, Amy R.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Micallef, Shirley A.] Univ Maryland, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA. [Micallef, Shirley A.] Univ Maryland, Ctr Food Safety & Secur Syst, College Pk, MD 20742 USA. [Gibbs, Shawn G.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Environm Agr & Occupat Hlth, Omaha, NE USA. [Davis, Johnnie A.; Mukherjee, Sampa] US FDA, Ctr Vet Med, Laurel, MD USA. [He, Xin] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Joseph, Sam W.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Sapkota, AR (reprint author), Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, 2234P SPH Bldg, College Pk, MD 20742 USA. EM ars@umd.edu RI Sapkota, Amir/A-5968-2011; Sapkota, Amy/A-6046-2011; He, Xin/N-6742-2016 FU R03 Small Grants Program of the National Institute for Occupational Safety and Health [R03-OH009598-01]; Maryland Water Resources Research Center FX This work was supported by grant R03-OH009598-01 from the R03 Small Grants Program of the National Institute for Occupational Safety and Health. The Maryland Water Resources Research Center also supported this work by providing a summer fellowship to R.E.R.G. NR 31 TC 16 Z9 16 U1 4 U2 52 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1551 EP 1558 DI 10.1289/ehp.1205436 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000024 ER PT J AU Stockbridge, N Zhang, J Garnett, C Malik, M AF Stockbridge, Norman Zhang, Joanne Garnett, Christine Malik, Marek TI Practice and challenges of thorough QT studies SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE QT interval; Torsade de pointes tachycardia; Drug safety ID TORSADE-DE-POINTES; PHARMACODYNAMIC-ANALYSIS; PHARMACOKINETICS; PROLONGATION; MOXIFLOXACIN; DISOPYRAMIDE; QUINIDINE; INTERVAL; DESIGN; MODEL AB The drug-induced Torsade de Pointes (TdP) tachycardia is a known regulatory problem which led to the concept of the so-called thorough QT (TQT) studies now required for practically every new pharmaceutical compound. This review summarizes the concept of the TQT studies, their statistical evaluation, and related pharmacodynamic /pharmacokinetic modeling. The review also lists suggestions of how to make TQT studies more efficient and how to improve the interpretation of clinical data obtained during drug development to identify drugs prone to TdP induction more effectively. (C) 2012 Elsevier Inc. All rights reserved. C1 [Malik, Marek] St Pauls Cardiac Electrophysiol, London, England. [Malik, Marek] Univ London, London, England. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Garnett, Christine] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Malik, M (reprint author), SPCE, Verulam Ave, Purley CR8 3NQ, Surrey, England. EM marek.malik@btinternet.com NR 45 TC 9 Z9 9 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 582 EP 587 DI 10.1016/j.jelectrocard.2012.07.020 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300008 PM 22999322 ER PT J AU Bacharova, L Estes, EH Hill, JA Pahlm, O Schillaci, G Strauss, D Wagner, G AF Bacharova, Ljuba Estes, E. Harvey Hill, Joseph A. Pahlm, Olle Schillaci, Giuseppe Strauss, David Wagner, Galen TI Changing role of ECG in the evaluation left ventricular hypertrophy SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Editorial Material ID ELECTROCARDIOGRAPHIC DIAGNOSIS; WORKING GROUP; STATEMENT; CRITERIA; MASS C1 [Bacharova, Ljuba] Comenius Univ, Ctr Int Laser, Inst Pathophysiol, Fac Med, Bratislava, Slovakia. [Estes, E. Harvey] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Hill, Joseph A.] UT SW Med Ctr, Dallas, TX USA. [Pahlm, Olle] Lund Univ, Dept Clin Physiol, Lund, Sweden. [Schillaci, Giuseppe] Univ Perugia, Sch Med, Dept Clin & Expt Med, I-06100 Perugia, Italy. [Strauss, David] US FDA, Silver Spring, MD USA. [Wagner, Galen] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Bacharova, L (reprint author), Comenius Univ, Ctr Int Laser, Inst Pathophysiol, Fac Med, Bratislava, Slovakia. EM bacharova@ilc.sk NR 12 TC 6 Z9 6 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 609 EP 611 DI 10.1016/j.jelectrocard.2012.08.010 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300013 PM 23022306 ER PT J AU Strauss, DG AF Strauss, David G. TI Differentiation between left bundle branch block and left ventricular hypertrophy: Implications for cardiac resynchronization therapy SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Left bundle branch block; Left ventricular hypertrophy; Cardiac resynchronization therapy; Electrocardiography ID CHRONIC HEART-FAILURE; MYOCARDIAL SCAR; CONDUCTION; MORPHOLOGY; ECG; ELECTROCARDIOGRAM; QUANTIFICATION; PREDICTORS; ACTIVATION; DIAGNOSIS AB Recent clinical trials have demonstrated that cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations and mortality in patients with complete left bundle branch block (LBBB), but potentially not those with right bundle branch block or nonspecific LV conduction delay, such as that due to LV hypertrophy (LVH). Furthermore, endocardial mapping and simulation studies have suggested that one-third of patients diagnosed with LBBB by conventional electrocardiographic criteria are misdiagnosed, and these patients likely have a combination of LVH, LV chamber dilatation and delayed initiation of LV activation (incomplete LBBB). Increase in LV size due to hypertrophy/dilatation and slowed intramyocardial conduction velocity prolong QRS duration in patients with LVH, which can frequently go above the QRS duration threshold of 120 ms conventionally used to diagnose LBBB. New strict criteria for diagnosing complete LBBB have been proposed that utilize longer QRS duration thresholds (130 ms in women and 140 ms in men) and require the presence of mid-QRS notching/slurring in at least 2 of the leads 1, aVL, V1, V2, V5 or V6. The emergence of CRT has led to an increased need to differentiate complete LBBB from LVH and other types of intraventricular conduction delay, which should be further studied. Published by Elsevier Inc. C1 US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 1126, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov NR 29 TC 12 Z9 12 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 635 EP 639 DI 10.1016/j.jelectrocard.2012.09.001 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300018 PM 23022304 ER PT J AU Hebling, CM Ross, MM Callahan, JH McFarland, MA AF Hebling, Christine M. Ross, Mark M. Callahan, John H. McFarland, Melinda A. TI Size-Selective Fractionation and Visual Mapping of Allergen Protein Chemistry in Arachis hypogaea SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE peanut allergens; Ara h; GELFrEE; disulfide bonds; mass spectrometry ID MAJOR PEANUT ALLERGEN; ARA H 2; DISULFIDE BOND FORMATION; IGE-BINDING EPITOPES; POSTTRANSLATIONAL CLEAVAGE; GEL-ELECTROPHORESIS; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; STORAGE PROTEIN AB Peanuts (Arachis hypogaea) in addition to milk, eggs, fish,. crustaceans, wheat, tree nuts, and soybean are commonly referred to as the "big eight" foods that contribute to the majority of food allergies worldwide. Despite the severity of allergic reactions and growing prevalence in children and adults, there is no cure for peanut allergy, leaving avoidance as the primary mode of treatment To improve analytical methods for peanut allergen detection, researchers must overcome obstacles involved in handling complex food matrices while attempting to decipher the chemistry that underlies allergen protein interactions. To address such challenges, we conducted a global proteome characterization of raw peanuts using a sophisticated GELFrEE-PAGE-LC-MS/MS platform consisting of gel-based protein fractionation followed by mass spectrometric identification. The in-solution mass-selective protein fractionation: (1) enhances the number of unique peptide identifications, (2) provides a visual map of protein isoforms, and (3) aids in the identification of disulfide linked protein complexes. GELFrEE-PAGE-LC-MS/MS not only overcomes many of the challenges involved in the study of plant proteomics, but enriches the understanding of peanut protein chemistry, which is typically unattainable in a traditional bottom-up proteomic analysis. A global understanding of protein chemistry in Arachis hypogaea ultimately will aid the development of improved methods for allergen detection in food. C1 [Hebling, Christine M.; Ross, Mark M.; Callahan, John H.; McFarland, Melinda A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hebling, CM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Christine.Hebling@fda.hhs.gov RI McFarland, Melinda/A-1866-2013; Hebling, Christine /H-3924-2012 NR 50 TC 5 Z9 5 U1 1 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV PY 2012 VL 11 IS 11 BP 5384 EP 5395 DI 10.1021/pr300617a PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 038RA UT WOS:000311190600023 PM 23020697 ER PT J AU Schueler, BA Baiter, S Miller, DL AF Schueler, Beth A. Baiter, Stephen Miller, Donald L. TI Radiation Protection Tools in Interventional Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Schueler, Beth A.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Baiter, Stephen] Columbia Univ, Dept Radiol, New York, NY USA. [Baiter, Stephen] Columbia Univ, Dept Med, New York, NY USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Schueler, BA (reprint author), Mayo Clin, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. EM schueler.beth@mayo.edu NR 13 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2012 VL 9 IS 11 BP 844 EP 845 DI 10.1016/j.jacr.2012.08.003 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 038QL UT WOS:000311189100019 PM 23122355 ER PT J AU Zhao, JQ Wang, X Ragupathy, V Zhang, PH Tang, W Ye, ZP Eichelberger, M Hewlett, I AF Zhao, Jiangqin Wang, Xue Ragupathy, Viswanath Zhang, Panhe Tang, Wei Ye, Zhiping Eichelberger, Maryna Hewlett, Indira TI Rapid Detection and Differentiation of Swine-Origin Influenza A Virus (H1N1/2009) from Other Seasonal Influenza A Viruses SO VIRUSES-BASEL LA English DT Article DE nanoparticle; H5N1; swine influenza A virus; nanomicroarray ID HEMAGGLUTININ; TRANSMISSION; REASSORTMENT; ASSAY AB We previously developed a rapid and simple gold nanoparticle(NP)-based genomic microarray assay for identification of the avian H5N1 virus and its discrimination from other influenza A virus strains (H1N1, H3N2). In this study, we expanded the platform to detect the 2009 swine-origin influenza A virus (H1N1/2009). Multiple specific capture and intermediate oligonucleotides were designed for the matrix (M), hemagglutinin (HA), and neuraminidase (NA) genes of the H1N1/2009 virus. The H1N1/2009 microarrays were printed in the same format as those of the seasonal influenza H1N1 and H3N2 for the HA, NA, and M genes. Viral RNA was tested using capture-target-intermediate oligonucleotide hybridization and gold NP-mediated silver staining. The signal from the 4 capture-target-intermediates of the HA and NA genes was specific for H1N1/2009 virus and showed no cross hybridization with viral RNA from other influenza strains H1N1, H3N2, and H5N1. All of the 3 M gene captures showed strong affinity with H1N1/2009 viral RNA, with 2 out of the 3 M gene captures showing cross hybridization with the H1N1, H3N2, and H5N1 samples tested. The current assay was able to detect H1N1/2009 and distinguish it from other influenza A viruses. This new method may be useful for simultaneous detection and subtyping of influenza A viruses and can be rapidly modified to detect other emerging influenza strains in public health settings. C1 [Zhao, Jiangqin; Wang, Xue; Ragupathy, Viswanath; Zhang, Panhe; Tang, Wei; Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Ye, Zhiping; Eichelberger, Maryna] US FDA, Div Viral Prod, Off Vaccines Res & Review, CBER, Bethesda, MD 20892 USA. RP Zhao, JQ (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM jiangqin.zhao@fda.hhs.gov; xue.wang@fda.hhs.gov; viswanath.ragupathy@fda.hhs.gov; panhe.zhang@fda.hhs.gov; annietang_93@yahoo.com; zhiping.ye@fda.hhs.gov; maryna.eichelberger@fda.hhs.gov; indira.hewlett@fda.hhs.gov FU CBER intramural; FDA MCM funds FX The authors wish to acknowledge Krishnakumar Devadas, Mingjie Zhang and Robin Biswas for review of the manuscript. This work was a collaboration with Nanosphere, Inc. through CRADA (#147-09), and was funded through CBER intramural and FDA MCM funds. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy NR 17 TC 8 Z9 8 U1 0 U2 17 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD NOV PY 2012 VL 4 IS 11 BP 3012 EP 3019 DI 10.3390/v4113012 PG 8 WC Virology SC Virology GA 041VS UT WOS:000311429900026 PM 23202513 ER PT J AU Ashley, DL Backinger, CL AF Ashley, David L. Backinger, Cathy L. TI The Food and Drug Administration's Regulation of Tobacco The Center for Tobacco Products' Office of Science SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID FAMILY SMOKING PREVENTION; CONTROL ACT; UNITED-STATES; RESEARCH OPPORTUNITIES; CIGARETTE-SMOKING; SURVEILLANCE; PREVALENCE; PRIORITIES; ADULTS; NEEDS C1 [Ashley, David L.; Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Off Sci, Rockville, MD 20850 USA. RP Ashley, DL (reprint author), US FDA, Ctr Tobacco Prod, Off Sci, 9200 Corp Blvd, Rockville, MD 20850 USA. EM David.Ashley@fda.hhs.gov FU ClearWay MinnesotaSM FX The printing of this journal supplement, including this article, was supported by ClearWay MinnesotaSM. The information in this article is not a formal dissemination of information by FDA and does not represent agency position or policy. The contents are the responsibility of the authors alone. NR 18 TC 22 Z9 22 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2012 VL 43 IS 5 SU 3 BP S255 EP S263 DI 10.1016/j.amepre.2012.08.004 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 032JJ UT WOS:000310713300015 PM 23079225 ER PT J AU Jia, HJ Li, Y Zhao, TS Li, X Hu, JD Yin, D Guo, BF Kopecko, DJ Zhao, XJ Zhang, L Xu, D AF Jia, Huijie Li, Yang Zhao, Tiesuo Li, Xin Hu, Jiadi Yin, Di Guo, Baofeng Kopecko, Dennis J. Zhao, Xuejian Zhang, Ling Xu, De Qi TI Antitumor effects of Stat3-siRNA and endostatin combined therapies, delivered by attenuated Salmonella, on orthotopically implanted hepatocarcinoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Combined gene therapy; Hepatocellular carcinoma; RNA interference; Anti-angiogenesis; Immune response ID REGULATORY T-CELLS; SMALL INTERFERING RNAS; HEPATOCELLULAR-CARCINOMA; TUMOR-GROWTH; MOLECULAR TARGETS; IN-VIVO; CANCER; EXPRESSION; VECTOR; ANGIOGENESIS AB Hepatocellular carcinoma (HCC) is one of the most aggressive carcinomas. Limited therapeutic options, mainly due to a fragmented genetic understanding of HCC, and major HCC resistance to conventional chemotherapy are the key reasons for a poor prognosis. Thus, new effective treatments are urgent and gene therapy may be a novel option. Signal transducer and activator of transcription 3 (Stat3) is a highly studied member of the STAT family. Inhibition of Stat3 signaling has been found to suppress tumor growth and improve survival, providing a molecular target for cancer therapy. Furthermore, HCC is a hypervascular tumor and angiogenesis plays a crucial role in tumor growth and metastasis. Thus, anti-angiogenic therapy, combined with inhibition of Stat3, may be an effective approach to combat HCC. We tested the effect that the combination therapy consisting of endostatin (a powerful angiogenesis inhibitor) and Stat3-specific small interfering RNA, using a DNA vector delivered by attenuated S. typhimurium, on an orthotopic HCC model in C57BL/6 mice. Although antitumor effects were observed with either single therapeutic treatment, the combination therapy provided superior antitumor effects. Correlated with this finding, the combination treatment resulted in significant alteration of Stat3 and endostatin levels and that of the downstream gene VEGF, decreased cell proliferation, induced cell apoptosis and inhibited angiogenesis. Importantly, combined treatment also elicited immune system regulation of various immune cells and cytokines. This study has provided a novel cancer gene therapeutic approach. C1 [Jia, Huijie; Li, Yang; Li, Xin; Yin, Di; Guo, Baofeng; Zhao, Xuejian; Zhang, Ling] Jilin Univ, Dept Pathophysiol, Prostate Dis Prevent & Treatment Res Ctr, Norman Bethune Coll Med, Changchun 130021, Peoples R China. [Zhao, Tiesuo] Jilin Univ, Dept Immunol, Norman Bethune Med Sch, Changchun 130021, Peoples R China. [Hu, Jiadi] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Xu, De Qi] Beijing Three Room S 4 Hosp, New Vaccine Natl Engn Res Ctr, Beijing 100024, Peoples R China. RP Zhang, L (reprint author), Jilin Univ, Dept Pathophysiol, Prostate Dis Prevent & Treatment Res Ctr, Norman Bethune Coll Med, Changchun 130021, Peoples R China. EM zhangling3@jlu.edu.cn; dqxujl@gmail.com FU National Natural Science Foundation of China [30801354, 30970791]; Specialized Research Fund for the Doctoral Program of Higher Education of China [200801831077]; Jilin Provincial Science & Technology Department [20080154] FX This study was supported by grands from the National Natural Science Foundation of China (No. 30801354 and No. 30970791), Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 200801831077) and Jilin Provincial Science & Technology Department (No. 20080154). We thank Professor Liying Wang and Professor Yongli Bao for helpful suggestions. NR 39 TC 18 Z9 22 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2012 VL 61 IS 11 BP 1977 EP 1987 DI 10.1007/s00262-012-1256-y PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 034QQ UT WOS:000310888400008 PM 22527247 ER PT J AU Jang, S Gao, Y Abdelmegeed, MA Banerjee, A Yu, LR Song, BJ AF Jang, Sehwan Gao, Yuan Abdelmegeed, Mohamed A. Banerjee, Atrayee Yu, Li-Rong Song, B. J. TI Role of JNK-Mediated Phosphorylation in Mitochondrial Dysfunction and Liver Injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Jang, Sehwan; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, B. J.] NIAAA, NIH, Bethesda, MD USA. [Gao, Yuan; Yu, Li-Rong] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S143 EP S144 DI 10.1016/j.freeradbiomed.2012.10.389 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600373 ER PT J AU Bond, M Ghosh, S Krause, M Hanover, J AF Bond, Michelle Ghosh, Salil Krause, Michael Hanover, John TI The Caenorhabditis elegans innate immune response to S-aureus is modulated by O-GlcNAc transferase SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Bond, Michelle; Krause, Michael; Hanover, John] NIDDK, NIH, Bethesda, MD 20892 USA. [Ghosh, Salil] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1551 EP 1552 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700105 ER PT J AU Muindi, K Vann, W AF Muindi, Karen Vann, Willie TI The Neisseria meningitidis serogroup X xcbA gene product catalyses synthesis of the bacterial capsular polysaccharide SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Muindi, Karen; Vann, Willie] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1596 EP 1597 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700235 ER PT J AU Salmon, D Yih, WK Lee, G Rosofsky, R Brown, J Vannice, K Tokars, J Roddy, J Ball, R Gellin, B Lurie, N Koh, H Platt, R Lieu, T AF Salmon, Daniel Yih, W. Katherine Lee, Grace Rosofsky, Robert Brown, Jeffrey Vannice, Kirsten Tokars, Jerome Roddy, James Ball, Robert Gellin, Bruce Lurie, Nicole Koh, Howard Platt, Richard Lieu, Tracy CA PRISM Program Grp TI Success Of Program Linking Data Sources To Monitor H1N1 Vaccine Safety Points To Potential For Even Broader Safety Surveillance SO HEALTH AFFAIRS LA English DT Article ID ADVERSE EVENTS; IMMUNIZATION; PROJECT; NETWORK; SYSTEM; FOOD AB In response to the 2009 H1N1 pandemic and subsequent vaccination program, the Department of Health and Human Services and collaborators developed the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration project to detect rare adverse events rapidly. The program monitored three million people who had received the H1N1 vaccine by linking data from large private health plans and from public immunization registries that had originally not been designed to share data, and on a larger scale than had been previously attempted. The program generated safety data in two weeks rather than three to six monty 10ths-the standard time frame achievable using health plan data. PRISM substantially contributed to the understanding of the safety of H1N1 vaccines. Its use in the case of H1N1 highlights the necessity of proactive planning, scalable infrastructure, and public-private partnerships in tracking adverse events after vaccination in epidemics. It also illustrates how data could be integrated to produce policy-relevant information for other medical products. C1 [Salmon, Daniel] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. [Yih, W. Katherine; Brown, Jeffrey; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Rosofsky, Robert] Hlth Informat Syst Consulting, Milton, MA USA. [Vannice, Kirsten] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Tokars, Jerome] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Roddy, James] Consulting firm CSC, Falls Church, VA USA. [Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gellin, Bruce] Dept Hlth & Human Serv HHS, Washington, DC USA. [Lurie, Nicole; Koh, Howard] HHS, Washington, DC USA. [Lieu, Tracy] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Salmon, D (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. EM dsalmon@jhsph.edu NR 19 TC 6 Z9 6 U1 1 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV PY 2012 VL 31 IS 11 BP 2518 EP 2527 DI 10.1377/hlthaff.2012.0104 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 036LH UT WOS:000311026900020 PM 23129683 ER PT J AU Lin, A Nguyen, L Clotilde, LM Kase, JA Son, I Lauzon, CR AF Lin, Andrew Lam Nguyen Clotilde, Laurie M. Kase, Julie A. Son, Insook Lauzon, Carol R. TI Isolation of Shiga Toxin-Producing Escherichia coli from Fresh Produce Using STEC Heart Infusion Washed Blood Agar with Mitomycin-C SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ASSAY AB The ability to detect and isolate Shiga toxin producing Escherichia coli (STEC) remains a major challenge for food microbiologists. Although methods based on nucleic acids and antibodies have improved detection of STECs in foods, isolation of these bacteria remains arduous. STEC isolation is necessary for matching food, environmental, and clinical isolates during outbreak investigations and for distinguishing between pathogenic and nonpathogenic organisms. STEC heart infusion washed blood agar with mitomycin-C (SHIBAM) is a modification of washed sheep blood agar prepared by adding mitomycin-C and optimizing both the washed blood and base agar to better isolate STECs. Most STEC isolates produce a zone of hemolysis on SHIBAM plates and are easily distinguishable from background microbiota. Here, we present data supporting the use of SHIBAM to isolate STECs from fresh produce. SHIBAM was tested for accuracy in identifying STECs (365 of 410 STEC strains were hemolytic, and 63 of 73 E. coli strains that did not produce Shiga toxin were not hemolytic) and for recovery from artificially inoculated fresh produce (11 of 24 romaine lettuce samples and 6 of 24 tomato samples). STEC recovery with SHIBAM agar was greatly improved when compared with recovery on Levine's eosin methylene blue agar as a reference method. C1 [Lin, Andrew; Clotilde, Laurie M.] US FDA, Alameda, CA 94502 USA. [Lam Nguyen; Lauzon, Carol R.] Calif State Univ Hayward, Dept Biol Sci, Hayward, CA 94542 USA. [Kase, Julie A.; Son, Insook] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Lin, A (reprint author), US FDA, Alameda, CA 94502 USA. EM andrew.lin@fda.hhs.gov FU FDA San Francisco District Laboratory; FDA Office of Regulatory Affairs Division of Field Science; California State University Program for Education and Research in Biotechnology FX The authors thank the STEC Center (National Food Safety and Toxicology Center, Michigan State University, East Lansing), Robert Mandrell (U.S. Department of Agriculture, Agricultural Research Service, Albany, CA), the Ohio Department of Agriculture (Reynoldsburg), Atin Datta and Keith Lampel (FDA, Center for Food Safety and Nutrition, Laurel, MD), the FDA Applied Technology Center, and the Orange County Public Health Laboratory (Santa Ana, CA) for generously sharing their bacterial cultures. The authors also thank the FDA San Francisco District Laboratory and the FDA Office of Regulatory Affairs Division of Field Science for their support of this research. This work was primarily supported by the California State University Program for Education and Research in Biotechnology. NR 11 TC 5 Z9 5 U1 3 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2012 VL 75 IS 11 BP 2028 EP 2030 DI 10.4315/0362-028X.JFP-12-157 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 036GK UT WOS:000311014200014 PM 23127712 ER PT J AU Fujisawa, T Rubin, B Suzuki, A Patel, PS Gahl, WA Joshi, BH Puri, RK AF Fujisawa, Toshio Rubin, Benjamin Suzuki, Akiko Patel, Prabhudas S. Gahl, Wiiliam A. Joshi, Bharat H. Puri, Raj K. TI Cysteamine Inhibits Invasion, Metastasis and Extends Survival by Down-regulating Matrix Metalloproteinases in vivo Mouse Model of Human Pancreatic Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Metastases; Animal model; Tumor microenvironment C1 [Fujisawa, Toshio; Suzuki, Akiko; Patel, Prabhudas S.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Fujisawa, Toshio] NTT Med Ctr Tokyo, Dept Gastroenterol, Tokyo, Japan. [Rubin, Benjamin] Suburban Hosp, Johns Hopkins Sch Med, Dept Ophthalmol, Bethesda, MD USA. [Gahl, Wiiliam A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 785 EP 785 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100194 ER PT J AU Garrett, P Lee, T Busch, M Patel, P Niedrig, M Anez, G Rios, M AF Garrett, P. Lee, T. Busch, M. Patel, P. Niedrig, M. Anez, G. Rios, M. TI Possible Dual or Triple Infection with Dengue Viruses DENV-1,-2, and-4 in an Early Infection Series SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Garrett, P.] SeraCare Life Sci Inc, Milford, MA USA. [Lee, T.; Busch, M.] Blood Syst Res Inst, San Francisco, CA USA. [Patel, P.; Niedrig, M.] Robert Koch Inst, Berlin, Germany. [Anez, G.; Rios, M.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 685 EP 686 PG 2 WC Pathology SC Pathology GA 025HG UT WOS:000310178600211 ER PT J AU Yamashiro, Y Martin, J Gazarian, M Kling, S Nakamura, H Matsui, A Cucchiara, S Aloi, M Wynn, EL Mulberg, AE AF Yamashiro, Yuichiro Martin, Jennifer Gazarian, Madlen Kling, Sharon Nakamura, Hidefumi Matsui, Akira Cucchiara, Salvatore Aloi, Marina Wynn, Erica L. Mulberg, Andrew E. TI Drug Development: The Use of Unlicensed/Off-label Medicines in Pediatrics SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID SEVERE CROHNS-DISEASE; CONSENSUS RECOMMENDATIONS; CHILDREN; INFLIXIMAB; MODERATE; THERAPY; SAFETY; MEDICATIONS; INDUCTION; EFFICACY C1 [Yamashiro, Yuichiro] Juntendo Univ, Grad Sch Med, Probiot Res Lab, Tokyo 1138421, Japan. [Martin, Jennifer] Univ Queensland, Princess Alexandra Hosp, Sch Med, Brisbane, Qld, Australia. [Gazarian, Madlen] Univ New S Wales, Sydney, NSW, Australia. [Kling, Sharon] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Kling, Sharon] Tygerberg Childrens Hosp, Dept Paediat & Child Hlth, Stellenbosch, South Africa. [Nakamura, Hidefumi; Matsui, Akira] Natl Ctr Child Hlth & Dev, Tokyo, Japan. [Cucchiara, Salvatore; Aloi, Marina] Univ Roma La Sapienza, Dept Pediat, Pediat Gastroenterol & Liver Unit, Rome, Italy. [Wynn, Erica L.; Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Errors Prod, Rockville, MD 20857 USA. RP Yamashiro, Y (reprint author), Juntendo Univ, Sch Med, Tokyo 1138421, Japan. EM yamasiro@juntendo.ac.jp RI Martin, Jennifer/E-9067-2010; OI Kling, Sharon/0000-0002-4498-1811; Martin, Jennifer/0000-0002-8614-0199; Cucchiara, Salvatore/0000-0002-2939-9698 NR 41 TC 2 Z9 2 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2012 VL 55 IS 5 BP 506 EP 510 DI 10.1097/MPG.0b013e318272af1f PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 030LH UT WOS:000310571700012 PM 22983373 ER PT J AU Boothe, D Smaha, T Carpenter, DM Shaheen, B Hatchcock, T AF Boothe, Dawn Smaha, Tim Carpenter, D. Mark Shaheen, Bashar Hatchcock, Terri TI Antimicrobial Resistance and Pharmacodynamics of Canine and Feline Pathogenic E. coli in the United States SO JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION LA English DT Article ID URINARY-TRACT-INFECTIONS; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; FLUOROQUINOLONE-RESISTANT; DOGS; VIRULENCE; POPULATION; PROFILES; SPECTRUM; ANIMALS AB Percent resistance and minimum inhibitory concentrations (MIC) were described for canine (n = 301) and feline (n = 75) pathogenic Escherichia coli (E. coli) isolates solicited during May 2005 to Sep 2005 from the Clinical Pharmacology Laboratory at Auburn University (n = 165) or commercial diagnostic laboratories ([CDL]; n = 211) from four regions in the USA. Drugs tested were amoxicillin (AMX), amoxicillin trihydrate/ clavulanate potassium (AMXC), cefpodoxime (CFP), doxycycline (DXY), enrofloxacin (ENR), gentamicin (GM) and trimethoprim- sulfamethoxazole (TMS). Urinary isolates were most common (n = 174). Percent resistance was greatest for isolates from the respiratory tract, urine, and skin compared with the ear. Resistance was also greatest for samples sent from the south and central states compared with the western states (P <= 0.001). Percent resistance by drug was AMX (46 +/- 2.6%) > AMXC (37 +/- 2.5%) > CFP (21.8 +/- 2%) = DXY (22 +/- 2.1%) = ENR (20 +/- 2.1%) = TMS (19 +/- 2%) > GM (12 +/- 1.7%). There was a significant difference in resistance between the different antibiotic drugs (P <= 0.001). Population MIC distributions were bimodal, and MICs were highest in samples from the southern states (P <= 0.001). E. coli resistance may limit its empirical treatment. For susceptible isolates, AMX and AMXC may be least effective and TMS most effective. (J Am Anim Hosp Assoc 2012; 48: 379-389. DOI 10.5326/JAAHA-MS-5805) C1 [Boothe, Dawn] Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. [Carpenter, D. Mark] Auburn Univ, Dept Math & Stat, Auburn, AL 36849 USA. [Hatchcock, Terri] Auburn Univ, Dept Pathobiol, Auburn, AL 36849 USA. [Smaha, Tim] Banfield Pet Hosp, Columbia, SC USA. [Shaheen, Bashar] USDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR USA. RP Boothe, D (reprint author), Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. EM boothdm@auburn.edu FU Waltham Foundation FX All authors declare no conflicts of interest. This study was supported (in part) by a Grant-in-Aid from the Waltham Foundation. The Waltham Foundation had no role in the design, implementation, or reporting of this study. NR 32 TC 6 Z9 6 U1 2 U2 27 PU AMER ANIMAL HOSPITAL ASSOC PI LAKEWOOD PA PO BOX 150899, LAKEWOOD, CO 80215-0899 USA SN 0587-2871 J9 J AM ANIM HOSP ASSOC JI J. Am. Anim. Hosp. Assoc. PD NOV-DEC PY 2012 VL 48 IS 6 BP 379 EP 389 DI 10.5326/JAAHA-MS-5805 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 030QX UT WOS:000310586300002 PM 23033458 ER PT J AU Dickey, JS Baird, BJ Redon, CE Avdoshina, V Palchik, G Wu, JF Kondratyev, A Bonner, WM Martin, OA AF Dickey, Jennifer S. Baird, Brandon J. Redon, Christophe E. Avdoshina, Valeriya Palchik, Guillermo Wu, Junfang Kondratyev, Alexei Bonner, William M. Martin, Olga A. TI Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; PRIMARY HUMAN FIBROBLASTS; IRRADIATED GLIOMA-CELLS; TOPOISOMERASE-I; NITRIC-OXIDE; INTERCELLULAR COMMUNICATION; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; EXCISION-REPAIR; HISTONE H2A.X AB Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by gamma-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-beta and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo. C1 [Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Bonner, William M.; Martin, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20952 USA. [Avdoshina, Valeriya; Wu, Junfang] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Palchik, Guillermo; Kondratyev, Alexei] Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20057 USA. [Kondratyev, Alexei] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA. RP Dickey, JS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost, Silver Spring, MD 20993 USA. EM Jennifer.Dickey@fda.hhs.gov; Olga.Martin@petermac.org OI Palchik, Guillermo/0000-0003-2161-3976 FU National Cancer Institute, National Institutes of Health, USA; National Institute for Allergies and Infectious Disease (NIAID) Trans-NIH Biodefense Program; National Institute of Neuorlogical Disorders and Stroke [NS056057] FX The Intramural Funding Program of the National Cancer Institute, National Institutes of Health, USA, and the National Institute for Allergies and Infectious Disease (NIAID) Trans-NIH Biodefense Program; National Institute of Neuorlogical Disorders and Stroke [NS056057 to A. K., in part]. Funding for open access charge: Intramural funding program of the National Cancer Institute, National Institutes of Health, USA. NR 59 TC 18 Z9 18 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2012 VL 40 IS 20 BP 10274 EP 10286 DI 10.1093/nar/gks795 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035TC UT WOS:000310970700035 PM 22941641 ER PT J AU Ahn, DG Choi, JK Taylor, DR Oh, JW AF Ahn, Dae-Gyun Choi, Jin-Kyu Taylor, Deborah R. Oh, Jong-Won TI Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates SO ARCHIVES OF VIROLOGY LA English DT Article ID DE-NOVO INITIATION; HEPATITIS-C VIRUS; POLY(A) TAIL; IN-VITRO; GENOME REPLICATION; POLIOVIRUS RNA; 3' END; POLYMERIZATION; REQUIREMENT; PSEUDOKNOT AB The severe acute respiratory syndrome coronavirus (SARS-CoV) RNA genome is replicated by a virus-encoded RNA replicase, the key component of which is the nonstructural protein 12 (nsp12). In this report, we describe the biochemical properties of a full-length recombinant SARS-CoV nsp12 RNA-dependent RNA polymerase (RdRp) capable of copying viral RNA templates. The purified SARS-CoV nsp12 showed both primer-dependent and primer-independent RNA synthesis activities using homopolymeric RNA templates. The RdRp activity was strictly dependent on Mn2+. The nsp12 preferentially copied homopolymeric pyrimidine RNA templates in the absence of an added oligonucleotide primer. It was also able to initiate de novo RNA synthesis from the 3'-ends of both the plus- and minus-strand genome of SARS-CoV, using the 3'-terminal 36- and 37-nt RNA, respectively. The in vitro RdRp assay system established with a full-length nsp12 will be useful for understanding the mechanisms of coronavirus replication and for the development of anti-SARS-CoV agents. C1 [Ahn, Dae-Gyun; Choi, Jin-Kyu; Oh, Jong-Won] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea. [Taylor, Deborah R.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Oh, Jong-Won] Yonsei Univ, Translat Res Ctr Prot Funct Control, Seoul 120749, South Korea. RP Oh, JW (reprint author), Yonsei Univ, Dept Biotechnol, 134 Shinchon Dong, Seoul 120749, South Korea. EM jwoh@yonsei.ac.kr FU Seoul RBD Program [10580]; Technology Innovation Program [MKE 10035159]; Ministry of Knowledge Economy (MKE, Korea); National Research Foundation of Korea [NRF-2011-0001236, 2011-0027650, 2010-0029116] FX This work was supported by the Seoul R&BD Program (Grant 10580), Technology Innovation Program (MKE 10035159) funded by the Ministry of Knowledge Economy (MKE, Korea), and in part by grants from the National Research Foundation of Korea (NRF-2011-0001236, 2011-0027650, and 2010-0029116). NR 39 TC 8 Z9 9 U1 0 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD NOV PY 2012 VL 157 IS 11 BP 2095 EP 2104 DI 10.1007/s00705-012-1404-x PG 10 WC Virology SC Virology GA 031AK UT WOS:000310611100005 PM 22791111 ER PT J AU John, K Pratt, M Beland, FA Churchwell, MI McMullen, G Olivero, OA Pogribny, IP Poirier, MC AF John, Kaarthik Pratt, M. Margaret Beland, Frederick A. Churchwell, Mona I. McMullen, Gail Olivero, Ofelia A. Pogribny, Igor P. Poirier, Miriam C. TI Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53 haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; METABOLIZING-ENZYMES; MASS-SPECTROMETRY; TUMOR-DEVELOPMENT; ULTRAVIOLET-B; MOUSE MODELS; XPA MICE; GENE XPA AB We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a] pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N-2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(-/-) p53(+/-) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(-/-) p53(+/-) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(-/-) p53(+/-) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP-DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-) p53(+/-) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs. C1 [John, Kaarthik; Pratt, M. Margaret; Olivero, Ofelia A.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Beland, Frederick A.; Churchwell, Mona I.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [McMullen, Gail] NCI, Off Director, NIH, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU Intramural Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD FX This study was funded by the Intramural Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 45 TC 2 Z9 4 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2012 VL 33 IS 11 BP 2236 EP 2241 DI 10.1093/carcin/bgs247 PG 6 WC Oncology SC Oncology GA 031FL UT WOS:000310624400026 PM 22828138 ER PT J AU Lawrence, JP Hung, J Wang, SJ AF Lawrence, John P. Hung, Jim Wang, Sue Jane TI Is pulmonary vascular resistance index predictive of exercise tolerance in adult patients with idiopathic pulmonary arterial hypertension SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Surrogate endpoint; Receiver operating characteristic curve ID END-POINTS AB Background: Clinical trials for adults with pulmonary arterial hypertension use exercise capacity, as measured by walking distance, as the primary endpoint to measure symptomatic improvement. In this article, we look at the relationship between walking distance and a hemodynamic variable, pulmonary vascular resistance index (PVRI), from the available trials. Methods: Patient-level data from 16 randomized controlled clinical trials were obtained. All idiopathic subjects with a baseline and study endpoint measurement of both hemodynamic and exercise endpoints were included. Changes from baseline in both endpoints and the relationship between the endpoints were summarized. Receiver operating characteristic curves were used to investigate the predictive ability. Measures of surrogacy were also calculated. Results: There is a weak correlation between changes in PVRI and exercise capacity. Receiver operating characteristic analysis shows a high false positive rate of using one variable to predict the other. Measures of surrogacy show the proportion of variability in exercise capacity explained by PVRI is approximately 5%. Conclusions: PVRI should not be used as a surrogate marker to predict changes in exercise capacity. Published by Elsevier Inc. C1 [Lawrence, John P.; Hung, Jim; Wang, Sue Jane] US FDA, Silver Spring, MD 20993 USA. RP Lawrence, JP (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM John.Lawrence@fda.hhs.gov NR 8 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2012 VL 33 IS 6 BP 1217 EP 1224 DI 10.1016/j.cct.2012.07.008 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 033UA UT WOS:000310825400014 PM 22820321 ER PT J AU Landray, MJ Grandinetti, C Kramer, JM Morrison, BW Ball, L Sherman, RE AF Landray, Martin J. Grandinetti, Cheryl Kramer, Judith M. Morrison, Briggs W. Ball, Leslie Sherman, Rachel E. TI Clinical Trials: Rethinking How We Ensure Quality SO DRUG INFORMATION JOURNAL LA English DT Article DE clinical trial; good clinical practice; monitoring; quality assurance C1 [Landray, Martin J.] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Landray, Martin J.] Univ Oxford, Epidemiol Studies Unit CTSU, Oxford OX3 7LF, England. [Grandinetti, Cheryl; Ball, Leslie; Sherman, Rachel E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kramer, Judith M.] Duke Translat Med Inst, Durham, NC USA. [Morrison, Briggs W.] AstraZeneca, Wilmington, DE USA. RP Landray, MJ (reprint author), Univ Oxford, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England. EM martin.landray@ctsu.ox.ac.uk OI Landray, Martin/0000-0001-6646-827X FU CTTI funds; US Food and Drug Administration (FDA) [U-19-FD003800] FX Martin Landray is a member of the Clinical Trials Transformation Initiative (CTTI) Steering Committee and was a team leader for CTTI's Monitoring Project. He works at the University of Oxford Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), which conducts large-scale clinical and receives research funding from government, charity, and the pharmaceutical industry. He complies fully with the CTSU staff policy of not accepting payments (including honoraria and speaker fees) from or holding stocks in pharmaceutical, tobacco, or alcohol companies. Judith Kramer received a one-time honorarium for participating in a 2-day advisory group for GlaxoSmithKline's Pharmacovigilance Center of Excellence. At the time of writing this manuscript, Dr Kramer was executive director of CTTI. She currently serves as the senior scientific advisor of CTTI and receives partial salary support from CTTI funds. Briggs Morrison was a co-chair of the CTTI Steering Committee and was a team leader for CTTI's Monitoring Project. At the time of this work, he is employed by AstraZeneca and has received equity in AstraZeneca as a component of his total compensation. Cheryl Grandinetti, Leslie Ball, and Rachel Sherman have no potential conflicts to disclose.; This article has been developed as part of a project on monitoring conducted by in-kind contribution of effort by authors and organizations working with the Clinical Trials Transformation Initiative (CTTI; https://www.ctti-clinicaltrials.org/project-topics/study-quality/effecti ve-and-efficient-monitoring-as-a-component-of-quality). CTTI receives partial funding from a US Food and Drug Administration (FDA) cooperative agreement (U-19-FD003800). NR 5 TC 6 Z9 6 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD NOV PY 2012 VL 46 IS 6 BP 657 EP 660 DI 10.1177/0092861512464372 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 032HF UT WOS:000310705100004 ER PT J AU Tu, CM Taylor, K Chai, G AF Tu, Chi-Ming Taylor, Kellie Chai, Grace TI Use of Proprietary Names by Prescribers for Discontinued Brand Drug Products With Existing Generic Equivalents SO DRUG INFORMATION JOURNAL LA English DT Article DE prescribing practice; proprietary name; discontinued drug; drug name confusion; medication error AB Purpose: To describe the endurance of continued use of proprietary names by prescribers for discontinued brand drug products with existing generic equivalents and to identify prescribing practice trends that can inform the formulation and evaluation of new proprietary names. Methods: A national outpatient prescription database, IMS's Vector One (R): National, was used to identify prescribing trends by examining drug use data for proprietary and generic names as they were written on actual prescriptions for 7 discontinued brand drug products from the years 2003 to 2010. Results: Drug use data from years 2003 to 2010 showed the endurance of continued use of proprietary names by prescribers for all 7 studied discontinued brand drug products. Overall, the number of prescriptions written in the proprietary name decreased over time but did not cease after brand drug product discontinuation. Of the 7 drugs studied, "Aldomet'' was the proprietary name with the longest continued use, such that approximately 8 out of 100 new prescriptions for methyldopa were still written in the proprietary name after 10 years of brand drug product discontinuation. Conclusions: This research identified that prescribers continued to prescribe by the proprietary names for many years after the discontinuation of brand drug products. This prescribing practice confirms the need to account for the proprietary names of discontinued brand drug products when formulating and evaluating new proprietary names. C1 [Tu, Chi-Ming; Taylor, Kellie] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Medicat Error Prevent & Anal,Off Medicat Erro, Silver Spring, MD 20993 USA. [Chai, Grace] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Off Pharmacovigilance & Epidemiol,Div Epidemiol 2, Silver Spring, MD 20993 USA. RP Tu, CM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Medicat Error Prevent & Anal,Off Medicat Erro, 10903 New Hampshire Ave,Mailstop 4447,Bldg 22,Roo, Silver Spring, MD 20993 USA. EM chi-ming.tu@fda.hhs.gov FU United States Food and Drug Administration (USFDA) FX This study was sponsored by the United States Food and Drug Administration (USFDA) and included commercial proprietary drug utilization data obtained by FDA under contract. All authors of this manuscript worked for the USFDA when this study was performed and do not have any financial conflicts of interest to disclose. The views expressed in this manuscript represent the opinions of the authors and do not necessarily represent the views of the USFDA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD NOV PY 2012 VL 46 IS 6 BP 677 EP 682 DI 10.1177/0092861512456282 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 032HF UT WOS:000310705100007 ER PT J AU Chen, L Wang, Y AF Chen, Ling Wang, Yang TI Heat Map Displays for Data From Human Abuse Potential Crossover Studies SO DRUG INFORMATION JOURNAL LA English DT Article DE drug abuse potential; crossover study; graphic method; heat map; Williams square design ID LIABILITY AB The human abuse potential study is an important part of the assessment of abuse potential of drugs. This type of study has multiple treatments and multiple abuse potential measures. The study is crossover and often uses a Williams square design. Data are collected for treatments from each treatment sequence and during each treatment period at many time points. This article proposes the use of heat maps to display complicated data sets. This graphic method provides a visual tool for exploring data from individual subjects and overall pictures of subject responses in human abuse potential studies. C1 [Chen, Ling; Wang, Yang] US FDA, ORISE, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, L (reprint author), US FDA, ORISE, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 21,Room 46, Silver Spring, MD 20993 USA. EM ling.chen@fda.hhs.gov FU Regulatory Science Review Enhancement Program; Controlled Substance Staff (CSS) at the Center for Drug Evaluation and Research, US Food and Drug Administration FX This research was supported by funding from the Regulatory Science Review Enhancement Program as well as the Controlled Substance Staff (CSS) at the Center for Drug Evaluation and Research, US Food and Drug Administration. NR 10 TC 0 Z9 0 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD NOV PY 2012 VL 46 IS 6 BP 701 EP 707 DI 10.1177/0092861512452120 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 032HF UT WOS:000310705100011 ER PT J AU Eydelman, MB Tarver, ME Kiang, T Alexander, KY Hutter, JC AF Eydelman, Malvina B. Tarver, Michelle E. Kiang, Tina Alexander, Kesia Y. Hutter, Joseph C. TI The Food and Drug Administration's Role in Establishing and Maintaining Safeguards for Contact Lenses and Contact Lens Care Products SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Editorial Material ID MICROBIAL KERATITIS; OUTBREAK C1 [Eydelman, Malvina B.; Tarver, Michelle E.; Kiang, Tina; Alexander, Kesia Y.; Hutter, Joseph C.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave,WO 66,Room 2410, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov NR 23 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 346 EP 349 DI 10.1097/ICL.0b013e318258e694 PG 4 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800002 PM 22990069 ER PT J AU Green, JA Phillips, KS Hitchins, VM Lucas, AD Shoff, ME Hutter, JC Rorer, EM Eydelman, MB AF Green, J. Angelo Phillips, K. Scott Hitchins, Victoria M. Lucas, Anne D. Shoff, Megan E. Hutter, Joseph C. Rorer, Eva M. Eydelman, Malvina B. TI Material Properties That Predict Preservative Uptake for Silicone Hydrogel Contact Lenses SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE FDA; PHMB; Material properties; Contact lens solutions; Care products; Silicone hydrogel lens; Contact lens ID CONFOCAL MICROSCOPY; MICROBIAL KERATITIS; WETTABILITY; RELEASE AB Objectives: To assess material properties that affect preservative uptake by silicone hydrogel lenses. Methods: We evaluated the water content (using differential scanning calorimetry), effective pore size (using probe penetration), and preservative uptake (using high-performance liquid chromatography with spectrophotometric detection) of silicone and conventional hydrogel soft contact lenses. Results: Lenses grouped similarly based on freezable water content as they did based on total water content. Evaluation of the effective pore size highlighted potential differences between the surface-treated and non-surface-treated materials. The water content of the lens materials and ionic charge are associated with the degree of preservative uptake. Conclusions: The current grouping system for testing contact lens-solution interactions separates all silicone hydrogels from conventional hydrogel contact lenses. However, not all silicone hydrogel lenses interact similarly with the same contact lens solution. Based upon the results of our research, we propose that the same material characteristics used to group conventional hydrogel lenses, water content and ionic charge, can also be used to predict uptake of hydrophilic preservatives for silicone hydrogel lenses. In addition, the hydrophobicity of silicone hydrogel contact lenses, although not investigated here, is a unique contact lens material property that should be evaluated for the uptake of relatively hydrophobic preservatives and tear components. C1 [Green, J. Angelo; Hutter, Joseph C.; Rorer, Eva M.; Eydelman, Malvina B.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. [Phillips, K. Scott] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Hitchins, Victoria M.; Lucas, Anne D.; Shoff, Megan E.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave,WO 66,Room 2410, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov RI Phillips, Kenneth/A-2156-2013; phillips, kenneth/F-7560-2014 OI Phillips, Kenneth/0000-0002-6552-0694; phillips, kenneth/0000-0002-6552-0694 FU Food and Drug Administration FX The Food and Drug Administration funded this work. NR 33 TC 12 Z9 12 U1 4 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 350 EP 357 DI 10.1097/ICL.0b013e318272c470 PG 8 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800003 PM 23085619 ER PT J AU Hutter, JC Green, JA Eydelman, MB AF Hutter, Joseph C. Green, J. Angelo Eydelman, Malvina B. TI Proposed Silicone Hydrogel Contact Lens Grouping System for Lens Care Product Compatibility Testing SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Editorial Material ID WETTABILITY C1 [Hutter, Joseph C.; Green, J. Angelo; Eydelman, Malvina B.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave,WO 66,Room 2410, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov NR 21 TC 9 Z9 9 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 358 EP 362 DI 10.1097/ICL.0b013e318260c959 PG 5 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800004 PM 23085615 ER PT J AU Shoff, ME Eydelman, MB AF Shoff, Megan E. Eydelman, Malvina B. TI Strategies to Optimize Conditions for Testing Multipurpose Contact Lens Solution Efficacy Against Acanthamoeba SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Acanthamoeba; contact lens solution; protocol; keratitis ID KERATITIS; OUTBREAK; STRAINS; CYSTS AB Objectives: To optimize the growth, culture, and life cycle conditions for testing multipurpose solutions (MPS) against Acanthamoebatrophozoites and cysts to better inform the development of an appropriate test protocol. Methods: Two strains of Acanthamoeba castellanii were grown using 2 different methods, bacterized and axenic. Amoebae grown from both methods and from both strains were treated with 4 different MPS as trophozoites and cysts, which were generated using 4 encystment methods. Experiments were run in triplicate with controls. A 5-tube most probable number method was used to enumerate the survivors and to determine the log kills. Statistical analysis was performed using effect screening. Results: There was a marked difference in effectiveness among solutions, which varied with growth conditions (P<0.0001) and encystment method. Growth medium affected survival. In addition, there was a significant difference in cyst survival, which was dependent on encystment method (P=0.0013). The strain used was less of a factor in trophozoite resistance to MPS. Cyst resistance to MPS varied depending on which strain was used, but it was not a significant factor. Conclusions: When designing a contact lens solution efficacy testing protocol for Acanthamoeba, care should be taken to control for variables that may distort results. An appropriate protocol should include growing Acanthamoeba bacterized and allowing them to encyst naturally. By choosing optimized testing conditions, a more realistic efficacy of contact lens solutions can be determined which will result in better and safer products on the market. C1 [Shoff, Megan E.] US FDA, Div Biol, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. [Eydelman, Malvina B.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. RP Shoff, ME (reprint author), Hodges Univ, 4501 Colonial Blvd, Ft Myers, FL 33966 USA. EM mshoff@hodges.edu FU Food and Drug Administration FX The Food and Drug Administration funded this work. NR 22 TC 10 Z9 10 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 EI 1542-233X J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 363 EP 367 DI 10.1097/ICL.0b013e31826e16e4 PG 5 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800005 PM 23085616 ER PT J AU Shoff, ME Lucas, AD Brown, JN Hitchins, VM Eydelman, MB AF Shoff, Megan E. Lucas, Anne D. Brown, Jennifer N. Hitchins, Victoria M. Eydelman, Malvina B. TI The Effects of Contact Lens Materials on a Multipurpose Contact Lens Solution Disinfection Activity Against Staphylococcus aureus SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Staphylococcus aureus; Polyhexamethylene biguanide; Contact lens; Contact lens solution; Microbial keratitis ID ACANTHAMOEBA-KERATITIS; DAILY WEAR; BIGUANIDE AB Objectives: To determine the effect of 8 different lens materials on polyhexamethylene biguanide (PHMB) concentration in multipurpose solution (MPS) levels over time and to determine the effect of lenses on lens solution microbial efficacy over time. Methods: Silicone hydrogel lenses and conventional hydrogel lenses were soaked in polypropylene lens cases filled with contact lens MPS containing 1 ppm PHMB for 6, 12, 24, 72, and 168 hours. Cases filled with the same solution without lenses were controls. After each time period, solutions from cases with the 8 types of lenses and controls were assayed for activity against Staphylococcus aureus according to International Organization for Standardization-14729 with modifications. Solutions were analyzed for PHMB concentration at each time point. Results: Some of the different lens materials significantly affected the PHMB concentration (P<0.0001) and the biocidal efficacy. Etafilcon A lenses significantly decreased PHMB levels after only 6 hours of lens soak time. The product lot of MPS used was also significant (P<0.0001). Enfilcon A, senofilcon A, and lotrafilcon B lenses did not significantly decrease PHMB levels. Conclusions: The efficacy of MPS was affected by some lens materials and PHMB concentration. Lens materials differ in their effect on PHMB concentration and the subsequent efficacy of the MPS. Over time, some lens materials can significantly reduce the PHMB concentration and the MPS's microbial activity against S. aureus. C1 [Shoff, Megan E.; Lucas, Anne D.; Hitchins, Victoria M.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Brown, Jennifer N.; Eydelman, Malvina B.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave,WO 66,Room 2410, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov FU Food and Drug Administration FX Supported by the Food and Drug Administration. NR 22 TC 6 Z9 6 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 368 EP 373 DI 10.1097/ICL.0b013e31826f0893 PG 6 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800006 PM 23085617 ER PT J AU Shoff, ME Lucas, AD Phillips, KS Brown, JN Hitchins, VM Eydelman, MB AF Shoff, Megan E. Lucas, Anne D. Phillips, K. Scott Brown, Jennifer N. Hitchins, Victoria M. Eydelman, Malvina B. TI The Effect of Contact Lens Materials on Disinfection Activity of Polyquaternium-1 and Myristamidopropyl Dimethylamine Multipurpose Solution Against Staphylococcus aureus SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Contact lens; MPS; Multipurpose solution; S. aureus; Microbial keratitis AB Objectives: This study examined the interaction of seven different lens materials with a multipurpose solution (MPS) containing the disinfectants polyquaternium-1 (0.001%) and myristamidopropyl dimethylamine (0.0005%). The objective of this study was to determine whether the different lens materials affect the concentration of a disinfectant in this commercially available MPS and the efficacy of the disinfectant against Staphylococcus aureus. Methods: Silicone hydrogel lenses (galyfilcon A, senofilcon A, comfilcon A, enfilcon A, balafilcon A, and lotrafilcon B) and a conventional hydrogel lens (etafilcon A) were soaked in polypropylene lens cases filled with commercially available MPS containing 0.001% polyquaternium-1 and 0.0005% myristamidopropyl dimethylamine for 6, 12, 24, 72, and 168 hours. Empty lens cases were also filled with MPS. After each time point, solutions from cases containing the seven types of lenses and controls were assayed for activity against S. aureus according to International Standards Organization 14729 standard with modifications. Test solutions were analyzed for polyquaternium-1 and myristamidopropyl dimethylamine concentration at each time point. Results: The concentration of polyquaternium-1 and myristamidopropyl dimethylamine remaining in the lens cases was reduced only slightly over time. Storage with the lenses did not adversely affect biocidal efficacy of the solution, and in some cases, it was significantly better (P=0.0029). Conclusion: The efficacy of this polyquaternium-1 and myristamidopropyl dimethylamine MPS to kill S. aureus was not adversely affected by the presence of lens materials soaking in the cases. Thus, current methods for performing solution antimicrobial testing should be reevaluated. C1 [Shoff, Megan E.; Lucas, Anne D.; Phillips, K. Scott; Hitchins, Victoria M.; Eydelman, Malvina B.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Brown, Jennifer N.; Eydelman, Malvina B.] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave,WO 66,Room 2410, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov RI Phillips, Kenneth/A-2156-2013; phillips, kenneth/F-7560-2014 OI Phillips, Kenneth/0000-0002-6552-0694; phillips, kenneth/0000-0002-6552-0694 FU Food and Drug Administration FX Supported by the Food and Drug Administration. NR 11 TC 3 Z9 3 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 374 EP 378 DI 10.1097/ICL.0b013e31826f0fdb PG 5 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800007 PM 23111451 ER PT J AU Clavet, CR Chaput, MP Silverman, MD Striplin, M Shoff, ME Lucas, AD Hitchins, VM Eydelman, MB AF Clavet, Charles R. Chaput, Maria P. Silverman, Matthew D. Striplin, Megan Shoff, Megan E. Lucas, Anne D. Hitchins, Victoria M. Eydelman, Malvina B. TI Impact of Contact Lens Materials on Multipurpose Contact Lens Solution Disinfection Activity Against Fusarium solani SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Fusarium solani; Multipurpose solutions; Fungal keratitis; Contact lens ID KERATITIS; WEAR; INFECTIONS; SURVIVAL; EFFICACY; OUTBREAK AB Objective: To investigate the effects of eight different soft contact lenses on disinfection efficacy of a multipurpose solution (MPS) containing polyhexamethylene biguanide (PHMB) against Fusarium solani. Methods: Six silicone hydrogel lenses (galyfilcon A, senofilcon A, comfilcon A, enfilcon A, balafilcon A, and lotrifilcon B) and two conventional hydrogel lenses (polymacon and etafilcon A) were placed in polypropylene lens cases filled with MPS containing 0.0001% PHMB and soaked for 6, 12, 24, 72, and 168 hours. After each interval, depleted MPS from lens cases were removed and assayed for activity against F. solani according to International Organization for Standardization (ISO) 14729 stand-alone procedure. A portion was aliquoted for chemical analysis. Results: Soaking etafilcon A, balafilcon A, and polymacon lenses for 6 hours reduced the concentration of PHMB in MPS by more than half the stated labeled concentration, with concentrations below the limit of detection for etafilcon A-depleted and balafilcon A-depleted solutions after 12 and 72 hours of soaking, respectively. Except for comfilcon A-depleted solutions, all others failed to consistently obtain one log reduction of F. solani. The solutions soaked with etafilcon A, balafilcon A, and polymacon lenses for 24 hours or more lost all or almost all fungicidal activity against F. solani. Conclusions: Over time, the disinfectant uptake by some lenses can significantly reduce the PHMB concentration and the fungicidal activity of the MPS against F. solani. Current ISO methodology does not address the reduction in microbiocidal efficacy when lenses are soaked in MPS. The ISO committee should consider adding "soaking experiments" to quantify the effect that contact lens materials have on the performance of MPSs. C1 [Clavet, Charles R.; Chaput, Maria P.; Silverman, Matthew D.; Striplin, Megan] Winchester Engn & Analyt Ctr, Winchester, MA USA. [Shoff, Megan E.; Lucas, Anne D.; Hitchins, Victoria M.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Eydelman, Malvina B.] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Eydelman, MB (reprint author), FDA CDRH ODE DONED, WO 66-2410,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM malvina.eydelman@fda.hhs.gov FU Food and Drug Administration FX Supported by the Food and Drug Administration. NR 33 TC 6 Z9 6 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 379 EP 384 DI 10.1097/ICL.0b013e31826f1004 PG 6 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800008 PM 23085618 ER PT J AU Eydelman, MB Kiang, T Tarver, ME Alexander, KY Hutter, JC AF Eydelman, Malvina B. Kiang, Tina Tarver, Michelle E. Alexander, Kesia Y. Hutter, Joseph C. TI Preclinical Research to Aid in the Development of Test Methods for Contact Lenses and Their Care Products SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Editorial Material C1 [Eydelman, Malvina B.; Kiang, Tina; Tarver, Michelle E.; Alexander, Kesia Y.; Hutter, Joseph C.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Eydelman, MB (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20093 USA. EM malvina.eydelman@fda.hhs.gov NR 18 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2012 VL 38 IS 6 BP 385 EP 387 DI 10.1097/ICL.0b013e318260c93f PG 3 WC Ophthalmology SC Ophthalmology GA 033YR UT WOS:000310837800009 PM 22990070 ER PT J AU Tryndyak, V de Conti, A Kobets, T Kutanzi, K Koturbash, I Han, T Fuscoe, JC Latendresse, JR Melnyk, S Shymonyak, S Collins, L Ross, SA Rusyn, I Beland, FA Pogribny, IP AF Tryndyak, Volodymyr de Conti, Aline Kobets, Tetyana Kutanzi, Kristy Koturbash, Igor Han, Tao Fuscoe, James C. Latendresse, John R. Melnyk, Stepan Shymonyak, Svitlana Collins, Leonard Ross, Sharon A. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. TI Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism SO FASEB JOURNAL LA English DT Article DE nonalcoholic fatty liver; interindividual; oxidative stress ID ELEMENT-BINDING PROTEIN; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE STRESS; PPAR-ALPHA; HEPATIC STEATOSIS; EXPRESSION; DISEASE; PROGRESSION; CHREBP; CYTOCHROME-P450 AB Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline-and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J approximate to C57BL/6J approximate to C3H/HeJ < 129S1/SvImJ approximate to CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor alpha (PPAR alpha)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPAR alpha-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice.-Tryndyak, V., de Conti, A., Kobets, T., Kutanzi, K., Koturbash, I., Han, T., Fuscoe, J. C., Latendresse, J. R., Melnyk, S., Shymonyak, S., Collins, L., Ross, S. A., Rusyn, I., Beland, F. A., Pogribny, I. P. Interstrain differences in the severity of liver injury induced by a choline-and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism. FASEB J. 26, 4592-4602 (2012). www.fasebj.org C1 [Tryndyak, Volodymyr; Kobets, Tetyana; Kutanzi, Kristy; Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] US FDA, NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao; Fuscoe, James C.] US FDA, NCTR, Div Syst Biol, Jefferson, AR 72079 USA. [Latendresse, John R.] US FDA, NCTR, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [de Conti, Aline] Univ Sao Paulo, Lab Diet Nutr & Canc, Sao Paulo, Brazil. [Kobets, Tetyana; Shymonyak, Svitlana; Collins, Leonard; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), US FDA, NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI de Conti, Aline/I-1666-2013; Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [P30 ES010126] NR 45 TC 15 Z9 15 U1 0 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4592 EP 4602 DI 10.1096/fj.12-209569 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200021 PM 22872676 ER PT J AU Schnackenberg, LK Sun, JC Pence, LM Bhattacharyya, S da Costa, GG Beger, RD AF Schnackenberg, Laura K. Sun, Jinchun Pence, Lisa M. Bhattacharyya, Sudeepa da Costa, Goncalo Gamboa Beger, Richard D. TI Metabolomics evaluation of hydroxyproline as a potential marker of melamine and cyanuric acid nephrotoxicity in male and female Fischer F344 rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Melamine; Cyanuric acid; Nephrotoxicity; Metabolomics; Hydroxyproline ID DOSE-RESPONSE ASSESSMENT; COMBINED-EXPOSURE; RENAL TOXICITY; KIDNEY; CATS; NORMALIZATION; CONTAMINANTS; METABOLISM; CREATININE; FOOD AB Following kidney failure in domesticated pets in the US and kidney issues requiring hospitalization with some deaths in children in China, investigators determined the cause was adulteration of pet foods and baby formula with melamine. It has since been noted that exposure of rats to melamine and cyanuric acid forms melamine cyanurate crystals in the kidney leading to acute nephrotoxicity. This metabolomics study aimed to identify biomarkers of melamine and cyanuric acid-induced renal injury. Male and female Fischer 344 rats were fed a diet fortified with varying doses of melamine and cyanuric acid for 28 days. Analysis of urinary amino acids showed hydroxyproline was increased in both sexes in a manner consistent with the clinical chemistry and histopathology data; most prominent when total urine output was taken into account. Furthermore, rats with the highest levels of urinary hydroxyproline were the only rats that exhibited fibrosis within the kidney. Clinical chemistry and histopathology indicated male rats were slightly more affected than female rats following dosing with the 120 and 180 ppm formulations: hydroxyproline excretion also supports this finding. Hydroxyproline may be a noninvasive urinary biomarker for detection of acute kidney injury potentially associated with kidney fibrosis. Published by Elsevier Ltd. C1 [Schnackenberg, Laura K.; Sun, Jinchun; Pence, Lisa M.; Bhattacharyya, Sudeepa; Beger, Richard D.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson Labs, Jefferson, AR 72079 USA. [Bhattacharyya, Sudeepa] Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. [da Costa, Goncalo Gamboa] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson Labs, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson Labs, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov FU FDA [FDA IAG: 224-12-0003]; National Toxicology Program at NIEHS [NIH AES12013] FX This study was supported through an interagency agreement between the FDA and the National Toxicology Program at NIEHS (FDA IAG: 224-12-0003; NIH AES12013). NR 30 TC 8 Z9 10 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2012 VL 50 IS 11 BP 3978 EP 3983 DI 10.1016/j.fct.2012.08.010 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 031PL UT WOS:000310654300014 PM 22902825 ER PT J AU Hamasaki-Katagiri, N Salari, R Simhadri, VL Tseng, SC Needlman, E Edwards, NC Sauna, ZE Grigoryan, V Komar, AA Przytycka, TM Kimchi-Sarfaty, C AF Hamasaki-Katagiri, N. Salari, R. Simhadri, V. L. Tseng, S. C. Needlman, E. Edwards, N. C. Sauna, Z. E. Grigoryan, V. Komar, A. A. Przytycka, T. M. Kimchi-Sarfaty, C. TI Analysis of F9 point mutations and their correlation to severity of haemophilia B disease SO HAEMOPHILIA LA English DT Article DE coagulation factor IX; genotype-phenotype association; haemophilia B; in silico analysis; mRNA free energy; predictive tools ID FACTOR-IX; PROTEIN; GENE AB Haemophilia B is an X-linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed-rank tests showed highly significant differences between severe and non-severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins. C1 [Hamasaki-Katagiri, N.; Simhadri, V. L.; Tseng, S. C.; Needlman, E.; Edwards, N. C.; Sauna, Z. E.; Kimchi-Sarfaty, C.] US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Salari, R.; Grigoryan, V.; Przytycka, T. M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Komar, A. A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. RP Kimchi-Sarfaty, C (reprint author), US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM chava.kimchi-sarfaty@fda.hhs.gov FU Intramural Research Programme of the National Institutes of Health, National Library of Medicine FX The authors thank Ms. Nechama Nelson for her assistance with mfold. This study was supported in part by the Intramural Research Programme of the National Institutes of Health, National Library of Medicine. The authors declare no competing financial interests. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 19 TC 6 Z9 7 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD NOV PY 2012 VL 18 IS 6 BP 933 EP 940 DI 10.1111/j.1365-2516.2012.02848.x PG 8 WC Hematology SC Hematology GA 030EY UT WOS:000310553600030 PM 22639855 ER PT J AU Cruciani, RA Zhang, JJ Manola, J Cella, D Ansari, B Fisch, MJ AF Cruciani, Ricardo A. Zhang, Jenny J. Manola, Judith Cella, David Ansari, Bilal Fisch, Michael J. TI L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIAL; DEFICIENCY; PROFILES; LIFE AB Purpose L-carnitine, a popular complementary and alternative medicine product, is used by patients with cancer for the treatment of fatigue, the most commonly reported symptom in this patient population. The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer. Patients and Methods In this double-blind, placebo-controlled trial, patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). Results Three hundred seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in significant carnitine plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline (L-carnitine: -0.96, 95% CI, -1.32 to -0.60; placebo: -1.11, 95% CI -1.44 to -0.78). There were no statistically significant differences between arms (P = .57). Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument, depression, and pain, did not show significant difference between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation. Conclusion Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status. J Clin Oncol 30: 3864-3869. (C) 2012 by American Society of Clinical Oncology C1 [Cruciani, Ricardo A.] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Cruciani, Ricardo A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Manola, Judith] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Stat Off, Boston, MA 02115 USA. [Cella, David] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Ansari, Bilal] Mem Hosp S Bend, South Bend, IN USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhang, Jenny J.] US FDA, Silver Spring, MD USA. RP Cruciani, RA (reprint author), Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. EM rcruciani@chpnet.org FU National Cancer Institute, US Department of Health and Human Services [CA-23318] FX Supported by Grant No. CA-23318, National Cancer Institute, US Department of Health and Human Services. NR 16 TC 26 Z9 27 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2012 VL 30 IS 31 BP 3864 EP 3869 DI 10.1200/JCO.2011.40.2180 PG 6 WC Oncology SC Oncology GA 030PT UT WOS:000310583300023 PM 22987089 ER PT J AU Bright, PL Nelson, RM AF Bright, Patricia L. Nelson, Robert M. TI A capacity-based approach for addressing ancillary care needs: implications for research in resource limited settings SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID HEALTH INTERVENTION RESEARCH; MEDICAL RESEARCHERS; CLINICAL CARE; RESPONSIBILITIES; TRIAGE AB A paediatric clinical trial conducted in a developing country is likely to encounter conditions or illnesses in participants unrelated to the study. Since local healthcare resources may be inadequate to meet these needs, research clinicians may face the dilemma of deciding when to provide ancillary care and to what extent. The authors propose a model for identifying ancillary care obligations that draws on assessments of urgency, the capacity of the local healthcare infrastructure and the capacity of the research infrastructure. The model lends itself to a decision tree that can be adapted to the local context and resources so as to provide procedural guidance. This approach can help in planning and establishing organisational policies that govern the provision of ancillary care. C1 [Bright, Patricia L.; Nelson, Robert M.] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. RP Bright, PL (reprint author), US FDA, Off Pediat Therapeut, 10903 New Hampshire Ave,WO51-6272, Silver Spring, MD 20993 USA. EM patricia.bright@fda.hhs.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD NOV PY 2012 VL 38 IS 11 BP 672 EP 676 DI 10.1136/medethics-2011-100205 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 030PE UT WOS:000310581800008 PM 22562947 ER PT J AU Bouladoux, N Hall, JA Grainger, JR dos Santos, LM Kann, MG Nagarajan, V Verthelyi, D Belkaid, Y AF Bouladoux, N. Hall, J. A. Grainger, J. R. dos Santos, L. M. Kann, M. G. Nagarajan, V. Verthelyi, D. Belkaid, Y. TI Regulatory role of suppressive motifs from commensal DNA SO MUCOSAL IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL IMMUNE-RESPONSES; RETINOIC-ACID; T-CELLS; TOXOPLASMA-GONDII; IFN-GAMMA; DENDRITIC CELLS; BACTERIAL-DNA; CPG MOTIFS; OLIGODEOXYNUCLEOTIDES AB The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T-reg cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes. C1 [Bouladoux, N.; Hall, J. A.; Grainger, J. R.; dos Santos, L. M.; Belkaid, Y.] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Hall, J. A.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY USA. [dos Santos, L. M.] Univ Fed Minas Gerais, Lab Gnotobiol & Immunol LAGI, Belo Horizonte, MG, Brazil. [Kann, M. G.] Univ Maryland, Baltimore, MD 21201 USA. [Nagarajan, V.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD USA. [Verthelyi, D.] Ctr Drug Evaluat & Res, Food & Drug Adm, Div Therapeut Proteins, Immunol Lab, Bethesda, MD USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov OI Grainger, John/0000-0002-4052-5923 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank C Eigsti and E Stregevsky from the NIAID sorting facility and K Beacht, V Wang, and T Peterson for technical assistance. We thank D Chou, M Molloy, S Naik, S Spencer, and E Wohlfert for their critical reading of the manuscript. NR 52 TC 23 Z9 23 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2012 VL 5 IS 6 BP 623 EP 634 DI 10.1038/mi.2012.36 PG 12 WC Immunology SC Immunology GA 030LS UT WOS:000310572800005 PM 22617839 ER PT J AU Chen, T Mei, N Woodruff, RS Yan, J Chen, Y Ding, W Bhalli, J Sadiq, R Li, Y Rice, P Zhang, YB Biris, A Howard, PC Zhou, T Moore, MM AF Chen, Tao Mei, Nan Woodruff, Robert S. Yan, Jian Chen, Ying Ding, Wei Bhalli, Javed Sadiq, Rakhshinda Li, Yan Rice, Penelope Zhang, Yongbin Biris, Alexandru Howard, Paul C. Zhou, Tong Moore, Martha M. TI Evaluation of the applicability of standard assays for assessing the genotoxicity of nanomaterials SO MUTAGENESIS LA English DT Meeting Abstract C1 [Chen, Tao; Mei, Nan; Yan, Jian; Chen, Ying; Ding, Wei; Bhalli, Javed; Sadiq, Rakhshinda; Li, Yan; Moore, Martha M.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Woodruff, Robert S.] US FDA, Div Microbiol, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Rice, Penelope] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhang, Yongbin; Howard, Paul C.] US FDA, NCTR ORA Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Biris, Alexandru] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Zhou, Tong] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2012 VL 27 IS 6 MA 25 BP 796 EP 797 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 031IR UT WOS:000310633200046 ER PT J AU Wang, PG Zhou, WL Wamer, WG Krynitsky, AJ Rader, JI AF Wang, Perry G. Zhou, Wanlong Wamer, Wayne G. Krynitsky, Alexander J. Rader, Jeanne I. TI Simultaneous determination of aloin A and aloe emodin in products containing Aloe vera by ultra-performance liquid chromatography with tandem mass spectrometry SO ANALYTICAL METHODS LA English DT Article ID CHENG-QI DECOCTION; CAPILLARY ELECTROCHROMATOGRAPHY; SIMULTANEOUS QUANTIFICATION; ANTHRAQUINONE DERIVATIVES; FLUORESCENCE DETECTION; POLYGONI-MULTIFLORI; HPLC DETERMINATION; PHENOLIC-COMPOUNDS; RAT PLASMA; EXTRACTION AB A novel method for the simultaneous determination of aloin A and aloe emodin in products labeled to contain Aloe vera has been developed and validated. This analytical procedure involved extracting a test portion of the product in acetonitrile : water (40 : 60, v/v), followed by centrifugation and filtration through a 0.2 mu m PTFE filter. Quantitation was achieved using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with electrospray ionization (ESI) in the negative mode. The separation was carried out using a Waters Acquity UPLC BEH C-18 column; 2.1 mm x 50 mm; 1.7 mu m particle size. A five-minute gradient program was optimized at a flow rate of 0.5 mL min(-1). Both water with 0.5% acetic acid and methanol with 0.5% acetic acid were used as mobile phases. The linear range was from 5.0 to 1000 ng mL(-1) for aloin A and from 1.0 to 500 ng mL(-1) for aloe emodin, with r > 0.995 for both analytes. Since serious matrix effects (both ion suppression and ion enhancement) were eliminated by dilution for all samples, the recoveries for aloin A and aloe emodin ranged from 89-118%, and 74-108%, respectively, in the matrices tested. The method has been successfully applied to various products labeled to contain Aloe vera including liquids, capsules, soft gels and tabs. The amount of aloin A and aloe emodin in the samples ranged from none detected to 160.0 mg g(-1) and from none detected to 3.8 mg g(-1), respectively. C1 [Wang, Perry G.; Zhou, Wanlong; Wamer, Wayne G.; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wang, PG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM perry.wang@fda.hhs.gov NR 51 TC 12 Z9 12 U1 3 U2 47 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 J9 ANAL METHODS-UK JI Anal. Methods PD NOV PY 2012 VL 4 IS 11 BP 3612 EP 3619 DI 10.1039/c2ay25599e PG 8 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 026MA UT WOS:000310281700018 ER PT J AU Tavris, DR Brennan, JM Sedrakyan, A Zhao, Y O'Brien, SM Peterson, ED Gross, TP Marinac-Dabic, D Horvath, KA AF Tavris, Dale R. Brennan, James Matthew Sedrakyan, Art Zhao, Yue O'Brien, Sean M. Peterson, Eric D. Gross, Thomas P. Marinac-Dabic, Danica Horvath, Keith A. TI Long-Term Outcomes After Transmyocardial Revascularization SO ANNALS OF THORACIC SURGERY LA English DT Article ID NORWEGIAN RANDOMIZED-TRIAL; REFRACTORY ANGINA-PECTORIS; LASER REVASCULARIZATION; SYMPTOMATIC IMPROVEMENT; MEDICAL THERAPY; HOLMIUM-YAG; CO2-LASER AB Background. Two independent reports documented substantially higher operative mortality associated with transmyocardial revascularization (TMR) when used in isolation than that reported in the premarket clinical trials. To clarify the state of the art, this article assesses temporal trends in the use of TMR, short-term and long-term outcomes, and outcomes stratified by procedure type (TMR only and TMR + coronary artery bypass graft [CABG]) and by the 2 specific TMR devices. Methods. The study population included all patients undergoing TMR in isolation or in combination with CABG at 435 cardiothoracic hospitals in the United States participating in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) from January 2000 through November 2006 (n = 15,386). Analysis of long-term outcomes was accomplished through linkage to Medicare claims data. Short-term and long-term (7 years) adverse outcomes were assessed and compared between the 2 TMR device types. Results. The use of TMR in conjunction with CABG surgery is increasing. This study showed modest differences in short-term morbidity and mortality between the 2 devices. In combination with CABG, after risk adjustment, patients treated with the holmium: YAG laser (experienced a higher rate of operative mortality (3.5% vs 2.5%; adjusted hazard ratio 1.39, 95% confidence level 1.03 to 1.87) but no difference in the composite short-term rate of major morbidity or mortality, compared with the Heart Laser CO2 transmyocardial revascularization system (PLC Medical Systems, Inc, Milford, MA). However, there were no clinically meaningful differences in long-term results. Conclusions. Modest differences in short-term morbidity and mortality between the 2 devices suggest the usefulness of further research. C1 [Tavris, Dale R.] US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. Duke Univ, Clin Res Inst, Durham, NC USA. Soc Thorac Surg, Chicago, IL USA. RP Tavris, DR (reprint author), US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, White Oak Bldg 66,Rm 4204,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM dale.tavris@fda.hhs.gov RI O'Brien, Sean/H-6268-2013 NR 23 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2012 VL 94 IS 5 BP 1500 EP 1508 DI 10.1016/j.athoracsur.2012.05.068 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 028RJ UT WOS:000310439700028 PM 22835557 ER PT J AU Morrissey, KM Wen, CC Johns, SJ Zhang, L Huang, SM Giacomini, KM AF Morrissey, K. M. Wen, C. C. Johns, S. J. Zhang, L. Huang, S-M Giacomini, K. M. TI The UCSF-FDA TransPortal: A Public Drug Transporter Database SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Drug transporters play a key role in the absorption, distribution, and elimination of many drugs, and they appear to be important determinants of therapeutic and adverse drug activities. Although a large body of data pertaining to drug transporters is available, there are few databases that inform drug developers, regulatory agencies, and academic scientists about transporters that are important in drug action and disposition. In this article, we inform the scientific community about the UCSF-FDA TransPortal, a new and valuable online resource for research and drug development. C1 [Morrissey, K. M.; Wen, C. C.; Giacomini, K. M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Johns, S. J.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Zhang, L.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Giacomini, KM (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. EM kathy.giacomini@ucsf.edu FU NIGMS NIH HHS [T32 GM007175, U01 GM061390] NR 2 TC 49 Z9 51 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2012 VL 92 IS 5 BP 545 EP 546 DI 10.1038/clpt.2012.44 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QF UT WOS:000310367400014 PM 23085876 ER PT J AU Borders-Hemphill, V Mosholder, A AF Borders-Hemphill, Vicky Mosholder, Andrew TI US utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Antiviral; H1N1; influenza; surveillance ID VISITS AB Please cite this paper as: Borders-Hemphill and Mosholder (2012) U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic. Influenza and Other Respiratory Viruses 6(601), e129e133. Background The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). Objectives To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDCs weekly reports of the number of visits for influenza-like-illnesses by the Influenza Sentinel Provider Surveillance Network. Methods A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. Results Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. Conclusion Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza-like-illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both overall and stratified by age), providing some corroboration for the surveillance data. C1 [Borders-Hemphill, Vicky; Mosholder, Andrew] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Borders-Hemphill, V (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM vicky.borders-hemphill@fda.hhs.gov NR 8 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD NOV PY 2012 VL 6 IS 6 BP e129 EP e133 DI 10.1111/j.1750-2659.2012.00384.x PG 5 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 026IY UT WOS:000310270300012 PM 22681766 ER PT J AU Lederman, ER Davidson, W Groff, HL Smith, SK Warkentien, T Li, Y Wilkins, KA Karem, KL Akondy, RS Ahmed, R Frace, M Shieh, WJ Zaki, S Hruby, DE Painter, WP Bergman, KL Cohen, JI Damon, IK AF Lederman, Edith R. Davidson, Whitni Groff, Harold L. Smith, Scott K. Warkentien, Tyler Li, Yu Wilkins, Kimberly A. Karem, Kevin L. Akondy, Rama S. Ahmed, Rafi Frace, Michael Shieh, Wun-Ju Zaki, Sherif Hruby, Dennis E. Painter, Wendy P. Bergman, Kimberly L. Cohen, Jeffrey I. Damon, Inger K. TI Progressive Vaccinia: Case Description and Laboratory-Guided Therapy With Vaccinia Immune Globulin, ST-246, and CMX001 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL RESPONSES; SMALLPOX VACCINATION; MONKEYPOX; VIRUS; INFECTION; CHALLENGE; CONTACT; MICE AB Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV. C1 [Lederman, Edith R.; Davidson, Whitni; Smith, Scott K.; Li, Yu; Wilkins, Kimberly A.; Karem, Kevin L.; Frace, Michael; Shieh, Wun-Ju; Zaki, Sherif; Damon, Inger K.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA USA. [Warkentien, Tyler; Akondy, Rama S.; Ahmed, Rafi] Emory Univ, Sch Med, Vaccine Ctr, Atlanta, GA USA. [Lederman, Edith R.; Groff, Harold L.] USN, Div Infect Dis, San Diego Med Ctr, San Diego, CA USA. [Hruby, Dennis E.] Siga Technol, Corvallis, OR USA. [Painter, Wendy P.] Chimerix, Durham, NC USA. [Bergman, Kimberly L.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cohen, Jeffrey I.] Natl Inst Allergy & Immunol, NIH, Bethesda, MD USA. RP Lederman, ER (reprint author), San Diego State Univ, Grad Sch Publ Hlth, Hardy Tower 119,5500 Campanile Dr, San Diego, CA 92182 USA. EM erlederman@yahoo.com OI Akondy, Rama/0000-0003-4737-5240 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases (to J. I. C.). NR 22 TC 18 Z9 18 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1372 EP 1385 DI 10.1093/infdis/jis510 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700009 PM 22904336 ER PT J AU Song, FH El-Demerdash, A Lee, SJSH AF Song, Fenhong El-Demerdash, Aref Lee, Shwn-Ji Susie H. TI Screening for multiple phosphodiesterase type 5 inhibitor drugs in dietary supplement materials by flow injection mass spectrometry and their quantification by liquid chromatography tandem mass spectrometry SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Phosphodiesterase type 5 inhibitor; Sildenafil; Tadalafil; Flow injection; LC-MS/MS ID PENILE ERECTILE DYSFUNCTION; LC-ESI-MS; STRUCTURE ELUCIDATION; SILDENAFIL; ANALOGS; IDENTIFICATION; VARDENAFIL; ADULTERANT; TADALAFIL; LC/MS/MS AB A flow injection tandem mass spectrometry method (FI-MS/MS) has been developed to detect enzyme phosphodiesterase type 5 inhibitors, including tadalafil, sildenafil, and vardenafil. Multiple reaction monitoring (MRM) was used to detect the drugs and product ion ratios were used for identification. FI-MS/MS was used for semi-quantification and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for further confirmation and quantification. One of 13 samples has been found to be adulterated with prescription levels of tadalafil and also low level of sildenafil. The method can be used for screening large numbers of herbal products for adulteration since it takes less than 1 min without chromatographic separation on a column. Published by Elsevier B.V. C1 [Song, Fenhong; El-Demerdash, Aref; Lee, Shwn-Ji Susie H.] US FDA, Method Dev & Total Diet Res Ctr, Lenexa, KS 66214 USA. RP Song, FH (reprint author), US FDA, Method Dev & Total Diet Res Ctr, 11630 W 80th St, Lenexa, KS 66214 USA. EM fenhong.song@fda.hhs.gov NR 23 TC 17 Z9 20 U1 1 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV PY 2012 VL 70 BP 40 EP 46 DI 10.1016/j.jpba.2012.05.017 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 013OL UT WOS:000309314600006 PM 22695818 ER PT J AU Botsis, T Buttolph, T Nguyen, MD Winiecki, S Woo, EJ Ball, R AF Botsis, Taxiarchis Buttolph, Thomas Nguyen, Michael D. Winiecki, Scott Woo, Emily Jane Ball, Robert TI Vaccine adverse event text mining system for extracting features from vaccine safety reports SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATION AB Objective To develop and evaluate a text mining system for extracting key clinical features from vaccine adverse event reporting system (VAERS) narratives to aid in the automated review of adverse event reports. Design Based upon clinical significance to VAERS reviewing physicians, we defined the primary (diagnosis and cause of death) and secondary features leg, symptoms) for extraction. We built a novel vaccine adverse event text mining (VaeTM) system based on a semantic text mining strategy. The performance of VaeTM was evaluated using a total of 300 VAERS reports in three sequential evaluations of 100 reports each. Moreover, we evaluated the VaeTM contribution to case classification; an information retrieval-based approach was used for the identification of anaphylaxis cases in a set of reports and was compared with two other methods: a dedicated text classifier and an online tool. Measurements The performance metrics of VaeTM were text mining metrics: recall, precision and F-measure. We also conducted a qualitative difference analysis and calculated sensitivity and specificity for classification of anaphylaxis cases based on the above three approaches. Results VaeTM performed best in extracting diagnosis, second level diagnosis, drug, vaccine, and lot number features (lenient F-measure in the third evaluation: 0.897, 0.817, 0.858, 0.874, and 0.914, respectively). In terms of case classification, high sensitivity was achieved (83.1%), this was equal and better compared to the text classifier (83.1%) and the online tool (40.7%), respectively. Conclusion Our VaeTM implementation of a semantic text mining strategy shows promise in providing accurate and efficient extraction of key features from VAERS narratives. C1 [Botsis, Taxiarchis] US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. [Botsis, Taxiarchis] Univ Tromso, Dept Comp Sci, Tromso, Norway. RP Botsis, T (reprint author), US FDA, Off Biostat & Epidemiol, CBER, Woodmont Off Complex 1,Room 306N,1401 Rockville P, Rockville, MD 20852 USA. EM taxiarchis.botsis@fda.hhs.gov OI Winiecki, Scott/0000-0003-4912-4621 NR 26 TC 13 Z9 13 U1 0 U2 17 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2012 VL 19 IS 6 BP 1011 EP 1018 DI 10.1136/amiajnl-2012-000881 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 028FP UT WOS:000310408500014 PM 22922172 ER PT J AU Kass-Hout, TA Xu, ZH McMurray, P Park, S Buckeridge, DL Brownstein, JS Finelli, L Groseclose, SL AF Kass-Hout, Taha A. Xu, Zhiheng McMurray, Paul Park, Soyoun Buckeridge, David L. Brownstein, John S. Finelli, Lyn Groseclose, Samuel L. TI Application of change point analysis to daily influenza-like illness emergency department visits SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PUBLIC-HEALTH SURVEILLANCE; SYNDROMIC SURVEILLANCE; DETECTION ALGORITHMS; BAYESIAN-ANALYSIS; PREPAREDNESS; OUTBREAK; MODELS AB Background The utility of healthcare utilization data from US emergency departments (EDs) for rapid monitoring of changes in influenza-like illness (ILI) activity was highlighted during the recent influenza A (H1N1) pandemic. Monitoring has tended to rely on detection algorithms, such as the Early Aberration Reporting System (EARS), which are limited in their ability to detect subtle changes and identify disease trends. Objective To evaluate a complementary approach, change point analysis (CPA), for detecting changes in the incidence of ED visits due to ILI. Methodology and principal findings Data collected through the Distribute project (isdsdistribute.org), which aggregates data on ED visits for ILI from over 50 syndromic surveillance systems operated by state or local public health departments were used. The performance was compared of the cumulative sum (CUSUM) CPA method in combination with EARS and the performance of three CPA methods (CUSUM, structural change model and Bayesian) in detecting change points in daily time-series data from four contiguous US states participating in the Distribute network. Simulation data were generated to assess the impact of autocorrelation inherent in these time-series data on CPA performance. The CUSUM CPA method was robust in detecting change points with respect to autocorrelation in time-series data (coverage rates at 90% when -0.2 <=rho <= 0.2 and 80% when -0.5 <=rho <= 0.5). During the 2008-9 season, 21 change points were detected and ILI trends increased significantly after 12 of these change points and decreased nine times. In the 2009-10 flu season, we detected 11 change points and ILI trends increased significantly after two of these change points and decreased nine times. Using CPA combined with EARS to analyze automatically daily ED-based ILI data, a significant increase was detected of 3% in ILI on April 27, 2009, followed by multiple anomalies in the ensuing days, suggesting the onset of the H1N1 pandemic in the four contiguous states. Conclusions and significance As a complementary approach to EARS and other aberration detection methods, the CPA method can be used as a tool to detect subtle changes in time-series data more effectively and determine the moving direction (ie, up, down, or stable) in ILI trends between change points. The combined use of EARS and CPA might greatly improve the accuracy of outbreak detection in syndromic surveillance systems. C1 [Kass-Hout, Taha A.; McMurray, Paul; Groseclose, Samuel L.] Ctr Dis Control & Prevent, Publ Hlth Surveillance & Informat Program Off, Off Surveillance Epidemiol, Atlanta, GA 30333 USA. [Kass-Hout, Taha A.; McMurray, Paul; Groseclose, Samuel L.] Ctr Dis Control & Prevent, Lab Serv, Atlanta, GA USA. [Xu, Zhiheng] US FDA, Silver Spring, MD USA. [Park, Soyoun] McKing Consulting Corp, Atlanta, GA USA. [Buckeridge, David L.; Brownstein, John S.] Int Soc Dis Surveillance, Boston, MA USA. [Buckeridge, David L.] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. [Buckeridge, David L.] Agence Sante & Serv Sociaux Montreal, Direct Sante Publ, Montreal, PQ, Canada. [Brownstein, John S.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Finelli, Lyn] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Off Infect Dis, Atlanta, GA USA. RP Kass-Hout, TA (reprint author), Ctr Dis Control & Prevent, Publ Hlth Surveillance & Informat Program Off, Off Surveillance Epidemiol, Atlanta, GA 30333 USA. EM kasshout@gmail.com OI Kass-Hout, Taha/0000-0002-0123-5157 NR 22 TC 16 Z9 17 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2012 VL 19 IS 6 BP 1075 EP 1081 DI 10.1136/amiajnl-2011-000793 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 028FP UT WOS:000310408500023 PM 22759619 ER PT J AU Verma, S Dimitrova, M Munjal, A Fontana, J Crevar, CJ Carter, DM Ross, TM Khurana, S Golding, H AF Verma, Swati Dimitrova, Milena Munjal, Ashok Fontana, Juan Crevar, Corey J. Carter, Donald M. Ross, Ted M. Khurana, Surender Golding, Hana TI Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLE; BROAD CROSS-PROTECTION; NEUTRALIZING ANTIBODIES; HEMAGGLUTININ PROTEINS; ELECTRON-MICROSCOPY; IMMUNE-RESPONSES; GLOBULAR HEAD; YOUNG-ADULTS; INSECT CELLS; A VIRUS AB Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission. C1 [Verma, Swati; Dimitrova, Milena; Khurana, Surender; Golding, Hana] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. [Verma, Swati; Munjal, Ashok] Banasthali Vidyapith, Dept Biosci & Biotechnol, Banasthali, Rajasthan, India. [Fontana, Juan] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. RP Khurana, S (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. EM surender.khurana@fda.hhs.gov; hana.golding@fda.hhs.gov RI Fontana, Juan/A-9138-2009 OI Fontana, Juan/0000-0002-9084-2927 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; NIH/NIAID [U01AI077771] FX This work was partly supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health to J.F. and NIH/NIAID award U01AI077771 to T.M.R. NR 55 TC 13 Z9 13 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2012 VL 86 IS 22 BP 12283 EP 12293 DI 10.1128/JVI.01596-12 PG 11 WC Virology SC Virology GA 027MK UT WOS:000310356400029 PM 22951833 ER PT J AU Robb, MA Racoosin, JA Worrall, C Chapman, S Coster, T Cunningham, FE AF Robb, Melissa A. Racoosin, Judith A. Worrall, Chris Chapman, Summer Coster, Trinka Cunningham, Francesca E. TI Active Surveillance of Postmarket Medical Product Safety in the Federal Partners' Collaboration SO MEDICAL CARE LA English DT Article DE FDA; Sentinel; safety monitoring; adverse events; surveillance ID VACCINATION; POPULATION AB After half a century of monitoring voluntary reports of medical product adverse events, the Food and Drug Administration (FDA) has launched a long-term project to build an adverse events monitoring system, the Sentinel System, which can access and evaluate electronic health care data to help monitor the safety of regulated medical products once they are marketed. On the basis of experience gathered through a number of collaborative efforts, the Federal Partners' Collaboration pilot project, involving FDA, the Centers for Medicare & Medicaid Services, the Department of Veteran Affairs, and the Department of Defense, is already enabling FDA to leverage the power of large public health care databases to assess, in near real time, the utility of analytical tools and methodologies that are being developed for use in the Sentinel System. Active medical product safety surveillance is enhanced by use of these large public health databases because specific populations of exposed patients can be identified and analyzed, and can be further stratified by key variables such as age, sex, race, socioeconomic status, and basis for eligibility to examine important subgroups. C1 [Robb, Melissa A.; Racoosin, Judith A.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Med Policy, Silver Spring, MD 20993 USA. [Worrall, Chris] Ctr Medicare & Medicaid Serv CMS, Ctr Medicare, Baltimore, MD USA. [Chapman, Summer; Cunningham, Francesca E.] Ctr Medicat Safety, Pharm Benefits Management Serv, Dept Vet Affairs, Hines, IL USA. [Coster, Trinka] US Army Off Surgeon Gen, Pharmacovigilance Ctr, Silver Spring, MD USA. RP Robb, MA (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Med Policy, 10903 New Hampshire Ave,Bldg 51,Room 6360, Silver Spring, MD 20993 USA. EM melissa.robb@fda.hhs.gov NR 21 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2012 VL 50 IS 11 BP 948 EP 953 DI 10.1097/MLR.0b013e31826c874d PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 022OL UT WOS:000309968600008 PM 23047784 ER PT J AU Du, DY Zhou, EH Goldsmith, J Nardinelli, C Hammad, TA AF Du, Dongyi (Tony) Zhou, Esther H. Goldsmith, John Nardinelli, Clark Hammad, Tarek A. TI Atomoxetine Use During a Period of FDA Actions SO MEDICAL CARE LA English DT Article DE boxed warning; utilization; postmarketing safety; risk management; ADHD ID INTERRUPTED TIME-SERIES; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; SEGMENTED REGRESSION-ANALYSIS; PEDIATRIC SUICIDALITY; MEDICATION USE; ANTIDEPRESSANT; CHILDREN; IMPACT; ADOLESCENTS AB Context: The Food and Drug Administration (FDA) issued a Public Health Advisory entitled "Suicidal Thinking in Children and Adolescents Being Treated with Strattera (Atomoxetine)" on September 29, 2005. At FDA's request, the manufacturer subsequently added a boxed warning to the drug's labeling on November 8, 2005. Objective: To evaluate whether the boxed warning for suicidal thinking in atomoxetine's labeling was associated with a change in the pattern of attention-deficit/hyperactivity disorder (ADHD) medication use. Methods: Patients who had an ADHD diagnosis and were prescribed either atomoxetine or stimulants between January 2004 and December 2007 were selected from IMS LifeLink Health Plan Claims database. In this ecologic analysis, the outcome measure is the incident atomoxetine use rate, defined as the proportion of atomoxetine incident users among all initial ADHD pharmacotherapy users. The impact of the boxed warning was evaluated using interrupted time series analysis. Results: A total of 16,311 patients met the definition of incident ADHD medication users. The incident atomoxetine use rate decreased from January 2004 to September 2005 among all age groups (range, -0.45% to -0.74%); and the rate among adult patients decreased by 11.89% (95% confidence interval, 3.05%-20.74%) from September 2005 to November 2005. No long-term impact was detected. Conclusions: Significant decline of the atomoxetine use rate was observed before the boxed warning in all age groups. No significant change was detected in the atomoxetine use rate among targeted children or adolescents after the FDA's boxed warning concerning suicidal thinking. C1 [Du, Dongyi (Tony); Goldsmith, John; Nardinelli, Clark] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. [Zhou, Esther H.; Hammad, Tarek A.] US FDA, CDER, Rockville, MD 20857 USA. RP Du, DY (reprint author), US FDA, Off Commissioner, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM dongyi.du@fda.hhs.gov NR 32 TC 6 Z9 6 U1 6 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2012 VL 50 IS 11 BP 987 EP 992 DI 10.1097/MLR.0b013e31826c86f1 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 022OL UT WOS:000309968600012 PM 23047788 ER PT J AU Timme, RE Allard, MW Luo, Y Strain, E Pettengill, J Wang, C Li, C Keys, CE Zheng, J Stones, R Wilson, MR Musser, SM Brown, EW AF Timme, Ruth E. Allard, Marc W. Luo, Yan Strain, Errol Pettengill, James Wang, Charles Li, Cong Keys, Christine E. Zheng, Jie Stones, Robert Wilson, Mark R. Musser, Steven M. Brown, Eric W. TI Draft Genome Sequences of 21 Salmonella enterica Serovar Enteritidis Strains SO JOURNAL OF BACTERIOLOGY LA English DT Article AB Salmonella enterica subsp. enterica serovar Enteritidis is a common food-borne pathogen, often associated with shell eggs and poultry. Here, we report draft genomes of 21 S. Enteritidis strains associated with or related to the U.S.-wide 2010 shell egg recall. Eleven of these genomes were from environmental isolates associated with the egg outbreak, and 10 were reference isolates from previous years, unrelated to the outbreak. The whole-genome sequence data for these 21 human pathogen strains are being released in conjunction with the newly formed 100K Genome Project. C1 [Timme, Ruth E.; Allard, Marc W.; Pettengill, James; Wang, Charles; Li, Cong; Keys, Christine E.; Zheng, Jie; Musser, Steven M.; Brown, Eric W.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Luo, Yan; Strain, Errol] US FDA, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Stones, Robert] Food & Environm Res Agcy, York, N Yorkshire, England. [Wilson, Mark R.] Western Carolina Univ, Forens Sci Program, Cullowhee, NC 28723 USA. RP Timme, RE (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM ruth.timme@fda.hhs.gov FU Center for Food Safety and Applied Nutrition at the U.S. Food and Drug Administration FX This work was supported by the Center for Food Safety and Applied Nutrition at the U.S. Food and Drug Administration. NR 5 TC 20 Z9 20 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2012 VL 194 IS 21 BP 5994 EP 5995 DI 10.1128/JB.01289-12 PG 2 WC Microbiology SC Microbiology GA 022VB UT WOS:000309990800044 PM 23045502 ER PT J AU Waites, KB Duffy, LB Bebear, CM Matlow, A Talkington, DF Kenny, GE Totten, PA Bade, DJ Zheng, XT Davidson, MK Shortridge, VD Watts, JL Brown, SD AF Waites, Ken B. Duffy, Lynn B. Bebear, Cecile M. Matlow, Anne Talkington, Deborah F. Kenny, George E. Totten, Patricia A. Bade, Donald J. Zheng, Xiaotian Davidson, Maureen K. Shortridge, Virginia D. Watts, Jeffrey L. Brown, Steven D. TI Standardized Methods and Quality Control Limits for Agar and Broth Microdilution Susceptibility Testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB An international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum using broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3-to4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans. C1 [Waites, Ken B.; Duffy, Lynn B.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Bebear, Cecile M.] Univ Bordeaux, Unite Contrat Mycoplasmal & Chlamydial Infect Hum, Bordeaux, France. [Matlow, Anne] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Talkington, Deborah F.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kenny, George E.; Totten, Patricia A.] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA. [Bade, Donald J.] Microbial Res Inc, Ft Collins, CO USA. [Zheng, Xiaotian] Childrens Mem Hosp, Chicago, IL 60614 USA. [Davidson, Maureen K.] FDA Ctr Vet Med, Laurel, MD USA. [Shortridge, Virginia D.] BioMerieux Inc, Hazewood, MO USA. [Watts, Jeffrey L.] Pfizer Anim Hlth, Kalamazoo, MI USA. [Brown, Steven D.] Inst Clin Microbiol, Wilsonville, OR USA. RP Waites, KB (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM waiteskb@uab.edu OI Bebear, Cecile/0000-0001-6065-2332 FU Abbott Laboratories; AstraZeneca Pharmaceuticals; Bayer Pharmaceuticals; Bristol-Myers Squibb; Ortho-McNeil Pharmaceuticals; Pharmacia Upjohn; Pfizer Animal Health; Sanofi-Aventis Pharmaceuticals FX This work was performed by the Clinical and Laboratory Standards (CLSI) Subcommittee on Antimicrobial Susceptibility Testing of Human Mycoplasmas. Financial support was provided by Abbott Laboratories, AstraZeneca Pharmaceuticals, Bayer Pharmaceuticals, Bristol-Myers Squibb, Ortho-McNeil Pharmaceuticals, Pharmacia & Upjohn, Pfizer Animal Health, and Sanofi-Aventis Pharmaceuticals. Remel Laboratories provided commercially prepared SP4 and 10B broth media. NR 11 TC 20 Z9 27 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2012 VL 50 IS 11 BP 3542 EP 3547 DI 10.1128/JCM.01439-12 PG 6 WC Microbiology SC Microbiology GA 022NU UT WOS:000309966900021 PM 22915608 ER PT J AU Schier, JG Sejvar, JJ Lutterloh, E Likaka, A Katsoudas, E Karaseva, YD Barr, BT Redwood, Y Monroe, S AF Schier, Joshua G. Sejvar, James J. Lutterloh, Emily Likaka, Andrew Katsoudas, Eugenia Karaseva, Yelena D. Barr, Beth Tippett Redwood, Yanique Monroe, Stephan TI Consumption of pesticide-treated wheat seed by a rural population in Malawi SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE pesticide; seed; exposure; environment; carboxin ID NEUROPSYCHIATRIC MANIFESTATIONS; BANGLADESH; EXPOSURE; OUTBREAK AB An outbreak of typhoid fever in rural Malawi triggered an investigation by the Malawi Ministry of Health and the Centers for Disease Control and Prevention in July 2009. During the investigation, villagers were directly consuming washed, donated, pesticide-treated wheat seed meant for planting. The objective of this study was to evaluate the potential for pesticide exposure and health risk in the outbreak community. A sample of unwashed (1430g) and washed (759g) wheat seed donated for planting, but which would have been directly consumed, was tested for 365 pesticides. Results were compared with each other (percentage change), the US Environmental Protection Agency's (EPA) health guidance values and estimated daily exposures were compared with their Reference dose (RfD). Unwashed and washed seed samples contained, respectively: carboxin, 244 and 57 p.p.m.; pirimiphos methyl, 8.18 and 8.56 p.p.m.; total permethrin, 3.62 and 3.27 p.p.m.; and carbaryl, 0.057 and 0.025 p.p.m.. Percentage change calculations (unwashed to washed) were as follows: carboxin, -76.6%; pirimiphos methyl, + 4.6%; total permethrin, -9.7%; and carbaryl -56.1%. Only carboxin and total permethrin concentration among washed seed samples exceeded US EPA health guidance values (285 x and seven times, respectively). Adult estimated exposure scenarios (1 kg seed) exceeded the RfD for carboxin (8 x) and pirimiphos methyl (12 x). Adult villagers weighing 70 kg would have to consume 0.123, 0.082, 1.06, and 280 kg of washed seed daily to exceed the RfD for carboxin, pirimiphos methyl, permethrins, and carbaryl, respectively. Carboxin, pirimiphos methyl, permethrins, and carbaryl were detected in both unwashed and washed samples of seed. Carboxin, total permethrin, and carbaryl concentration were partially reduced by washing. Health risks from chronic exposure to carboxin and pirimiphos methyl in these amounts are unclear. The extent of this practice among food insecure communities receiving relief seeds and resultant health impact needs further study. C1 [Schier, Joshua G.; Redwood, Yanique] Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA USA. [Sejvar, James J.; Monroe, Stephan] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Natl Ctr Emerging & Zoonot Dis, Atlanta, GA USA. [Lutterloh, Emily] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Kentucky State Hlth Dept, Atlanta, GA 30333 USA. [Likaka, Andrew] Minist Hlth, Lilongwe, Malawi. [Katsoudas, Eugenia; Karaseva, Yelena D.] US FDA, NE Reg Lab, US Dept HHS, Jamaica, NY USA. [Barr, Beth Tippett] Ctr Dis Control & Prevent, Ctr Global Hlth, Global AIDS Program, Lilongwe, Malawi. RP Schier, JG (reprint author), CDC NCEH EHHE HSB, MS F-57,4770 Buford Hwy NE, Chamblee, GA 30341 USA. EM jschier@cdc.gov RI Schier, Joshua/F-9861-2013; OI Monroe, Stephan/0000-0002-5424-716X FU CDC FX This study was supported from the CDC. NR 26 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD NOV-DEC PY 2012 VL 22 IS 6 BP 569 EP 573 DI 10.1038/jes.2012.47 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 022US UT WOS:000309989900004 PM 23047320 ER PT J AU Zhang, H Schaubel, DE Kalbfleisch, JD Robinson, BM Pisoni, RL Port, FK Saran, R AF Zhang, Hui Schaubel, Douglas E. Kalbfleisch, John D. Robinson, Bruce M. Pisoni, Ronald L. Port, Friedrich K. Saran, Rajiv TI Association between dialysis schedule and mortality in maintenance hemodialysis Reply SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Schaubel, Douglas E.; Kalbfleisch, John D.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Robinson, Bruce M.; Pisoni, Ronald L.; Port, Friedrich K.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. [Schaubel, Douglas E.; Kalbfleisch, John D.; Saran, Rajiv] Univ Michigan, Kidney Epidemiol & Cost Ctr, Ann Arbor, MI 48109 USA. [Zhang, Hui] US FDA, Silver Spring, MD USA. RP Schaubel, DE (reprint author), Univ Michigan, Dept Biostat, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM deschau@umich.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2012 VL 82 IS 9 BP 1035 EP 1035 DI 10.1038/ki.2012.298 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 022SD UT WOS:000309981700018 ER PT J AU Doub, WH Adams, WP Wokovich, AM Black, JC Shen, M Buhse, LF AF Doub, William H. Adams, Wallace P. Wokovich, Anna M. Black, John C. Shen, Meiyu Buhse, Lucinda F. TI Measurement of Drug in Small Particles from Aqueous Nasal Sprays by Andersen Cascade Impactor SO PHARMACEUTICAL RESEARCH LA English DT Article DE analytical chemistry; cascade impaction; drug delivery system; nasal spray ID SIZE CHARACTERIZATION; INHALERS; AEROSOLS; PUMP AB To determine if cascade impactor (CI) measurement of drug in small particles from aqueous nasal sprays, described in FDA's 2003 draft Nasal Bioavailability/Bioequivalence Guidance, can be optimized to reduce measurement variability. To examine the influence of flow rate configurations and number of impactor stages on CI deposition and explore the importance of inlet volume. A total of eight assemblies and manual vs. automatic actuation were tested for deposition on the sum of all stages of the CI, and for Group 2 total drug mass per the Guidance. Mean deposition and variance about the mean were determined for each assembly. The path length for a spherical 1 l inlet was too short to allow adequate aerosol formation. Data variance was reduced by a factor of two or more by using an automatic actuator relative to manual actuation. Impactor assembly modification did not improve variance over the standard assembly. Use of a spherical inlet (a parts per thousand yen2 l volume) and automatic actuation are recommended for comparative measurements of drug in small particles arising from aqueous nasal sprays. The standard (8-stage) 28.3 lpm CI flow rate configuration is recommended when using the Andersen Cascade Impactor (ACI), as no other assembly showed a distinct advantage. C1 [Doub, William H.; Wokovich, Anna M.; Black, John C.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, CDER, OPS, St Louis, MO USA. [Adams, Wallace P.] US FDA, Off Gener Drugs, CDER, OPS, Rockville, MD 20857 USA. [Shen, Meiyu] US FDA, OTS Div Biostat 6, CDER, Silver Spring, MD USA. RP Doub, WH (reprint author), US FDA, Div Pharmaceut Anal, CDER, OPS, St Louis, MO USA. EM william.doub@fda.hhs.gov NR 26 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD NOV PY 2012 VL 29 IS 11 BP 3122 EP 3130 DI 10.1007/s11095-012-0804-7 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 025QG UT WOS:000310206100016 PM 22752252 ER PT J AU Abraham, A Wang, YS El Said, KR Plakas, SM AF Abraham, Ann Wang, Yuesong El Said, Kathleen R. Plakas, Steven M. TI Characterization of brevetoxin metabolism in Karenia brevis bloom-exposed clams (Mercenaria sp.) by LC-MS/MS SO TOXICON LA English DT Article DE Brevetoxins; Karenia brevis; Clams; LC-MS ID OYSTER CRASSOSTREA-VIRGINICA; MUSSELS PERNA-CANALICULUS; NEW-ZEALAND; RED TIDE; GREENSHELL MUSSELS; AUSTROVENUS-STUTCHBURYI; CONTROLLED EXPOSURES; PTYCHODISCUS-BREVIS; SHELLFISH; TOXIN AB Brevetoxin metabolites were identified and characterized in the hard clam (Mercenaria sp.) after natural exposure to Karenia brevis blooms by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Principal brevetoxins BTX-1 and BTX-2 produced by K. brevis were not detectable in clams. Metabolites of these brevetoxins found in clams included products of oxidation, reduction, hydrolysis and amino acid/fatty acid conjugation. Of highest abundance were cysteine and taurine conjugates. We also found glutathione, glycine-cysteine, and gamma-glutamyl-cysteine conjugates. A series of fatty acid derivatives of cysteine-brevetoxin conjugates were also identified. Published by Elsevier Ltd. C1 [Abraham, Ann; Wang, Yuesong; El Said, Kathleen R.; Plakas, Steven M.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Abraham, A (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, 1 Iberville Dr,POB 158, Dauphin Isl, AL 36528 USA. EM ann.abraham@fda.hhs.gov NR 17 TC 10 Z9 10 U1 5 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD NOV PY 2012 VL 60 IS 6 BP 1030 EP 1040 DI 10.1016/j.toxicon.2012.06.016 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 020XK UT WOS:000309849700010 PM 22884629 ER PT J AU Behravesh, CB Blaney, D Medus, C Bidol, SA Phan, Q Soliva, S Daly, ER Smith, K Miller, B Taylor, T Nguyen, T Perry, C Hill, TA Fogg, N Kleiza, A Moorhead, D Al-Khaldi, S Braden, C Lynch, MF AF Behravesh, C. Barton Blaney, D. Medus, C. Bidol, S. A. Phan, Q. Soliva, S. Daly, E. R. Smith, K. Miller, B. Taylor, T., Jr. Nguyen, T. Perry, C. Hill, T. A. Fogg, N. Kleiza, A. Moorhead, D. Al-Khaldi, S. Braden, C. Lynch, M. F. TI Multistate outbreak of Salmonella serotype Typhimurium infections associated with consumption of restaurant tomatoes, USA, 2006: hypothesis generation through case exposures in multiple restaurant clusters SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Food safety; foodborne infections; outbreaks; public health; Salmonella Typhimurium ID UNITED-STATES; SURVEILLANCE; RODENTS; SEEDS AB Multiple salmonellosis outbreaks have been linked to contaminated tomatoes. We investigated a multistate outbreak of Salmonella Typhimurium infections among 190 cases. For hypothesis generation, review of patients' food histories from four restaurant-associated clusters in four states revealed that large tomatoes were the only common food consumed by patients. Two case-control studies were conducted to identify food exposures associated with infections. In a study conducted in nine states illness was significantly associated with eating raw, large, round tomatoes in a restaurant [matched odds ratio (mOR) 3.1, 95% confidence interval (CI) 1.3-7.3]. In a Minnesota study, illness was associated with tomatoes eaten at a restaurant (OR 6.3, mid-P 95% CI 1.05-50.4, P=0.046). State, local and federal regulatory officials traced the source of tomatoes to Ohio tomato fields, a growing area not previously identified in past tomato-associated outbreaks. Because tomatoes are commonly eaten raw, prevention of tomato contamination should include interventions on the farm, during packing, and at restaurants. C1 [Behravesh, C. Barton] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Outbreak Response & Prevent Branch, Atlanta, GA 30333 USA. [Behravesh, C. Barton; Blaney, D.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Sci Educ & Profess Dev Program Off, Div Appl Sci, Atlanta, GA 30333 USA. [Blaney, D.; Daly, E. R.] New Hampshire Dept Hlth & Human Serv, Div Publ Hlth Serv, Concord, NH 03301 USA. [Medus, C.; Smith, K.] Minnesota Dept Hlth, St Paul, MN USA. [Bidol, S. A.] Michigan Dept Community Hlth, Lansing, MI USA. [Phan, Q.] Connecticut Dept Publ Hlth, Hartford, CT USA. [Soliva, S.] Massachusetts Dept Publ Hlth, Jamaica Plain, MA USA. [Miller, B.] Minnesota Dept Agr, St Paul, MN USA. [Taylor, T., Jr.] Ctr Dis Control & Prevent, Div Bacterial Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Hill, T. A.; Fogg, N.; Al-Khaldi, S.] US FDA, College Pk, MD USA. [Kleiza, A.; Moorhead, D.] US FDA, Cincinnati Dist Off, Cincinnati, OH USA. RP Behravesh, CB (reprint author), Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Outbreak Response & Prevent Branch, 1600 Clifton Rd NE,Mail Stop A-38, Atlanta, GA 30333 USA. EM CBartonBehravesh@cdc.gov OI Miller, Benjamin/0000-0003-1647-0122 NR 28 TC 10 Z9 10 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD NOV PY 2012 VL 140 IS 11 BP 2053 EP 2061 DI 10.1017/S0950268811002895 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 019GC UT WOS:000309724500017 PM 22261286 ER PT J AU Bobo, WV Davis, RL Toh, S Li, DK Andrade, SE Cheetham, TC Pawloski, P Dublin, S Pinheiro, S Hammad, T Scott, PE Epstein, RA Arbogast, PG Morrow, JA Dudley, JA Lawrence, JM Avalos, LA Cooper, WO AF Bobo, William V. Davis, Robert L. Toh, Sengwee Li, De-Kun Andrade, Susan E. Cheetham, T. Craig Pawloski, Pamala Dublin, Sascha Pinheiro, Simone Hammad, Tarek Scott, Pamela E. Epstein, Richard A., Jr. Arbogast, Patrick G. Morrow, James A. Dudley, Judith A. Lawrence, Jean M. Avalos, Lyndsay A. Cooper, William O. TI Trends in the Use of Antiepileptic Drugs among Pregnant Women in the US, 2001-2007: A Medication Exposure in Pregnancy Risk Evaluation Program Study SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE pregnancy; anticonvulsant; antiepileptic drugs; drug utilisation; prescription practices ID BIPOLAR DISORDER; BIRTH-DEFECTS; EPILEPSY; LAMOTRIGINE; REGISTRY; BENZODIAZEPINE; RECURRENCE; PATTERNS; CHILDREN; DATE AB Background: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 20012007. Methods: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 1545 years on delivery date, who were members of MEPREP health plans (n = 585 615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Results: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. Conclusions: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed. C1 [Bobo, William V.; Epstein, Richard A., Jr.] Vanderbilt Univ, Dept Psychol, Sch Med, Nashville, TN 37240 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Toh, Sengwee] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Li, De-Kun; Avalos, Lyndsay A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Clin, Worcester, MA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Fallon Community Hlth Plan Worcester, Worcester, MA USA. [Cheetham, T. Craig; Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Pawloski, Pamala] Hlth Partners Res Fdn, Minneapolis, MN USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Pinheiro, Simone; Hammad, Tarek; Scott, Pamela E.] US FDA, Rockville, MD 20857 USA. [Arbogast, Patrick G.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Morrow, James A.; Dudley, Judith A.; Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. RP Bobo, WV (reprint author), 1500 21st Ave S,Suite 2200, Nashville, TN 37211 USA. EM william.v.bobo@vanderbilt.edu RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU US Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research) [HHSF223200510012C, HHSF223200510009C, HHSF223200510008C]; National Institute of Mental Health [K23 MH087747] FX This study was supported through funding from contracts HHSF223200510012C, HHSF223200510009C and HHSF223200510008C from the US Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research). William V. Bobo is supported by a National Institute of Mental Health grant K23 MH087747. NR 41 TC 20 Z9 20 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2012 VL 26 IS 6 BP 578 EP 588 DI 10.1111/ppe.12004 PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 023KJ UT WOS:000310031000011 PM 23061694 ER PT J AU Whitehead, J Zaslavsky, BG AF Whitehead, John Zaslavsky, Boris G. TI Zaslavsky, B. G. (2012), "Bayesian Sample Size Estimates for One Sample Test in Clinical Trials With Dichotomous and Countable Outcomes," Statistics in Biopharmaceutical Research, 4, 76-85: Comment by Whitehead and Zaslavsky SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Letter C1 [Whitehead, John] Univ Lancaster, Fylde Coll, Dept Math & Stat, Lancaster LA1 4YW, England. [Zaslavsky, Boris G.] FDA Ctr Biol Evaluat & Res CBER, Rockville, MD USA. RP Whitehead, J (reprint author), Univ Lancaster, Fylde Coll, Dept Math & Stat, Lancaster LA1 4YW, England. NR 2 TC 2 Z9 2 U1 1 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2012 VL 4 IS 4 BP 395 EP 395 DI 10.1080/19466315.2012.713319 PG 1 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 019PE UT WOS:000309751000008 ER PT J AU Bowyer, JF Thomas, M Patterson, TA George, NI Runnells, JA Levi, MS AF Bowyer, John F. Thomas, Monzy Patterson, Tucker A. George, Nysia I. Runnells, Jeffrey A. Levi, Mark S. TI A Visual Description of the Dissection of the Cerebral Surface Vasculature and Associated Meninges and the Choroid Plexus from Rat Brain SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 69; Medicine; Anatomy; Physiology; Toxicology; brain; dissection; choroid plexus; meninges and associated vasculature AB This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia(1,2). As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley(3,4,5,6). The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function. C1 [Bowyer, John F.; Thomas, Monzy; Patterson, Tucker A.; Levi, Mark S.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [George, Nysia I.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR USA. [Runnells, Jeffrey A.] Natl Ctr Toxicol Res, Off Planning Finance & Informat Technol, Jefferson, AR USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov FU NCTR/FDA FX This work was funded by NCTR/FDA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD NOV PY 2012 IS 69 DI 10.3791/4285 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QM UT WOS:000209226000026 ER PT J AU Valerio, LG Choudhuri, S AF Valerio, Luis G., Jr. Choudhuri, Supratim TI Chemoinformatics and chemical genomics: potential utility of in silico methods SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE in silico toxicology; in silico methods; informatics; QSAR; computational toxicology; drug safety; safety assessment; genotoxicity; cardiac safety; chemoinformatics; chemical genomics; chemical epigenomics ID GENE-EXPRESSION SIGNATURES; VALIDATED QSAR MODELS; E-STATE INDEXES; COMPUTATIONAL TOXICOLOGY; MDL-QSAR; SAFETY EVALUATION; NEURAL-NETWORKS; DRUG DISCOVERY; TOXICITY; SELECTION AB Computational life sciences and informatics are inseparably intertwined and they lie at the heart of modern biology, predictive quantitative modeling and high-performance computing. Two of the applied biological disciplines that are poised to benefit from such progress are pharmacology and toxicology. This review will describe in silico chemoinformatics methods such as (quantitative) structureactivity relationship modeling and will overview how chemoinformatic technologies are considered in applied regulatory research. Given the post-genomics era and large-scale repositories of omics data that are available, this review will also address potential applications of in silico techniques in chemical genomics. Chemical genomics utilizes small molecules to explore the complex biological phenomena that may not be not amenable to straightforward genetic approach. The reader will gain the understanding that chemoinformatics stands at the interface of chemistry and biology with enabling systems for mapping, statistical modeling, pattern recognition, imaging and database tools. The great potential of these technologies to help address complex issues in the toxicological sciences is appreciated with the applied goal of the protection of public health. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Choudhuri, Supratim] US FDA, Div Biotechnol & GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, Silver Spring, MD 20993 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51,Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM luis.valerio@fda.hhs.gov NR 85 TC 11 Z9 11 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV PY 2012 VL 32 IS 11 BP 880 EP 889 DI 10.1002/jat.2804 PG 10 WC Toxicology SC Toxicology GA 011UH UT WOS:000309190200002 PM 22886396 ER PT J AU Woodruff, RS Li, Y Yan, J Bishop, M Jones, MY Watanabe, F Biris, AS Rice, P Zhou, T Chen, T AF Woodruff, Robert S. Li, Yan Yan, Jian Bishop, Michelle Jones, M. Yvonne Watanabe, Fumiya Biris, Alexandru S. Rice, Penelope Zhou, Tong Chen, Tao TI Genotoxicity evaluation of titanium dioxide nanoparticles using the Ames test and Comet assay SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE titanium dioxide nanoparticles; Ames test; Comet assay; mutations; genotoxicity ID OXIDATIVE DNA-DAMAGE; ULTRAFINE TIO2 PARTICLES; IN-VITRO; CARBON NANOTUBES; ZINC-OXIDE; FISH CELLS; CYTOTOXICITY; NANOMATERIALS; MUTAGENICITY; PHOTOACTIVATION AB Titanium dioxide nanoparticles (TiO2-NPs) are being used increasingly for various industrial and consumer products, including cosmetics and sunscreens because of their photoactive properties. Therefore, the toxicity of TiO2-NPs needs to be thoroughly understood. In the present study, the genotoxicity of 10nm uncoated sphere TiO2-NPs with an anatase crystalline structure, which has been well characterized in a previous study, was assessed using the Salmonella reverse mutation assay (Ames test) and the single-cell gel electrophoresis (Comet) assay. For the Ames test, Salmonella strains TA102, TA100, TA1537, TA98 and TA1535 were preincubated with eight different concentrations of the TiO2-NPs for 4?h at 37?degrees C, ranging from 0 to 4915.2?mu g per plate. No mutation induction was found. Analyses with transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS) showed that the TiO2-NPs were not able to enter the bacterial cell. For the Comet assay, TK6 cells were treated with 0200?mu g ml1 TiO2-NPs for 24?h at 37?degrees C to detect DNA damage. Although the TK6 cells did take up TiO2-NPs, no significant induction of DNA breakage or oxidative DNA damage was observed in the treated cells using the standard alkaline Comet assay and the endonuclease III (EndoIII) and human 8-hydroxyguanine DNA-glycosylase (hOGG1)-modified Comet assay, respectively. These results suggest that TiO2-NPs are not genotoxic under the conditions of the Ames test and Comet assay. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Woodruff, Robert S.] US FDA, Div Microbiol, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Li, Yan; Yan, Jian; Bishop, Michelle; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, M. Yvonne] US FDA, Nanotechnol Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Watanabe, Fumiya; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Dept Appl Sci, Little Rock, AR 72211 USA. [Rice, Penelope] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhou, Tong] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Chen, T (reprint author), 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov RI Li, Yan/G-5158-2012; Woodruff, Robert/K-4839-2012 FU Collaborative Opportunities for Research Excellence in Science (CORES) program from the U.S. FDA FX Yan Li and Robert S. Woodruff were supported by appointments to the Postgraduate Research Program and Research Participation Program, respectively, at the National Center for Toxicological Research. The appointments were administered by Oak Ridge Institute for Science Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration (FDA). This project was partially funded by the Collaborative Opportunities for Research Excellence in Science (CORES) program from the U.S. FDA. NR 51 TC 26 Z9 27 U1 2 U2 61 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV PY 2012 VL 32 IS 11 BP 934 EP 943 DI 10.1002/jat.2781 PG 10 WC Toxicology SC Toxicology GA 011UH UT WOS:000309190200008 PM 22744910 ER PT J AU Vallejos, JR Uplekar, S da Silva, JF Brorson, KA Moreira, AR Rao, G AF Vallejos, Jose R. Uplekar, Shaunak da Silva, Joao F. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI A case study in converting disposable process scouting devices into disposable bioreactors as a future bioprocessing tool SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE disposable bioreactors; optical sensors; spinner flasks; mass transfer; mixing; seed train ID CELL-CULTURE PROCESS; MASS-TRANSFER; OXYGEN-TRANSFER; DISSOLVED-OXYGEN; SPINNER-FLASK; SCALE-UP; VESSELS AB In this study, we perform mass transfer characterization (kLa) on a novel mechanically driven/stirred Process Scouting Device, PSD, (SuperSpinner D 1000 (R), SSD) and demonstrate that this novel device can be viewed as disposable bioreactor. Using patch-based optical sensors, we were able to monitor critical cell culture environmental conditions such as dissolved oxygen (DO) and pH in SSD for comparison to a 1?L standard spinner (SS) flask. We also coupled these mass transfer studies with mixing time studies where we observed relative high mixing times (5.2?min) that are typically observed in production scale bioreactors. Decreasing the mixing time 3.5-fold resulted in 30% increase in kLa (from 2.3 to 3.0?h-1) and minimum DO level increased from 0% to 20% for our model hybridoma cell line. Finally, maximum viable cell density and protein titer stayed within +/- 20% of historical data, from our standard 5?L stirred bioreactor (Biostat (R)) operated under active DO control. Biotechnol. Bioeng. 2012; 109: 27902797. (c) 2012 Wiley Periodicals, Inc. C1 [Vallejos, Jose R.; Uplekar, Shaunak; da Silva, Joao F.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem Biochem & Environm Engn, Baltimore, MD 21250 USA. [Brorson, Kurt A.] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem Biochem & Environm Engn, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM grao@umbc.edu FU Sartorius-Stedim Biotech FX Contract grant sponsor: Sartorius-Stedim Biotech NR 24 TC 7 Z9 7 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD NOV PY 2012 VL 109 IS 11 BP 2790 EP 2797 DI 10.1002/bit.24541 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 011SP UT WOS:000309185600010 PM 22549482 ER PT J AU Bonacci, TM Hirsch, DS Shen, Y Dokmanovic, M Wu, WJ AF Bonacci, Tabetha M. Hirsch, Dianne S. Shen, Yi Dokmanovic, Milos Wu, Wen Jin TI Small GTPase Rho regulates R-cadherin through Dia1/profilin-1 SO CELLULAR SIGNALLING LA English DT Article DE R-cadherin; Rho; Dia1; Profilin-1; Adherens junction ID CELL-CELL-ADHESION; BREAST-CANCER CELLS; ADHERENS JUNCTIONS; RECEPTOR DEGRADATION; TUMOR PROGRESSION; P120 CATENIN; EXPRESSION; PROFILIN; ESTABLISHMENT; PROTEINS AB R-cadherin is a member of the classical cadherins. Though much is known about E-cadherin in adherens junction formation in epithelial cells, the role of R-cadherin in epithelial cells remains elusive. This study examines regulation of R-cadherin adherens junctions by the small GTPase Rho and its downstream effectors in MDA-MB-231 breast cancer cells, MDA-MB-231 cells stably expressing the N-terminus of c-Cbl, and MCF10A normal breast epithelial cells. We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dial (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells. Importantly. R-cadherin adherens junction formation facilitates a mesenchymal to epithelial-like transition in MDA-MB-231 cells. Additionally, our data suggest an inverse relationship between EGFR signaling and R-cadherin adherens junction formation. Taken together, results from this study indicate that R-cadherin is a critical regulator of epithelial phenotype. Published by Elsevier Inc. C1 [Bonacci, Tabetha M.; Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, OBP, OPS,CDER, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, OBP, OPS,CDER, HFD-123,29 Lincoln Dr,NIH Bldg 29B,Room 3NN-15, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov FU Interagency Oncology Task Force Joint Fellowship Program; U.S. Food and Drug Administration; National Cancer Institute, NIH FX Grant support: Interagency Oncology Task Force Joint Fellowship Program sponsored by the U.S. Food and Drug Administration and the National Cancer Institute, NIH. NR 42 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD NOV PY 2012 VL 24 IS 11 BP 2102 EP 2110 DI 10.1016/j.cellsig.2012.07.015 PG 9 WC Cell Biology SC Cell Biology GA 013MI UT WOS:000309309100015 PM 22820501 ER PT J AU El-tahtawy, A Harrison, F Zirkelbach, JF Jackson, AJ AF El-tahtawy, Ahmed Harrison, Ferrin Zirkelbach, Jeanne Fourie Jackson, Andre J. TI Bioequivalence of long half-life drugsuInformative sampling determinationuUsing truncated area in parallel-designed studies for slow sustained-release formulations SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE bioequivalence; absorption; pharmacokinetics ID HIGHLY VARIABLE DRUGS; LIVES; PRODUCTS; CURVES; EXTENT AB A simulation study was done to determine if 72?h is the most informative sampling duration for bioequivalence (BE) determination in parallel-designed BE studies with drugs that have half-lives of at least 30?h. The impact of absorption and elimination half-lives on informative sampling was evaluated. Two-treatment parallel-designed BE studies using a one-compartment oral absorption model with half-lives of 30 and 350?h was simulated. Area under the curve (AUC) values were truncated at 12-360?h. Experimental BE data [median time to reach the maximum concentration (Tmax) = 20?h and low clearance = 0.192?L/h) indicated a decrease and then an increase in the intrasubject variability [root mean square error (RMSE)] for truncated AUC as a function of time. Simulations supported these findings with the highest probability of passing the BE confidence interval criteria being between 60 and 96?h, depending on half-life and percent coefficient of variation. The 30-h simulation exhibited a minimum in RMSE at 24-h truncation that continued to increase up to 360?h, whereas the 350-h simulation exhibited a minimum at 60?h, which increased after 96?h. Power curves at the 350-h half-life showed higher probabilities of rejection of BE for true test/reference ratios greater than 0.9. For parallel-designed BE studies, sampling beyond 120?h will not affect the BE decision and therefore is unnecessary. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:43374346, 2012 C1 [Harrison, Ferrin; Zirkelbach, Jeanne Fourie; Jackson, Andre J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [El-tahtawy, Ahmed] Pfizer Labs, Div Global Clin Pharmacol, New York, NY USA. [Harrison, Ferrin] US FDA, Ctr Drug Evaluat & Res, Off Bioastat, Off Translat Sci, Silver Spring, MD USA. RP Jackson, AJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Andre.Jackson@fda.hhs.gov NR 16 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD NOV PY 2012 VL 101 IS 11 BP 4337 EP 4346 DI 10.1002/jps.23296 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 008FH UT WOS:000308942300027 PM 22927120 ER PT J AU Von Tungeln, LS Doerge, DR da Costa, GG Marques, MM Witt, WM Koturbash, I Pogribny, IP Beland, FA AF Von Tungeln, Linda S. Doerge, Daniel R. da Costa, Goncalo Gamboa Matilde Marques, M. Witt, William M. Koturbash, Igor Pogribny, Igor P. Beland, Frederick A. TI Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE acrylamide; glycidamide; tumorigenicity ID DNA ADDUCT FORMATION; BIG-BLUE MICE; DIETARY ACRYLAMIDE; LIVER-TUMORS; CANCER-RISK; HEMOGLOBIN ADDUCTS; PROSPECTIVE COHORT; RAS PROTOONCOGENE; MAILLARD REACTION; B6C3F1 MOUSE AB Acrylamide is a high-volume industrial chemical, a component of cigarette smoke, and a product formed in certain foods prepared at high temperatures. Previously, we compared the extent of DNA adduct formation and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide to obtain information concerning the mechanism of acrylamide genotoxicity. We have now examined the tumorigenicity of acrylamide and glycidamide in mice treated neonatally. Male B6C3F1 mice were injected intraperitoneally on postnatal days 1, 8 and 15 with 0.0, 0.14 or 0.70 mmol acrylamide or glycidamide per kg body weight per day and the tumorigenicity was assessed after 1 year. Survival in each of the groups was >87%, there were no differences in body weights among the groups, and the only treatment-related neoplasms involved the liver. The incidence of combined hepatocellular adenoma or carcinoma was 3.8% in the control group, 8.3% in the 0.14 mmol acrylamide and glycidamide per kg body weight groups, 4.2% in the 0.70 mmol acrylamide per kg body weight group and 71.4% in the 0.70 mmol glycidamide per kg body weight group. Analysis of the hepatocellular tumors indicated that the increased incidence observed in mice administered 0.70 mmol glycidamide per kg body weight was associated with A ? G and A ? T mutations at codon 61 of H-ras. These results, combined with our previous data on DNA adduct formation and mutation induction, suggest that the carcinogenicity of acrylamide is dependent on its metabolism to glycidamide, a pathway that is deficient in neonatal mice. C1 [Matilde Marques, M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1096 Lisbon, Portugal. [Witt, William M.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Von Tungeln, Linda S.; Doerge, Daniel R.; da Costa, Goncalo Gamboa; Koturbash, Igor; Pogribny, Igor P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol HFT 110, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014 OI Marques, M. Matilde/0000-0002-7526-4962; FU National Institute of Environmental Health Sciences, National Toxicology Program [224-07-007, Y1ES1027]; U.S. Food and Drug Administration, National Center for Toxicological Research [224-07-007, Y1ES1027]; Fundacao para a Ciencia e a Tecnologia, Portugal [PTDC/SAU-OSM/105572/2008] FX Grant sponsor: Interagency Agreement between the National Institute of Environmental Health Sciences, National Toxicology Program and the U.S. Food and Drug Administration, National Center for Toxicological Research; Grant number: NCTR/FDA IAG #224-07-007; NIH/NTP IAG #Y1ES1027; Grant sponsor: Fundacao para a Ciencia e a Tecnologia, Portugal; Grant number: PTDC/SAU-OSM/105572/2008 NR 50 TC 12 Z9 12 U1 6 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2012 VL 131 IS 9 BP 2008 EP 2015 DI 10.1002/ijc.27493 PG 8 WC Oncology SC Oncology GA 993XP UT WOS:000307893600007 PM 22336951 ER PT J AU Belai, N Harp, BP Mazzola, EP Lam, YF Abdeldayem, E Aziz, A Mossoba, MM Barrows, JN AF Belai, Nebebech Harp, Bhakti Petigara Mazzola, Eugene P. Lam, Yiu-fai Abdeldayem, Ehab Aziz, Aaron Mossoba, Magdi M. Barrows, Julie N. TI Subsidiary colors in D&C Red No. 34 and its lakes: Synthesis, structural characterization, and analysis by ultra-performance liquid chromatography SO DYES AND PIGMENTS LA English DT Article DE D&C Red No. 34; Color additive; Lakes; C.I. Pigment Red 63:1; Subsidiary colors; Azo dyes ID IDENTIFICATION; ACID; DYES AB D&C Red No. 34 is the calcium salt of 3-hydroxy-4-[(1-sulfo-2-naphthalenyl)azo]-2-naphthalenecarboxylic acid. Its lakes are insoluble pigments formed by precipitating the dye anion onto an insoluble substratum, typically rosin. Subsidiary colors are colored impurities that are positional isomers of the dye anion or have higher or lower numbers of substituent groups. D&C Red No. 34 and its lakes are color additives listed in the U.S. Code of Federal Regulations (CFR) for use in externally applied drugs and cosmetics. These color additives are required to be batch certified by the U.S. Food and Drug Administration (FDA) to ensure compliance with the CFR requirements, including a limit of not more than four percent subsidiary colors in the straight color. There is no specified limit for subsidiary colors in the lakes, but the impurities may be analyzed for compliance with good manufacturing practices. In this paper, the syntheses of seven D&C Red No. 34 subsidiary colors are reported. Various combinations of impurities in the two intermediate starting materials for the dye, 2-amino-1-naphthalenesulfonic acid and 3-hydroxy-2-naphthalenecarboxylic acid, were used to synthesize the new compounds, which were purified by recrystallization and fully characterized by elemental analysis, ultra-performance liquid chromatography (UPLC), nuclear magnetic resonance spectroscopy, infrared spectroscopy, and visible spectrophotometry. The new compounds were used as reference materials in UPLC analyses of test samples from 33 certified lots of D&C Red No. 34 and its lakes. FDA is currently using these new reference materials for batch certification of the color additives. Published by Elsevier Ltd. C1 [Belai, Nebebech; Harp, Bhakti Petigara; Barrows, Julie N.] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Mazzola, Eugene P.; Mossoba, Magdi M.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lam, Yiu-fai; Abdeldayem, Ehab; Aziz, Aaron] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20740 USA. RP Belai, N (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM nebebech.belai@fda.hhs.gov NR 16 TC 1 Z9 1 U1 4 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0143-7208 EI 1873-3743 J9 DYES PIGMENTS JI Dyes Pigment. PD NOV PY 2012 VL 95 IS 2 BP 304 EP 312 DI 10.1016/j.dyepig.2012.05.001 PG 9 WC Chemistry, Applied; Engineering, Chemical; Materials Science, Textiles SC Chemistry; Engineering; Materials Science GA 987NV UT WOS:000307425100021 ER PT J AU Bishop-Lilly, KA Plaut, RD Chen, PE Akmal, A Willner, KM Butani, A Dorsey, S Mokashi, V Mateczun, AJ Chapman, C George, M Luu, T Read, TD Calendar, R Stibitz, S Sozhamannan, S AF Bishop-Lilly, Kimberly A. Plaut, Roger D. Chen, Peter E. Akmal, Arya Willner, Kristin M. Butani, Amy Dorsey, Shakia Mokashi, Vishwesh Mateczun, Alfred J. Chapman, Carol George, Matroner Truong Luu Read, Timothy D. Calendar, Richard Stibitz, Scott Sozhamannan, Shanmuga TI Whole genome sequencing of phage resistant Bacillus anthracis mutants reveals an essential role for cell surface anchoring protein CsaB in phage AP50c adsorption SO VIROLOGY JOURNAL LA English DT Article DE Phage resistance; WGS; Mutation mapping; SNP; B. anthracis ID WALL POLYSACCHARIDE; GAMMA-PHAGE; CEREUS; BACTERIOPHAGE; TRANSDUCTION; IDENTIFICATION; THURINGIENSIS; MECHANISMS; VARIANT; SYSTEM AB Background: Spontaneous Bacillus anthracis mutants resistant to infection by phage AP50c (AP50(R)) exhibit a mucoid colony phenotype and secrete an extracellular matrix. Methods: Here we utilized a Roche/454-based whole genome sequencing approach to identify mutations that are candidates for conferring AP50c phage resistance, followed by genetic deletion and complementation studies to validate the whole genome sequence data and demonstrate that the implicated gene is necessary for AP50c phage infection. Results: Using whole genome sequence data, we mapped the relevant mutations in six AP50(R) strains to csaB. Eleven additional spontaneous mutants, isolated in two different genetic backgrounds, were screened by PCR followed by Sanger sequencing of the csaB gene. In each spontaneous mutant, we found either a non-synonymous substitution, a nonsense mutation, or a frame-shift mutation caused by single nucleotide polymorphisms or a 5 base pair insertion in csaB. All together, 5 and 12 of the 17 spontaneous mutations are predicted to yield altered full length and truncated CsaB proteins respectively. As expected from these results, a targeted deletion or frame-shift mutations introduced into csaB in a different genetic background, in a strain not exposed to AP50c, resulted in a phage resistant phenotype. Also, substitution of a highly conserved histidine residue with an alanine residue (H270A) in CsaB resulted in phage resistance, suggesting that a functional CsaB is necessary for phage sensitivity. Conversely, introduction of the wild type allele of csaB in cis into the csaB deletion mutant by homologous recombination or supplying the wild type CsaB protein in trans from a plasmid restored phage sensitivity. The csaB mutants accumulated cell wall material and appeared to have a defective S-layer, whereas these phenotypes were reverted in the complemented strains. Conclusions: Taken together, these data suggest an essential role for csaB in AP50c phage infection, most likely in phage adsorption. (The whole genome sequences generated from this study have been submitted to GenBank under SRA project ID: SRA023659.1 and sample IDs: AP50 R1: SRS113675.1, AP50 R2: SRS113676.1, AP50 R3: SRS113728.1, AP50 R4: SRS113733.1, AP50 R6: SRS113734.1, JB220 Parent: SRS150209.1, JB220 Mutant: SRS150211.1). C1 [Bishop-Lilly, Kimberly A.; Chen, Peter E.; Akmal, Arya; Willner, Kristin M.; Butani, Amy; Dorsey, Shakia; Mokashi, Vishwesh; Mateczun, Alfred J.; Chapman, Carol; George, Matroner; Truong Luu; Sozhamannan, Shanmuga] NMRC Frederick, Ft Detrick, MD 21702 USA. [Plaut, Roger D.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Read, Timothy D.] Emory Univ, Sch Med, Dept Human Genet, Dept Med,Div Infect Dis, Atlanta, GA 30322 USA. [Calendar, Richard] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Mokashi, V (reprint author), NMRC Frederick, 8400 Res Plaza, Ft Detrick, MD 21702 USA. EM Vishwesh.Mokashi@med.navy.mil RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X NR 39 TC 12 Z9 12 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD OCT 26 PY 2012 VL 9 AR 246 DI 10.1186/1743-422X-9-246 PG 14 WC Virology SC Virology GA 075VB UT WOS:000313913900001 PM 23098174 ER PT J AU Colman, E Golden, J Roberts, M Egan, A Weaver, J Rosebraugh, C AF Colman, Eric Golden, Julie Roberts, Mary Egan, Amy Weaver, Joyce Rosebraugh, Curtis TI The FDA's Assessment of Two Drugs for Chronic Weight Management SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Colman, Eric; Golden, Julie; Roberts, Mary; Egan, Amy; Weaver, Joyce; Rosebraugh, Curtis] US FDA, Silver Spring, MD USA. RP Colman, E (reprint author), US FDA, Silver Spring, MD USA. NR 4 TC 74 Z9 77 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 25 PY 2012 VL 367 IS 17 BP 1577 EP 1579 DI 10.1056/NEJMp1211277 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 024TO UT WOS:000310131700001 PM 23050510 ER PT J AU Gross, TP Crowley, J AF Gross, Thomas P. Crowley, Jay TI Unique Device Identification in the Service of Public Health SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Gross, Thomas P.; Crowley, Jay] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Gross, TP (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 4 TC 13 Z9 13 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 25 PY 2012 VL 367 IS 17 BP 1583 EP 1585 DI 10.1056/NEJMp1113608 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 024TO UT WOS:000310131700004 PM 23013051 ER PT J AU Barnes, CA Rasmussen, SL Petrich, JW Rasmussen, MA AF Barnes, Charles A. Rasmussen, Sharon L. Petrich, Jacob W. Rasmussen, Mark A. TI Determination of the Concentration of Potential Efflux Pump Inhibitors, Pheophorbide a and Pyropheophorbide a, in the Feces of Animals by Fluorescence Spectroscopy SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE efflux pump inhibitor; pheophorbide a; pyropheophorbide a; feces; multidrug resistance ID STAPHYLOCOCCUS-AUREUS; CHLOROPHYLL BREAKDOWN; DRUG EFFLUX; RESISTANCE; BERBERIS; STRATEGIES; BACTERIA; PLANT AB Efflux pumps are vital bacterial components, and research has demonstrated that some plant compounds such as pheophorbide a (php) possess efflux pump inhibitor (EPI) activity. This study determined the quantity of php present in feces as an indicator of EPI activity. Feces were collected from different species of animals fed a variety of feeds. The chlorophyll metabolites php and pyropheophorbide a (pyp) were determined using fluorescense spectroscopy. The average concentrations [mu g/g dry matter (DM) feces] of pyp/php in feces were as follows: guinea pig, 180; goat, 150; rabbit, 150; dairy cow, 120; feedlot cattle, 60; rat, <1; pig, <1; chicken, <1. These data indicate that animals consuming "green" diets will excrete feces with concentrations of php/pyp that exceed levels demonstrated to be inhibitory to bacterial efflux pumps (0.5 mu g/mL). The natural presence EPIs in the gastrointestinal tract may modulate the activity of microbial efflux pumps and exert selection pressure upon resident microbial populations. C1 [Barnes, Charles A.; Petrich, Jacob W.; Rasmussen, Mark A.] Iowa State Univ, Ames, IA 50011 USA. [Rasmussen, Sharon L.; Rasmussen, Mark A.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Rasmussen, MA (reprint author), Iowa State Univ, Ames, IA 50011 USA. EM jwp@iastate.edu RI Petrich, Jacob/L-1005-2015 NR 22 TC 1 Z9 1 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 24 PY 2012 VL 60 IS 42 BP 10456 EP 10460 DI 10.1021/jf3023063 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 024IX UT WOS:000310104000009 PM 23002917 ER PT J AU Gallauresi, B Dave, D AF Gallauresi, Beverly Dave, Dipali TI Food And Drug Administration Approved Cardiovascular Medical Devices: A Ten Year Review Of The Participation Of Women And Ethnic Subgroups SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY OCT 22-26, 2012 CL Miami, FL SP ACC C1 [Gallauresi, Beverly; Dave, Dipali] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 23 PY 2012 VL 60 IS 17 SU S BP B102 EP B102 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025RM UT WOS:000310210101157 ER PT J AU Sullivan, R Yoder, D AF Sullivan, Roberta Yoder, Deborah TI Vascular Hemostasis Devices: Food And Drug Administration Perspective On Reported Risks SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY OCT 22-26, 2012 CL Miami, FL SP ACC C1 [Sullivan, Roberta; Yoder, Deborah] FDA CDRH, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 23 PY 2012 VL 60 IS 17 SU S BP B116 EP B116 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025RM UT WOS:000310210101206 ER PT J AU Hampp, C Kauf, TL Saidi, AS Winterstein, AG AF Hampp, Christian Kauf, Teresa L. Saidi, Arwa S. Winterstein, Almut G. TI Methodological Concerns Regarding Cost-effectiveness Analysis of Palivizumab in Florida Medicaid reply SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 [Hampp, Christian] US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. [Kauf, Teresa L.; Winterstein, Almut G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Saidi, Arwa S.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Winterstein, Almut G.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol & Biostat, Gainesville, FL USA. RP Hampp, C (reprint author), US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, 10903 New Hampshire Ave,Bldg 22,Room 2441, Silver Spring, MD 20993 USA. EM christian.hampp@fda.hhs.gov RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 4 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT 23 PY 2012 VL 166 IS 10 BP 969 EP 970 PG 2 WC Pediatrics SC Pediatrics GA 014ZL UT WOS:000309414400020 ER PT J AU Zhou, ZH Rajabi, M Chen, T Karnaukhova, E Kozlowski, S AF Zhou, Zhao-Hua Rajabi, Mohsen Chen, Trina Karnaukhova, Elena Kozlowski, Steven TI Oversulfated Chondroitin Sulfate Inhibits the Complement Classical Pathway by Potentiating C1 Inhibitor SO PLOS ONE LA English DT Article ID ADVERSE CLINICAL EVENTS; POLYSULFATED GLYCOSAMINOGLYCAN; CONTAMINATED HEPARIN; ACTIVATION; SYSTEM; MECHANISM; C3; PATHOGENESIS; POPULATION; INFECTION AB Oversulfated chondroitin sulfate (OSCS) has become the subject of multidisciplinary investigation as a non-traditional contaminant in the heparin therapeutic preparations that were linked to severe adverse events. In this study, it was found that OSCS inhibited complement fixation on bacteria and bacterial lysis mediated by the complement classical pathway. The inhibition of complement by OSCS is not due to interference with antibody/antigen interaction or due to consumption of C3 associated with FXII-dependent contact system activation. However, OSCS complement inhibition is dependent on C1 inhibitor (C1inh) since the depletion of C1inh from either normal or FXII-deficient complement plasma prevents OSCS inhibition of complement activity. Surface plasmon resonance measurements revealed that immobilized C1inhibitor bound greater than 5-fold more C1s in the presence of OSCS than in presence of heparin. Although heparin can also inhibit complement, OSCS and OSCS contaminated heparin are more potent inhibitors of complement. Furthermore, polysulfated glycosaminoglycan (PSGAG), an anti-inflammatory veterinary medicine with a similar structure to OSCS, also inhibited complement in the plasma of dogs and farm animals. This study provides a new insight that in addition to the FXII-dependent activation of contact system, oversulfated and polysulfated chondroitin-sulfate can inhibit complement activity by potentiating the classical complement pathway regulator C1inh. This effect on C1inh may play a role in inhibiting inflammation as well as impacting bacterial clearance. C1 [Zhou, Zhao-Hua; Chen, Trina; Kozlowski, Steven] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rajabi, Mohsen; Karnaukhova, Elena] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Silver Spring, MD USA. RP Kozlowski, S (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Steven.Kozlowski@fda.hhs.gov FU US Food and Drug Administration and Food and Drug Administration/Center for Drug Evaluation and Research FX This research was supported by the Intramural Research Program of the US Food and Drug Administration and Food and Drug Administration/Center for Drug Evaluation and Research, Critical Path Funds. The views expressed in this manuscript represent the opinions of the authors, and do not necessarily represent the official views of the FDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 5 Z9 5 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 15 PY 2012 VL 7 IS 10 AR e47296 DI 10.1371/journal.pone.0047296 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 022WO UT WOS:000309995100088 PM 23077587 ER PT J AU Zhang, LW Tobin, GAM Rouse, RL AF Zhang, Leshuai W. Tobin, Grainne A. McMahon Rouse, Rodney L. TI Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Exenatide; Diabetes; Oleic acid; Glucagon-like peptide 1 receptor; Pancreatic duct ID STIMULATED INSULIN-SECRETION; HELODERMA-SUSPECTUM VENOM; GLP-1 RECEPTOR; INTRACELLULAR TRYPSINOGEN; AMYLASE RELEASE; FATTY-ACIDS; DIETARY-FAT; LIPOTOXICITY; ACTIVATION; EXENDIN-4 AB The glucagon-like peptide 1 receptor (GLP1R) plays a critical role in glucose metabolism and has become an important target for a growing class of drugs designed to treat type 2 diabetes. In vitro studies were designed to investigate the effect of the GLP1R agonist, exenatide (Ex4), in "on-target" RIN-5mF (islet) cells as well as in "off-target" AR42J (acinar) and DSL-6A/C1 (ductal) cells in a diabetic environment Ex4 increased islet cell proliferation but did not affect acinar cells or ductal cells at relevant concentrations. A high caloric, high fat diet is a risk factor for impaired glucose tolerance and type-2 diabetes. An in vitro Oleic acid (OA) model was used to investigate the effect of Ex4 in a high calorie, high fat environment. At 0.1 and 0.4 mM, OA mildly decreased the proliferation of all pancreatic cell types. Ex4 did not potentiate the inhibitory effect of OA on cell proliferation. Akt phosphorylation in response to Ex4 was diminished in OA-treated ductal cells. GLP1R protein detected by western blot was time and concentration dependently decreased after glucose stimulation in OA-treated ductal cells. In ductal cells, OA treatment altered the intracellular localization of GLP1R and its co-localization with early endosome and recycling endosomes. Chloroquine (lysosomal inhibitor), N-acetyl-L-cysteine (reactive oxygen species scavenger) and wortmannin (a phosphatidylinositol-3-kinase inhibitor), fully or partially, rescued GLP1R protein in OA-pretreated, glucose-stimulated ductal cells. The impact of altered regulation on phenotype/function is presently unknown. However, these data suggest that GLP1R regulation in ductal cells can be altered by a high fat, high calorie environment. Published by Elsevier Inc. C1 [Zhang, Leshuai W.; Tobin, Grainne A. McMahon; Rouse, Rodney L.] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rouse, RL (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20904 USA. EM rodney.rouse@fda.hhs.gov RI Zhang, Leshuai/C-8077-2012 FU CDER; OPS; OTS, Division of Drug Safety Research; FDA Critical Path Grant "Models for Evaluation of Drug-Induced Pancreatitis and Ductal Metaplasia"; U.S. Department of Energy FX This study was supported by CDER, OPS, OTS, Division of Drug Safety Research, and FDA Critical Path Grant "Models for Evaluation of Drug-Induced Pancreatitis and Ductal Metaplasia". This project was supported in part by an appointment of the ORISE Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER. NR 47 TC 2 Z9 3 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 2012 VL 264 IS 2 BP 274 EP 283 DI 10.1016/j.taap.2012.08.008 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 020XM UT WOS:000309849900014 PM 22925809 ER PT J AU Toerner, JG Burke, L Komo, S Papadopoulos, E AF Toerner, Joseph G. Burke, Laurie Komo, Scott Papadopoulos, Elektra TI A Collaborative Model for Endpoint Development for Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 [Toerner, Joseph G.] US FDA, Off Antimicrobial Prod, CDER, Off New Drugs, Silver Spring, MD 20993 USA. [Komo, Scott] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Toerner, JG (reprint author), US FDA, Off Antimicrobial Prod, CDER, Off New Drugs, 10903 New Hampshire Ave,White Oak Bldg,22 Room 62, Silver Spring, MD 20993 USA. EM joseph.toerner@fda.hhs.gov NR 3 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2012 VL 55 IS 8 BP 1122 EP 1123 DI 10.1093/cid/cis567 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 010BX UT WOS:000309070500019 PM 22744886 ER PT J AU Rahman, Z Zidan, AS Khan, SR Reddy, IK Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Khan, Saeed R. Reddy, Indra K. Khan, Mansoor A. TI Cholorpheniramine tannate complexes: Physicochemical, chemometric, and taste masking evaluation SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Cholorpheniramine maleate; Tannic acid; Complex; Solubility; Dissolution; Bitter taste; Chemometric model ID SUSTAINED-RELEASE; CHLORPHENIRAMINE MALEATE; QUANTITATIVE-DETERMINATION; FORMULATION DEVELOPMENT; ELECTRONIC TONGUE; TANNIC-ACID; DELIVERY; DRUGS; ABSORPTION AB The focus of present investigation was to evaluate the tannic acid (TA) complexes of cholorpheniramine maleate (CPM) and characterize it by a variety of physicochemical, dissolution, and electronic tongue methods. The complexes were prepared in various molar ratios by solvent evaporation method. They were characterized by spectroscopic, thermal, powder X-ray, electronic tongue, solubility and dissolution methods. FTIR (infrared red) spectra showed complex formation between the TA and CPM. Complex formation has significantly lowered the drug solubility and sustained its release for more than 24 h in phosphate buffer pH 6.8. On the contrary, the release was much faster in the presence of Avicel PH 113 in the same molar ratio complex. The complex formulation has suppressed the bitter taste of CPM as indicated by Euclidean distance in electronic tongue evaluation. NIR-CI (near infrared chemical imaging) showed lower skew value that indicated the homogenous distribution of formulation components. The chemometric models were also developed using the NIR data. The model based on second derivative data was better in predicting the TA and CPM loading as indicated by higher values of R, R-2 and lower values of root mean square error and standard errors. Furthermore, it has a better accuracy and less biased in comparison to other models. In conclusion, the CPM tannate has a sustained release behavior and excipients play a major role in modifying its release. Additionally, the complexes with varying molar ratio of tannate to CPM have differential taste masking abilities than that of the pure drug. Published by Elsevier B.V. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; Khan, Saeed R.; Khan, Mansoor A.] US FDA, CDER, DPQR, Silver Spring, MD 20993 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. [Rahman, Ziyaur; Reddy, Indra K.] Texas A&M Hlth Sci Ctr, Irma Lerma Rangel Coll Pharm, Kingsville, TX USA. RP Khan, MA (reprint author), US FDA, CDER, DPQR, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012; OI Reddy, Indra K./0000-0002-5798-1458; Rahman, Ziyaur/0000-0002-0402-825X FU Oak Ridge Institute for Science and Education (ORISE); NIH-FDA IAA grant FX The authors would like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting the post doctoral research program and part of the work is supported by the NIH-FDA IAA grant. NR 37 TC 7 Z9 7 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD OCT 15 PY 2012 VL 436 IS 1-2 BP 582 EP 592 DI 10.1016/j.ijpharm.2012.07.037 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 003GS UT WOS:000308597600064 PM 22868234 ER PT J AU Tran, K Eide, D Nickols, SM Cromer, MR Sabaa-Srur, A Smith, RE AF Tran, Kevin Eide, David Nickols, Susan M. Cromer, Michele R. Sabaa-Srur, Armando Smith, Robert E. TI Finding of pesticides in fashionable fruit juices by LC-MS/MS and GC-MS/MS SO FOOD CHEMISTRY LA English DT Article DE Acai; Goji; Mangosteen; Noni; Pomegranate; Sea buckthorn; LC-MS AB Products labelled as containing extracts from two mushrooms (cordyceps plus reishi) and the juices from acai, goji, mangosteen, noni, pomegranate, and sea buckthorn have been analysed for 174 different pesticides, using the validated QuEChERS method for sample preparation and electrospray LC-MS/MS in the positive ion mode for analysis. Pesticides were found in 10 of the 21 samples analysed. Most pesticides found were below the tolerance levels (1-6 mu g/g, depending on the pesticide), but some were not. This included boscalid, dimethomorph, iprovalicarb, pyridaben, pyrimethanil, and imazalil, for which there is no tolerance reported or zero tolerance in any fruit. However, genuine acai that was harvested in the state of Para and lyophilised in Rio de Janeiro had no detectable pesticides, when analysed by both LC-MS/MS and GC-MS/MS, which can detect 213 more pesticides and industrial chemicals. Likewise no pesticides were found in one sample each of cordyceps plus reishi, sea buckthorn and noni. Published by Elsevier Ltd. C1 [Tran, Kevin; Eide, David; Nickols, Susan M.; Cromer, Michele R.; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov NR 10 TC 14 Z9 16 U1 3 U2 65 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD OCT 15 PY 2012 VL 134 IS 4 BP 2398 EP 2405 DI 10.1016/j.foodchem.2012.04.034 PG 8 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 966TH UT WOS:000305859800091 PM 23442701 ER PT J AU Landis, SC Amara, SG Asadullah, K Austin, CP Blumenstein, R Bradley, EW Crystal, RG Darnell, RB Ferrante, RJ Fillit, H Finkelstein, R Fisher, M Gendelman, HE Golub, RM Goudreau, JL Gross, RA Gubitz, AK Hesterlee, SE Howells, DW Huguenard, J Kelner, K Koroshetz, W Krainc, D Lazic, SE Levine, MS Macleod, MR McCall, JM Moxley, RT Narasimhan, K Noble, LJ Perrin, S Porter, JD Steward, O Unger, E Utz, U Silberberg, SD AF Landis, Story C. Amara, Susan G. Asadullah, Khusru Austin, Chris P. Blumenstein, Robi Bradley, Eileen W. Crystal, Ronald G. Darnell, Robert B. Ferrante, Robert J. Fillit, Howard Finkelstein, Robert Fisher, Marc Gendelman, Howard E. Golub, Robert M. Goudreau, John L. Gross, Robert A. Gubitz, Amelie K. Hesterlee, Sharon E. Howells, David W. Huguenard, John Kelner, Katrina Koroshetz, Walter Krainc, Dimitri Lazic, Stanley E. Levine, Michael S. Macleod, Malcolm R. McCall, John M. Moxley, Richard T., III Narasimhan, Kalyani Noble, Linda J. Perrin, Steve Porter, John D. Steward, Oswald Unger, Ellis Utz, Ursula Silberberg, Shai D. TI A call for transparent reporting to optimize the predictive value of preclinical research SO NATURE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; CONTROLLED CLINICAL-TRIALS; EXPERIMENTAL STROKE; EMPIRICAL-EVIDENCE; STATISTICAL-ANALYSIS; CONSORT STATEMENT; PUBLICATION BIAS; DRUG DEVELOPMENT; ANIMAL RESEARCH; CANCER-RESEARCH AB The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress. C1 [Landis, Story C.; Finkelstein, Robert; Gubitz, Amelie K.; Koroshetz, Walter; Porter, John D.; Utz, Ursula; Silberberg, Shai D.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Amara, Susan G.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Asadullah, Khusru] Bayer HealthCare, D-13342 Berlin, Germany. [Austin, Chris P.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20854 USA. [Blumenstein, Robi] CHDI Management CHDI Fdn, New York, NY 10001 USA. [Bradley, Eileen W.] NIH, Ctr Review, Bethesda, MD 20892 USA. [Crystal, Ronald G.] Weill Cornell Med Coll, Dept Genet Med, New York, NY 10021 USA. [Darnell, Robert B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Fillit, Howard] Alzheimers Drug Discovery Fdn, New York, NY 10019 USA. [Fisher, Marc] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01545 USA. [Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Golub, Robert M.] JAMA, Chicago, IL 60654 USA. [Goudreau, John L.] Michigan State Univ, Dept Neurol, E Lansing, MI 48824 USA. [Gross, Robert A.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Hesterlee, Sharon E.] Parent Project Muscular Dystrophy, Hackensack, NJ 07601 USA. [Howells, David W.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic 3081, Australia. [Huguenard, John] Stanford Univ, Stanford, CA 94305 USA. [Kelner, Katrina] AAAS, Washington, DC USA. [Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lazic, Stanley E.] F Hoffmann La Roche & Co Ltd, CH-4070 Basel, Switzerland. [Levine, Michael S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Macleod, Malcolm R.] Univ Edinburgh, Western Gen Hosp, Dept Clin Neurosci, Edinburgh EH4 2XU, Midlothian, Scotland. [Moxley, Richard T., III] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [McCall, John M.] PharMac LLC, Boca Grande, FL 33921 USA. [Narasimhan, Kalyani] Nat Neurosci, New York, NY 10013 USA. [Noble, Linda J.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Perrin, Steve] ALS Therapy Dev Inst, Cambridge, MA 02139 USA. [Steward, Oswald] Univ Calif Irvine, Reeve Irvine Res Ctr, Irvine, CA 92697 USA. [Unger, Ellis] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Silberberg, SD (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. EM silberbs@ninds.nih.gov RI Lazic, Stanley/F-1160-2011; Huguenard, John/I-5016-2012; Darnell, Robert/B-9022-2008; OI Huguenard, John/0000-0002-6950-1191; Darnell, Robert/0000-0002-5134-8088; Steward, Oswald/0000-0001-7069-8756; Macleod, Malcolm Robert/0000-0001-9187-9839 FU NINDS FX Funded by NINDS. NR 64 TC 380 Z9 386 U1 9 U2 91 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 11 PY 2012 VL 490 IS 7419 BP 187 EP 191 DI 10.1038/nature11556 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 019IY UT WOS:000309733300036 PM 23060188 ER PT J AU Chen, Y Al-Taher, F Juskelis, R Wong, JW Zhang, K Hayward, DG Zweigenbaum, J Stevens, J Cappozzo, J AF Chen, Yang Al-Taher, Fadwa Juskelis, Rima Wong, Jon W. Zhang, Kai Hayward, Douglas G. Zweigenbaum, Jerry Stevens, Joan Cappozzo, Jack TI Multiresidue Pesticide Analysis of Dried Botanical Dietary Supplements Using an Automated Dispersive SPE Cleanup for QuEChERS and High-Performance Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE QuEChERS; multiresidue pesticide residue analysis; botanical dietary supplements; LC-MS/MS; dynamic multiple-reaction monitoring; automated dispersive SPE ID RESIDUE ANALYSIS; SAMPLE PREPARATION; VEGETABLES; EXTRACTION; FRUITS; MS/MS; MS AB An automated dispersive solid phase extraction (dSPE) cleanup procedure as part of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method, coupled with liquid chromatography-tandem mass spectrometry using electrospray ionization in positive mode, was used for the simultaneous analysis of 236 pesticides in three dried powdered botanical dietary supplements (ginseng, saw palmetto, and gingko biloba). The procedure involved extraction of the dried powdered botanical samples with salt-out acetonitrile/water extraction using anhydrous magnesium sulfate and sodium chloride, followed by an automated dSPE cleanup using a mixture of octadodecyl- (C-18) and primary-secondary amine (PSA)-linked silica sorbents and anhydrous MgSO4 and online LC-MS/MS analysis. Dynamic multiple-reaction monitoring (DMRM) based on the collection of two precursor-to-product ion transitions with their retention time windows was used for all of the targeted pesticides and the internal standard. Matrix-matched calibration standards were used for quantitation, and standard calibration curves showed linearity (r(2) > 0.99) across a concentration range of 0.2-400 ng/mL for the majority of the 236 pesticides evaluated in the three botanical matrices. Mean recoveries (average %RSD, n = 4) were 91 (6), 93 (4), 96 (3), and 99 (3)% for ginseng, 101 (9), 98 (6), 99 (4), and 102 (3)% for gingko biloba, and 100 (9), 98 (6), 96 (4), and 96 (3)% for saw palmetto at fortification concentrations of 25, 100, 250, and 500 mu g/kg, respectively. The geometric mean matrix-dependent instrument detection limits were 0.17, 0.09, and 0.14 mu g/kg on the basis of the studies of 236 pesticides tested in ginseng roots, gingko biloba leaves, and saw palmetto berries, respectively. The method was used to analyze incurred ginseng samples that contained thermally labile pesticides with a concentration range of 2-200 mu g/kg, indicating different classes of pesticides are being applied to these botanicals other than the traditional pesticides that are commonly used and analyzed by gas chromatography techniques. The method demonstrates the use of an automated cleanup procedure and the LC-MS/MS detection of multiple pesticide residues in dried, powdered botanical dietary supplements. C1 [Chen, Yang; Al-Taher, Fadwa; Juskelis, Rima; Cappozzo, Jack] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zweigenbaum, Jerry; Stevens, Joan] Agilent Technol, Wilmington, DE 19808 USA. RP Chen, Y (reprint author), IIT, Inst Food Safety & Hlth, Moffett Campus,6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM yang.chen@fda.hhs.gov NR 23 TC 20 Z9 20 U1 3 U2 56 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 10 PY 2012 VL 60 IS 40 BP 9991 EP 9999 DI 10.1021/jf301723g PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 017BW UT WOS:000309566100008 PM 22931171 ER PT J AU Bedard, B Kennedy, B Escuyer, V Mitchell, K Duchin, JS Pottinger, P Hurst, S Sharp, K Wickham, T Jackson, S Bamberg, W LeBlanc, P Katz, LM MacCannell, T Noble-Wang, J O'Connell, H Kallen, A Jensen, B Nguyen, DB Kinzer, MH AF Bedard, Brenden Kennedy, Byron Escuyer, Vincent Mitchell, Kara Duchin, Jeffrey S. Pottinger, Paul Hurst, Stanley Sharp, Ken Wickham, Timothy Jackson, Sarah Bamberg, Wendy LeBlanc, Pamela Katz, Linda M. MacCannell, Taranisia Noble-Wang, Judith O'Connell, Heather Kallen, Alexander Jensen, Bette Nguyen, Duc B. Kinzer, Michael H. TI Tattoo-Associated Nontuberculous Mycobacterial Skin Infections-Multiple States, 2011-2012 (Reprinted from MMWR, vol 61, pg 653-656, 2012) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Nguyen, Duc B.; Kinzer, Michael H.] CDC, Atlanta, GA 30333 USA. [Escuyer, Vincent; Mitchell, Kara] New York State Dept Hlth, Mycobacteriol Lab, Wadsworth Ctr, Albany, NY 12237 USA. [Duchin, Jeffrey S.] Publ Hlth Seattle & King Cty, Washington, DC USA. [Pottinger, Paul; Hurst, Stanley] Univ Washington, Seattle, WA 98195 USA. [Sharp, Ken; Wickham, Timothy] Iowa Dept Publ Hlth, Des Moines, IA 50319 USA. [Katz, Linda M.] US FDA, Off Colors & Cosmet, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Nguyen, DB (reprint author), CDC, Atlanta, GA 30333 USA. EM vif8@cdc.gov; michael.kinzer@kingcounty.gov NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 10 PY 2012 VL 308 IS 14 BP 1424 EP 1426 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 017GY UT WOS:000309579300009 ER PT J AU Easterbrook, JD Schwartzman, LM Gao, J Kash, JC Morens, DM Couzens, L Wan, HQ Eichelberger, MC Taubenberger, JK AF Easterbrook, Judith D. Schwartzman, Louis M. Gao, Jin Kash, John C. Morens, David M. Couzens, Laura Wan, Hongquan Eichelberger, Maryna C. Taubenberger, Jeffery K. TI Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice SO VIROLOGY LA English DT Article DE Cross-protection; Virus-like particle (VLP); Vaccine ID BROADER IMMUNE-RESPONSES; HEMAGGLUTININ; VACCINE; ANTIBODY; INFECTION; FERRETS; HUMANS; NA AB Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4. Mice immunized with H5N1 or H1N1pdm09 NA VLPs were also fully protected from death, with a 100-fold and 10-fold reduction in infectious virus, respectively, and reduced pathology in the lungs. Human influenza vaccines that elicit not only HA, but also NA immunity may provide enhanced protection against the emergence of seasonal and pandemic viruses. Published by Elsevier Inc. C1 [Easterbrook, Judith D.; Schwartzman, Louis M.; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Gao, Jin; Couzens, Laura; Wan, Hongquan; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU NIH; BARDA MCM Initiative IV: Influenza Vaccine Manufacturing Improvement; FDA CBER PanFlu funds; NIAID FX We thank the Comparative Medicine Branch (NIH/NIAID) for their assistance with animal studies. We would also like to thank Dr. David Dorward at the Rocky Mountain Laboratories, NIAID, NIH for the TEM images and Aline Sandouk for the IHC staining. This work was supported in part by the Intramural Research Program of the NIH and the NIAID, by the BARDA MCM Initiative IV: Influenza Vaccine Manufacturing Improvement (JKT), and by FDA CBER PanFlu funds (MCE). We want to further acknowledge Dr. Edwin Kilbourne's remarkable and important contributions to our understanding of neuraminidase immunity. NR 38 TC 27 Z9 27 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2012 VL 432 IS 1 BP 39 EP 44 DI 10.1016/j.virol.2012.06.003 PG 6 WC Virology SC Virology GA 982FB UT WOS:000307027100005 PM 22727831 ER PT J AU Zhang, WD Wang, C Li, ZJ Lu, ZZ Li, YY Yin, JJ Zhou, YT Gao, XF Fang, Y Nie, GJ Zhao, YL AF Zhang, Wendi Wang, Chi Li, Zhongjun Lu, Zhenzhen Li, Yiye Yin, Jun-Jie Zhou, Yu-Ting Gao, Xingfa Fang, Ying Nie, Guangjun Zhao, Yuliang TI Unraveling Stress-Induced Toxicity Properties of Graphene Oxide and the Underlying Mechanism SO ADVANCED MATERIALS LA English DT Article DE functional materials; graphene oxide; nanotoxicity; electron transfer ID CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; CYTOCHROME-C; MODEL ORGANISM; SUPEROXIDE; CARBON; CELLS; CYTOTOXICITY; FIBROBLASTS; GENERATION C1 [Zhang, Wendi; Wang, Chi; Li, Zhongjun; Lu, Zhenzhen; Li, Yiye; Fang, Ying; Nie, Guangjun; Zhao, Yuliang] Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. [Yin, Jun-Jie; Zhou, Yu-Ting] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Gao, Xingfa; Zhao, Yuliang] Chinese Acad Sci, Inst High Energy Phys, Beijing 1000049, Peoples R China. RP Fang, Y (reprint author), Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. EM fangy@nanoctr.cn; niegj@nanoctr.cn; zhaoyuliang@ihep.ac.cn RI Zhou, Yuting/I-9125-2012; Nie, Guangjun/A-9954-2011; Gao, Xingfa/E-5691-2010; Yin, Jun Jie /E-5619-2014; OI Gao, Xingfa/0000-0002-1636-6336; Lu, Zhenzhen/0000-0002-4394-7232; nie, guangjun/0000-0001-5040-9793 FU MOST 973 [2012CB934000, 2011CB933400]; NSFC [10979011, 30900278]; FY11 FDA Nanotechnology CORES Program FX W.Z. and C. W. contributed equally to this work. In this work we thank Xie Jiayi, Dr. Ao Zhuo and Prof. Han Dong for performing environmental scanning electron microscopy (ESEM, FEI Quanta 200F) experiments. This work was supported by MOST 973 (2012CB934000 and 2011CB933400), and NSFC (10979011 and 30900278). This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was partially supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (J.Y.) NR 49 TC 80 Z9 84 U1 17 U2 178 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD OCT 9 PY 2012 VL 24 IS 39 BP 5391 EP 5397 DI 10.1002/adma.201202678 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 014WA UT WOS:000309405200015 PM 22927326 ER PT J AU Bull, RJ Kolisetty, N Zhang, XL Muralidhara, S Quinones, O Lim, KY Guo, ZX Cotruvo, JA Fisher, JW Yang, XX Delker, D Snyder, SA Cummings, BS AF Bull, Richard J. Kolisetty, Narendrababu Zhang, Xiaoling Muralidhara, Srinivasa Quinones, Oscar Lim, Kok Yong Guo, Zhongxian Cotruvo, Joseph A. Fisher, Jeffrey W. Yang, Xiaoxia Delker, Don Snyder, Shane A. Cummings, Brian S. TI Absorption and disposition of bromate in F344 rats SO TOXICOLOGY LA English DT Article DE Bromate; Absorption; Disposition; Reaction products; Rat ID IN-VIVO MUTAGENICITY; POTASSIUM BROMATE; OXIDATIVE STRESS; DRINKING-WATER; ION CHROMATOGRAPHY; CELL-PROLIFERATION; HYPOBROMOUS ACID; DNA-DAMAGE; PLASMA; CARCINOGENICITY AB Bromate (BrO3-) is a ubiquitous by-product of using ozone to disinfect water containing bromide (Br-). The reactivity of Bro(3)(-) with biological reductants suggests that its systemic absorption and distribution to target tissues may display non-linear behavior as doses increase. The intent of this study is to determine the extent to which BrO3- is systemically bioavailable via oral exposure and broadly identify its pathways of degradation. In vitro experiments of BrO3- degradation in rat blood indicate a rapid initial degradation immediately upon addition that is >98% complete at concentrations up to 66 mu M in blood. As initial concentrations are increased, progressively lower fractions are lost prior to the first measurement. Secondary to this initial loss, a slower and predictable first order degradation rate was observed (10%/min). Losses during both phases were accompanied by increases in Br- concentrations indicating that the loss of Bro(3)(-) was due to its reduction. In vivo experiments were conducted using doses of Bro(3)(-) ranging from 0.077 to 15.3 mg/kg, administered intravenously (IV) or orally (gavage) to female F344 rats. The variable nature and uncertain source of background concentrations of BrO3- limited derivation of terminal half-lives, but the initial half-life was approximately 10 min for all dose groups. The area under the curve (AUC) and peak concentrations (C-t=5') were linearly related to IV dose up to 0.77 mg/kg; however, disproportionate increases in the AUC and C-t=5' and a large decrease in the volume of distribution was observed when IV doses of 1.9 and 3.8 mg/kg were administered. The average terminal half-life of BrO3- from oral administration was 37 min, but this was influenced by background levels of BrO3- from at lower doses. With oral doses, the AUC and C-max increased linearly with dose up to 15.3 mg BrO3-/kg. BrO3- appeared to be 19-25% bioavailable without an obvious dose-dependency between 0.077 and 1.9 mg/kg. The urinary elimination of BrO3- and Br- was measured from female F344 rats for four days following administration of single doses of 8.1 mg KBrO3/kg and for 15 days after a single dose of 5.0 mg KBr/kg. BrO3- elimination was detected over the first 12h, but Br- elimination from BrO3- over the first 48 h was 18% lower than expected based on that eliminated from an equimolar dose of Br- (15.5 +/- 1.6 vs. 18.8 +/- 1.2 mu mol/kg, respectively). The cumulative excretion of Br- from KBr vs. KBrO3 was equivalent 72 h after administration. The recovery of unchanged administered BrO3- in the urine ranged between 6.0 and 11.3% (creatinine corrected) on the 27th day of treatment with concentrations of KBrO3 of 15, 60, and 400 mg/L of drinking water. The recovery of total urinary bromine as Br- + BrO3- ranged between 61 and 88%. An increase in the fraction of the daily BrO3- dose recovered in the urine was observed at the high dose to both sexes. The deficit in total bromine recovery raises the possibility that some brominated biochemicals may be produced in vivo and more slowly metabolized and eliminated. This was supported by measurements of dose-dependent increases of total organic bromine (TOBr) that was eliminated in the urine. The role these organic by-products play in BrO3- -induced cancer remains to be established. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Bull, Richard J.] MoBull Consulting, Richland, WA USA. [Kolisetty, Narendrababu; Zhang, Xiaoling; Muralidhara, Srinivasa; Cummings, Brian S.] Univ Georgia, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. [Quinones, Oscar; Snyder, Shane A.] So Nevada Water Author, Appl R&D Ctr, Henderson, NV USA. [Lim, Kok Yong; Guo, Zhongxian] Publ Util Board, Water Qual Off, Singapore, Singapore. [Cotruvo, Joseph A.] Joseph Cotruvo & Associates LLC, Washington, DC USA. [Fisher, Jeffrey W.; Yang, Xiaoxia] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Delker, Don] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Bull, RJ (reprint author), 1928 Meadows Dr N, Richland, WA 99352 USA. EM rjbull@earthlink.net RI Snyder, Shane/A-3302-2011 OI Snyder, Shane/0000-0003-2709-9840 FU Water Research Foundation Project [4042]; International Ozone Assoc.; Environment Agency of Abu Dhabi; Veolia Water; Metropolitan Water District of Southern Calif.; Los Angeles Department of Water and Power, Public Utilities Board (PUB), Singapore; National Water Research Institute; Walkerton Clean Water Centre; Calleguas Municipal Water District; Long Beach Water Department; Water Research Foundation FX This study was supported by grants to Joseph Cotruvo & Associates LLC from the Water Research Foundation Project #4042 - International Ozone Assoc., Environment Agency of Abu Dhabi, Veolia Water, Metropolitan Water District of Southern Calif., Los Angeles Department of Water and Power, Public Utilities Board (PUB), Singapore, National Water Research Institute, Walkerton Clean Water Centre, Calleguas Municipal Water District, Long Beach Water Department, and in-kind contributions of the participants. We gratefully acknowledge and thank the Water Research Foundation and all of the sponsors for their financial, technical and administrative assistance in funding the project through which this information was discovered. NR 35 TC 9 Z9 9 U1 1 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 9 PY 2012 VL 300 IS 1-2 BP 83 EP 91 DI 10.1016/j.tox.2012.06.002 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 982KO UT WOS:000307042200009 PM 22699156 ER PT J AU Klimov, AI Garten, R Russell, C Barr, IG Besselaar, TG Daniels, R Engelhardt, OG Grohmann, G Itamura, S Kelso, A McCauley, J Odagiri, T Smith, D Tashiro, M Xu, XY Webby, R Wang, DY Ye, ZP Shu, YL Zhang, WQ Cox, N AF Klimov, Alexander I. Garten, Rebecca Russell, Colin Barr, Ian G. Besselaar, Terry G. Daniels, Rod Engelhardt, Othmar G. Grohmann, Gary Itamura, Shigeyuki Kelso, Anne McCauley, John Odagiri, Takato Smith, Derek Tashiro, Masato Xu, Xiyan Webby, Richard Wang, Dayan Ye, Zhiping Shu Yuelong Zhang, Wenqing Cox, Nancy CA Writing Committee World Hlth Org C TI WHO recommendations for the viruses to be used in the 2012 Southern Hemisphere Influenza Vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from February to September 2011 SO VACCINE LA English DT Article DE Influenza; Vaccine; Human; Seasonal ID SUBSTITUTION AB In February and September each year the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winters in the Northern and Southern Hemispheres respectively. These recommendations are based on data collected by National Influenza Centres (NIC) through the Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations for the 2012 Southern Hemisphere influenza vaccine composition. Published by Elsevier Ltd. C1 [Klimov, Alexander I.] Ctr Dis Control & Prevent, WHO Collaborating Ctr Surveillance Epidemiol & Co, Influenza Div, Atlanta, GA 30333 USA. [Barr, Ian G.; Kelso, Anne] WHO Collaborating Ctr Reference & Res Influenza, VIDRL, Melbourne, Australia. [Daniels, Rod; McCauley, John] Natl Inst Med Res, WHO Collaborating Ctr Reference & Res Influenza, London, England. [Itamura, Shigeyuki; Odagiri, Takato; Tashiro, Masato] NIID, WHO Collaborating Ctr Reference & Res Influenza, Tokyo, Japan. [Webby, Richard] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Wang, Dayan; Shu Yuelong] CNIC, WHO Collaborating Ctr Reference & Res Influenza, Beijing, Peoples R China. [Besselaar, Terry G.; Zhang, Wenqing] WHO Global Influenza Programme GIP, Geneva, Switzerland. [Engelhardt, Othmar G.] HPA, NIBSC, Potters Bar, Herts, England. [Ye, Zhiping] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Grohmann, Gary] TGA, Canberra, ACT, Australia. [Russell, Colin; Smith, Derek] Univ Cambridge, Cambridge CB2 1TN, England. [Russell, Colin; Smith, Derek] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Klimov, AI (reprint author), Ctr Dis Control & Prevent, WHO Collaborating Ctr Surveillance Epidemiol & Co, Influenza Div, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM AKlimov@cdc.gov OI Russell, Colin/0000-0002-2113-162X FU Medical Research Council [MC_U117512708, MC_U117512723, MC_U117585868] NR 13 TC 33 Z9 34 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 5 PY 2012 VL 30 IS 45 BP 6461 EP 6471 DI 10.1016/j.vaccine.2012.07.089 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 024NZ UT WOS:000310117200018 PM 22917957 ER PT J AU Khan, MA Wu, KS Gupta, A AF Khan, Mansoor A. Wu, Kuangshi Gupta, Abhay TI FDA: Contribution to developing pediatric formulations and transatlantic collaboration SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article C1 [Khan, Mansoor A.; Wu, Kuangshi; Gupta, Abhay] US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov NR 2 TC 0 Z9 0 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD OCT 5 PY 2012 VL 435 IS 2 BP 146 EP 148 DI 10.1016/j.ijpharm.2012.05.060 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993RH UT WOS:000307876800014 PM 22883702 ER PT J AU Adams, LV Craig, SR Mmbaga, EJ Naburi, H Lahey, T Kisenge, R Spielberg, SP AF Adams, Lisa V. Craig, Sienna R. Mmbaga, Elia John Naburi, Helga Lahey, Timothy Kisenge, Rodrick Spielberg, Stephen P. TI Current administration practices and preferred formulations of children's medicines in Tanzania: Summary of survey findings SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article C1 [Adams, Lisa V.; Lahey, Timothy] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Craig, Sienna R.] Dartmouth Coll, Hanover, NH 03755 USA. [Mmbaga, Elia John; Naburi, Helga; Kisenge, Rodrick] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Spielberg, Stephen P.] Inst Pediat Innovat, Cambridge, MA USA. [Spielberg, Stephen P.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Spielberg, Stephen P.] US FDA, Silver Spring, MD USA. RP Adams, LV (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. EM Lisa.V.Adams@Dartmouth.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD OCT 5 PY 2012 VL 435 IS 2 BP 150 EP 151 DI 10.1016/j.ijpharm.2012.05.062 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993RH UT WOS:000307876800016 PM 22883704 ER PT J AU Throckmorton, DC Compton, WM Lurie, P AF Throckmorton, Douglas C. Compton, Wilson M. Lurie, Peter TI Management of Opioid Analgesic Overdose SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Throckmorton, Douglas C.; Lurie, Peter] Food & Drug Adm, Silver Spring, MD USA. [Compton, Wilson M.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Throckmorton, DC (reprint author), Food & Drug Adm, Silver Spring, MD USA. EM douglas.throckmorton@fda.hhs.gov NR 3 TC 2 Z9 2 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 4 PY 2012 VL 367 IS 14 BP 1371 EP 1371 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 014WJ UT WOS:000309406100032 PM 23034041 ER PT J AU Genter, MB Newman, NC Shertzer, HG Ali, SF Bolon, B AF Genter, Mary Beth Newman, Nicholas C. Shertzer, Howard G. Ali, Syed F. Bolon, Brad TI Distribution and Systemic Effects of Intranasally Administered 25 nm Silver Nanoparticles in Adult Mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE silver; nanoparticles; intranasal instillation; spleen; glutathione; autometallography ID BLOOD-BRAIN-BARRIER; PARTICLES; TRANSLOCATION; EXPOSURE; INFLAMMATION; TOXICITY; CHILDREN; METALS AB Previous work indicates that silver nanoparticles (AgNPs) given IP to mice alter the regulation of inflammation-and oxidative stress-related genes in brain. Here we assessed the distribution and toxic potential of AgNP following intranasal (IN) exposure. Adult male C57BL/6J mice received 25-nm AgNP (100 or 500 mg/kg) once IN. After 1 or 7 days, histopathology of selected organs was performed, and tissue reduced glutathione (GSH) levels were measured as an indicator of oxidative stress. Aggregated AgNP were found in spleen, lung, kidney, and nasal airway by routine light microscopy. Splenic AgNP accumulation was greatest in red pulp and occurred with modestly reduced cellularity and elevated hemosiderin deposition. Aggregated AgNP were not associated with microscopic changes in other tissues except for nasal mucosal erosions. Autometallography revealed AgNP in olfactory bulb and the lateral brain ventricles. Neither inflammatory cell infiltrates nor activated microglia were detected in brains of AgNP-treated mice. Elevated tissue GSH levels was observed in nasal epithelia (both doses at 1 day, 500 mg/kg at 7 days) and blood (500 mg/kg at 7 days). Therefore, IN administration of AgNP permits systemic distribution, produces reversible oxidative stress in the nose and in blood, and mildly enhances macrophage-mediated erythrocyte destruction in the spleen. C1 [Genter, Mary Beth; Newman, Nicholas C.; Shertzer, Howard G.] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Genter, Mary Beth; Newman, Nicholas C.; Shertzer, Howard G.] Univ Cincinnati, Ctr Environm Genet, Cincinnati, OH 45267 USA. [Newman, Nicholas C.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45267 USA. [Ali, Syed F.] US FDA, Neurochem Lab, Natl Ctr Toxicol Res, Coll Vet Med, Jefferson, AR USA. [Bolon, Brad] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. RP Genter, MB (reprint author), Univ Cincinnati, Dept Environm Hlth, ML 670056,3223 Eden Ave,144 Kettering Lab, Cincinnati, OH 45267 USA. EM marybeth.genter@uc.edu FU University of Cincinnati Center for Environmental Genetics [P30-ES006096]; NIOSH ERC [T42-OH008432]; Molecular Epidemiology in Children's Environmental Health [T32-ES10957]; University of Cincinnati Dean's Bridge Fund FX This research was supported through the University of Cincinnati Center for Environmental Genetics P30-ES006096, NIOSH ERC T42-OH008432, Molecular Epidemiology in Children's Environmental Health T32-ES10957, and the University of Cincinnati Dean's Bridge Fund. NR 25 TC 24 Z9 24 U1 3 U2 21 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2012 VL 40 IS 7 BP 1004 EP 1013 DI 10.1177/0192623312444470 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 119DS UT WOS:000317078200003 PM 22549977 ER PT J AU Gaddipati, H Liu, K Pariser, A Pazdur, R AF Gaddipati, Himabindu Liu, Ke Pariser, Anne Pazdur, Richard TI Rare Cancer Trial Design: Lessons from FDA Approvals SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; ACCELERATED APPROVAL; ONCOLOGY PRODUCTS; IMPROVED ACCESS; LUNG-CANCER; EXPERIENCE; DRUGS AB A systematic analysis of clinical trials supporting rare cancer drug approvals may identify concepts and terms that can inform the effective design of prospective clinical trials for rare cancers. In this article, using annual incidence <= 6 of 100,000 individuals to define "rare cancer," we identified clinical trials for rare cancers, supporting U. S. Food and Drug Administration (FDA) drug approvals for rare cancer indications between December 1987 and May 2011. We characterized each selected trial for study design, sample size, primary efficacy endpoints, and statistical comparisons. We also profiled trials with regard to type of submission, review designation, and approval type. Our results indicated that, of 99 trials that supported the approvals of 45 drugs for 68 rare cancer indications, one third of these trials were randomized; 69% of approvals relied on objective response rate as the primary efficacy endpoint; and 63% were based on a single trial. Drugs granted accelerated approval appeared more likely to be associated with postmarketing safety findings, relative to drugs approved under the regular approval. Data collected across clinical trials were robust: Use of different lower incidence rates in analyzing these trials did not have effects on trial characteristics. The absolute number of drug approvals for rare cancer indications increased markedly over time. We concluded that one third of clinical trials supporting drug approvals for rare cancer indications were randomized, affirming the feasibility and value of randomized trial design to evaluate drugs for rare cancers. Postmarketing safety data may relate to trial design and approval type. An operational definition of " rare cancer" can be useful for the analysis of trial data and for the path toward harmonizing the terminology in the area of clinical research on rare cancers. Clin Cancer Res; 18(19); 5172-8. (C)2012 AACR. C1 [Liu, Ke; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Gaddipati, Himabindu] US FDA, Natl Canc Inst Interagency Oncol Task Force, Silver Spring, MD USA. RP Liu, K (reprint author), US FDA, Off Hematol & Oncol Prod, Off New Drugs, Ctr Drug Evaluat & Res, 1401 Rockville Pike,HFM 760, Rockville, MD 20852 USA. EM ke.liu@fda.hhs.gov NR 18 TC 13 Z9 14 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2012 VL 18 IS 19 BP 5172 EP 5178 DI 10.1158/1078-0432.CCR-12-1135 PG 7 WC Oncology SC Oncology GA 048JF UT WOS:000311906600004 PM 22718862 ER PT J AU Wright, DJ Adkins, KK Minck, DR Bailey, S Warner, G Leach, MW AF Wright, David J. Adkins, Karissa K. Minck, Daniel R. Bailey, Steven Warner, Garvin Leach, Michael W. TI Reproductive Performance and Early Postnatal Development in Interleukin (IL)-13-Deficient Mice SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE IL-13; genotype; reproduction; development ID IL-13; RESPONSES; INTERFACE; CYTOKINES; TARGET; ROLES AB The purpose of this study was to assess the effect of interleukin (IL)-13 deficiency on fertility and reproductive performance of adult mice and on morphological and behavioral development of the offspring. METHODS: Wild-type and homozygous IL-13-deficient (KO) mice were grouped by genotype, and male and female mice were mated within each group. Adult (F-0) mice were evaluated for reproductive performance, and development was assessed in F-1 fetuses on gestation day 18, and in F-1 pups to postnatal day 35. RESULTS: In F-0 males, there were no differences in the number of males that mated or impregnated females, or in total sperm count or sperm motility, between the wild-type and KO groups. In F-0 females, there were no observed genotype-related differences in fertility, length of gestation, number of viable fetuses per litter, or viability of offspring. There were no differences in embryo-fetal development (external/palate, skeletal, visceral) of the F-1 fetuses between genotypes. Similarly, IL-13 deficiency had no impact on any postnatal parameters assessed including reflex, sexual maturation, learning, and memory. CONCLUSIONS: IL-13 deficiency had no observed effect on reproductive performance or morphological and behavioral development in mice. Birth Defects Res (Part B) 95:346-353, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wright, David J.; Adkins, Karissa K.; Bailey, Steven; Leach, Michael W.] Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA. [Minck, Daniel R.] US FDA, Div Metab & Endocrinol Prod, Silver Spring, MD USA. [Warner, Garvin] Alnylam Pharmaceut, Cambridge, MA USA. RP Wright, DJ (reprint author), Pfizer Drug Safety Res & Dev, Groton, CT 06340 USA. EM david.wright@pfizer.com NR 15 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD OCT PY 2012 VL 95 IS 5 BP 346 EP 353 DI 10.1002/bdrb.21023 PG 8 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 051UQ UT WOS:000312153600003 PM 22930549 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database SO SPINE JOURNAL LA English DT Article DE Bone morphogenetic protein; Adverse event; Off-label use; Postmarketing safety ID LUMBAR INTERBODY FUSION; ANTERIOR CERVICAL-SPINE; OFF-LABEL USE; ECTOPIC BONE; RHBMP-2; COMPLICATIONS; SURGERY; RESORPTION; LESSONS; RING AB BACKGROUND CONTEXT: Adverse effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal surgery have previously been observed. However, because of its size, scope, and nature, the US Food and Drug Administration's database of postmarketing reports is useful for detecting new and unexpected safety concerns. PURPOSE: To characterize adverse events reported to the FDA; to characterize off-label use of rhBMP-2. STUDY DESIGN: Review of adverse events reported to the FDA after the use of rhBMP-2 (INFUSE Bone Graft) in spinal surgery. METHODS: The Manufacturer and User Facility Device Experience database was searched for the brand name "infuse bone graft," for reports received from July 2, 2002, through August 31, 2011. Adverse events were reviewed, summarized, and classified by an MD. For each report, the most important clinical entity was identified as the principal adverse event. Off-label uses were summarized. RESULTS: Of 834 reports, four (0.5%) described procedures in which rhBMP-2 was used in accordance with the approved indication. Nearly half of all the reports, 370 (44.4%), stated that the patient required revision surgery or other invasive interventions to address the reported adverse event. Swelling, fluid collections, osteolysis, pain/radiculopathy, heterotopic bone, pseudarthrosis, surgical site infections and other wound complications, thromboembolic events, respiratory distress, cancer, and other events were reported. CONCLUSIONS: Because of their duration, scope, and expense, prospective studies designed to estimate the risk of rare adverse events may be impractical. Despite its imperfections, postmarketing surveillance helps to narrow the focus by revealing patterns and prioritizing topics for further research. One should not extrapolate from these results to the rhBMP-2 experience as a whole; the findings reported here might not be representative. This analysis indicates that serious adverse events can occur after the use of rhBMP-2 in spinal surgery and raises many points that surgeons may wish to consider when deciding when and how to use this product in their patients. Published by Elsevier Inc. C1 US FDA, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 21 TC 33 Z9 33 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD OCT PY 2012 VL 12 IS 10 BP 894 EP 899 DI 10.1016/j.spinee.2012.09.052 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 045GY UT WOS:000311684600007 PM 23098616 ER PT J AU Alam, HB Pusateri, AE Kindzelski, A Egan, D Hoots, K Andrews, MT Rhee, P Tisherman, S Mann, K Vostal, J Kochanek, PM Scalea, T Deal, V Sheppard, F Sopko, G AF Alam, Hasan B. Pusateri, Anthony E. Kindzelski, Andrei Egan, Debra Hoots, Keith Andrews, Matthew T. Rhee, Peter Tisherman, Samuel Mann, Kenneth Vostal, Jaroslav Kochanek, Patrick M. Scalea, Thomas Deal, Virgil Sheppard, Forest Sopko, George CA HYPOSTAT Workshop Participants TI Hypothermia and hemostasis in severe trauma: A new crossroads workshop report SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Hypothermia; trauma; coagulopathy; injury; protection ID ISCHEMIA-REPERFUSION INJURY; PROFOUND HYPOTHERMIA; SWINE MODEL; HEMORRHAGIC-SHOCK; LETHAL HEMORRHAGE; CARDIAC-ARREST; CIRCULATORY ARREST; BRAIN-INJURY; EMERGENCY PRESERVATION; CARDIOPULMONARY BYPASS AB OBJECTIVE: The hypothermia and hemostasis in severe trauma (HYPOSTAT): a new crossroads workshop was convened to evaluate the interplay among hypothermia, hemostasis, and severe trauma/hemorrhage. Trauma is the major cause of death in young individuals in the United States, with uncontrolled hemorrhage representing the major cause of preventable deaths. DATA SOURCES: This workshop organized by the National Heart, Lung, and Blood Institute and the US Army Medical Research and Material Command as a forum for exchange of ideas among experts from diverse fields. The specific workshop goals were to (1) identify state-of-the-art and needs in knowledge of biology of hypothermia and hemostasis in the setting of significant traumatic injury; (2) provide an interdisciplinary forum to enhance knowledge regarding early detection of traumatic shock and monitoring of the level and effect of controlled hypothermia in severe trauma settings; and (3) identify future research directions of the role of therapeutic-oriented hypothermia and hemostasis in trauma with severe blood loss. STUDY SELECTION: Not applicable. DATA EXTRACTION: Expert opinion and literature review. CONCLUSION: This document provides a summary of the expert opinion and highlights the recommendations that came out of the discussions at this workshop to guide scientific efforts in basic, translational, and clinical research in this area. (J Trauma Acute Care Surg. 2012;73:809-817. Copyright (C) 2012 by Lippincott Williams & Wilkins) C1 [Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA USA. [Pusateri, Anthony E.; Deal, Virgil; Sheppard, Forest] US Dept Def, Washington, DC 20305 USA. [Kindzelski, Andrei; Egan, Debra; Hoots, Keith; Sopko, George] NIH, Bethesda, MD 20892 USA. [Vostal, Jaroslav] US FDA, Silver Spring, MD USA. [Scalea, Thomas] Univ Maryland, College Pk, MD 20742 USA. [Andrews, Matthew T.] Univ Minnesota, Duluth, MN 55812 USA. [Rhee, Peter] Univ Arizona, Tucson, AZ USA. [Tisherman, Samuel; Kochanek, Patrick M.] Univ Pittsburgh, Pittsburgh, PA USA. [Mann, Kenneth] Univ Vermont, Burlington, VT USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 87 TC 7 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD OCT PY 2012 VL 73 IS 4 BP 809 EP 817 DI 10.1097/TA.0b013e318265d1b8 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 029OL UT WOS:000310505100003 PM 23026915 ER PT J AU Daniel, GW Menis, M Sridhar, G Scott, D Wallace, AE Ovanesov, MV Golding, B Anderson, SA Epstein, J Martin, D Ball, R Izurieta, HS AF Daniel, Gregory W. Menis, Mikhail Sridhar, Gayathri Scott, Dorothy Wallace, Anna E. Ovanesov, Mikhail V. Golding, Basil Anderson, Steven A. Epstein, Jay Martin, David Ball, Robert Izurieta, Hector S. TI Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010 SO TRANSFUSION LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; FACTOR-XI CONCENTRATE; COAGULATION-FACTOR XI; THROMBOEMBOLIC EVENTS; DEFICIENT PATIENTS; VENOUS THROMBOSIS; INFUSION; RISK; IVIG; COMPLICATIONS AB BACKGROUND: Thrombotic events (TEs) are rare but often serious adverse events that could occur after administration of immune globulin (IG) products. Our study objective was to assess occurrence of recorded TEs after administration of different US-licensed IG products and investigate potential risk factors using a large administrative database. STUDY DESIGN AND METHODS: This is a retrospective claims-based cohort study of individuals exposed to IG products from January 1, 2008, through September 30, 2010, using HealthCore's Integrated Research Database, a longitudinal health care database. IG products were identified by recorded Healthcare Common Procedure Coding System codes. TEs were ascertained via International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for same-day TEs by IG product, while controlling for confounders. RESULTS: Of 11,785 individuals exposed to IG products in the study period, 122 (1%) had TE(s) recorded on the same day as IG administration. TE rates per 1000 persons exposed ranged from 6.1 to 20.5 for different IG product groups. Vivaglobin users had an increased same-day TE risk compared to reference Gammagard Liquid users (OR, 3.56; 95% CI, 1.54-8.23). An increased TE risk was also found with older age (>= 45 years), prior TE(s), and hypercoagulable state(s). CONCLUSION: The study suggests potentially elevated TE rates for different IG products, including subcutaneous. It also identifies important recipient TE risk factors and suggests that risk-benefit profiles should be weighed before IG administration. The observed differences may be due to various factors such as dosage, administration rates, and product manufacturing processes that warrant further evaluation. C1 [Sridhar, Gayathri] HealthCore Inc, Alexandria, VA 22311 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Sridhar, G (reprint author), HealthCore Inc, 1801 N Beauregard St,Suite 10, Alexandria, VA 22311 USA. EM gsridhar@healthcore.com FU US Food and Drug Administration, Center for Biologics Evaluation and Research FX This study was funded by the US Food and Drug Administration, Center for Biologics Evaluation and Research. NR 42 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2012 VL 52 IS 10 BP 2113 EP 2121 DI 10.1111/j.1537-2995.2012.03589.x PG 9 WC Hematology SC Hematology GA 030CM UT WOS:000310545600009 PM 22448967 ER PT J AU Stine, CB Nochetto, CB Evans, ER Gieseker, CM Mayer, TD Hasbrouck, NR Reimschuessel, R AF Stine, Cynthia B. Nochetto, Cristina B. Evans, Eric R. Gieseker, Charles M. Mayer, Tamara D. Hasbrouck, Nicholas R. Reimschuessel, Renate TI Depletion of melamine and cyanuric acid in serum from catfish Ictalurus punctatus and rainbow trout Onchorhynchus mykiss SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Melamine; Cyanuric acid; Catfish; Trout; Serum; Depletion ID TEMPERATURE-RELATED ABSORPTION; TANDEM MASS-SPECTROMETRY; SPRAGUE-DAWLEY RATS; LIQUID-CHROMATOGRAPHY; ONCORHYNCHUS-MYKISS; RENAL-FAILURE; F344 RATS; EXCRETION; PIGS; PHARMACOKINETICS AB Melamine and its triazine analogs, such as cyanuric acid, have been used to artificially inflate protein content both in animal feed ingredients, as well as in milk products produced for human consumption. We report here a LC-MS/MS method to quantify and confirm melamine and cyanuric acid in serum from channel catfish and rainbow trout with a limit of quantification of 0.8 mu g/mL The method was applied to serum samples from a residue depletion study in which fish were given a single oral dose of 20 mg/kg body weight melamine, cyanuric acid, or both compounds together. Samples were taken at 1, 3, 7, 14, and 28 days (an additional 42 day was added for trout). When given alone or in combination with cyanuric acid, melamine residues were highest on day 1 in both catfish and trout. Cyanuric acid was only quantifiable at day 1 in trout when given alone, and not at all in catfish. The serum half life of melamine in catfish was 1.50-1.62 days and 3.09-3.67 days in trout. This work highlights the differences of depletion kinetics in fish, which can be measured in days, as compared to the depletion in mammals, measured in hours. Published by Elsevier Ltd. C1 [Stine, Cynthia B.; Nochetto, Cristina B.; Evans, Eric R.; Gieseker, Charles M.; Mayer, Tamara D.; Hasbrouck, Nicholas R.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Stine, CB (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM cynthia.stine@fda.hhs.gov; cristina.nochetto@fda.hhs.gov; eric.evans@fda.hhs.gov; charles.gieseker@fda.hhs.gov; nicholas.hasbrouck@fda.hhs.gov; renate.reimschuessel@fda.hhs.gov NR 53 TC 10 Z9 10 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2012 VL 50 IS 10 BP 3426 EP 3432 DI 10.1016/j.fct.2012.07.055 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 021PF UT WOS:000309897100007 PM 22889901 ER PT J AU Martinez, MNM AF Martinez, M. N. M. TI Bioequivalence: accomplishments, on-going initiatives, and remaining challenges. SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Meeting Abstract C1 [Martinez, M. N. M.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2012 VL 35 SU 3 SI SI BP 16 EP 16 PG 1 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 026CY UT WOS:000310251900024 ER PT J AU Herndon, TM Demko, SG Jiang, XP He, K Gootenberg, JE Cohen, MH Keegan, P Pazdur, R AF Herndon, Thomas M. Demko, Suzanne G. Jiang, Xiaoping He, Kun Gootenberg, Joseph E. Cohen, Martin H. Keegan, Patricia Pazdur, Richard TI US Food and Drug Administration Approval: Peginterferon-alfa-2b for the Adjuvant Treatment of Patients with Melanoma SO ONCOLOGIST LA English DT Article DE FDA; PEG-IFN; Interferon-alpha; Melanoma ID HIGH-RISK MELANOMA; STAGE-III MELANOMA; INTERFERON-ALPHA; PEGYLATED INTERFERON-ALPHA-2B; THERAPY; CANCER; TRIAL; METAANALYSIS AB On March 29, 2011, the U. S. Food and Drug Administration approved peginterferon alfa-2b (PEG-IFN) (Sylatron (TM); Schering Corporation, Kenilworth, NJ) for the adjuvant treatment of melanoma patients with microscopic or gross nodal involvement following definitive surgical resection including complete lymphadenectomy. The approval was based on a single, open-label, multicenter trial enrolling 1,256 patients. After surgical resection, patients were randomized (1: 1) to either PEG-IFN or observation for 5 years. PEG-IFN, 6 mu g/kg per week, was administered s.c. for eight doses, followed by 3 mu g/kg per week for up to 252 weeks. Stratification factors included microscopic or gross nodal involvement, number of positive nodes, Breslow thickness, ulceration, sex, and study center. Patients were assessed for recurrence by the investigators based on physical examination every 3 months for 2 years and every 6 months thereafter. The relapse-free survival (RFS) interval, the primary efficacy endpoint, was significantly longer in PEG-IFN-treated patients. The median RFS times were 34.8 months and 25.5 months, respectively. There was no statistically significant difference in the overall survival time. The most common (>60%) grade 1-4 adverse reactions were fatigue, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), pyrexia, headache, anorexia, myalgia, nausea, chills, and injection site reactions. The most common serious adverse reactions were fatigue, increased ALT and AST, and pyrexia. Thirty-three percent of patients receiving PEG-IFN discontinued treatment as a result of adverse reactions. Five deaths were reported within 30 days of the last treatment dose, two resulting from cardiovascular disease considered as possibly related to treatment. The Oncologist 2012; 17: 1323-1328 C1 [Herndon, Thomas M.] US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evalut & Res,Div Biol Oncol Prod, Silver Spring, MD 20993 USA. [Jiang, Xiaoping; He, Kun] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Herndon, TM (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evalut & Res,Div Biol Oncol Prod, 10903 New Hampshire Ave,Bldg 22,Room 5222, Silver Spring, MD 20993 USA. EM Thomas.Herndon@fda.hhs.gov NR 14 TC 14 Z9 14 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2012 VL 17 IS 10 BP 1323 EP 1328 DI 10.1634/theoncologist.2012-0123 PG 6 WC Oncology SC Oncology GA 029MT UT WOS:000310500600015 PM 23002124 ER PT J AU Preston, C Valdez, ML Bond, K AF Preston, Charles Valdez, Mary Lou Bond, Katherine TI Strengthening Medical Product Regulation in Low- and Middle-Income Countries SO PLOS MEDICINE LA English DT Editorial Material C1 [Preston, Charles; Valdez, Mary Lou; Bond, Katherine] US FDA, Off Int Programs, Silver Spring, MD USA. RP Preston, C (reprint author), US FDA, Off Int Programs, Silver Spring, MD USA. EM charles.preston@fda.hhs.gov NR 27 TC 6 Z9 6 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD OCT PY 2012 VL 9 IS 10 AR e1001327 DI 10.1371/journal.pmed.1001327 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 030OC UT WOS:000310579000009 PM 23109912 ER PT J AU Bates, KE Vetter, VL Li, JS Cummins, S Aguel, F Almond, C Dubin, AM Elia, J Finkle, J Hausner, EA Joseph, F Karkowsky, AM Killeen, M Lemacks, J Mathis, L McMahon, AW Pinnow, E Rodriguez, I Stockbridge, NL Stockwell, M Tassinari, M Krucoff, MW AF Bates, Katherine E. Vetter, Victoria L. Li, Jennifer S. Cummins, Susan Aguel, Fernando Almond, Christopher Dubin, Anne M. Elia, Josephine Finkle, John Hausner, Elizabeth A. Joseph, Francesca Karkowsky, Abraham M. Killeen, Matthew Lemacks, Jodi Mathis, Lisa McMahon, Ann W. Pinnow, Ellen Rodriguez, Ignacio Stockbridge, Norman L. Stockwell, Margaret Tassinari, Melissa Krucoff, Mitchell W. TI Pediatric cardiovascular safety: Challenges in drug and device development and clinical application SO AMERICAN HEART JOURNAL LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CONGENITAL HEART-DISEASE; OFF-LABEL USE; DE-POINTES; I-KS; CHILDREN; ADOLESCENTS; MEDICATIONS; DEATH; TRIAL AB Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic. (Am Heart J 2012;164:481-92.) C1 [Bates, Katherine E.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA. [Li, Jennifer S.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Cummins, Susan; Aguel, Fernando; Hausner, Elizabeth A.; Joseph, Francesca; Karkowsky, Abraham M.; Mathis, Lisa; McMahon, Ann W.; Pinnow, Ellen; Stockbridge, Norman L.; Tassinari, Melissa] US FDA, Silver Spring, MD USA. [Almond, Christopher] Childrens Hosp, Boston, MA 02115 USA. [Dubin, Anne M.] Stanford Univ, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Finkle, John] GlaxoSmithKline, Upper Providence, PA USA. [Lemacks, Jodi] Mended Little Hearts, Dallas, TX USA. [Rodriguez, Ignacio] Hoffman LaRoche, Nutley, NJ USA. [Stockwell, Margaret] Hlth Canada, Ottawa, ON K1A 0L2, Canada. RP Bates, KE (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Cardiol, 3401 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bateske1@email.chop.edu NR 24 TC 7 Z9 7 U1 2 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2012 VL 164 IS 4 BP 481 EP 492 DI 10.1016/j.ahj.2012.07.019 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 029OU UT WOS:000310506000010 PM 23067905 ER PT J AU Popescu, LM AF Popescu, Lucretiu M. TI PET Energy-Based Scatter Estimation in the Presence of Randoms, and Image Reconstruction With Energy-Dependent Scatter and Randoms Corrections SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Positron emission tomography; PET; scatter correction; signal detection ID TIME-OF-FLIGHT; WINDOW METHOD; SPECT; OBSERVERS; MODEL AB In this paper, we address the problem of energy-based scatter estimation in PET in the presence of randoms. We refine a previous proposed model for comprehensive use of the energy information in PET [Phys. Med. Biol., vol. 51, pp. 2919-2937, 2006] by introducing a model for the random coincidences. This model is used to estimate the scatter components in randoms from delayed coincidence data, and then of the nonrandom coincidence scatters from the prompt coincidence data. By performing these estimations on a spatial grid covering the data space, we obtain scatter and randoms correction terms that depend both on position and energy. These terms are incorporated into the list-mode image reconstruction algorithm, thus allowing for an individual treatment of each event according to its position and energy information. We test this approach by using a recently developed image quality evaluation procedure that measures the detectability of signals at unknown locations. The procedure combines a three-dimensional image scanning technique with a novel nonparametric free-response data analysis method that provides a signal detectability metric by using an exponential transformation of the free-response operating characteristic (EFROC). The method allows for scaling of the detectability index to any given image size, a property that makes it advantageous for application to phantom experiments with multiple signals, or large background volumes that can be scanned for false signals. Such experiments can provide substantial signal detectability information with only a few images, as we show here. Image reconstructions using traditional, no energy-dependent, and energy-dependent corrections are compared for different time-of-flight (TOF) resolutions, and number of counts. A comparison of PET time-of-flight (TOF) performance versus no-TOF is also presented. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Popescu, LM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. EM lucretiu.popescu@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health [R21-EB005434] FX Manuscript received November 03, 2011; revised February 29, 2012; accepted May 02, 2012. Date of publication July 18, 2012; date of current version October 09, 2012. The work on energy-based scatter estimation and image reconstruction for PET was supported in part by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, under Grant R21-EB005434, while the author was at the University of Pennsylvania. NR 27 TC 1 Z9 1 U1 4 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2012 VL 59 IS 5 BP 1958 EP 1966 DI 10.1109/TNS.2012.2201170 PN 1 PG 9 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 024WY UT WOS:000310142800024 ER PT J AU Lin, ZN Lin, YC Zhang, XM Kadlubar, S Tuo, JS Green, B Deng, HL Ning, BT AF Lin, Zhong-Ning Lin, Yu-Chun Zhang, Xuemei Kadlubar, Susan Tuo, Jingsheng Green, Bridgett Deng, Helen Ning, Baitang TI Differential promoter activities of functional haplotypes in the 5 '-flanking region of human Sulfotransferase 1A1 SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE SULT1A1; Polymorphism; Haplotypes; Functional Genome; Promoter ID HUMAN PHENOL SULFOTRANSFERASE; SULT1A1 GENE; BIOCHEMICAL-PROPERTIES; ENZYMATIC-ACTIVITY; EXPRESSION; POLYMORPHISMS; ASSOCIATION; ENZYMES; BRAIN; CELLS AB Previously, we reported five common single nucleotide polymorphisms (SNPs), -624G>C, -396G>A, -358A>C, -341C>G, and -294T>C, and six common haplotypes (CGACT, GAACT, GGAGC, GGACC, CAACT, and GAACC) in the 5'-flanking region of the SULT1A1 gene that were associated with altered enzymatic activity. In the present study, we performed in vitro assays to determine the functional impact of these genetic variations on the promoter activity. Dual luciferase reporter assays revealed that these SNPs are located in a negative regulatory fragment of the SULT1A1 gene. Further experiments demonstrated that these SNPs and haplotypes affected promoter activities of SULT1A1. Electrophoretic mobility shift assays showed distinctive binding patterns for the SNPs -396G>A and -294T>C, due to differential binding affinities of the G/A alleles and the T/C alleles to nuclear proteins extracted from the liver carcinoma cell lines, HepG2 and Huh7. (c) 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:422428, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21437 C1 [Lin, Zhong-Ning; Green, Bridgett; Ning, Baitang] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lin, Zhong-Ning; Lin, Yu-Chun] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China. [Zhang, Xuemei; Kadlubar, Susan] Univ Arkansas Med Sci, Colege Med, Div Med Genet, Little Rock, AR 72205 USA. [Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Deng, Helen] Arkansas Dept Hlth, Little Rock, AR 72205 USA. RP Ning, BT (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM baitang.ning@fda.hhs.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU U.S. Food and Drug Administration [E0715801] FX Contract Grant Sponsor: U.S. Food and Drug Administration.; Contract Grant Number: E0715801. NR 18 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PD OCT PY 2012 VL 26 IS 10 BP 422 EP 428 DI 10.1002/jbt.21437 PG 7 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 027BQ UT WOS:000310327200006 PM 23080433 ER PT J AU Miller, DL Hilohi, CM Spelic, DC AF Miller, Donald L. Hilohi, C. Michael Spelic, David C. TI Patient radiation doses in interventional cardiology in the US: Advisory data sets and possible initial values for US reference levels SO MEDICAL PHYSICS LA English DT Article DE percutaneous coronary intervention; coronary angiography; radiation physics; quality improvement; quality assurance; health care; diagnostic cardiac catheterization ID DIAGNOSTIC REFERENCE LEVELS; CARDIOVASCULAR PROCEDURES; CORONARY ANGIOPLASTY; IMAGE QUALITY; AREA PRODUCT; TASK-FORCE; RADIOLOGY; FLUOROSCOPY; EXPOSURE; MULTICENTER AB Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnostic cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K-a,K-r), cumulative air kerma-area product (P-KA), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P-KA is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4754300] C1 [Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Miller, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donald.miller@fda.hhs.gov NR 57 TC 11 Z9 12 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2012 VL 39 IS 10 BP 6276 EP 6286 DI 10.1118/1.4754300 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 024IC UT WOS:000310101900046 PM 23039663 ER PT J AU Petros, WP Younis, IR Ford, JN Weed, SA AF Petros, William P. Younis, Islam R. Ford, James N. Weed, Scott A. TI Effects of Tobacco Smoking and Nicotine on Cancer Treatment SO PHARMACOTHERAPY LA English DT Review DE tobacco; nicotine; pharmacokinetics; cancer ID CELL-LUNG-CANCER; CIGARETTE-SMOKING; ALPHA-1-ACID GLYCOPROTEIN; INTERINDIVIDUAL VARIABILITY; CLINICAL PHARMACOKINETICS; CYTOCHROME-P450 1A2; MEDIATED ACTIVATION; GENETIC-VARIANTS; BREAST-CANCER; PLASMA-LEVELS AB A substantial number of the world's population continues to smoke tobacco, even in the setting of a cancer diagnosis. Studies have shown that patients with cancer who have a history of smoking have a worse prognosis than nonsmokers. Modulation of several physiologic processes involved in drug disposition has been associated with long-term exposure to tobacco smoke. The most common of these processes can be categorized into the effects of smoking on cytochrome P450-mediated metabolism, glucuronidation, and protein binding. Perturbation in the pharmacokinetics of anticancer drugs could result in clinically significant consequences, as these drugs are among the most toxic, but potentially beneficial, pharmaceuticals prescribed. Unfortunately, the effect of tobacco smoking on drug disposition has been explored for only a few marketed anticancer drugs; thus, little prescribing information is available to guide clinicians on the vast majority of these agents. The carcinogenic properties of several compounds found in tobacco smoke have been well studied; however, relatively little attention has been given to the effects of nicotine itself on cancer growth. Data that identify nicotine's effect on cancer cell apoptosis, tumor angiogenesis, invasion, and metastasis are emerging. The implications of these data are still unclear but may lead to important questions regarding approaches to smoking cessation in patients with cancer. C1 [Petros, William P.; Weed, Scott A.] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Petros, William P.; Ford, James N.] W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. [Petros, William P.; Weed, Scott A.] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA. [Younis, Islam R.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Petros, WP (reprint author), W Virginia Univ, Mary Babb Randolph Canc Ctr, POB 9300, Morgantown, WV 26506 USA. EM wpetros@hsc.wvu.edu FU National Institutes of Health [RR16440]; Mylan Chair of Pharmacology at West Virginia University FX Dr. Weed was supported by a National Institutes of Health grant (RR16440), and Dr. Petros was supported by the Mylan Chair of Pharmacology at West Virginia University. NR 75 TC 17 Z9 17 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2012 VL 32 IS 10 BP 920 EP 931 DI 10.1002/j.1875-9114.2012.01117 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 015NH UT WOS:000309452700462 PM 23033231 ER PT J AU Lakhal-Naouar, I Jardim, A Strasser, R Luo, S Kozakai, Y Nakhasi, HL Duncan, RC AF Lakhal-Naouar, Ines Jardim, Armando Strasser, Rona Luo, Shen Kozakai, Yukiko Nakhasi, Hira L. Duncan, Robert C. TI Leishmania donovani Argininosuccinate Synthase Is an Active Enzyme Associated with Parasite Pathogenesis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID PEROXISOMAL TARGETING SIGNALS; AMASTIGOTE-SPECIFIC PROTEIN; NITRIC-OXIDE-PRODUCTION; CITRULLINE-NO CYCLE; IMMUNOCYTOCHEMICAL CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; MILD CITRULLINEMIA; MITOCHONDRIAL-DNA; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI AB Background: Gene expression analysis in Leishmania donovani (Ld) identified an orthologue of the urea cycle enzyme, argininosuccinate synthase (LdASS), that was more abundantly expressed in amastigotes than in promastigotes. In order to characterize in detail this newly identified protein in Leishmania, we determined its enzymatic activity, subcellular localization in the parasite and affect on virulence in vivo. Methodology/Principal Findings: Two parasite cell lines either over expressing wild type LdASS or a mutant form (G128S) associated with severe cases of citrullinemia in humans were developed. In addition we also produced bacterially expressed recombinant forms of the same proteins. Our results demonstrated that LdASS has argininosuccinate synthase enzymatic activity that is abolished using an ASS specific inhibitor (MDLA: methyl-D-L-Aspartic acid). However, the mutant form of the protein is inactive. We demonstrate that though LdASS has a glycosomal targeting signal that binds the targeting apparatus in vitro, only a small proportion of the total cellular ASS is localized in a vesicle, as indicated by protection from protease digestion of the crude organelle fraction. The majority of LdASS was found to be in the cytosolic fraction that may include large cytosolic complexes as indicated by the punctate distribution in IFA. Surprisingly, comparison to known glycosomal proteins by IFA revealed that LdASS was located in a structure different from the known glycosomal vesicles. Significantly, parasites expressing a mutant form of LdASS associated with a loss of in vitro activity had reduced virulence in vivo in BALB/c mice as demonstrated by a significant reduction in the parasite load in spleen and liver. Conclusion/Significance: Our study suggests that LdASS is an active enzyme, with unique localization and essential for parasite survival and growth in the mammalian host. Based on these observations LdASS could be further explored as a potential drug target. C1 [Lakhal-Naouar, Ines; Kozakai, Yukiko; Nakhasi, Hira L.; Duncan, Robert C.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, CBER, Bethesda, MD 20014 USA. [Jardim, Armando; Strasser, Rona] McGill Univ, Inst Parasitol, Quebec City, PQ, Canada. [Jardim, Armando; Strasser, Rona] Ctr Host Parasite Interact, Quebec City, PQ, Canada. [Luo, Shen] US FDA, Chem Lab, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. RP Lakhal-Naouar, I (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, CBER, Bethesda, MD 20014 USA. EM robert.duncan@fda.hhs.gov FU Center for Biologics Evaluation and Research; Canadian Institutes of Health Research; FQRNT Regroupment strategiques FX This project was supported in part by an appointment for IEN to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science Education and the U.S. Food and Drug Administration. These studies were partially supported by an operating grant from the Canadian Institutes of Health Research and FQRNT Regroupment strategiques. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 4 Z9 4 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2012 VL 6 IS 10 AR e1849 DI 10.1371/journal.pntd.0001849 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 029WH UT WOS:000310527200016 PM 23094117 ER PT J AU Orogo, AM Choi, SS Minnier, BL Kruhlak, NL AF Orogo, Amabel M. Choi, Sydney S. Minnier, Barbara L. Kruhlak, Naomi L. TI Construction and Consensus Performance of (Q)SAR Models for Predicting Phospholipidosis Using a Dataset of 743 Compounds SO MOLECULAR INFORMATICS LA English DT Article DE QSAR; Computational toxicology; Phospholipidosis; in Silico; Modeling ID DRUG-INDUCED PHOSPHOLIPIDOSIS; MDL-QSAR; GENETIC TOXICITY; MOLECULES; SOFTWARE; RODENTS; WINDOWS; MC4PC; DEREK AB Drug-induced phospholipidosis (PLD) continues to be a safety concern for pharmaceutical companies and regulatory agencies, prompting the FDA/CDER Phospholipidosis Working Group to develop a database of PLD findings that was recently expanded to contain a total of 743 compounds (385 positive and 358 negative). Three commercial (quantitative) structure-activity relationship [(Q)SAR)] software platforms [MC4PC, Leadscope Predictive Data Miner (LPDM), and Derek for Windows (DfW)] were used to build and/or test models with the database and evaluated individually and together for their ability to predict PLD induction. Models constructed with MC4PC showed improved sensitivity over previous models constructed with an earlier version of the database and software (61.2?% vs. 50.0?%), but lower specificity in cross-validation experiments (58.2?% vs. 91.9?%) due in part to the more balanced ratio of positives to negatives in the training set. A new model created with LPDM gave good cross-validation statistics (79.0?% sensitivity, 78.0?% specificity) and the single DfW structural alert for PLD was found to have high positive predictivity (83.3?%) but low sensitivity (10.4?%) when tested with the entire PLD database. Combining the predictions of MC4PC, LPDM and/or DfW resulted in increased sensitivity and coverage over using one software platform alone, although it did not enhance the overall prediction accuracy beyond that of the best performing individual software platform. The comparison across software platforms, however, facilitated the identification and analysis of chemicals that were consistently predicted incorrectly by all platforms. The prevalence of cationic amphiphilic drug (CAD) structural motifs in the database contributed heavily to many of the structural alerts and discriminating features in the models, but the subset of incorrectly predicted structures across all models underscores the need to account for mitigating features and/or additional filtering criteria to assess PLD, in particular for PLD-inducing non-CADs and non-PLD-inducing CADs. (Q)SAR tools may be used as part of an early screening battery or regulatory risk assessment approach to identify those compounds with the greatest chance of inducing PLD and potentially toxicity. C1 [Orogo, Amabel M.; Choi, Sydney S.; Minnier, Barbara L.; Kruhlak, Naomi L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Orogo, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Naomi.Kruhlak@fda.hhs.gov NR 38 TC 13 Z9 13 U1 2 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1868-1743 J9 MOL INFORM JI Mol. Inf. PD OCT PY 2012 VL 31 IS 10 BP 725 EP 739 DI 10.1002/minf.201200048 PG 15 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Pharmacology & Pharmacy; Computer Science; Mathematical & Computational Biology GA 021MH UT WOS:000309888400005 PM 27476455 ER PT J AU Burwen, DR Sandhu, SK MaCurdy, TE Kelman, JA Gibbs, JM Garcia, B Markatou, M Forshee, RA Izurieta, HS Ball, R AF Burwen, Dale R. Sandhu, Sukhminder K. MaCurdy, Thomas E. Kelman, Jeffrey A. Gibbs, Jonathan M. Garcia, Bruno Markatou, Marianthi Forshee, Richard A. Izurieta, Hector S. Ball, Robert CA Safety Surveillance Working Grp TI Surveillance for Guillain-Barre Syndrome After Influenza Vaccination Among the Medicare Population, 2009-2010 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ADVERSE EVENTS; UNITED-STATES; 2009-JANUARY 2010; SAFETY; VACCINES; ASSOCIATION; COVERAGE; RECEIPT; HUMANS; SYSTEM AB Objectives. We implemented active surveillance for Guillain Barre syndrome (GBS) following seasonal or H1N1 influenza vaccination among the Medicare population during the 2009-2010 influenza season. Methods. We used weekly Medicare claims data to monitor vaccinations and subsequent hospitalizations with principal diagnosis code for GBS within 42 days. Group sequential testing assessed whether the observed GBS rate exceeded a critical limit based on the expected rate from 5 previous years adjusted for claims delay. We evaluated the lag between date of service and date of claims availability and used it for adjustment. Results. By July 30, 2010 (after 26 interim surveillance tests), 14.0 million seasonal and 3.3 million H1N1 vaccinations had accrued. Taking into account claims delay appropriately lowered the critical limit during early monitoring. The observed GBS rate was below the critical limit throughout the surveillance. Conclusions. Medicare data contributed rapid safety monitoring among millions of 2009-2010 influenza vaccine recipients. Adjustment for claims delay facilitates early detection of potential safety issues. Although limited by lack of medical record review to confirm cases, this claims-based surveillance did not indicate a statistically significant elevated GBS rate following seasonal or H1N1 influenza vaccination. (Am J Public Health. 2012;102:1921-1927. doi:10.2105/AJPH.2011.300510) C1 [Burwen, Dale R.; Sandhu, Sukhminder K.; Forshee, Richard A.; Izurieta, Hector S.; Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Markatou, Marianthi] IBM Corp, TJ Watson Res Ctr, Hawthorne, NY USA. [MaCurdy, Thomas E.; Gibbs, Jonathan M.; Garcia, Bruno] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. [Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv CMS, Ctr Medicare, Baltimore, MD USA. RP Burwen, DR (reprint author), NIH, 6701 Rockledge Dr,Room 9186,Rockledge 2,MSC 7913, Bethesda, MD 20892 USA. EM dale.burwen@nih.gov FU FDA; CMS; National Vaccine Program Office, US Department of Health and Human Services FX This work was funded by the FDA, CMS, and National Vaccine Program Office, US Department of Health and Human Services. NR 41 TC 21 Z9 21 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2012 VL 102 IS 10 BP 1921 EP 1927 DI 10.2105/AJPH.2011.300510 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 015GU UT WOS:000309435200020 PM 22970693 ER PT J AU Griffin, JP Godfrey, BM Sherman, RE AF Griffin, Joseph P. Godfrey, Bryant M. Sherman, Rachel E. TI Regulatory Requirements Of The Food And Drug Administration Would Preclude Product Claims Based On Observational Research SO HEALTH AFFAIRS LA English DT Article AB As norms of comparative effectiveness research are sought within the biomedical and health care communities, and the science of conducting and interpreting this research develops, the Food and Drug Administration (FDA) must balance diverse interests. The agency's overarching interest is the development of high-quality comparative effectiveness information that contributes to improved patient care. To further this interest, the FDA can provide expertise in trial design and postmarketing surveillance. The FDA can also ensure that manufacturers of medical products use comparative effectiveness information in product promotion in a manner consistent with regulatory requirements. In this article we observe that these requirements would preclude the manufacturer's use in a promotional context of comparative effectiveness findings derived from an observational study. The FDA recognizes, however, that there are ongoing efforts to address the methodological problems inherent in observational approaches and to foster consensus on enhanced methods. The FDA must work to navigate challenges that relate to both the science of comparative effectiveness research and the agency's statutory responsibilities to the public health. C1 [Griffin, Joseph P.; Godfrey, Bryant M.] US FDA, Off Med Policy, Off Prescript Drug Promot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Griffin, JP (reprint author), US FDA, Off Med Policy, Off Prescript Drug Promot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Joseph.Griffin@fda.hhs.gov FU National Pharmaceutical Council FX This article grew out of a May 9, 2012, roundtable hosted by Health Affairs and sponsored by the National Pharmaceutical Council on issues surrounding the communication of comparative effectiveness research results. NR 5 TC 4 Z9 4 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2012 VL 31 IS 10 BP 2188 EP 2192 DI 10.1377/hlthaff.2012.0958 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 020MU UT WOS:000309815900006 PM 23048095 ER PT J AU Henderson, IC AF Henderson, I. Craig TI Guide To The 'Right' Answers In Medicine? SO HEALTH AFFAIRS LA English DT Book Review C1 [Henderson, I. Craig] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Henderson, I. Craig] US FDA, Oncol Drugs Advisory Comm, Rockville, MD 20857 USA. RP Henderson, IC (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM ichenderson@hotmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2012 VL 31 IS 10 BP 2351 EP 2352 DI 10.1377/hlthaff.2012.0892 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 020MU UT WOS:000309815900029 ER PT J AU Wang, YN Jadhav, PR Lala, M Gobburu, JV AF Wang, Yaning Jadhav, Pravin R. Lala, Mallika Gobburu, Jogarao V. TI Clarification on Precision Criteria to Derive Sample Size When Designing Pediatric Pharmacokinetic Studies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE pediatric drug development; pharmacokinetics; regulatory requirement; precision C1 [Wang, Yaning; Jadhav, Pravin R.; Lala, Mallika; Gobburu, Jogarao V.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Wang, YN (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 1252, Silver Spring, MD 20903 USA. EM Yaning.Wang@fda.hhs.gov NR 8 TC 18 Z9 18 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2012 VL 52 IS 10 BP 1601 EP 1606 DI 10.1177/0091270011422812 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005PV UT WOS:000308763200016 PM 22162537 ER PT J AU Rostron, B AF Rostron, Brian TI Lung Cancer Mortality Risk for U.S. Menthol Cigarette Smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID UNITED-STATES; AMERICANS; SMOKING AB The U.S. Food and Drug Administration is currently assessing the public health impact of menthol cigarettes. Results from a recent U.S. cohort study, composed largely of Blacks and limited to 12 Southern states, found that menthol cigarette smokers had lower risks of lung cancer incidence and mortality than nonmenthol smokers. We conducted a survival analysis of current smokers from the 1987 National Health Interview Survey Cancer Control Supplement (n = 4,832), followed for mortality through linkage with the National Death Index. We estimated mortality hazard ratios (HRs) for menthol smokers compared with nonmenthol smokers, adjusting for a full set of demographic and smoking characteristics. The overall HR for lung cancer mortality for menthol smokers was 0.69 (95% CI = 0.45-1.06). The HR for lung cancer mortality for menthol smokers at ages 50 and over was 0.59 (95% CI = 0.37-0.95). All-cause mortality net of lung cancer mortality did not differ for menthol and nonmenthol smokers. We found evidence of lower lung cancer mortality risk among menthol smokers compared with nonmenthol smokers at ages 50 and over in the U.S. population. It is not known, however, if these differences are due to the impact of menthol on cigarette smoking or long-term differences in cigarette design between menthol and nonmenthol cigarettes. C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Rostron, B (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd,Room 300G, Rockville, MD 20850 USA. EM brian.rostron@fda.hhs.gov NR 24 TC 7 Z9 8 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2012 VL 14 IS 10 BP 1140 EP 1144 DI 10.1093/ntr/nts014 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 015SE UT WOS:000309465600002 PM 22387991 ER PT J AU Rostron, B AF Rostron, Brian TI Response to "Menthol Cigarettes and Lung Cancer Mortality" SO NICOTINE & TOBACCO RESEARCH LA English DT Letter C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20580 USA. RP Rostron, B (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20580 USA. EM brian.rostron@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2012 VL 14 IS 10 BP 1248 EP 1248 DI 10.1093/ntr/nts157 PG 1 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 015SE UT WOS:000309465600017 PM 23012335 ER PT J AU Ishiguro, C Hall, M Neyarapally, GA Dal Pan, G AF Ishiguro, Chieko Hall, Marni Neyarapally, George A. Dal Pan, Gerald TI Post-market drug safety evidence sources: an analysis of FDA drug safety communications SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Letter ID APROTININ; RISK; ROSIGLITAZONE; DEATH C1 [Ishiguro, Chieko] Pharmaceut & Med Devices Agcy, Off Safety 1, Div Surveillance & Anal, Tokyo, Japan. [Hall, Marni; Neyarapally, George A.; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ishiguro, C (reprint author), Pharmaceut & Med Devices Agcy, Off Safety 1, Div Surveillance & Anal, Tokyo, Japan. EM George.neyarapally@fda.hhs.gov NR 17 TC 10 Z9 10 U1 0 U2 4 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2012 VL 21 IS 10 BP 1134 EP 1136 DI 10.1002/pds.3317 PG 3 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 015ND UT WOS:000309452300015 PM 23033257 ER PT J AU Yang, L Krefting, I Gorovets, A Marzella, L Kaiser, J Boucher, R Rieves, D AF Yang, Lucie Krefting, Ira Gorovets, Alex Marzella, Louis Kaiser, James Boucher, Robert Rieves, Dwaine TI Nephrogenic Systemic Fibrosis and Class Labeling of Gadolinium-based Contrast Agents by the Food and Drug Administration SO RADIOLOGY LA English DT Article AB In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. (C) RSNA, 2012 C1 [Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine] US FDA, Off New Drugs, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Yang, L (reprint author), US FDA, Off New Drugs, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Room 2335, Silver Spring, MD 20993 USA. EM Lucie.Yang@fda.hhs.gov NR 10 TC 34 Z9 35 U1 2 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2012 VL 265 IS 1 BP 248 EP 253 DI 10.1148/radiol.12112783 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016KR UT WOS:000309517600029 PM 22923714 ER PT J AU Ratani, SS Siletzky, RM Dutta, V Yildirim, S Osborne, JA Lin, W Hitchins, AD Ward, TJ Kathariou, S AF Ratani, Shakir S. Siletzky, Robin M. Dutta, Vikrant Yildirim, Suleyman Osborne, Jason A. Lin, Wen Hitchins, Anthony D. Ward, Todd J. Kathariou, Sophia TI Heavy Metal and Disinfectant Resistance of Listeria monocytogenes from Foods and Food Processing Plants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BENZALKONIUM CHLORIDE RESISTANCE; FIELD GEL-ELECTROPHORESIS; PLASMID-BORNE CADMIUM; EPIDEMIC CLONE II; UNITED-STATES; STRAINS; DETERMINANTS; ENVIRONMENT; VIRULENCE; PATHOGEN AB The persistence of Listeria monocytogenes in food processing plants and other ecosystems reflects its ability to adapt to numerous stresses. In this study, we investigated 138 isolates from foods and food processing plants for resistance to the quaternary ammonium disinfectant benzalkonium chloride (BC) and to heavy metals (cadmium and arsenic). We also determined the prevalence of distinct cadmium resistance determinants (cadA1, cadA2, and cadA3) among cadmium-resistant isolates. Most BC-resistant isolates were resistant to cadmium as well. Arsenic resistance was encountered primarily in serotype 4b and was an attribute of most isolates of the serotype 4b epidemic clonal group ECIa. Prevalence of the known cadmium resistance determinants was serotype associated: cadA1 was more common in isolates of serotypes 1/2a and 1/2b than 4b, while cadA2 was more common in those of serotype 4b. A subset (15/77 [19%]) of the cadmium-resistant isolates lacked the known cadmium resistance determinants. Most of these isolates were of serotype 4b and were also resistant to arsenic, suggesting novel determinants that may confer resistance to both cadmium and arsenic in these serotype 4b strains. The findings may reflect previously unrecognized components of the ecological history of different serotypes and clonal groups of L. monocytogenes, including exposures to heavy metals and disinfectants. C1 [Siletzky, Robin M.; Yildirim, Suleyman; Kathariou, Sophia] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. [Ratani, Shakir S.] N Carolina State Univ, Dept Genom Sci, Raleigh, NC 27695 USA. [Dutta, Vikrant] N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. [Osborne, Jason A.] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Lin, Wen] US FDA, Irvine, CA USA. [Hitchins, Anthony D.] US FDA, College Pk, MD USA. [Ward, Todd J.] USDA, Peoria, IL USA. RP Kathariou, S (reprint author), N Carolina State Univ, Dept Food Sci, Box 7624, Raleigh, NC 27695 USA. EM Sophia_kathariou@ncsu.edu FU American Meat Institute Foundation; USDA [2006-35201-17377] FX This work was partially supported by a grant from the American Meat Institute Foundation and USDA grant 2006-35201-17377. NR 32 TC 21 Z9 22 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2012 VL 78 IS 19 BP 6938 EP 6945 DI 10.1128/AEM.01553-12 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 005KM UT WOS:000308749300020 PM 22843526 ER PT J AU Rump, LV Bodeis-Jones, S Abbott, J Zhao, SH Kase, J Lorenz, S Fischer, M Brown, E Meng, JH AF Rump, Lydia V. Bodeis-Jones, Sonya Abbott, Jason Zhao, Shaohua Kase, Julie Lorenz, Sandra Fischer, Markus Brown, Eric Meng, Jianghong TI Genetic Characterization of Escherichia coli O104 Isolates from Different Sources in the United States (vol 78, pg 1615, 2012) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction C1 [Rump, Lydia V.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Rump, LV (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 1 TC 0 Z9 0 U1 3 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2012 VL 78 IS 19 BP 7170 EP 7170 DI 10.1128/AEM.01878-12 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 005KM UT WOS:000308749300054 ER PT J AU Johnson, CN Bowers, JC Griffitt, KJ Molina, V Clostio, RW Pei, SF Laws, E Paranjpye, RN Strom, MS Chen, A Hasan, NA Huq, A Noriea, NF Grimes, DJ Colwell, RR AF Johnson, Crystal N. Bowers, John C. Griffitt, Kimberly J. Molina, Vanessa Clostio, Rachel W. Pei, Shaofeng Laws, Edward Paranjpye, Rohinee N. Strom, Mark S. Chen, Arlene Hasan, Nur A. Huq, Anwar Noriea, Nicholas F., III Grimes, D. Jay Colwell, Rita R. TI Ecology of Vibrio parahaemolyticus and Vibrio vulnificus in the Coastal and Estuarine Waters of Louisiana, Maryland, Mississippi, and Washington (United States) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GULF-OF-MEXICO; OYSTERS CRASSOSTREA-VIRGINICA; THERMOSTABLE DIRECT HEMOLYSIN; NORTHERN GULF; ENVIRONMENTAL-FACTORS; SEASONAL ABUNDANCE; INFECTIOUS-DISEASE; PATHOGENIC VIBRIOS; ATLANTIC COAST; CHOLERAE AB Vibrio parahaemolyticus and Vibrio vulnificus, which are native to estuaries globally, are agents of seafood-borne or wound infections, both potentially fatal. Like all vibrios autochthonous to coastal regions, their abundance varies with changes in environmental parameters. Sea surface temperature (SST), sea surface height (SSH), and chlorophyll have been shown to be predictors of zooplankton and thus factors linked to vibrio populations. The contribution of salinity, conductivity, turbidity, and dissolved organic carbon to the incidence and distribution of Vibrio spp. has also been reported. Here, a multicoastal, 21-month study was conducted to determine relationships between environmental parameters and V. parahaemolyticus and V. vulnificus populations in water, oysters, and sediment in three coastal areas of the United States. Because ecologically unique sites were included in the study, it was possible to analyze individual parameters over wide ranges. Molecular methods were used to detect genes for thermolabile hemolysin (A), thermostable direct hemolysin (tdh), and tdh-related hemolysin (trh) as indicators of V. parahaemolyticus and the hemolysin gene vvhA for V. vulnificus. SST and suspended particulate matter were found to be strong predictors of total and potentially pathogenic V. parahaetnolyticus and V. vulnificus. Other predictors included chlorophyll a, salinity, and dissolved organic carbon. For the ecologically unique sites included in the study, SST was confirmed as an effective predictor of annual variation in vibrio abundance, with other parameters explaining a portion of the variation not attributable to SST. C1 [Johnson, Crystal N.; Molina, Vanessa; Clostio, Rachel W.; Pei, Shaofeng; Laws, Edward] Louisiana State Univ, Dept Environm Sci, Baton Rouge, LA 70803 USA. [Bowers, John C.] US FDA, College Pk, MD USA. [Griffitt, Kimberly J.; Noriea, Nicholas F., III; Grimes, D. Jay] Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS USA. [Paranjpye, Rohinee N.; Strom, Mark S.] NOAA, NW Fisheries Sci Ctr, Natl Marine Fisheries Serv, Seattle, WA USA. [Chen, Arlene; Hasan, Nur A.; Huq, Anwar; Colwell, Rita R.] Univ Maryland, College Pk, MD 20742 USA. [Colwell, Rita R.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Johnson, CN (reprint author), Louisiana State Univ, Dept Environm Sci, Baton Rouge, LA 70803 USA. EM cnjohnson@lsu.edu FU NSF RAPID grant [1043126]; NSF grant as part of the joint NSF-NIH Ecology of Infectious Diseases program [EF-0813285/EF-0813066]; NASA grant [NNX09AR57G]; National Oceanic and Atmospheric Administration's Oceans and Human Health Initiative [NA04-OAR-4600214]; NOAA's National Marine Fisheries Service FX This work was supported by NSF RAPID grant 1043126 and NSF grant EF-0813285/EF-0813066 as part of the joint NSF-NIH Ecology of Infectious Diseases program and by NASA grant NNX09AR57G. Additional support was provided by the National Oceanic and Atmospheric Administration's Oceans and Human Health Initiative (NA04-OAR-4600214) and NOAA's National Marine Fisheries Service. NR 82 TC 51 Z9 52 U1 1 U2 42 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2012 VL 78 IS 20 BP 7249 EP 7257 DI 10.1128/AEM.01296-12 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 013TL UT WOS:000309328700009 PM 22865080 ER PT J AU Reynolds, KS AF Reynolds, K. S. TI Achieving the Promise of Personalized Medicine SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PHARMACOGENETICS AB Individualized therapy is the practice of tailoring therapeutic intervention to a patient's disease, demographic characteristics, genetics, environment, lifestyle, and health status. In addition to previous methods of individualization, individualization based on pharmacogenomics is an emerging practice. Although tools are available to aid the determination of the need to individualize therapy, there are barriers to implementation. Various institutions have instituted programs to demonstrate the benefit of individualization, including programs that involve preemptive genotyping. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Reynolds, KS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. EM kellie.reynolds@fda.hhs.gov NR 21 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2012 VL 92 IS 4 BP 401 EP 405 DI 10.1038/clpt.2012.147 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 009HN UT WOS:000309017000001 PM 22992663 ER PT J AU Lumpkin, MM Eichler, HG Breckenridge, A Hamburg, MA Lonngren, T Woods, K AF Lumpkin, M. M. Eichler, H-G Breckenridge, A. Hamburg, M. A. Loenngren, T. Woods, K. TI Advancing the Science of Medicines Regulation: The Role of the 21st-Century Medicines Regulator SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG; PERSPECTIVE AB The history of medicines regulation is punctuated with sudden swings in focus mandated by a public injured by medicines and skeptical of regulators' abilities to protect them. As stakeholder communities and the science that undergirds medicines have both grown more sophisticated, seemingly conflicting mission equities, such as public health protection vs. promotion or population vs. individual patient product development focus, have created new challenges to defining the mission and role of twenty-first-century medicines regulators. The role of medicines regulators as a nationally focused, retrospective assessor of data is rapidly shifting to that of a prospective generator of public data and tools to help drive what has now become a global product development and regulatory enterprise that is fast gaining recognition as an integral part of any truly effective twenty-first-century health-care system. This article discusses this evolution and describes how regulatory science will help to both drive and define it. C1 [Lumpkin, M. M.; Hamburg, M. A.] US FDA, Silver Spring, MD USA. [Breckenridge, A.; Woods, K.] Med & Healthcare Prod Regulatory Agcy, London, England. [Woods, K.] European Med Agcy, Management Board, London, England. RP Lumpkin, MM (reprint author), US FDA, Silver Spring, MD USA. EM Murray.Lumpkin@fda.hhs.gov NR 23 TC 7 Z9 7 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2012 VL 92 IS 4 BP 486 EP 493 DI 10.1038/clpt.2012.146 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 009HN UT WOS:000309017000025 PM 22948890 ER PT J AU Gannavaram, S Connelly, PS Daniels, MP Duncan, R Salotra, P Nakhasi, HL AF Gannavaram, Sreenivas Connelly, Patricia S. Daniels, Mathew P. Duncan, Robert Salotra, Poonam Nakhasi, Hira L. TI Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of ss-oxidation of fatty acids and blocks cell division in the amastigote stage SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRYPANOSOMA-BRUCEI; PLASMODIUM-FALCIPARUM; METABOLISM; PATHWAY; IDENTIFICATION; METACASPASES; EXPRESSION; ENZYMES; SYSTEM AB Recently, we described the existence of the ubiquitin fold modifier 1 (Ufm1) and its conjugation pathway in Leishmania donovani. We demonstrated the conjugation of Ufm1 to proteins such as mitochondrial trifunctional protein (MTP) that catalyses beta-oxidation of fatty acids in L. donovani. To elucidate the biological roles of the Ufm1-mediated modifications, we made an L. donovani Ufm1 null mutant (Ufm1-/-). Loss of Ufm1 and consequently absence of Ufm1 conjugation with MTP resulted in diminished acetyl-CoA, the end-product of the beta-oxidation in the Ufm1-/- amastigote stage. The Ufm1-/- mutants showed reduced survival in the amastigote stage in vitro and ex vivo in human macrophages. This survival was restored by re-expression of wild-type Ufm1 with concomitant induction of acetyl-CoA but not by re-expressing the non-conjugatable Ufm1, indicating the essential nature of Ufm1 conjugation and beta-oxidation. Both cell cycle analysis and ultrastructural studies of Ufm1-/- parasites confirmed the role of Ufm1 in amastigote growth. The defect in vitro growth of amastigotes in human macrophages was further substantiated by reduced survival. Therefore, these studies suggest the importance of Ufm1 in Leishmania pathogenesis with larger impact on other organisms and further provide an opportunity to test Ufm1-/- parasites as drug and vaccine targets. C1 [Gannavaram, Sreenivas; Duncan, Robert; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Connelly, Patricia S.; Daniels, Mathew P.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Salotra, Poonam] Natl Inst Pathol, New Delhi, India. RP Nakhasi, HL (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM hira.nakhasi@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU Intramural NIH HHS [ZIC HL005906-06] NR 39 TC 12 Z9 13 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2012 VL 86 IS 1 BP 187 EP 198 DI 10.1111/j.1365-2958.2012.08183.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 009ZH UT WOS:000309063600016 PM 22897198 ER PT J AU Reesink, HW Lee, J Keller, A Dennington, P Pink, J Holdsworth, R Schennach, H Goldman, M Petraszko, T Sun, J Meng, Y Qian, K Rehacek, V Turek, P Krusius, T Juvonen, E Tiberghien, P Legrand, D Semana, G Muller, JY Bux, J Reil, A Lin, CK Daly, H McSweeney, E Porretti, L Greppi, N Rebulla, P Okazaki, H Sanchez-Guerrero, SA Baptista-Gonzalez, HA Martinez-Murillo, C Guerra-Marquez, A Rodriguez-Moyado, H Middelburg, RA Wiersum-Osselton, JC Brand, A van Tilburg, C Dinesh, D Dagger, J Dunn, P Brojer, E Letowska, M Maslanka, K Lachert, E Uhrynowska, M Zhiburt, E Palfi, M Berlin, G Frey, BM Rovira, LP Muniz-Diaz, E Castro, E Chapman, C Green, A Massey, E Win, N Williamson, L Silliman, CC Chaffin, DJ Ambruso, DR Blumberg, N Tomasulo, P Land, KJ Norris, PJ Illoh, OC Davey, RJ Benjamin, RJ Eder, AF McLaughlin, L Kleinman, S Panzer, S AF Reesink, H. W. Lee, J. Keller, A. Dennington, P. Pink, J. Holdsworth, R. Schennach, H. Goldman, M. Petraszko, T. Sun, J. Meng, Y. Qian, K. Rehacek, V. Turek, P. Krusius, T. Juvonen, E. Tiberghien, P. Legrand, D. Semana, G. Muller, J. Y. Bux, J. Reil, A. Lin, C. K. Daly, H. McSweeney, E. Porretti, L. Greppi, N. Rebulla, P. Okazaki, H. Sanchez-Guerrero, S. A. Baptista-Gonzalez, H. A. Martinez-Murillo, C. Guerra-Marquez, A. Rodriguez-Moyado, H. Middelburg, R. A. Wiersum-Osselton, J. C. Brand, A. van Tilburg, C. Dinesh, D. Dagger, J. Dunn, P. Brojer, E. Letowska, M. Maslanka, K. Lachert, E. Uhrynowska, M. Zhiburt, E. Palfi, M. Berlin, G. Frey, B. M. Puig Rovira, L. Muniz-Diaz, E. Castro, E. Chapman, C. Green, A. Massey, E. Win, N. Williamson, L. Silliman, C. C. Chaffin, D. J. Ambruso, D. R. Blumberg, N. Tomasulo, P. Land, K. J. Norris, P. J. Illoh, O. C. Davey, R. J. Benjamin, R. J. Eder, A. F. McLaughlin, L. Kleinman, S. Panzer, S. TI Measures to prevent transfusion-related acute lung injury (TRALI) SO VOX SANGUINIS LA English DT Letter C1 [Reesink, H. W.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Panzer, S.] Univ Vienna, Univ Klin Blutgruppenserolgie & Tranzfus Med, Klinsche Abt Blutgruppenserol, A-1090 Vienna, Austria. [Lee, J.; Keller, A.; Dennington, P.; Pink, J.; Holdsworth, R.] Australian Red Cross Blood Serv, Osborne Pk, WA 6017, Australia. [Schennach, H.] TILAK Univ Clin Reg Hosp, Cent Inst Blood Transfus & Immunol ZIB, A-6020 Innsbruck, Austria. [Goldman, M.] Canadian Blood Serv, Ottawa, ON K1G 4S5, Canada. [Petraszko, T.] Canadian Blood Serv, Vancouver, BC V6H 2N9, Canada. [Sun, J.; Meng, Y.; Qian, K.] Shanghai Blood Ctr, Dept Social Affairs, Shanghai, Peoples R China. [Rehacek, V.] Univ Hosp, Hradec Kralove, Czech Republic. [Turek, P.] Thomayer Hosp, Prague, Czech Republic. [Krusius, T.; Juvonen, E.] Finnish Red Cross Blood Serv, Helsinki 00310, Finland. [Tiberghien, P.; Legrand, D.; Muller, J. Y.] Etab Francais Sang, F-93218 La Plaine St Denis, France. [Semana, G.] Etab Francais Sang Bretagne, F-35016 Rennes, France. [Bux, J.; Reil, A.] German Red Cross Blood Serv W, D-58097 Hagen, Germany. [Lin, C. K.] Hong Kong Red Cross Blood Transfus Serv, Kowloon, Hong Kong, Peoples R China. [Daly, H.; McSweeney, E.] Natl Blood Ctr, Irish Blood Transfus Serv, Dublin 8, Ireland. [Porretti, L.; Rebulla, P.] Fdn Ca Granda Osped Maggiore Policlin, Dept Regenerat Med, Ctr Transfus Med Cellular Therapy & Cryobiol, I-20122 Milan, Italy. [Greppi, N.] Fdn Ca Granda Osped Maggiore Policlin, Dept Regenerat Med, Ctr Blood Transfus & Immunohematol, I-20122 Milan, Italy. [Okazaki, H.] Blood Serv Headquarters, Japanese Red Cross Soc, Koto Ku, Tokyo 1358521, Japan. [Sanchez-Guerrero, S. A.] Natl Inst Cancerol, Mexico City, DF, Mexico. [Baptista-Gonzalez, H. A.] Med Hosp, Transfus Med & Blood Bank, Mexico City, DF, Mexico. [Martinez-Murillo, C.] Siglo XXI Natl Med Ctr Mexican Social Secur, Cent Blood Bank, Mexico City, DF, Mexico. [Guerra-Marquez, A.] La Raza Natl Med Ctr Mexican Social Secur, Cent Blood Bank, Mexico City, DF, Mexico. [Rodriguez-Moyado, H.] Consejo Mexicano Hematol, Mexico City, DF, Mexico. [Middelburg, R. A.; Wiersum-Osselton, J. C.; Brand, A.] Sanquin JJ van Rood Ctr, Leiden, Netherlands. [Middelburg, R. A.; Wiersum-Osselton, J. C.; Brand, A.] TRIP, Dutch Hemovigilance Grp, The Hague, Netherlands. [van Tilburg, C.; Dunn, P.] New Zealand Blood Serv, Auckland 1142, New Zealand. [Dinesh, D.; Dagger, J.] New Zealand Blood Serv, Wellington 6021, New Zealand. [Brojer, E.; Letowska, M.; Maslanka, K.; Lachert, E.; Uhrynowska, M.] Inst Hematol & Transfus Med, Warsaw, Poland. [Zhiburt, E.] Russian Transfusionist Assoc, Pirogov Russian Natl Med Surg Ctr, Moscow 105203, Russia. [Castro, E.] Crus Roja Espanola, Ctr Transfus, Madrid 28040, Spain. [Puig Rovira, L.] Banc Sang & Teixits Catalonia, Dept Immunohaematol, Blood Div, Barcelona 08005, Spain. [Palfi, M.; Berlin, G.] Linkoping Univ Hosp, Dept Clin Immunol & Transfus Med, SE-58185 Linkoping, Sweden. [Frey, B. M.] Blood Transfus Serv SRC, Zurich, Switzerland. Swissmedic, Swiss Agcy Therapeut Prod, CH-3000 Bern, Switzerland. [Chapman, C.] NHSBT Newcastle Ctr, Newcastle Upon Tyne NE2 4NQ, Tyne & Wear, England. [Green, A.; Massey, E.] NHSBT, Bristol BS34 7QH, Avon, England. [Win, N.] NHSBT Tooting Ctr, London SW17 0RB, England. [Williamson, L.] NHSBT, Watford WD24 4QN, Herts, England. [Benjamin, R. J.; Eder, A. F.; McLaughlin, L.] Amer Red Cross, Rockville, MD 20855 USA. [Illoh, O. C.; Davey, R. J.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Silliman, C. C.] Bonfils Blood Ctr, Res Dept, Denver, CO 80230 USA. [Blumberg, N.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Tomasulo, P.] Blood Syst, Scottsdale, AZ USA. [Land, K. J.; Norris, P. J.] Blood Syst, San Antonio, TX USA. [Land, K. J.; Norris, P. J.] Blood Syst, San Francisco, CA USA. RP Reesink, HW (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM internationalforum@kpnplanet.nl; harald.schennach@uki.at; mindy.goldman@blood.ca; tanya.petraszko@blood.ca; sunjie@sbc.org.cn; RehacekV@lfhk.cuni.cz; petr.turek@ftn.cz; tom.krusius@bts.redcross.fi; eeva.juvonen@bts.red-cross.fi; pierre.tiberghien@efs.sante.fr; j.bux@bsdwest.de; cklin@ha.org.hk; helena.daly@ibts.ie; ellen.mcsweeney@ibts.ie; l.porretti@policlinico.mi.it; h-okazaki@jrc.or.jp; elisahec@prodigy.net.mx; christine.vantilburg@nzblood.co.nz; ebrojer@ihit.waw.pl; ezhiburt@yandex.ru; miodrag.palfi@lio.se; gosta.berlin@lio.se; bm.frey@zhbsd.ch; lpuig@bst.cat; asatur@cruzroja.es; catherine.chapman@nhsbt.ns.uk; christopher.silliman@ucdenver.edu; orieji.illoh@fda.hhs.gov; richard.davey@fda.hhs.gov; skleinman@shaw.ca; internationalforum@kpnplanet.nl RI Rebulla, Paolo/I-7684-2015; Porretti, Laura/J-6748-2015; OI Rebulla, Paolo/0000-0002-3875-5754; Porretti, Laura/0000-0001-8100-4262; Dunn, Paul/0000-0003-3080-8126 NR 0 TC 25 Z9 28 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD OCT PY 2012 VL 103 IS 3 BP 231 EP 259 DI 10.1111/j.1423-0410.2012.01596.x PG 29 WC Hematology SC Hematology GA 007GU UT WOS:000308877600007 PM 22519920 ER PT J AU Kim, IW Noh, H Ji, E Han, N Hong, SH Ha, J Burckart, GJ Oh, JM AF Kim, In-Wha Noh, Hyejin Ji, Eunhee Han, Nayoung Hong, Su Hyun Ha, Jongwon Burckart, Gilbert J. Oh, Jung Mi TI Identification of Factors Affecting Tacrolimus Level and 5-Year Clinical Outcome in Kidney Transplant Patients SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Article ID RENAL-TRANSPLANTATION; CALCINEURIN INHIBITORS; GENETIC-POLYMORPHISMS; ABCB1 POLYMORPHISMS; MYCOPHENOLIC-ACID; DOSE REQUIREMENTS; ACUTE REJECTION; TROUGH CONCENTRATIONS; RECIPIENTS; CYP3A5 AB The purpose of this study was to identify and characterize the association of various clinical variables and CYP3A5 genotypes with the pharmacokinetics of tacrolimus and outcome over 15 years in kidney transplantation patients in Korea. A total of 129 recipients (aged 1865 years) administered tacrolimus were genotyped for CYP3A5 (6986A>G in intron 3; rs776746). Clinical covariates and trough levels, doses and dose-adjusted trough levels of tacrolimus, as well as complications during the 15 years after transplantation, were analysed. A linear mixed model was used to investigate potential factors affecting the trough levels, doses and dose-adjusted levels of tacrolimus. We identified factors affecting chronic allograft nephropathy (CAN) and tacrolimus-related complications. After adjusting for sex, body-weight and doses of corticosteroids and mycophenolate mofetil, we noted that CYP3A5 genotypes had the most profound effect on the dose and dose-adjusted trough levels of tacrolimus 15 years after transplantation (p < 0.001). Trough levels of tacrolimus were associated with post-transplantation hyperlipidaemia (p < 0.05), and estimated glomerular filtration rate was associated with CAN (p < 0.05). Therefore, the CYP3A5 genotype is a variable marker for tacrolimus dose requirement, and the trough level of tacrolimus should be controlled to minimize post-transplant hyperlipidaemia to achieve optimum outcome. C1 [Oh, Jung Mi] Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Seoul 151742, South Korea. [Ha, Jongwon] Seoul Natl Univ, Coll Med, Transplantat Res Inst, Dept Surg, Seoul 151742, South Korea. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Oh, JM (reprint author), Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, 1 Gwanak Ro, Seoul 151742, South Korea. EM jmoh@snu.ac.kr OI Oh, JungMi/0000-0002-1836-1707 FU National Research Foundation of Korea (NRF); Korean government (MEST) [2011-0000354] FX This work was supported by National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (no. 2011-0000354). NR 39 TC 4 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-7835 J9 BASIC CLIN PHARMACOL JI Basic Clin. Pharmacol. Toxicol. PD OCT PY 2012 VL 111 IS 4 BP 217 EP 223 DI 10.1111/j.1742-7843.2012.00892.x PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 008CN UT WOS:000308935000001 PM 22469198 ER PT J AU Dave, VS Fahmy, RM Bensley, D Hoag, SW AF Dave, Vivek S. Fahmy, Raafat M. Bensley, Dennis Hoag, Stephen W. TI Eudragit (R) RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE Eudragit (R) RL PO; Eudragit (R) RS PO; roller-compaction; plasticizer; sintering ID EXTRUDED DOSAGE FORMS; SUSTAINED-RELEASE; DRUG-RELEASE; IN-VITRO; CHLORPHENIRAMINE MALEATE; THERMAL-TREATMENT; ACRYLIC POLYMER; PARTICLE-SIZE; SOLUBLE DRUG; THEOPHYLLINE AB The influence of plasticizer level, roll pressure and sintering temperature was investigated on the granule properties, tablet breaking force and theophylline release from tablets. Nine formulations using theophylline as a model drug, Eudragit (R) RL PO, Eudragit (R) RS PO, or both as a matrix former and triethyl citrate (TEC) as a plasticizer were prepared. The formulations were roller compacted and the granules obtained were evaluated for particle size distribution and flowability. These granules were compacted into tablets at a compression force of 7 kN. The tablets were thermally treated at different temperatures (50 and 75 degrees C) for 5 h and were evaluated for breaking force and dissolution. Increase in roll pressure and TEC levels resulted in a progressive increase in the mean particle size of the granules. The flowability of the granules also improved with increasing roll pressures and TEC levels. Tablet breaking force increased with an increase in TEC levels and sintering temperatures. But these effects were significant only at the highest level of plasticizer and sintering temperature respectively. For the tablets containing Eudragit (R) RS PO, theophylline release decreased proportionately with increase in TEC levels and sintering temperatures. Tablets containing either Eudragit (R) RL PO or a mixture of RS PO and RL PO failed to impart an extended-release property to the tablets at the studied variables i.e. roll pressure, TEC levels and sintering temperature. It was clearly demonstrated that with suitable optimization of these parameters, the release-rate of a water soluble drug from the matrix tablets prepared via roller compaction can be finely controlled. C1 [Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Fahmy, Raafat M.; Bensley, Dennis] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. [Dave, Vivek S.] Lubrizol Adv Mat, Brecksville, OH USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu FU CIPET (Consortium for Industrial Pharmaceutics Education and Training); FDA FX The authors are thankful to Alexanderwerk Inc., Horsham, PA, USA for the equipment loan. The authors are also thankful to CIPET (Consortium for Industrial Pharmaceutics Education and Training) and FDA for funding the study. NR 57 TC 6 Z9 7 U1 4 U2 16 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PD OCT PY 2012 VL 38 IS 10 BP 1240 EP 1253 DI 10.3109/03639045.2011.645831 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 004BI UT WOS:000308654700010 PM 22257339 ER PT J AU Beleche, T Fairris, D Marks, M AF Beleche, Trinidad Fairris, David Marks, Mindy TI Do course evaluations truly reflect student learning? Evidence from an objectively graded post-test SO ECONOMICS OF EDUCATION REVIEW LA English DT Article DE Course evaluations; Student learning; Grades ID RATINGS; INSTRUCTION; PERFORMANCE; INFLATION; LENIENCY; TEACHERS; VALIDITY; FACULTY AB It is difficult to assess the extent to which course evaluations reflect how much students truly learn from a course because valid measures of learning are rarely available. This paper makes use of a unique setting in which students take a common, high-stakes post-test which is centrally graded and serves as the basis for capturing actual student learning. We match these student-specific measures of learning to student-specific course evaluation scores from electronic records and a rich set of student-level covariates, including a pre-test score and other measures of skills prior to entering the course. While small in magnitude, we find a robust positive, and statistically significant, association between our measure of student learning and course evaluations. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Fairris, David; Marks, Mindy] Univ Calif Riverside, Dept Econ, Riverside, CA 92521 USA. [Beleche, Trinidad] US FDA, Silver Spring, MD 20993 USA. RP Marks, M (reprint author), Univ Calif Riverside, Dept Econ, Riverside, CA 92521 USA. EM mindy.marks@ucr.edu NR 29 TC 13 Z9 13 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7757 J9 ECON EDUC REV JI Econ. Educ. Rev. PD OCT PY 2012 VL 31 IS 5 BP 709 EP 719 DI 10.1016/j.econedurev.2012.05.001 PG 11 WC Economics; Education & Educational Research SC Business & Economics; Education & Educational Research GA 006XD UT WOS:000308852200015 ER PT J AU Chen, E AF Chen, Eric TI Orphanage at the FDA SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Editorial Material C1 US FDA, Humanitarian Use Devices Designat Program, Off Orphan Prod Dev, Silver Spring, MD USA. RP Chen, E (reprint author), US FDA, Humanitarian Use Devices Designat Program, Off Orphan Prod Dev, Silver Spring, MD USA. EM eric.chen@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD OCT PY 2012 VL 5 IS 5 SI SI BP 735 EP 736 DI 10.1007/s12265-010-9242-2 PG 2 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 008KJ UT WOS:000308955500016 PM 21080134 ER PT J AU Chiquette, J Allison, MJ Rasmussen, M AF Chiquette, J. Allison, M. J. Rasmussen, M. TI Use of Prevotella bryantii 25A and a commercial probiotic during subacute acidosis challenge in midlactation dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE dairy cow; Enterococcus faecium and Saccharomyces cerevisiae; Prevotella bryantii 25A; subacute ruminal acidosis ID FED MICROBIAL SUPPLEMENTATION; CONTROLLED-RELEASE CAPSULE; RUMINAL ACIDOSIS; INFLAMMATORY RESPONSE; QUANTITATIVE PCR; MILK-PRODUCTION; RUMEN ACIDOSIS; CATTLE; LIPOPOLYSACCHARIDE; FERMENTATION AB The objective of this study was to determine the efficacy of Prevotella bryantii 25A as a probiotic during a subacute ruminal acidosis (SARA) challenge using a commercial probiotic as a positive control. Six multiparous ruminally fistulated cows (BW = 685 +/- 65 kg; (mean +/- SD) in the mid-phase of lactation (70 to 148 DIM) received the following treatments in a replicated 3 x 3 Latin square design: (1) total mixed ration (TMR; control, CON), (2) TMR + 2 g/head per day of a probiotic combination of Enterococcus faecium and Saccharomyces cerevisiae (EFSC), or (3) TMR + Prevotella bryantii 25A. The Latin square consisted of 3 wk of adaptation to the respective treatments during which the animals were fed ad libitum once per day a conventional early-lactation TMR and 1.5 kg of hay. The adaptation was followed by 4 d of SARA (no hay) and 10 d of rest (adaptation diet without probiotics). Dry matter intake and milk production were depressed during SARA (22.0 and 31.8 kg/d, respectively) compared with adaptation (24.4 and 34.0 kg/d, respectively) and did not recover during rest (22.3 and 30.7 kg/d, respectively). During SARA, P. bryantii 25A had no effect on rumen pH, whereas EFSC reduced the percentage of time with pH <6.0 (71%) compared with CON (85%) and increased maximum pH. The EFSC treatment tended to increase mean pH over 24 h (5.65) compared with CON (5.45). Proportion of time with pH <5.6 tended to be lower with EFSC (46%) than with CON (62%). Populations of bacteria considered to be the most important cellulose digesters in the rumen (Ruminococcus flavefaciens, Ruminococcus albus, and Fibrobacter succinogenes) were also monitored during these treatments using culture-independent real-time PCR methods. The population of R. flavefaciens was similar between the 2 feeding phases, whereas F. succinogenes and R. albus were lower during SARA compared with rest. In light of the present study, P. bryantii 25A did not prove to be an effective preventative for SARA. The role of EFSC in regulating rumen pH was confirmed, with a possible effect of maintaining R. flavefaciens populations during SARA. C1 [Chiquette, J.] Agr & Agri Food Canada, Dairy & Swine Res & Dev Ctr, Sherbrooke, PQ J1M 0C8, Canada. [Allison, M. J.] Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA. [Rasmussen, M.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Chiquette, J (reprint author), Agr & Agri Food Canada, Dairy & Swine Res & Dev Ctr, Sherbrooke, PQ J1M 0C8, Canada. EM chiquettej@agr.gc.ca RI Rasmussen, Mark/N-9509-2014 FU Dairy Farmers of Canada (Ottawa, ON, Canada); Agriculture and Agri-Food Canada (Ottawa, ON, Canada) FX The authors acknowledge the technical work of F. Markwell, L. Marier, M.-C. Benoit, C. Richer (all of Agriculture and Agri-Food Canada, Sherbrooke), and A. Payet-Maugeron (School of Engineers in Agriculture, Esitpa, Val de Reuil, France). We thank C. Bolduc, R. Lanctot, and M. Poitras (all of Agriculture and Agri-Food Canada) for animal care. The statistical support of S. Methot (Agriculture and Agri-Food Canada, Sherbrooke) is also greatly acknowledged. Finally, thanks to Chr. Hansen (S. A. Graham, Milwaukee, WI) for the provision of EFSC. This project was partly funded by Dairy Farmers of Canada (Ottawa, ON, Canada) and Agriculture and Agri-Food Canada (Ottawa, ON, Canada). NR 47 TC 11 Z9 11 U1 1 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD OCT PY 2012 VL 95 IS 10 BP 5985 EP 5995 DI 10.3168/jds.2012-5511 PG 11 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 010HD UT WOS:000309084600052 PM 22901468 ER PT J AU Marszal, E Fowler, E AF Marszal, Ewa Fowler, Elizabeth TI Workshop on predictive science of the immunogenicity aspects of particles in biopharmaceutical products SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE protein aggregation; injectables; immunology; particle size; physical characterization; physical stability AB Particles in protein therapeutics and concerns for a potential correlation with product immunogenicity are increasingly becoming the focus of recent publications and scientific forums. The consensus of academic, industrial, and regulatory scientists is that this area is not well understood and will require in-depth research because of the potential impact on the product safety and efficacy. This commentary presents a summary of the 1-day workshop entitled Predictive Science of the Immunogenicity Aspects of Particles in Biopharmaceutical Products, which discussed the current state of analytical resources for quantitation and characterization of protein aggregates and potential paths for developing predictive preclinical tools. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:35553559, 2012 C1 [Marszal, Ewa] US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Fowler, Elizabeth] CMC Consulting Serv, Brunswick, ME 04011 USA. RP Marszal, E (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM ewa.marszal@fda.hhs.gov NR 4 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2012 VL 101 IS 10 BP 3555 EP 3559 DI 10.1002/jps.23243 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 994XA UT WOS:000307966600003 PM 22736535 ER PT J AU Rosenberg, AS Verthelyi, D Cherney, BW AF Rosenberg, Amy S. Verthelyi, Daniela Cherney, Barry W. TI Managing uncertainty: A perspective on risk pertaining to product quality attributes as they bear on immunogenicity of therapeutic proteins. SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE immunology; particle size; protein aggregation; microparticles; physicochemical properties ID CELL RESPONSES; PARTICLES; VACCINE; VOLUNTEERS; ADJUVANTS; GLASS; MICE AB The critical question addressed in this paper regards how industry and regulatory agencies should manage the risk of adverse events to patients posed by product quality attributes for which a preponderance of evidence from clinical and/or non-clinical studies supports it as a risk, but for which the probability of clinical adverse events arising from the attribute is uncertain. We here provide our perspective on the principles that can be applied to determine the need for and the manner in which to control quality attributes when their impact on safety and/or efficacy is suspected, but uncertain. As an example, we use the risk of immune responses to protein therapeutics posed by sub-visible protein particulates in therapeutic proteins. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:35603567, 2012 C1 [Rosenberg, Amy S.; Verthelyi, Daniela; Cherney, Barry W.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.hhs.gov NR 27 TC 33 Z9 33 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2012 VL 101 IS 10 BP 3560 EP 3567 DI 10.1002/jps.23244 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 994XA UT WOS:000307966600004 PM 22736548 ER PT J AU Bee, JS Goletz, TJ Ragheb, JA AF Bee, Jared S. Goletz, Theresa J. Ragheb, Jack A. TI The future of protein particle characterization and understanding its potential to diminish the immunogenicity of biopharmaceuticals: A shared perspective SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE immunology; protein aggregation; protein formulation; stability; regulatory science; biotechnology; microparticles; nanoparticles; therapeutic drug monitoring ID HUMAN INTERFERON-BETA; STABILITY; NANOPARTICLES; AGGREGATION; ANTIBODY; MODEL; GLASS AB Biopharmaceuticals represent an important and growing class of medicines. Immunogenic responses to biopharmaceuticals in patients can sometimes result in reduced safety and efficacy. Although multiple factors are known to influence immunogenicity, our understanding of the complex underlying mechanisms remains imperfect. In particular, the potential impact of protein aggregates (particulates) on immunogenicity is currently not well understood. This commentary discusses emerging technologies for particle assessment, what is known about the link between particulates and product safety and efficacy, and current regulatory guidances and perspectives. We consider approaches that in the future may permit specific particle attributes to be correlated with relative immunogenic risk, including the value of data derived from clinical and postmarketing surveillance. Finally, we identify some key remaining questions, which, when answered, may guide future strategies for decreasing the immunogenicity of biopharmaceuticals. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:35803585, 2012 C1 [Ragheb, Jack A.] US FDA, Div Therapeut Prot, OBP OPS, CDER, Bethesda, MD 20892 USA. [Bee, Jared S.] Medimmune Inc, Formulat Sci Dept, Gaithersburg, MD 20878 USA. [Goletz, Theresa J.] Amgen Inc, Clin Immunol Dept, Seattle, WA 98119 USA. RP Ragheb, JA (reprint author), US FDA, Div Therapeut Prot, OBP OPS, CDER, Bethesda, MD 20892 USA. EM jack.ragheb@fda.hhs.gov OI Bee, Jared/0000-0002-4391-0560 NR 35 TC 17 Z9 18 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2012 VL 101 IS 10 BP 3580 EP 3585 DI 10.1002/jps.23247 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 994XA UT WOS:000307966600006 PM 22736570 ER PT J AU Turk, DC O'Connor, AB Dworkin, RH Chaudhry, A Katz, NP Adams, EH Brownstein, JS Comer, SD Dart, R Dasgupta, N Denisco, RA Klein, M Leiderman, DB Lubran, R Rappaport, BA Zacny, JP Ahdieh, H Burke, LB Cowan, P Jacobs, P Malamut, R Markman, J Michna, E Palmer, P Peirce-Sandner, S Potter, JS Raja, SN Rauschkolb, C Roland, CL Webster, LR Weiss, RD Wolf, K AF Turk, Dennis C. O'Connor, Alec B. Dworkin, Robert H. Chaudhry, Amina Katz, Nathaniel P. Adams, Edgar H. Brownstein, John S. Comer, Sandra D. Dart, Richard Dasgupta, Nabarun Denisco, Richard A. Klein, Michael Leiderman, Deborah B. Lubran, Robert Rappaport, Bob A. Zacny, James P. Ahdieh, Harry Burke, Laurie B. Cowan, Penney Jacobs, Petra Malamut, Richard Markman, John Michna, Edward Palmer, Pamela Peirce-Sandner, Sarah Potter, Jennifer S. Raja, Srinivasa N. Rauschkolb, Christine Roland, Carl L. Webster, Lynn R. Weiss, Roger D. Wolf, Kerry TI Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations SO PAIN LA English DT Review DE Abuse; Abuse deterrent formulation; Abuse liability; Opioids; Risk of abuse; Study design ID INJECTION-DRUG USERS; CHRONIC NONCANCER PAIN; UNITED-STATES; ANTIRETROVIRAL TREATMENT; TEMAZEPAM CAPSULES; PROSPECTIVE COHORT; PRESCRIPTION; MISUSE; LIABILITY; TRIALS AB Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [O'Connor, Alec B.; Dworkin, Robert H.; Markman, John; Peirce-Sandner, Sarah] Univ Rochester, Rochester, NY USA. [Chaudhry, Amina; Lubran, Robert; Raja, Srinivasa N.] Johns Hopkins Univ, Baltimore, MD USA. [Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA. [Katz, Nathaniel P.] Analges Solut, Boston, MA 02111 USA. [Adams, Edgar H.] Covance, Conshohocken, PA USA. [Brownstein, John S.; Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA. [Comer, Sandra D.] Columbia Univ, New York, NY USA. [Dart, Richard] Rocky Mt Poison & Drug Ctr, Denver, CO USA. [Dart, Richard] Denver Hlth Author, Denver, CO USA. [Dasgupta, Nabarun] Univ N Carolina, Chapel Hill, NC USA. [Denisco, Richard A.; Jacobs, Petra] NIDA, Bethesda, MD 20892 USA. [Klein, Michael; Rappaport, Bob A.; Burke, Laurie B.] US FDA, Silver Spring, MD USA. [Leiderman, Deborah B.] CNS Drug Consulting, Mclean, VA USA. [Zacny, James P.] Univ Chicago, Chicago, IL 60637 USA. [Ahdieh, Harry] Endo Pharmaceut, Chadds Ford, PA USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Malamut, Richard] AstraZeneca, Wilmington, DE USA. [Michna, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA. [Palmer, Pamela] AcelRx Pharmaceut, Redwood City, CA USA. [Potter, Jennifer S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. [Roland, Carl L.] Pfizer, New Brunswick, NJ USA. [Webster, Lynn R.] Clin Res & Pain Clin, Salt Lake City, UT USA. [Wolf, Kerry] NAMA Recovery, Cedar Pk, TX USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Box 356540, Seattle, WA 98195 USA. EM turkdc@uw.edu RI Potter, Jennifer/C-6720-2008; OI Potter, Jennifer/0000-0002-7250-4422; Lubran, Robert/0000-0003-1235-5207; Yang, Shuman/0000-0002-9638-0890 FU NIDA NIH HHS [K24 DA022288, R01 DA016759, R01 DA031022] NR 77 TC 11 Z9 11 U1 6 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2012 VL 153 IS 10 BP 1997 EP 2008 DI 10.1016/j.pain.2012.05.029 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 009WG UT WOS:000309055500007 PM 22770841 ER PT J AU Mollan, TL Abraham, B Strader, MB Jia, YP Lozier, JN Olson, JS Alayash, AI AF Mollan, Todd L. Abraham, Bindu Strader, Michael Brad Jia, Yiping Lozier, Jay N. Olson, John S. Alayash, Abdu I. TI Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (a2 ss 2Pro100Leu) SO PROTEIN SCIENCE LA English DT Article DE hemoglobin; allostery; kinetics; ligand binding ID INOSITOL HEXAPHOSPHATE; R-STATE; SURFACE HYDROPHOBICITY; SUBUNIT DISSOCIATION; LIGAND-BINDING; RATE CONSTANTS; CO BINDING; AMINO-ACID; G GEORGIA; AUTOXIDATION AB Hemoglobin Brigham (beta Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O2 affinity compared with normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37 degrees C). O2 affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest that the rate constants for ligand binding and release in the high (R) and low (T) affinity quaternary states of Hb Brigham are similar to those of native hemoglobin. However, the Brigham mutation decreases the T to R equilibrium constant (L) which accelerates the switch to the R state during ligand binding to deoxy-Hb, increasing the rate of association by approximately twofold, and decelerates the switch during ligand dissociation from HbO2, decreasing the rate approximately twofold. These kinetic data help explain the high O2 affinity characteristics of Hb Brigham and provide further evidence for the importance of the contribution of Pro100 to intersubunit contacts and stabilization of the T quaternary structure. C1 [Lozier, Jay N.; Alayash, Abdu I.] NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Mollan, Todd L.; Abraham, Bindu; Strader, Michael Brad; Jia, Yiping; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA. RP Alayash, AI (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, 8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU Food and Drug Administration (MODSCI); Oak Ridge Institute for Science Education; National Institutes of Health [HL47020, GM35649]; Welch [C-0612] FX Grant sponsors: Food and Drug Administration (MODSCI) and Oak Ridge Institute for Science Education (to T. L. M.); Grant sponsor: National Institutes of Health; Grant numbers: HL47020 and GM35649 (to J.S.O.); Grant sponsor: Welch; Grant number: C-0612 (to J.S.O.). NR 56 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD OCT PY 2012 VL 21 IS 10 BP 1444 EP 1455 DI 10.1002/pro.2130 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 008ZE UT WOS:000308994300004 PM 22821886 ER PT J AU Saikumar, J Hoffmann, D Kim, TM Gonzalez, VR Zhang, Q Goering, PL Brown, RP Bijol, V Park, PJ Waikar, SS Vaidya, VS AF Saikumar, Janani Hoffmann, Dana Kim, Tae-Min Ramirez Gonzalez, Victoria Zhang, Qin Goering, Peter L. Brown, Ronald P. Bijol, Vanesa Park, Peter J. Waikar, Sushrut S. Vaidya, Vishal S. TI Expression, Circulation, and Excretion Profile of MicroRNA-21,-155, and-18a Following Acute Kidney Injury SO TOXICOLOGICAL SCIENCES LA English DT Article DE MicroRNAs; kidney; biomarker; ischemia/reperfusion injury; nephrotoxicity ID ACUTE-RENAL-FAILURE; COLORECTAL-CANCER; DOWN-REGULATION; CELL CARCINOMA; LUNG-CANCER; MICRORNAS; DISEASE; BIOMARKERS; IDENTIFICATION; SERUM AB MicroRNAs (miRNAs) are endogenous noncoding RNA molecules that are involved in post-transcriptional gene silencing. Using global miRNA expression profiling, we found miR-21, -155, and 18a to be highly upregulated in rat kidneys following tubular injury induced by ischemia/reperfusion (I/R) or gentamicin administration. Mir-21 and -155 also showed decreased expression patterns in blood and urinary supernatants in both models of kidney injury. Furthermore, urinary levels of miR-21 increased 1.2-fold in patients with clinical diagnosis of acute kidney injury (AKI) (n = 22) as compared with healthy volunteers (n = 25) (p < 0.05), and miR-155 decreased 1.5-fold in patients with AKI (p < 0.01). We identified 29 messenger RNA core targets of these 3 miRNAs using the context likelihood of relatedness algorithm and found these predicted gene targets to be highly enriched for genes associated with apoptosis or cell proliferation. Taken together, these results suggest that miRNA-21 and -155 could potentially serve as translational biomarkers for detection of AM and may play a critical role in the pathogenesis of kidney injury and tissue repair process. C1 [Vaidya, Vishal S.] Harvard Univ, Sch Med, Dept Med,Renal Div, Brigham & Womens Hosp,Lab Kidney Toxicol & Regene, Boston, MA 02115 USA. [Kim, Tae-Min; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Ramirez Gonzalez, Victoria] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nefrol & Metab Mineral, Mexico City, DF, Mexico. [Zhang, Qin; Goering, Peter L.; Brown, Ronald P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Bijol, Vanesa] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Vaidya, Vishal S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Vaidya, VS (reprint author), Harvard Univ, Sch Med, Dept Med,Renal Div, Brigham & Womens Hosp,Lab Kidney Toxicol & Regene, Rm 562,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vvaidya@partners.org RI Ramirez, Victoria/I-8087-2012; OI Ramirez, Victoria/0000-0002-2782-1381 FU Outstanding New Environmental Scientist Award through National Institute of Environmental Health Sciences (NIEHS) [ES017543] FX This work was supported by Outstanding New Environmental Scientist Award (ES017543) to V.S.V. through the National Institute of Environmental Health Sciences (NIEHS). NR 66 TC 68 Z9 77 U1 4 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2012 VL 129 IS 2 BP 256 EP 267 DI 10.1093/toxsci/kfs210 PG 12 WC Toxicology SC Toxicology GA 009PM UT WOS:000309037700003 PM 22705808 ER PT J AU Andrade, SE Davis, RL Cheetham, TC Cooper, WO Li, DK Amini, T Beaton, SJ Dublin, S Hammad, TA Pawloski, PA Raebel, MA Smith, DH Staffa, JA Toh, S Dashevsky, I Haffenreffer, K Lane, K Platt, R Scott, PE AF Andrade, Susan E. Davis, Robert L. Cheetham, T. Craig Cooper, William O. Li, De-Kun Amini, Thushi Beaton, Sarah J. Dublin, Sascha Hammad, Tarek A. Pawloski, Pamala A. Raebel, Marsha A. Smith, David H. Staffa, Judy A. Toh, Sengwee Dashevsky, Inna Haffenreffer, Katherine Lane, Kimberly Platt, Richard Scott, Pamela E. TI Medication Exposure in Pregnancy Risk Evaluation Program SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Pregnancy; Birth outcomes; Distributed data network ID HEALTH AB To describe a program to study medication safety in pregnancy, the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). MEPREP is a multi-site collaborative research program developed to enable the conduct of studies of medication use and outcomes in pregnancy. Collaborators include the U.S. Food and Drug Administration and researchers at the HMO Research Network, Kaiser Permanente Northern and Southern California, and Vanderbilt University. Datasets have been created at each site linking healthcare data for women delivering an infant between January 1, 2001 and December 31, 2008 and infants born to these women. Standardized data files include maternal and infant characteristics, medication use, and medical care at 11 health plans within 9 states; birth certificate data were obtained from the state departments of public health. MEPREP currently involves more than 20 medication safety researchers and includes data for 1,221,156 children delivered to 933,917 mothers. Current studies include evaluations of the prevalence and patterns of use of specific medications and a validation study of data elements in the administrative and birth certificate data files. MEPREP can support multiple studies by providing information on a large, ethnically and geographically diverse population. This partnership combines clinical and research expertise and data resources to enable the evaluation of outcomes associated with medication use during pregnancy. C1 [Andrade, Susan E.] Meyers Primary Care Inst, Worcester, MA 01605 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Atlanta, GA USA. [Cheetham, T. Craig] Kaiser Permanente So Calif, Downey, CA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Li, De-Kun] Kaiser Permanente No Calif, Oakland, CA USA. [Amini, Thushi; Hammad, Tarek A.; Staffa, Judy A.; Scott, Pamela E.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Beaton, Sarah J.] LCF Res, Albuquerque, NM USA. [Dublin, Sascha] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine; Lane, Kimberly; Platt, Richard] Harvard Univ, Sch Med, Boston, MA USA. [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine; Lane, Kimberly; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Andrade, SE (reprint author), Meyers Primary Care Inst, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU NIA NIH HHS [K23 AG028954, K23 AG028954-03] NR 6 TC 16 Z9 16 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD OCT PY 2012 VL 16 IS 7 BP 1349 EP 1354 DI 10.1007/s10995-011-0902-x PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 006LT UT WOS:000308821400002 PM 22002179 ER PT J AU He, WW Zhou, YT Wamer, WG Boudreau, MD Yin, JJ AF He, Weiwei Zhou, Yu-Ting Wamer, Wayne G. Boudreau, Mary D. Yin, Jun-Jie TI Mechanisms of the pH dependent generation of hydroxyl radicals and oxygen induced by Ag nanoparticles SO BIOMATERIALS LA English DT Article DE Ag nanoparticles; Hydroxyl radicals; Oxygen; Nanosafety; ESR; Hydrogen peroxide ID COATED SILVER NANOPARTICLES; ION RELEASE KINETICS; HYDROGEN-PEROXIDE; OXIDATIVE DISSOLUTION; NANOSILVER TOXICITY; NANOCRYSTALLITES; CYTOTOXICITY; REDUCTION; CHEMISTRY; RESONANCE AB Many of the chemical and biological effects of silver nanoparticles (Ag NPs) are attributed to the generation of reactive oxygen species (ROS). ESR spectroscopy was used to provide direct evidence for generating ROS during decomposition of H2O2 assisted by Ag NPs. Hydroxyl radical formation was observed under acidic conditions and was accompanied by dissolution of Ag NPs. In contrast, evolution of O-2 was observed in alkaline solutions containing H2O2 and Ag NPs: however, no net dissolution of Ag NPs was observed due to re-reduction of Ag+ as evidenced by a cyclic reaction. Since H2O2 is a biologically relevant product being continuously generated in cells, these results obtained under conditions mimicking different biological microenvironments may provide insights for finding new biomedical applications for Ag NPs and for risk assessment. (C) 2012 Elsevier Ltd. All rights reserved. C1 [He, Weiwei; Zhou, Yu-Ting; Wamer, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Mat Energy Storage & Convers He, Xuchang 461000, Henan, Peoples R China. [Boudreau, Mary D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Zhou, Yuting/I-9125-2012; Yin, Jun Jie /E-5619-2014 FU FY11 FDA Nanotechnology CORES Program; Maryland NanoCenter; Maryland NanoCenter, NispLab; NSF as a MRSEC Shared Experimental Facility FX This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program. We thank Dr. John H. Callahan (CFSAN/FDA) for valuable suggestions and comments on this manuscript. We acknowledge the support of the Maryland NanoCenter and its NispLab. The NispLab is supported in part by the NSF as a MRSEC Shared Experimental Facility. NR 49 TC 76 Z9 78 U1 4 U2 96 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2012 VL 33 IS 30 BP 7547 EP 7555 DI 10.1016/j.biomaterials.2012.06.076 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 002HZ UT WOS:000308524000024 PM 22809647 ER PT J AU Morris, SM Petibone, DM Lin, WJ Chen, JJ Vitiello, B Witt, KL Mattison, DR AF Morris, Suzanne M. Petibone, Dayton M. Lin, Wei-Jiun Chen, James J. Vitiello, Benedetto Witt, Kristine L. Mattison, Donald R. TI The genetic toxicity of methylphenidate: a review of the current literature SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE methylphenidate; ADHD; chromosome damage; mutation ID ATTENTION DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; OXIDATIVE DNA-DAMAGE; IN-VIVO; CHROMOSOMAL-ABERRATIONS; RAT-BRAIN; CHILDREN; HYDROCHLORIDE; CANCER; RISK AB Attention deficit/hyperactivity disorder (ADHD), a common children's behavioral disorder, is characterized by inattention, hyperactivity and impulsivity. The disorder is thought to stem from abnormalities in the catecholamine pathway and the symptoms of the disorder have been successfully treated with methylphenidate (MPH) since the FDA approved the drug in the 1950s. MPH underwent the appropriate safety testing as part of the FDA approval process; however, a publication in 2005 that reported significant increases in cytogenetic damage in the lymphocytes of MPH-treated pediatric patients caused concern for patients and their families, the pharmaceutical industry and regulatory agencies. This communication will review the many studies that were subsequently initiated worldwide to address the genetic safety of MPH in both animal models and human subjects. Animal experiments broadened the study protocols used in the 2005 investigation to include a wider dose-range, a longer treatment period and automated scoring of biological endpoints, where possible, to reduce observer bias. The human subject studies replicated the experimental design used in the 2005 study, but increased the treatment periods and the sizes of the study populations. Neither the laboratory animal nor human subject studies found an increase in any of the measures of genetic damage that were evaluated. Taken together, these new studies are consistent with the original safety evaluation of the FDA and do not support the hypothesis that MPH treatment increases the risk of genetic damage in ADHD patients. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Morris, Suzanne M.; Petibone, Dayton M.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lin, Wei-Jiun; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Branch, NIH, Bethesda, MD 20892 USA. [Witt, Kristine L.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Morris, SM (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM suzanne.morris@fda.hhs.gov RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 47 TC 3 Z9 3 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD OCT PY 2012 VL 32 IS 10 BP 756 EP 764 DI 10.1002/jat.2721 PG 9 WC Toxicology SC Toxicology GA 996JU UT WOS:000308082800002 PM 22337063 ER PT J AU Tamta, H Pawar, RS Wamer, WG Grundel, E Krynitsky, AJ Rader, JI AF Tamta, Hemlata Pawar, Rahul S. Wamer, Wayne G. Grundel, Erich Krynitsky, Alexander J. Rader, Jeanne I. TI Comparison of metabolism-mediated effects of pyrrolizidine alkaloids in a HepG2/C3A cell-S9 co-incubation system and quantification of their glutathione conjugates SO XENOBIOTICA LA English DT Article DE Pyrrolizidine alkaloids (PA); metabolism; glutathione conjugates; toxicity ID PERFUSED-RAT-LIVER; VENOOCCLUSIVE DISEASE; IN-VITRO; LIQUID-CHROMATOGRAPHY; MEDICINAL-PLANTS; N-OXIDES; HEPATOTOXICITY; MONOCROTALINE; GENOTOXICITY; DERIVATIVES AB 1. Toxicity of pyrrolizidine alkaloids (PAs) largely depends on their metabolic activation by hepatic enzymes, including cytochrome P450s, to become chemically reactive pyrrolic derivatives. These then spontaneously release the esterifying acids to generate carbonium ions that form covalent adducts with cellular nucleophiles to exhibit toxicity. 2. In our investigation, metabolism-mediated toxicity of monocrotaline, retrorsine, lycopsamine, echimidine (retronecine-type PAs), heliotrine (a heliotridine-type PA) and senkirkine (an otonecine-type PA) was studied using an in vitro co-incubation assay. 3. Human hepatocarcinoma (HepG2/ C3A) cells were incubated with PAs in the presence and absence of rat liver S9 fraction and the toxicity was assessed as lowered mitochondrial activity. 4. Bioactivation potential was measured by incubating PAs with rat liver S9 fraction, NADPH and GSH in a cell free system. Pyrrolic metabolites generated were entrapped as glutathione conjugates (7-GSH-DHP and 7,9-di-GSHDHP) which were quantified using LC-MS-MS analysis. 5. Our results indicated that PAs were metabolized by rat liver S9 fraction into reactive pyrrolic derivatives which were toxic to HepG2/ C3A cells. This approach can be used to determine and compare bioactivation potential and metabolism-mediated toxicity of various PAs. C1 [Tamta, Hemlata; Pawar, Rahul S.; Wamer, Wayne G.; Grundel, Erich; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Tamta, H (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD USA. EM hemlata.tamta@fda.hhs.gov NR 39 TC 15 Z9 16 U1 5 U2 23 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD OCT PY 2012 VL 42 IS 10 BP 1038 EP 1048 DI 10.3109/00498254.2012.679978 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 000TM UT WOS:000308411600010 PM 22519982 ER PT J AU Diack, AB Ritchie, D Bishop, M Pinion, V Brandel, JP Haik, S Tagliavini, F Van Duijn, C Belay, ED Gambetti, P Schonberger, LB Piccardo, P Will, RG Manson, JC AF Diack, Abigail B. Ritchie, Diane Bishop, Matthew Pinion, Victoria Brandel, Jean-Philippe Haik, Stephane Tagliavini, Fabrizio Van Duijn, Cornelia Belay, Ermias D. Gambetti, Pierluigi Schonberger, Lawrence B. Piccardo, Pedro Will, Robert G. Manson, Jean C. TI Constant Transmission Properties of Variant Creutzfeldt-Jakob Disease in 5 Countries SO EMERGING INFECTIOUS DISEASES LA English DT Article ID UNITED-KINGDOM; SCRAPIE; AGENT; MICE; STRAINS; FRANCE; BSE AB Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases. C1 [Diack, Abigail B.; Pinion, Victoria; Manson, Jean C.] Roslin Inst, Easter Bush, Scotland. [Ritchie, Diane; Bishop, Matthew; Will, Robert G.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Brandel, Jean-Philippe; Haik, Stephane] Univ Paris 06, INSERM, Paris, France. [Brandel, Jean-Philippe; Haik, Stephane] CNRS, Paris, France. [Tagliavini, Fabrizio] Fdaz IRCCS Ist Neurol Carlo Besta, Milan, Italy. [Van Duijn, Cornelia] Erasmus Univ, Sch Med, Rotterdam, Netherlands. [Belay, Ermias D.; Schonberger, Lawrence B.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Gambetti, Pierluigi] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Piccardo, Pedro] US FDA, Rockville, MD 20857 USA. RP Manson, JC (reprint author), Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland. EM jean.manson@roslin.ed.ac.uk FU Neuroprion; Department of Health (England) FX This project was funded by Neuroprion and the Department of Health (England). NR 14 TC 6 Z9 6 U1 1 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2012 VL 18 IS 10 BP 1574 EP 1579 DI 10.3201/eid1810.120792 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268LP UT WOS:000328172500003 PM 23017202 ER PT J AU Ragupathy, V Casado, C Jacob, SM Samuel, NM Lopez-Galindez, C AF Ragupathy, Viswanath Casado, Concepcion Jacob, Saramma Mini Samuel, Narasappa Mathew Lopez-Galindez, C. TI Circulation of HIV-1 subtype A within the subtype C HIV-1 epidemic in Tamil Nadu, India SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HIV; subtype; diversity; India; risk group ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHYLOGENETIC ANALYSIS; IDENTIFICATION; SEQUENCES; VARIANTS; CALCUTTA; MUMBAI AB The HIV-1 epidemic in India is caused mainly by subtype C viruses that are transmitted sexually and by injecting drug use. The state of Tamil Nadu in Southern India has an HIV-1 median prevalence of 16.8% among injecting drug users, 6.6% in men who have sex with men, and 4.6% in female sex workers. In the rural district of Namakkal, a prevalence >3% was detected among antenatal women. The goal of this study was to determine the HIV-1 molecular epidemiology in Tamil Nadu. Blood samples were collected from 40 high-risk HIV-seropositive individuals from Chennai and Namakkal. HIV-1 subtype was determined by envelope nucleotide sequencing. Among the samples studied, 85% were subtype C, however, a cluster of subtype A samples (12.5%) and one subtype E recombinant form CRF01_AE (close to the Thailand strains) were detected. The average genetic distance of subtype C samples from Chennai and Namakkal were 9.44?+/-?0.77% and 11.8?+/-?0.7%, respectively indicating an evolved epidemic. This pilot study confirmed that subtype C was predominant in these regions but an outbreak of subtype A was detected in Namakkal. These results stress the importance of periodic monitoring of circulating HIV-1 subtypes in South India. J. Med. Virol. 84:15071513, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Ragupathy, Viswanath; Jacob, Saramma Mini; Samuel, Narasappa Mathew] Tamil Nadu Dr MGR Med Univ, Dept Expt Med, Madras, Tamil Nadu, India. [Casado, Concepcion; Lopez-Galindez, C.] Inst Salud Carlos III, CNM, Madrid 28220, Spain. RP Ragupathy, V (reprint author), FDA-CBER 8800,Rockville Pike NIH Campus,Bldg 29B,, Bethesda, MD 20892 USA. EM ragupathy.viswanath@fda.hhs.gov; clopez@isciii.es RI Lopez-Galindez, Cecilio/A-3603-2008; Casado, Concepcion/F-3060-2016 OI Lopez-Galindez, Cecilio/0000-0002-2324-9584; FU Fundacion para la Investigacion Prevencion del SIDA en Espana (FIPSE) [36558/06, 36641/07, 36779/08, 360766/09]; Red Tematica Cooperativa de Investigacion en SIDA of the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISss); [SAF 2007-61036]; [2010-17226] FX Work in CNM is supported by grant SAF 2007-61036 and 2010-17226, by Fundacion para la Investigacion Prevencion del SIDA en Espana (FIPSE) grants 36558/06, 36641/07, 36779/08, 360766/09 and in part by the Red Tematica Cooperativa de Investigacion en SIDA (Red de grupos 173) of the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISss). NR 20 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD OCT PY 2012 VL 84 IS 10 BP 1507 EP 1513 DI 10.1002/jmv.23383 PG 7 WC Virology SC Virology GA 996QF UT WOS:000308106500001 PM 22930495 ER PT J AU Wagner, RD Johnson, SJ AF Wagner, R. Doug Johnson, Shemedia J. TI Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans (vol 19, pg 58, 2012) SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Correction C1 [Wagner, R. Doug; Johnson, Shemedia J.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP 29 PY 2012 VL 19 AR 84 DI 10.1186/1423-0127-19-84 PG 1 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 026JV UT WOS:000310273700001 ER PT J AU Kee, CL Lai, CS Ge, XW Low, MY Ciolino, LA AF Kee, Chee Leong Lai, Chian Sing Ge, Xiaowei Low, Min Yong Ciolino, Laura A. TI Partial conversion of methanol to formaldehyde in the gas chromatography injection port and reactivity with amines SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE GC-MS; Methanol; Injection port; Variable inlet temperature; Oxazolidine; Amines ID MASS-SPECTROMETRY; TOXICOLOGICAL DETECTION; DESIGNER DRUG; LEGAL HIGHS; WEIGHT-LOSS; IDENTIFICATION; METABOLISM; URINE; SIBUTRAMINE; EPHEDRINE AB The partial conversion of methanol (MeOH) to formaldehyde (HCHO) in the gas chromatograph (GC) injection port was studied. The presence of formaldehyde in the injection port can result in reaction with injected analytes, especially primary and secondary amines. A systematic study of this problem was undertaken using norephedrine and ephedrine as probe analytes, and experiments involving varying inlet temperature, comparisons among solvents and solvent mixtures, isotopic labeling, and formaldehyde spiking. These experiments showed a direct correlation between inlet temperature and formation of the amine-formaldehyde condensation products. The mass spectra of the norephedrine and ephedrine condensation products were consistent with addition of the methylene group derived from formaldehyde across the amine and alcohol moieties to form the corresponding oxazolidine-ring compounds. Results for the imine condensation product of didesmethylsibutramine formed in the injection port are also presented. (C) 2012 Elsevier B.V. All rights reserved. C1 [Kee, Chee Leong; Lai, Chian Sing; Ge, Xiaowei; Low, Min Yong] Hlth Sci Author, Pharmaceut Lab, Appl Sci Grp, Singapore 169078, Singapore. [Ciolino, Laura A.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Kee, CL (reprint author), Hlth Sci Author, Pharmaceut Lab, Appl Sci Grp, 11 Outram Rd, Singapore 169078, Singapore. EM Kee_Chee_Leong@hsa.gov.sg NR 38 TC 3 Z9 3 U1 3 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 28 PY 2012 VL 1257 BP 158 EP 170 DI 10.1016/j.chroma.2012.08.021 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 010ID UT WOS:000309087200019 PM 22907044 ER PT J AU Arcidiacono, JA Blair, JW Benton, KA AF Arcidiacono, Judith A. Blair, Joan W. Benton, Kimberly A. TI US Food and Drug Administration international collaborations for cellular therapy product regulation SO STEM CELL RESEARCH & THERAPY LA English DT Review AB Cellular therapy products are an emerging medical product class undergoing rapid scientific and clinical innovation worldwide. These products pose unique regulatory challenges both for countries with existing regulatory frameworks and for countries where regulatory frameworks for cellular therapy products are under development. The United States Food and Drug Administration (US FDA) has a history of productive working relationships with international regulatory authorities, and seeks to extend this to the cellular therapy field. The US FDA and its global regulatory counterparts are engaged in collaborations focused on the convergence of scientific and regulatory approaches, and the education of scientists, clinicians, regulators, and the public at large on the development of cellular therapies. C1 [Arcidiacono, Judith A.; Benton, Kimberly A.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Blair, Joan W.] US FDA, Immediate Off Ctr Director, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Arcidiacono, JA (reprint author), US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM Judith.Arcidiacono@FDA.HHS.GOV NR 1 TC 9 Z9 9 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD SEP 28 PY 2012 VL 3 AR 38 DI 10.1186/scrt129 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 012SB UT WOS:000309255700002 PM 23021082 ER PT J AU Kanungo, J Cuevas, E Guo, XQ Lopez, AG Ramirez-Lee, MA Trickler, W Paule, MG Ali, SF AF Kanungo, Jyotshna Cuevas, Elvis Guo, Xiaoqing Lopez, Aida G. Ramirez-Lee, Manuel A. Trickler, William Paule, Merle G. Ali, Syed F. TI Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish SO NEUROSCIENCE LETTERS LA English DT Article DE Zebrafish; Gene expression; Endocrine disruption; Nicotine; Estradiol; Aromatase ID SALMON SALMO-SALAR; DANIO-RERIO; AROMATASE-ACTIVITY; GENE-EXPRESSION; TELEOST FISH; ESTROGEN-RECEPTORS; DENTATE GYRUS; CYP19 GENES; BRAIN; CHEMICALS AB Nicotine, a drug of abuse, has been reported to have many adverse effects on the developing nervous system. In rodents, chronic nicotine exposure inhibits estrogen-mediated neuroprotection against cerebral ischemia in females suggesting that nicotine could disrupt endocrine targets. Zebrafish have been used as a model system for examining mechanisms underlying nicotinic effects on neuronal development. Here, using zebrafish embryos, we demonstrate that nicotine alters the expression of the validated endocrine disruption (ED) biomarkers, vitellogenin (vtg 1 and vtg 2) and cytochrome p450 aromatase (cyp19a1a and cyp19a1b) at the transcriptional level. Increased expression of three of these molecular markers (vtg 1, vtg 2 and cyp19a1b) in response to 17 beta-estradiol (E2) was more pronounced in 48 hpf (hours post-fertilization) embryos than in the 24 hpf embryos. While 24 hpf embryos were non-responsive in this regard to 25 mu M nicotine, a similar exposure of the 48 hpf embryos for 24h significantly down-regulated the expression of all four ED biomarker genes indicating that nicotine's anti-estrogenic effects are detectable in the 48 hpf zebrafish embryos. These results provide direct molecular evidence that nicotine is an endocrine disruptor in zebrafish. Published by Elsevier Ireland Ltd. C1 [Kanungo, Jyotshna; Cuevas, Elvis; Guo, Xiaoqing; Lopez, Aida G.; Ramirez-Lee, Manuel A.; Trickler, William; Paule, Merle G.; Ali, Syed F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA). We thank Melanie Dumas for zebrafish breeding. NR 42 TC 13 Z9 13 U1 4 U2 28 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 27 PY 2012 VL 526 IS 2 BP 133 EP 137 DI 10.1016/j.neulet.2012.08.027 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 013NW UT WOS:000309313100011 PM 22922325 ER PT J AU He, Y Wang, YG Struble, EB Zhang, P Chowdhury, S Reed, JL Kennedy, M Scott, DE Fisher, RW AF He, Yong Wang, Yonggang Struble, Evi B. Zhang, Pei Chowdhury, Soma Reed, Jennifer L. Kennedy, Michael Scott, Dorothy E. Fisher, Robert W. TI Epitope mapping by random peptide phage display reveals essential residues for vaccinia extracellular enveloped virion spread SO VIROLOGY JOURNAL LA English DT Article DE Orthopoxviruses; Monoclonal antibody; B-cell epitope; Immunogen; Vaccinia; Phage display library ID PROTECTS NONHUMAN-PRIMATES; SMALLPOX DNA VACCINE; TO-CELL SPREAD; VIRUS ENVELOPE; IN-VITRO; MONOCLONAL-ANTIBODIES; LETHAL MONKEYPOX; IMMUNE GLOBULIN; INFECTED-CELLS; NAIVE ADULTS AB Background: A33 is a type II integral membrane protein expressed on the extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33-directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers protection against lethal poxvirus challenge in animal models. Homologs of A33 are highly conserved among members of the Orthopoxvirus genus and are potential candidates for inclusion in vaccines or assays targeting extracellular enveloped virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has been shown to target a conformation-dependent epitope. Interestingly, while it recognizes VACV A33 as well as the corresponding variola homolog, it does not bind to the monkeypox homolog. In this study, we utilized a random phage display library to investigate the epitope recognized by MAb-1G10 that is critical for facilitating cell-to-cell spread of the vaccinia virus. Results: By screening with linear or conformational random phage libraries, we found that phages binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond formed between two cysteine residues required for MAb-1G10 binding. Although the phage motif contained no linear sequences homologous to VACV A33, structure modeling and analysis suggested that residue D115 is important to form the minimal epitope core. A panel of point mutants expressing the ectodomain of A33 protein was generated and analyzed by either binding assays such as ELISA and immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated comet inhibition in cell culture. Conclusions: These results confirm L118 as a component of the MAb-1G10 binding epitope, and further identify D115 as an essential residue. By defining the minimum conformational structure, as well as the conformational arrangement of a short peptide sequence recognized by MAb-1G10, these results introduce the possibility of designing small molecule mimetics that may interfere with the function of A33 in vivo. This information will also be useful for designing improved assays to evaluate the potency of monoclonal and polyclonal products that target A33 or A33-modulated EV dissemination. C1 [He, Yong; Wang, Yonggang; Struble, Evi B.; Zhang, Pei; Chowdhury, Soma; Reed, Jennifer L.; Kennedy, Michael; Scott, Dorothy E.; Fisher, Robert W.] US FDA, Lab Plasma Derivat, Div Hematol,FDA CBER OBRR DH LPD, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Fisher, RW (reprint author), US FDA, Lab Plasma Derivat, Div Hematol,FDA CBER OBRR DH LPD, Off Blood Res & Review,Ctr Biol Evaluat & Res, HFM 345,1401 Rockville Pike, Rockville, MD 20852 USA. EM Robert.Fisher@fda.hhs.gov FU FDA CBER; NIH/NIAID [HHSN266200400036C]; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200900041C]; U.S. Department of Energy; U.S. Food and Drug Administration FX The authors would like to thank Jay Hooper and Joseph Golden for thoughtful discussions and reagents, Ana Damjanovic for help with energy minimization of the in silico model peptide, and Bernard Moss for the VACV-IHDJ strain. This study was supported by FDA CBER operating funds. VBRC was funded by NIH/NIAID contract number HHSN266200400036C, and ViPR has been wholly funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272200900041C. This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through and interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The findings and conclusions in this manuscript have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 56 TC 6 Z9 6 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD SEP 24 PY 2012 VL 9 AR 217 DI 10.1186/1743-422X-9-217 PG 11 WC Virology SC Virology GA 037SC UT WOS:000311125800001 PM 23006741 ER PT J AU Selvapandiyan, A Kumar, P Salisbury, JL Wang, CC Nakhasi, HL AF Selvapandiyan, Angamuthu Kumar, Praveen Salisbury, Jeffrey L. Wang, Ching C. Nakhasi, Hira L. TI Role of Centrins 2 and 3 in Organelle Segregation and Cytokinesis in Trypanosoma brucei SO PLOS ONE LA English DT Article ID BASAL-BODY DUPLICATION; NUCLEOTIDE EXCISION-REPAIR; CELL-CYCLE PROGRESSION; FLAGELLUM ATTACHMENT; RNA INTERFERENCE; PROCYCLIC-FORM; YEAST CENTRIN; PROTEIN; GENE; EXPRESSION AB Centrins are calcium binding proteins involved in cell division in eukaryotes. Previously, we have shown that depletion of centrin1 in Trypanosoma brucei (T. brucei) displayed arrested organelle segregation resulting in loss of cytokinesis. In this study we analyzed the role of T. brucei centrin2 (TbCen2) and T. brucei 3 (TbCen3) in the early events of T. brucei procyclic cell cycle. Both the immunofluorescence assay and electron microscopy showed that TbCen2 and 3-deficient cells were enlarged in size with duplicated basal bodies, multinuclei and new flagella that are detached along the length of the cell body. In both TbCen2 and TbCen3 depleted cells segregation of the organelles i.e. basal bodies, kinetoplast and nucleus was disrupted. Further analysis of the cells with defective organelle segregation identified three different sub configurations of organelle mis-segregations (Type 1-3). In addition, in majority of the TbCen2 depleted cells and in nearly half of the TbCen3 depleted cells, the kinetoplasts were enlarged and undivided. The abnormal segregations ultimately led to aborted cytokinesis and hence affected growth in these cells. Therefore, both centrin2 and 3 are involved in organelle segregation similar to centrin1 as was previously observed. In addition, we identified their role in kinetoplast division which may be also linked to overall mis-segregation. C1 [Selvapandiyan, Angamuthu; Nakhasi, Hira L.] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. [Selvapandiyan, Angamuthu] Okhla Ind Estate, Infect Dis, Inst Mol Med, New Delhi, India. [Kumar, Praveen; Wang, Ching C.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA. [Salisbury, Jeffrey L.] Mayo Clin, Dept Biochem & Mol Biol, Coll Med, Rochester, MN USA. RP Selvapandiyan, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. EM selvapandiyan@immindia.org FU Department of Biotechnology, Government of India [BT/PR12883/AGR/36/618/2009] FX Part of the study was supported by a grant from Department of Biotechnology, Government of India (Grant # BT/PR12883/AGR/36/618/2009) to A. S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 51 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 21 PY 2012 VL 7 IS 9 AR e45288 DI 10.1371/journal.pone.0045288 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 014RG UT WOS:000309392800036 PM 23028908 ER PT J AU Chi, X Zhi, L Gelderman, MP Vostal, JG AF Chi, Xuan Zhi, Li Gelderman, Monique P. Vostal, Jaroslav G. TI Host Platelets and, in Part, Neutrophils Mediate Lung Accumulation of Transfused UVB-Irradiated Human Platelets in a Mouse Model of Acute Lung Injury SO PLOS ONE LA English DT Article ID ULTRAVIOLET-A LIGHT; RED-BLOOD-CELLS; PHOTOCHEMICAL INACTIVATION; PATHOGEN INACTIVATION; AMOTOSALEN HCL; IN-VITRO; MICE; RECEPTORS; ANTIBODIES; AGGREGATION AB We previously reported that ultraviolet light B (UVB)-treated human platelets (hPLTs) can cause acute lung injury (ALI) in a two-event SCID mouse model in which the predisposing event was Lipopolysaccharide (LPS) injection and the second event was infusion of UVB-treated hPLTs. To delineate contributions of host mouse platelets (mPLTs) and neutrophils in the pathogenesis of ALI in this mouse model, we depleted mPLTs or neutrophils and measured hPLT accumulation in the lung. We also assessed lung injury by protein content in bronchoalveolar lavage fluid (BALF). LPS injection followed by infusion of UVB-treated hPLTs resulted in sequestration of both mPLTs and hPLTs in the lungs of SCID mice, although the numbers of neutrophils in the lung were not significantly different from the control group. Depletion of mouse neutrophils caused only a mild reduction in UVB-hPLTs accumulation in the lungs and a mild reduction in protein content in BALF. In comparison, depletion of mPLTs almost completely abolished hPLTs accumulation in the lung and significantly reduced protein content in BALF. UVB-treated hPLTs bound to host mPLTs, but did not bind to neutrophils in the lung. Aspirin treatment of hPLTs in vitro abolished hPLT accumulation in the lung and protected mice from lung injury. Our data indicate that host mPLTs accumulated in the lungs in response to an inflammatory challenge and subsequently mediated the attachment of transfused UVB-hPLTs. Neutrophils also recruited a small percentage of platelets to the lung. These findings may help develop therapeutic strategies for ALI which could potentially result from transfusion of UV illuminated platelets. C1 [Chi, Xuan; Zhi, Li; Gelderman, Monique P.; Vostal, Jaroslav G.] US FDA, Lab Cellular Hematol, Div Hematol, OBRR,Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, OBRR,Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Jaroslav.Vostal@fda.hhs.gov FU Food and Drug Administration (FDA) FX This work was supported by the Food and Drug Administration's (FDA) Critical Path Research Funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 7 Z9 7 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 19 PY 2012 VL 7 IS 9 AR e44829 DI 10.1371/journal.pone.0044829 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 014PP UT WOS:000309388400042 PM 23028636 ER PT J AU Conklin, SD Shockey, N Kubachka, K Howard, KD Carson, MC AF Conklin, Sean D. Shockey, Nohora Kubachka, Kevin Howard, Karyn D. Carson, Mary C. TI Development of an Ion Chromatography-Inductively Coupled Plasma-Mass Spectrometry Method To Determine Inorganic Arsenic in Liver from Chickens Treated with Roxarsone SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Arsenic speciation; roxarsone; IC-ICP-MS; chicken liver ID POULTRY LITTER; LIQUID-CHROMATOGRAPHY; ARSANILIC ACID; SPECIATION; METABOLITES; MANURE; FATE; MEAT AB Roxarsone, (4-hydroxy-3-nitrophenyl)arsonic acid, is an arsenic-containing compound that has been approved as a feed additive for poultry and swine since the 1940s; however, little information is available regarding residual arsenic species present in edible tissues. We developed a novel method for the extraction and quantification of arsenic species in chicken liver. A strongly basic solution solubilized the liver, and ultrafiltration removed macromolecules and particulate material. Ion chromatography separated the species [arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, (4-hydroxy-3-aminophenyl)arsonic acid, (4-hydroxy-3-acetaminophenyl)arsonic acid, and roxarsone] in the extracts, which were then detected by inductively coupled plasma-mass spectrometry. The extraction oxidized most arsenite to arsenate. For fortification concentrations at 2 mu g kg(-1) and above, recoveries ranged from 70 to 120%, with relative standard deviations from 7 to 34%. We detected roxarsone, its 3-amino and 3-acetamido metabolites, inorganic arsenic, and additional unknown arsenic species in livers from roxarsone-treated chickens. Both the originating laboratory and a second laboratory validated the method. C1 [Howard, Karyn D.; Carson, Mary C.] US FDA, Res Off, CVM, Laurel, MD 20708 USA. [Conklin, Sean D.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Shockey, Nohora; Kubachka, Kevin] US FDA, Forens Chem Ctr, Off Regulatory Affairs, Cincinnati, OH 45237 USA. RP Carson, MC (reprint author), US FDA, Res Off, CVM, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mary.carson@fda.hhs.gov NR 25 TC 16 Z9 17 U1 4 U2 64 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 19 PY 2012 VL 60 IS 37 BP 9394 EP 9404 DI 10.1021/jf302366a PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 006PE UT WOS:000308830500003 PM 22897610 ER PT J AU Gucinski, AC Boyne, MT AF Gucinski, Ashley C. Boyne, Michael T., II TI Evaluation of Intact Mass Spectrometry for the Quantitative Analysis of Protein Therapeutics SO ANALYTICAL CHEMISTRY LA English DT Article ID TOP-DOWN PROTEOMICS; ABSOLUTE QUANTIFICATION; POSTTRANSLATIONAL MODIFICATIONS; ISOTOPE TAGS; PHARMACEUTICALS AB Implementation of modern analytical techniques, such as intact mass spectrometry, may allow for more detailed quality assessments of protein therapeutics. The complexity of the protein therapeutic manufacturing process as well as the sensitivity of these drugs to different storage conditions can lead to the presence of several undesired products, including truncations, degradation products, byproducts, and differentially modified protein variants that are difficult to detect by peptide mapping. Intact mass spectrometry can be used to identify the intact protein composition, inclusive of post-translational modifications (PTMs) but can also generate a chemical fingerprint of the different protein species present in a given sample. In this work, we systematically evaluated the influence of multiple charge states, multiple isotopes per charge state, and operating resolution on the suitability of intact mass spectrometry for quantitative analysis using insulin and somatotropin as model systems. Standard curves could be generated using absolute intensity data or using the relative ratio between the analyte and internal standard. These methods demonstrate the validity of quantitative intact mass spectrometry for the analysis of protein therapeutic drugs, thus providing a foundation for future comparative methods. C1 [Gucinski, Ashley C.; Boyne, Michael T., II] US FDA, Div Pharmaceut Res, Off Testing & Res, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Boyne, MT (reprint author), US FDA, Div Pharmaceut Res, Off Testing & Res, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM Michael.boyne@fda.hhs.gov FU Research Participation Program at the Center for Drug Evaluation and Research; FDA Center for Drug Evaluation and Research Critical Path Program; Regulatory Science and Review Enhancement (RSR) Program FX This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Engineering and the U.S. Food and Drug Administration for A.C.G. This work was funded by the FDA Center for Drug Evaluation and Research Critical Path Program and the Regulatory Science and Review Enhancement (RSR) Program. NR 18 TC 17 Z9 17 U1 1 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 18 PY 2012 VL 84 IS 18 BP 8045 EP 8051 DI 10.1021/ac301949j PG 7 WC Chemistry, Analytical SC Chemistry GA 006OY UT WOS:000308829700067 PM 22916992 ER PT J AU Lawrence, J Bai, S Hung, HMJ O'Neill, R AF Lawrence, John Bai, Steve Hung, H. M. James O'Neill, Robert TI Regional Treatment Effects in Studies of Cardiorenal Drugs A Summary of Recent Clinical Trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter C1 [Lawrence, John] US FDA, Silver Spring, MD 20993 USA. RP Lawrence, J (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM John.Lawrence@fda.hhs.gov NR 6 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 18 PY 2012 VL 60 IS 12 BP 1117 EP 1118 DI 10.1016/j.jacc.2012.04.051 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 005JG UT WOS:000308746100015 PM 22939557 ER PT J AU Lu, XJ Gibbs, JS Hickman, HD David, A Dolan, BP Jin, YT Kranz, DM Bennink, JR Yewdell, JW Varma, R AF Lu, Xiuju Gibbs, James S. Hickman, Heather D. David, Alexandre Dolan, Brian P. Jin, Yetao Kranz, David M. Bennink, Jack R. Yewdell, Jonathan W. Varma, Rajat TI Endogenous viral antigen processing generates peptide-specific MHC class I cell-surface clusters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MHC class; clustering; CD8 T cell recognition; dual-color TIRF imaging; antigen processing/presentation; intracellular trafficking ID ENDOPLASMIC-RETICULUM; INTRACELLULAR-LOCALIZATION; MEMBRANE-GLYCOPROTEINS; CYTOPLASMIC DOMAIN; MOLECULES; COMPLEX; KINETICS; GOLGI; TRANSPORT; PROTEINS AB Sensitivity is essential in CD8+ T-cell killing of virus-infected cells and tumor cells. Although the affinity of the T-cell receptor (TCR) for antigen is relatively low, the avidity of T cell-antigen-presenting cell interactions is greatly enhanced by increasing the valence of the interaction. It is known that TCRs cluster into protein islands after engaging their cognate antigen (peptides bound to MHC molecules). Here, we show that mouse K-b class I molecules segregate into preformed, long-lasting (hours) clusters on the antigen-presenting cell surface based on their bound viral peptide. Peptide-specific K-b clustering occurs when source antigens are expressed by vaccinia or vesicular stomatitis virus, either as proteasome-liberated precursors or free intracellular peptides. By contrast, K-b-peptide complexes generated by incubating cells with synthetic peptides are extensively intermingled on the cell surface. Peptide-specific complex sorting is first detected in the Golgi complex, and compromised by removing the K-b cytoplasmic tail. Peptide-specific clustering is associated with increased T-cell sensitivity: on a per-complex basis, endogenous SIINFEKL activates T cells more efficiently than synthetic SIINFEKL, and wild-type K-b presents endogenous SIINFEKL more efficiently than tailless K-b. We propose that endogenous processing generates peptide-specific clusters of class I molecules to maximize the sensitivity and speed of T-cell immunosurveillance. C1 [Lu, Xiuju; Gibbs, James S.; Hickman, Heather D.; David, Alexandre; Dolan, Brian P.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Jin, Yetao] US FDA, Chem Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Kranz, David M.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. [Varma, Rajat] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI Varma, Rajat/I-1209-2012; Jin, Yong-Su/L-4530-2013; OI Varma, Rajat/0000-0001-5131-0402; David, Alexandre/0000-0003-3365-1339 FU National Institute of Allergy and Infectious Diseases Division of Intramural Research and National Institutes of Health [P01 CA097296] FX We thank Phil Holler for original engineering of the 2C-m67 TCR, and Natalie Bowerman for development of the single-chain form of the TCR for detection. This work was generously supported by the National Institute of Allergy and Infectious Diseases Division of Intramural Research and National Institutes of Health Grant P01 CA097296 (to D.M.K.). NR 44 TC 24 Z9 24 U1 0 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 18 PY 2012 VL 109 IS 38 BP 15407 EP 15412 DI 10.1073/pnas.1208696109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 012BS UT WOS:000309211000069 PM 22949678 ER PT J AU Zhang, JJ Blumenthal, GM He, K Tang, SH Cortazar, P Sridhara, R AF Zhang, Jenny J. Blumenthal, Gideon M. He, Kun Tang, Shenghui Cortazar, Patricia Sridhara, Rajeshwari TI Overestimation of the Effect Size in Group Sequential Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; CLINICAL-TRIALS; INTERFERON-ALPHA; SUNITINIB; BIAS AB Group sequential designs (GSD), which provide for interim monitoring of efficacy data and allow potential early trial termination while preserving the type I error rate, have become commonplace in oncology clinical trials. Although ethically appealing, GSDs tend to overestimate the true treatment effect size at early interim analyses. Overestimation of the treatment effect may exaggerate the benefit of a drug and provide imprecise information for physicians and their patients about a drug's true effect. The cause and effect of such a phenomenon are generally not well understood by many in clinical trial practice. In this article, we provide a graphical explanation for why the phenomenon of overestimation in GSDs occurs. The potential overestimation of the magnitude of the treatment effect is of particular concern in oncology, in which the more subjective endpoint of progression-free survival has increasingly been adopted as the primary endpoint in pivotal phase III trials. Clin Cancer Res; 18(18); 4872-6. (c) 2012 AACR. C1 [Zhang, Jenny J.; He, Kun; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, CDER OTS OB DBV, Silver Spring, MD 20993 USA. [Blumenthal, Gideon M.; Cortazar, Patricia] US FDA, CDER OND OHOP DOP 1, Silver Spring, MD 20993 USA. RP Zhang, JJ (reprint author), US FDA, CDER OTS OB DBV, Silver Spring, MD 20993 USA. EM jenny.zhang@fda.hhs.gov NR 16 TC 8 Z9 8 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2012 VL 18 IS 18 BP 4872 EP 4876 DI 10.1158/1078-0432.CCR-11-3118 PG 5 WC Oncology SC Oncology GA 022NI UT WOS:000309965700003 PM 22753584 ER PT J AU Yakes, BJ Prezioso, SM De Grasse, SL AF Yakes, Betsy Jean Prezioso, Samantha M. De Grasse, Stacey L. TI Developing improved immunoassays for paralytic shellfish toxins: The need for multiple, superior antibodies SO TALANTA LA English DT Article DE Surface plasmon resonance; Paralytic shellfish poisoning; Saxitoxin; Lateral flow immuno-chromatography; Immunoassay; Cross-reactivity ID RECEPTOR-BINDING ASSAY; SINGLE-LABORATORY VALIDATION; OPTICAL BIOSENSOR TECHNOLOGY; POISONING TOXINS; LIQUID-CHROMATOGRAPHY; SCREENING METHOD; CELL BIOASSAY; PSP TOXINS; CHANNEL; SPECTROMETRY AB Paralytic shellfish toxins (PSTs) are a risk to humans upon consumption of contaminated seafood. The PST family is comprised of more than twenty congeners, with each form having a different potency. In order to adequately protect consumers yet reduce unnecessary closures of non-contaminated harvesting areas, a rapid method that allows for analysis of sample toxicity is needed. While a number of PST immunoassays exist, the outstanding challenge is linking quantitative response to sample toxicity, as no single antibody reacts to the PST congeners in a manner that correlates with potency. A novel approach, then, is to combine multiple antibodies of varying reactivity to create a screening assay. This research details our investigation of three currently available antibodies for their reactivity profiles determined using a surface plasmon resonance biosensor assay. While our study shows challenges with detection of the R1-hydroxylated PSTs, results indicate that using multiple antibodies may provide more confidence in determining overall toxicity and the toxin profile. A multiplexed approach would not only improve biosensor assays but could also be applied to lateral flow immuno-chromatographic platforms, and such a theoretical device incorporating the three antibodies is presented. These improved assays could reduce the number of animal bioassays and confirmatory analyses (e.g.. LC/MS), thereby improving food safety and economic use of shellfish resources. Published by Elsevier B.V. C1 [Yakes, Betsy Jean; De Grasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Prezioso, Samantha M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr JIFSAN, College Pk, MD 20742 USA. RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 NR 43 TC 7 Z9 7 U1 1 U2 47 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 EI 1873-3573 J9 TALANTA JI Talanta PD SEP 15 PY 2012 VL 99 BP 668 EP 676 DI 10.1016/j.talanta.2012.06.073 PG 9 WC Chemistry, Analytical SC Chemistry GA 020CC UT WOS:000309785300096 PM 22967609 ER PT J AU Yin, ZW Dai, JH Deng, J Sheikh, F Natalia, M Shih, T Lewis-Antes, A Amrute, SB Garrigues, U Doyle, S Donnelly, RP Kotenko, SV Fitzgerald-Bocarsly, P AF Yin, Zhiwei Dai, Jihong Deng, Jing Sheikh, Faruk Natalia, Mahwish Shih, Tiffany Lewis-Antes, Anita Amrute, Sheela B. Garrigues, Ursula Doyle, Sean Donnelly, Raymond P. Kotenko, Sergei V. Fitzgerald-Bocarsly, Patricia TI Type III IFNs Are Produced by and Stimulate Human Plasmacytoid Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; INTERFERON-PRODUCING CELLS; POTENT ANTIVIRAL ACTIVITY; ALPHA PRODUCING CELLS; I INTERFERON; VIRAL-INFECTIONS; GENE-REGULATION; T-CELLS; RECEPTOR; LAMBDA AB Plasmacytoid dendritic cells (pDC) are rare cells found in peripheral blood and lymphoid tissues. pDC are considered to be "professional" type I IFN-producing cells and produce 10- to 100-fold more IFN-alpha than other cell types in response to enveloped viruses or synthetic TLR7 and TLR9 agonists. In this study, purified pDC were found to express high levels of IFN-lambda receptor mRNA, as well as cell-surface IFN-lambda receptor. We have developed intracellular flow cytometry assays using Abs to IFN-lambda 1/3 or -lambda 2 to assess the expression of IFN-lambda proteins by pDC. We observed that a subset of human pDC expresses only intracellular IFN-alpha, whereas another subset produces both IFN-alpha and IFN-lambda after stimulation with virus or the TLR9 agonist, CpG A; the cells that coexpressed IFN-alpha and IFN-lambda were the cells with the highest levels of IFN-alpha expression. Ab cross-linking of CD4 or CD303 molecules on pDC inhibited both HSV-induced IFN-lambda and IFN-alpha production. Like the production of IFN-alpha, the HSV-induced IFN-lambda production in pDC was mediated through TLR9 and independent of virus replication. Exogenous IFN-lambda treatment of pDC resulted in increased virus-induced expression of both IFN-alpha and IFN-lambda. In addition, both exogenous IFN-lambda and -alpha inhibited dexamethasone-induced apoptosis of pDC. We conclude that pDC are major producers of IFN-lambda 1 and -lambda 2 in response to viral stimulation and also express functional receptors for this cytokine. Thus, IFN-lambda can serve as an autocrine signal to strengthen the antiviral response of pDC by increasing IFN-alpha and IFN-lambda production, resulting in prolonged pDC survival. The Journal of Immunology, 2012, 189: 2735-2745. C1 [Yin, Zhiwei; Dai, Jihong; Deng, Jing; Natalia, Mahwish; Shih, Tiffany; Amrute, Sheela B.; Fitzgerald-Bocarsly, Patricia] UMDNJ, New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ 07103 USA. [Yin, Zhiwei; Lewis-Antes, Anita; Kotenko, Sergei V.] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. [Yin, Zhiwei; Deng, Jing; Natalia, Mahwish; Shih, Tiffany; Kotenko, Sergei V.; Fitzgerald-Bocarsly, Patricia] Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Newark, NJ 07103 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Garrigues, Ursula; Doyle, Sean] ZymoGenetics Inc, Seattle, WA 98102 USA. RP Fitzgerald-Bocarsly, P (reprint author), UMDNJ, New Jersey Med Sch, Dept Pathol & Lab Med, 185 S Orange Ave,Room MSB C567, Newark, NJ 07103 USA. EM bocarsly@umdnj.edu FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI026806, AI082994, AI057468, AI076937]; University of Medicine and Dentistry of New Jersey-Graduate School for Biomedical Sciences; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by National Institutes of Health, National Institute of Allergy and Infectious Diseases Contracts AI026806 (to P.F.-B.), AI082994 (subcontracts to P.F.-B. and S. V. K.), AI057468, and AI076937 (to S. V. K.), and a fellowship from the University of Medicine and Dentistry of New Jersey-Graduate School for Biomedical Sciences (to Z.Y.). These experiments also used HIV-1 provided by the AIDS and Cancer Virus Program, Science Applications International Corp.-Frederick, Inc./National Cancer Institute, Frederick, which is supported by the National Cancer Institute, National Institutes of Health (Contract HHSN261200800001E). NR 60 TC 57 Z9 59 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2012 VL 189 IS 6 BP 2735 EP 2745 DI 10.4049/jimmunol.1102038 PG 11 WC Immunology SC Immunology GA 004RK UT WOS:000308698600009 PM 22891284 ER PT J AU Babu, US Sommers, K Harrison, LM Balan, KV AF Babu, Uma S. Sommers, Katelyn Harrison, Lisa M. Balan, Kannan V. TI Effects of fructooligosaccharide-inulin on Salmonella-killing and inflammatory gene expression in chicken macrophages SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Prebiotics; Chicken macrophage cells; Salmonella Enteritidis ID ENTERICA SEROVAR TYPHIMURIUM; CARRIER STATE; CELL-LINE; INFECTION; RESPONSES; ENTERITIDIS; COLONIZATION; EVASION; SUBPOPULATIONS; MANNOBIOSE AB Salmonella Enteritidis (SE) is one of the leading causes of food-borne salmonellosis, and macrophages play an essential role in eliminating this pathogen. Among the interventions to improve Salmonella clearance in chickens are the use of prebiotics and direct fed microbials (DFM) in animal feed as they have immunomodulatory effects. Therefore, we tested the influence of a prebiotic fructooligosaccharide (FOS)-inulin on the ability of the chicken macrophage HD11 cell line to phagocytose and kill SE, and express selected inflammatory cytokines and chemokines in an in vitro model. There were significantly fewer viable intracellular SE in HD11 cells treated with FOS-inulin than the untreated cells. However, SE phagocytosis, nitric oxide expression or production were not influenced by the prebiotic treatment. Among the inflammatory markers tested, IL-1 beta expression was significantly lower in HD11 cells treated with FOS-inulin. These results suggest that FOS-inulin has the ability to modulate the innate immune system as shown by the enhanced killing of SE and decreased inflammasome activation. Published by Elsevier B.V. C1 [Babu, Uma S.; Sommers, Katelyn; Harrison, Lisa M.; Balan, Kannan V.] US FDA, Immunobiol Branch, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, Immunobiol Branch, MOD 1,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Uma.Babu@fda.hhs.gov FU Food and Drug Administration Commissioner's Fellowship Program; Oak Ridge Institute for Science and Education FX This study was supported by the Food and Drug Administration Commissioner's Fellowship Program and the Oak Ridge Institute for Science and Education. NR 35 TC 8 Z9 8 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD SEP 15 PY 2012 VL 149 IS 1-2 BP 92 EP 96 DI 10.1016/j.vetimm.2012.05.003 PG 5 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 006PM UT WOS:000308831300013 PM 22627194 ER PT J AU Banerjee, S Jia, YP Siburt, CJP Abraham, B Wood, F Bonaventura, C Henkens, R Crumbliss, AL Alayash, AI AF Banerjee, Sambuddha Jia, Yiping Siburt, Claire J. Parker Abraham, Bindu Wood, Francine Bonaventura, Celia Henkens, Robert Crumbliss, Alvin L. Alayash, Abdu I. TI Haptoglobin alters oxygenation and oxidation of hemoglobin and decreases propagation of peroxide-induced oxidative reactions SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Haptoglobin; Hemoglobin; Peroxidase; Oxygen; Redox potential; Ferryl hemoglobin ID MASS-SPECTROMETRY; CARBON MONOXIDE; HEME-PROTEINS; ALPHA-CHAINS; MYOGLOBIN; KINETICS; COMPLEX; SPECTROELECTROCHEMISTRY; SULFHEMOGLOBIN; IDENTIFICATION AB We compared oxygenation and anaerobic oxidation reactions of a purified complex of human hemoglobin (Hb) and haptoglobin (Hb-Hp) to those of uncomplexed Hb. Under equilibrium conditions, Hb-Hp exhibited active-site heterogeneity and noncooperative, high-affinity O-2 binding (n(1/2)=0.88, P-1/2=0.33 mm Hg in inorganic phosphate buffer at pH 7 and 25 degrees C). Rapid-reaction kinetics also exhibited active-site heterogeneity, with a slower process of O-2 dissociation and a faster process of CO binding relative to uncomplexed Hb. Deoxygenated Hb-Hp had significantly reduced absorption at the lambda(max) of 430 nm relative to uncomplexed Fib, as occurs for isolated Hb subunits that lack T-state stabilization. Under comparable experimental conditions, the redox potential (E-1/2) of Hb-Hp was found to be +54 mV, showing that it is much more easily oxidized than uncomplexed Fib (E-1/2 =+125 mV). The Nernst plots for Hb-Hp oxidation showed no cooperativity and slopes less than unity indicated active-site heterogeneity. The redox potential of Hb-Hp was unchanged by pH over the range of 6.4-8.3. Exposure of Hb-Hp to excess hydrogen peroxide (H2O2) produced ferryl heme, which was found to be more kinetically inert in the Hb-Hp complex than in uncomplexed Hb. The negative shift in the redox potential of Hb-Hp and its stabilized ferryl state may be central elements in the protection against Fib-induced oxidative damage afforded by formation of the Hb-Hp complex. Published by Elsevier Inc. C1 [Banerjee, Sambuddha; Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke Univ, French Family Sci Ctr, Dept Chem, Durham, NC 27708 USA. [Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, CBER, NIH, Bethesda, MD 20892 USA. [Bonaventura, Celia; Henkens, Robert] Duke Univ, Nicholas Sch Environm, Marine Lab, Beaufort, NC 28516 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, CBER, NIH, Bldg 29,Rm 112, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU CBER's MODSCI Funding; National Science Foundation [CHE 0809466]; Duke University FX This work was supported by CBER's MODSCI Funding (A.I.A.). A.L.C. thanks the National Science Foundation (CHE 0809466) and Duke University for financial support and the Santa Fe Institute for hospitality during the period this manuscript was written. We thank Dr. Jin Baek (CBER/FDA) for technical advice and suggestions for the immunoblot experiments. NR 46 TC 16 Z9 16 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 15 PY 2012 VL 53 IS 6 BP 1317 EP 1326 DI 10.1016/j.freeradbiomed.2012.07.023 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 007QS UT WOS:000308903800011 PM 22841869 ER PT J AU Stultz, BG Park, SY Mortin, MA Kennison, JA Hursh, DA AF Stultz, Brian G. Park, Sung Yeon Mortin, Mark A. Kennison, James A. Hursh, Deborah A. TI Hox proteins coordinate peripodial decapentaplegic expression to direct adult head morphogenesis in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Decapentaplegic; Labial; Deformed; Homothorax; Peripodial epithelium; Adult head ID WING IMAGINAL DISC; VISCERAL MESODERM; DEVELOPMENTAL ANALYSIS; EYE DISC; TRANSCRIPTIONAL ACTIVATION; MIDGUT MORPHOGENESIS; SHAPE DIFFERENCES; GENE; DPP; EXTRADENTICLE AB The Drosophila BMP, decapentaplegic (dpp), controls morphogenesis of the ventral adult head through expression limited to the lateral peripodial epithelium of the eye-antennal disc by a 3.5 kb enhancer in the 5' end of the gene. We recovered a 15 bp deletion mutation within this enhancer that identified a homeotic (Hox) response element that is a direct target of labial and the homeotic cofactors homothorax and extradenticle. Expression of labial and homothorax are required for dpp expression in the peripodial epithelium, while the Hox gene Deformed represses labial in this location, thus limiting its expression and indirectly that of dpp to the lateral side of the disc. The expression of these homeodomain genes is in turn regulated by the dpp pathway, as dpp signalling is required for labial expression but represses homothorax. This Hox-BMP regulatory network is limited to the peripodial epithelium of the eye-antennal disc, yet is crucial to the morphogenesis of the head, which fate maps suggest arises primarily from the disc proper, not the peripodial epithelium. Thus Hox/BMP interactions in the peripodial epithelium of the eye-antennal disc contribute inductively to the shape of the external form of the adult Drosophila head. Published by Elsevier Inc. C1 [Hursh, Deborah A.] US FDA, Cellular & Tissue Therapy Branch, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Stultz, Brian G.; Park, Sung Yeon; Hursh, Deborah A.] US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Mortin, Mark A.; Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Hursh, DA (reprint author), US FDA, Cellular & Tissue Therapy Branch, Ctr Biol Evaluat & Res, HFM 740 Bldg,29B Rm,1E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM deborah.hursh@fda.hhs.gov FU Intramural Research Program of the National Institutes of Health, NICHD; Center for Biologics Evaluation and Research, FDA; Center for Biologics Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration FX We thank Kathleen McGinnis for expert technical assistance and Aditya Sen for assistance in the construction of dpps-hc-GFP. We thank Bill McGinnis, Kevin Moses, Henry Sun, Deborah Andrew, Jessica Treisman, Gerard Campbell, Adi Salzberg, and the Bloomington Stock Center for stocks, Richard Mann for plasmids and antibody, and the Developmental Studies Hybridoma Bank for antibodies. We express our gratitude to Thom Kaufman and his lab for generously acceding to multiple requests for stocks and antibodies during this work. Brent McCright, Tehyen Chu, Malcolm Moos, and two anonymous reviewers made valuable comments that greatly improved the manuscript. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NICHD, and by the Center for Biologics Evaluation and Research, FDA. S.Y. Park was supported by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 76 TC 4 Z9 4 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2012 VL 369 IS 2 BP 362 EP 376 DI 10.1016/j.ydbio.2012.07.012 PG 15 WC Developmental Biology SC Developmental Biology GA 996TG UT WOS:000308117100020 PM 22824425 ER PT J AU Warfel, JM Beren, J Merkel, TJ AF Warfel, Jason M. Beren, Joel Merkel, Tod J. TI Airborne Transmission of Bordetella pertussis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EFFICACY; VACCINE AB Pertussis is a contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Although it is widely believed that transmission of B. pertussis occurs via aerosolized respiratory droplets, no controlled study has ever documented airborne transmission of pertussis. We set out to determine if airborne transmission occurs between infected and naive animals, utilizing the baboon model of pertussis. Our results showed that 100% of exposed naive animals became infected even when physical contact was prevented, demonstrating that pertussis transmission occurs via aerosolized respiratory droplets. C1 [Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bethesda, MD 20892 USA. [Beren, Joel] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Rm 419,29 Lincoln Dr, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov FU Food and Drug Administration; National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [Y1-AI-1727-01]; NIH National Center For Research Resources [P40RR012317, 5R24RR016556-10] FX This work was supported by the Food and Drug Administration and National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) through interagency agreement #Y1-AI-1727-01. Baboons were obtained from the Oklahoma Baboon Research Resource. The Oklahoma Baboon Research Resource was supported by grant numbers P40RR012317 and 5R24RR016556-10 from the NIH National Center For Research Resources. NR 15 TC 37 Z9 39 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2012 VL 206 IS 6 BP 902 EP 906 DI 10.1093/infdis/jis443 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 998JI UT WOS:000308233500015 PM 22807521 ER PT J AU Xu, XM Costa, AP Khan, MA Burgess, DJ AF Xu, Xiaoming Costa, Antonio P. Khan, Mansoor A. Burgess, Diane J. TI Application of quality by design to formulation and processing of protein liposomes SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Liposome; QbD; Superoxide dismutase; Freeze-and-thaw unilamellar vesicles (FAT-ULV); Encapsulation efficiency; D-optimal design; Design space; Risk analysis ID PROCESS ANALYTICAL TECHNOLOGY; SUPEROXIDE-DISMUTASE; DRUG-DELIVERY; UNILAMELLAR LIPOSOMES; ENCAPSULATION; CHOLESTEROL; PERSPECTIVE; BILAYER AB Quality by design (QbD) principles were explored in the current study to gain a comprehensive understanding of the preparation of superoxide dismutase (SOD) containing liposome formulations prepared using freeze-and-thaw unilamellar vesicles (FAT-ULV). Risk analysis and D-optimal statistical design were performed. Of all the variables investigated, lipid concentration, cholesterol mol%, main lipid type and protein concentration were identified as critical parameters affecting SOD encapsulation efficiency, while the main lipid type was the only factor influencing liposome particle size. Using a model generated by the D-optimal design, a series of three-dimensional response spaces for SOD liposome encapsulation efficiency were established. The maximum values observed in the response surfaces indirectly confirmed the existence of a specific SOD-lipid interaction, which took place in the lipid bilayer under the following optimal conditions: (1) appropriate membrane thickness and curvature (DPPC liposomes); and (2) optimal "pocket size" generated by cholesterol content. With respect to storage stability, the prepared SOD liposomes remained stable for at least 6 months in aqueous dispersion state at 4 degrees C. This research highlights the level of understanding that can be accomplished through a well-designed study based on the philosophy of QbD. (C) 2012 Elsevier B.V. All rights reserved. C1 [Xu, Xiaoming; Costa, Antonio P.; Burgess, Diane J.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Khan, Mansoor A.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut Sci, 69 N Eagleville Rd,U3092, Storrs, CT 06269 USA. EM xiaoming.xu@fda.hhs.gov; antonio.costa@uconn.edu; mansoor.khan@fda.hhs.gov; d.burgess@uconn.edu OI Xu, Xiaoming/0000-0003-1672-0830 FU FDA [HHSF223201011124P] FX This research was supported by FDA critical path funding (HHSF223201011124P). NR 28 TC 18 Z9 18 U1 2 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD SEP 15 PY 2012 VL 434 IS 1-2 BP 349 EP 359 DI 10.1016/j.ijpharm.2012.06.002 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975AQ UT WOS:000306479400041 PM 22683453 ER PT J AU Wang, Y He, T Han, J Wang, J Foley, SL Yang, GY Wan, SX Shen, JZ Wu, CM AF Wang, Yang He, Tao Han, Jing Wang, Juan Foley, Steven L. Yang, Guangyou Wan, Shuangxiu Shen, Jianzhong Wu, Congming TI Prevalence of ESBLs and PMQR genes in fecal Escherichia coli isolated from the non-human primates in six zoos in China SO VETERINARY MICROBIOLOGY LA English DT Article DE Zoos; Primates; E. coli; Antimicrobial resistance; ESBLs; PMQR ID MEDIATED QUINOLONE RESISTANCE; SPECTRUM BETA-LACTAMASES; ANTIMICROBIAL RESISTANCE; KLEBSIELLA-PNEUMONIAE; MULTIPLEX PCR; ENTEROBACTERIACEAE; ANIMALS; DISSEMINATION; EPIDEMIOLOGY; THREAT AB The aim of this study is to characterize the prevalence of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli from captive non-human primates. A total of 206 E. coli isolates were collected from primates in six zoos in China in 2009 and their susceptibility to 10 antimicrobials were tested by broth microdilution. The susceptibility patterns of E. coli strains varied greatly among different zoos reflecting different backgrounds of antimicrobial usage. Both the ESBL-encoding genes and the PMQR genes were detected by PCR. Of the 206 strains, 65 (32%) were confirmed as phenotypic ESBL producers with bla(CTX-M) (27%, bla(CTX-M-15), n = 31, bla(CTX-M-3), n = 23 and bla(CTX-M-14), n = 2) mainly mediating the ESBL phenotype. qnrS1 (18%, n = 36) and oqxAB (15%, n = 31) were the predominant PMQR genes and the prevalence of PMQR genes was much higher among phenotypic ESBL producers than that among phenotypic non-ESBL producers from any zoo. Notably, the PMQR genes qnrS1 and oqxAB and beta-lactamase genes bla(TEM-1), and bla(CTX-M-3) were found together in 23 E. coli isolates in two zoos in Shanghai. PFGE analysis of these 23 isolates demonstrated nearly identical PFGE profiles (similarity matrix >97%) indicating this specific E. coli genotype was prevalent in these two zoos. To the best of our knowledge, this is the first report of these four genes coexisting in an E. coli genotype and the first report of antimicrobial resistance profiles in E. coli isolated from primates in China. (C) 2012 Elsevier B.V. All rights reserved. C1 [Wang, Yang; He, Tao; Shen, Jianzhong; Wu, Congming] China Agr Univ, Coll Vet Med, Key Lab Dev & Evaluat Chem & Herbal Drugs Anim Us, Beijing 100193, Peoples R China. [Han, Jing; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Juan] China Inst Vet Drugs Control, Beijing 100084, Peoples R China. [Yang, Guangyou] Sichuan Agr Univ, Coll Vet Med, Dept Vet Prevent Med, Yaan 625014, Peoples R China. [Wan, Shuangxiu] Heze Univ, Dept Pharmaceut Engn, Heze 274000, Peoples R China. RP Wu, CM (reprint author), China Agr Univ, Coll Vet Med, Key Lab Dev & Evaluat Chem & Herbal Drugs Anim Us, Beijing 100193, Peoples R China. EM wucm@cau.edu.cn FU National Natural Science Foundation of China [U1031004]; Program for Chang Jiang Scholars and the Innovative Research Team at the University of China [IRT0866]; Oak Ridge Institute for Science and Education FX This work was supported by Grants both from the National Natural Science Foundation of China (No. U1031004) and from the Program for Chang Jiang Scholars and the Innovative Research Team at the University of China (No. IRT0866). Dr. Jing Han is supported through the Oak Ridge Institute for Science and Education. NR 22 TC 17 Z9 19 U1 2 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 EI 1873-2542 J9 VET MICROBIOL JI Vet. Microbiol. PD SEP 14 PY 2012 VL 159 IS 1-2 BP 53 EP 59 DI 10.1016/j.vetmic.2012.03.009 PG 7 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 996UY UT WOS:000308121500007 PM 22487457 ER PT J AU Berkower, I Ni, Y Virnik, K AF Berkower, I. Ni, Y. Virnik, K. TI Live, attenuated rubella vectors expressing HIV and SIV vaccine antigens SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Berkower, I.; Ni, Y.; Virnik, K.] US FDA, Ctr Biol, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 13 PY 2012 VL 9 SU 2 AR P1 DI 10.1186/1742-4690-9-S2-P1 PG 1 WC Virology SC Virology GA 015UO UT WOS:000309472100074 ER PT J AU LeBlanc, PM Hollinger, KA Klontz, KC AF LeBlanc, Pamela M. Hollinger, Katherine A. Klontz, Karl C. TI Tattoo Ink-Related Infections - Awareness, Diagnosis, Reporting, and Prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [LeBlanc, Pamela M.; Hollinger, Katherine A.; Klontz, Karl C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP LeBlanc, PM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 5 TC 17 Z9 17 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 13 PY 2012 VL 367 IS 11 BP 985 EP 987 DI 10.1056/NEJMp1206063 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 003ZE UT WOS:000308649100003 PM 22913662 ER PT J AU Kennedy, BS Bedard, B Younge, M Tuttle, D Ammerman, E Ricci, J Doniger, AS Escuyer, VE Mitchell, K Noble-Wang, JA O'Connell, HA Lanier, WA Katz, LM Betts, RF Mercurio, MG Scott, GA Lewis, MA Goldgeier, MH AF Kennedy, Byron S. Bedard, Brenden Younge, Mary Tuttle, Deborah Ammerman, Eric Ricci, John Doniger, Andrew S. Escuyer, Vincent E. Mitchell, Kara Noble-Wang, Judith A. O'Connell, Heather A. Lanier, William A. Katz, Linda M. Betts, Robert F. Mercurio, Mary Gail Scott, Glynis A. Lewis, Matthew A. Goldgeier, Mark H. TI Outbreak of Mycobacterium chelonae Infection Associated with Tattoo Ink SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; ATYPICAL MYCOBACTERIA; SKIN INFECTION; ABSCESSUS; IDENTIFICATION; PATTERNS; VECTOR AB Background In January 2012, on the basis of an initial report from a dermatologist, we began to investigate an outbreak of tattoo-associated Mycobacterium chelonae skin and soft-tissue infections in Rochester, New York. The main goals were to identify the extent, cause, and form of transmission of the outbreak and to prevent further cases of infection. Methods We analyzed data from structured interviews with the patients, histopathological testing of skin-biopsy specimens, acid-fast bacilli smears, and microbial cultures and antimicrobial susceptibility testing. We also performed DNA sequencing, pulsed-field gel electrophoresis (PFGE), cultures of the ink and ingredients used in the preparation and packaging of the ink, assessment of source water and faucets at tattoo parlors, and investigation of the ink manufacturer. Results Between October and December 2011, a persistent, raised, erythematous rash in the tattoo area developed in 19 persons (13 men and 6 women) within 3 weeks after they received a tattoo from a single artist who used premixed gray ink; the highest occurrence of tattooing and rash onset was in November (accounting for 15 and 12 patients, respectively). The average age of the patients was 35 years (range, 18 to 48). Skin-biopsy specimens, obtained from 17 patients, showed abnormalities in all 17, with M. chelonae isolated from 14 and confirmed by means of DNA sequencing. PFGE analysis showed indistinguishable patterns in 11 clinical isolates and one of three unopened bottles of premixed ink. Eighteen of the 19 patients were treated with appropriate antibiotics, and their condition improved. Conclusions The premixed ink was the common source of infection in this outbreak. These findings led to a recall by the manufacturer. C1 [Kennedy, Byron S.; Bedard, Brenden; Younge, Mary; Tuttle, Deborah; Ammerman, Eric; Ricci, John; Doniger, Andrew S.] Monroe Cty Dept Publ Hlth, Rochester, NY 14620 USA. [Escuyer, Vincent E.; Mitchell, Kara] New York State Dept Hlth, Albany, NY USA. [Betts, Robert F.; Mercurio, Mary Gail; Scott, Glynis A.; Lewis, Matthew A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Goldgeier, Mark H.] Clinton Crossings Dermatol, Rochester, NY USA. [Noble-Wang, Judith A.; O'Connell, Heather A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lanier, William A.; Katz, Linda M.] US FDA, College Pk, MD USA. RP Kennedy, BS (reprint author), Monroe Cty Dept Publ Hlth, 111 Westfall Rd,Rm 950, Rochester, NY 14620 USA. EM bkennedy@monroecounty.gov NR 25 TC 38 Z9 38 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 13 PY 2012 VL 367 IS 11 BP 1020 EP 1024 DI 10.1056/NEJMoa1205114 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 003ZE UT WOS:000308649100008 PM 22913660 ER PT J AU Deng, L Langley, RJ Wang, Q Topalian, SL Mariuzza, RA AF Deng, Lu Langley, Ries J. Wang, Qian Topalian, Suzanne L. Mariuzza, Roy A. TI Structural insights into the editing of germ-line-encoded interactions between T-cell receptor and MHC class II by V alpha CDR3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; THYMIC SELECTION; AMINO-ACIDS; RECOGNITION; PEPTIDE; SELF; CORECEPTORS; MOLECULES; FEATURES; DOCKING AB The conserved diagonal docking mode observed in structures of T-cell receptors (TCRs) bound to peptide-MHC ligands is believed to reflect coevolution of TCR and MHC genes. This coevolution is supported by the conservation of certain interactions between the germ-line-encoded complementarity-determining region (CDR) 1 and CDR2 loops of TCR and MHC. However, the rules governing these interactions are not straightforward, even when the same variable (V) region recognizes the same MHC molecule. Here, we demonstrate that the somatically generated CDR3 loops can markedly alter evolutionarily selected contacts between TCR and MHC ("CDR3 editing"). To understand CDR3 editing at the atomic level, we determined the structure of a human melanoma-specific TCR (G4) bound to the MHC class II molecule HLA-DR1 and an epitope from mutant triose phosphate isomerase (mutTPI). A comparison of the G4-mutTPI-DR1 complex with a complex involving a TCR (E8) that uses the same V alpha region to recognize the same mutTPI-DR1 ligand as G4 revealed that CDR1 alpha adopts markedly different conformations in the two TCRs, resulting in an almost entirely different set of contacts with MHC. Based on the structures of unbound G4 and E8, the distinct conformations of CDR1 alpha in these TCRs are not induced by binding to mutTPI-DR1 but result from differences in the length and sequence of CDR3 alpha that are transmitted to CDR1 alpha. The editing of germ-line-encoded TCR-MHC interactions by CDR3 demonstrates that these interactions possess sufficient intrinsic flexibility to accommodate large structural variations in CDR3 and, consequently, in the TCR-binding site. C1 [Topalian, Suzanne L.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. [Topalian, Suzanne L.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Deng, Lu; Langley, Ries J.; Wang, Qian; Mariuzza, Roy A.] Univ Maryland, WM Keck Lab Struct Biol, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. [Deng, Lu] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Wang, Qian; Mariuzza, Roy A.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Topalian, SL (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. EM stopali1@jhmi.edu; rmariuzz@umd.edu FU National Institutes of Health [AI073654, AI036900]; Department of Energy Offices of Biological and Environmental Research and Basic Energy Sciences; National Center for Research Resources of the National Institutes of Health; Irvington Institute Fellowship Program of the Cancer Research Institute FX We thank H. Robinson (Brookhaven National Synchrotron Light Source) for X-ray data collection. This work was supported by National Institutes of Health Grants AI073654 (to R. A. M. and S. L. T.) and AI036900 (to R. A. M.). Beamline X29 is supported by the Department of Energy Offices of Biological and Environmental Research and Basic Energy Sciences and by the National Center for Research Resources of the National Institutes of Health. L. D. was supported by the Irvington Institute Fellowship Program of the Cancer Research Institute. NR 36 TC 19 Z9 19 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 11 PY 2012 VL 109 IS 37 BP 14960 EP 14965 DI 10.1073/pnas.1207186109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 012AP UT WOS:000309208000054 PM 22930819 ER PT J AU Bisgin, H Liu, ZC Kelly, R Fang, H Xu, XW Tong, WD AF Bisgin, Halil Liu, Zhichao Kelly, Reagan Fang, Hong Xu, Xiaowei Tong, Weida TI Investigating drug repositioning opportunities in FDA drug labels through topic modeling SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 9th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society (MCBIOS) - Dealing with the Omics Data Deluge CY FEB 17-18, 2012 CL Oxford, MS SP MidSouth Computat Biol & Bioinformat Soc (MCBIOS) ID DISEASE AB Background: Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U. S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach. Method: A probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels. Results: Given a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In addition, we identified two therapeutic groups of drugs (Musculo-skeletal system and Anti-infective for systemic use) where over 80% of the drugs have a potential replacement with high significance. Conclusion: Topic modeling can be a powerful tool for the identification of repositioning opportunities by examining the adverse event terms in FDA approved drug labels. The proposed framework not only suggests drugs that can be repurposed, but also provides insight into the safety of repositioned drugs. C1 [Bisgin, Halil; Xu, Xiaowei] Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA. [Liu, Zhichao; Xu, Xiaowei; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kelly, Reagan; Fang, Hong] US FDA, ICF Int Co, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Xu, XW (reprint author), Univ Arkansas, Dept Informat Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM xwxu@ualr.edu; weida.tong@fda.hhs.gov RI Liu, Zhichao/C-4035-2011 NR 34 TC 18 Z9 18 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD SEP 11 PY 2012 VL 13 SU 15 AR S6 DI 10.1186/1471-2105-13-S15-S6 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 014EU UT WOS:000309358800006 PM 23046522 ER PT J AU Hong, HX Xu, L Liu, J Jones, WD Su, ZQ Ning, BT Perkins, R Ge, WG Miclaus, K Zhang, L Park, K Green, B Han, T Fang, H Lambert, CG Vega, SC Lin, SM Jafari, N Czika, W Wolfinger, RD Goodsaid, F Tong, WD Shi, LM AF Hong, Huixiao Xu, Lei Liu, Jie Jones, Wendell D. Su, Zhenqiang Ning, Baitang Perkins, Roger Ge, Weigong Miclaus, Kelci Zhang, Li Park, Kyunghee Green, Bridgett Han, Tao Fang, Hong Lambert, Christophe G. Vega, Silvia C. Lin, Simon M. Jafari, Nadereh Czika, Wendy Wolfinger, Russell D. Goodsaid, Federico Tong, Weida Shi, Leming TI Technical Reproducibility of Genotyping SNP Arrays Used in Genome-Wide Association Studies SO PLOS ONE LA English DT Article ID SUSCEPTIBILITY LOCI; GENETIC VARIANT; HAPMAP SAMPLES; BREAST-CANCER; RISK LOCI; DISEASE; ALGORITHM; GWAS; INCONSISTENCIES; REPLICATION AB During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. Moreover, discordance observed in results between independent GWAS indicates the potential for Type I and II errors. High reliability of genotyping technology is needed to have confidence in using SNP data and interpreting GWAS results. Therefore, reproducibility of two widely genotyping technology platforms from Affymetrix and Illumina was assessed by analyzing four technical replicates from each of the six individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within a laboratory for the sample platform, 98.59% to 99.86% across laboratories for the same platform, and 98.80% across genotyping platforms was observed. Moreover, arrays with low quality data were detected when comparing genotyping data from technical replicates, but they could not be detected according to venders' quality control (QC) suggestions. Our results demonstrated the technical reliability of currently available genotyping platforms but also indicated the importance of incorporating some technical replicates for genotyping QC in order to improve the reliability of GWAS results. The impact of discordant genotypes on association analysis results was simulated and could explain, at least in part, the irreproducibility of some GWAS findings when the effect size (i.e. the odds ratio) and the minor allele frequencies are low. C1 [Hong, Huixiao; Xu, Lei; Perkins, Roger; Ge, Weigong; Tong, Weida; Shi, Leming] US FDA, Ctr Excellence Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Liu, Jie; Ning, Baitang; Green, Bridgett] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Jones, Wendell D.] Express Anal Inc, Durham, NC USA. [Su, Zhenqiang; Fang, Hong] US FDA, ICF Int Co, Natl Ctr Toxicol Res, Jefferson, AR USA. [Miclaus, Kelci; Czika, Wendy; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC USA. [Zhang, Li; Goodsaid, Federico] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Park, Kyunghee] Samsung Adv Inst Technol, Yongin Si Gyeonggi Do, South Korea. [Han, Tao] US FDA, Ctr Excellence Genom, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Lambert, Christophe G.] Golden Helix Inc, Bozeman, MT USA. [Vega, Silvia C.] Microsoft Corp, Rosetta BioSoftware, Hlth Solut Grp, Seattle, WA USA. [Lin, Simon M.] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. [Jafari, Nadereh] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA. RP Hong, HX (reprint author), US FDA, Ctr Excellence Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov; leming.shi@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 FU Expression Analysis, Inc; Golden Helix Inc FX The authors have read the journal's policy and have the following conflicts: Wendell Jones is a paid employee of Expression Analysis, Inc; Wendy Czika, Kelci Miclaus and Russell D. Wolfinger are employed by SAS Institute Inc; Zhenqiang Su and Hong Fang are employed by ICF International Company at NCTR/FDA (National Center for Toxicological Research/Food and Drug Administration); Christophe G. Lambert is a paid employee of Golden Helix Inc; Silvia Vega has been employed by Rosetta BioSoftware and for Microsoft Corp. in the last five years but at present has no competing interests. All other authors have no competing interests. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. NR 42 TC 16 Z9 17 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 7 PY 2012 VL 7 IS 9 AR e44483 DI 10.1371/journal.pone.0044483 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 001LK UT WOS:000308462000024 PM 22970228 ER PT J AU Yang, LC Rieves, D Ganley, C AF Yang, Lucie Rieves, Dwaine Ganley, Charles TI Brain Amyloid Imaging - FDA Approval of Florbetapir F18 Injection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Yang, Lucie; Rieves, Dwaine] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Med Imaging Prod, Silver Spring, MD USA. [Ganley, Charles] Food & Drug Adm, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. [Ganley, Charles] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Drug Evaluat 4, Silver Spring, MD USA. RP Yang, LC (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Div Med Imaging Prod, Silver Spring, MD USA. NR 5 TC 66 Z9 67 U1 1 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 6 PY 2012 VL 367 IS 10 BP 885 EP 887 DI 10.1056/NEJMp1208061 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 999VO UT WOS:000308343300002 PM 22931256 ER PT J AU Thompson, KL Zhang, J Stewart, S Rosenzweig, BA Shea, K Mans, D Colatsky, T AF Thompson, Karol L. Zhang, Jun Stewart, Sharron Rosenzweig, Barry A. Shea, Katherine Mans, Daniel Colatsky, Thomas TI Comparison of urinary and serum levels of di-22:6-bis(monoacylglycerol)phosphate as noninvasive biomarkers of phospholipidosis in rats SO TOXICOLOGY LETTERS LA English DT Article DE Phospholipidosis; Phospholipids; Bis(monoacylglycerol)phosphate; Serum biomarkers; Acetaminophen ID DRUG-INDUCED PHOSPHOLIPIDOSIS; AMIODARONE-TREATED RATS; LYSOSOMAL STORAGE; GENE-EXPRESSION; LIPIDOSIS; MONITOR; LIVER AB Phospholipidosis (PLD), an abnormal accumulation of phospholipids within tissues, is observed during the preclinical testing of many pharmaceutical drugs. Diagnosis of PLD is currently based on morphologic criteria. An understanding of the clinical incidence of PLD and its possible relationship to adverse drug reactions has been hampered by the absence of noninvasive biomarkers for PLD. The uncommon phospholipid di-docosahexaenoyl bis(monoacylglycerol) phosphate (di-22:6-BMP) has been proposed as a potential urinary biomarker for PLD, but data on the utility of serum di-22:6-BMP measurements in diagnosing PLD is more limited. In this report, we compared the performance of serum and urinary di-22:6-BMP as biomarkers for PLD in rats treated with the PLD-inducing drugs amiodarone and 4,4'-diethylaminoethoxyhexestrol dihydrochloride or the hepatotoxicant acetaminophen (APAP). Serum levels of di-22:6-BMP showed a higher correlation to a generalized PLD incidence score than did levels in urine, but were unexpectedly elevated in rats with marked levels of APAP-induced liver necrosis. When samples were filtered based on serum ALT or liver histopathology thresholds, the diagnostic accuracy of serum di-22:6-BMP for PLD improved to the high level observed for urinary di-22:6-BMP without sample exclusion. These data help define the potential context-of-use of serum di-22:6-BMP as a non-clinical biomarker of PLD. Published by Elsevier Ireland Ltd. C1 [Thompson, Karol L.; Zhang, Jun; Stewart, Sharron; Rosenzweig, Barry A.; Shea, Katherine; Colatsky, Thomas] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mans, Daniel] US FDA, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. RP Thompson, KL (reprint author), White Oak Fed Res Ctr, WO64-2036,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Karol.thompson@fda.hhs.gov; Jun.zhang@fda.hhs.gov; Sharron.stewart@fda.hhs.gov; Barry.rosenzweig@fda.hhs.gov; Katherine.shea@fda.hhs.gov; Daniel.mans@fda.hhs.gov; Thomas.colatsky@fda.hhs.gov FU FDA Critical Path Initiative; CDER Regulatory Science Research program FX This project received intramural funding from the FDA Critical Path Initiative and the CDER Regulatory Science Research program. NR 29 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 3 PY 2012 VL 213 IS 2 BP 285 EP 291 DI 10.1016/j.toxlet.2012.07.013 PG 7 WC Toxicology SC Toxicology GA 005SH UT WOS:000308769700019 PM 22828012 ER PT J AU Rogers, HL Bhattaram, A Zineh, I Gobburu, J Mathis, M Laughren, TP Pacanowski, M AF Rogers, Hobart L. Bhattaram, Atul Zineh, Issam Gobburu, Jogarao Mathis, Mitchell Laughren, Thomas P. Pacanowski, Michael TI CYP2D6 Genotype Information to Guide Pimozide Treatment in Adult and Pediatric Patients: Basis for the US Food and Drug Administration's New Dosing Recommendations SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TOURETTES DISORDER; DOUBLE-BLIND; PHARMACOKINETICS; CLARITHROMYCIN; HALOPERIDOL; RISPERIDONE; PLACEBO AB Objective: The occurrence of pimozide-induced arrhythmias is concentration dependent. Hence, it is important for prescribers to consider causes of increased pimozide exposure. This article summarizes the US Food and Drug Administration's (FDA's) review of drug interaction and pharmacogenomic studies and discusses pharmacokinetic simulations we performed to develop new cytochrome P450 2D6 (CYP2D6) genotype guided dosing recommendations for pimozide. Method: Pharmacokinetic parameters by CYP2D6 genotype were derived from a published single-dose pharmacogenomic study of pimozide. We simulated what pimozide exposures would result from a multiple-dose scenario in different CYP2D6 genotype groups: extensive, intermediate, and poor metabolizers. The maximum dose for poor metabolizers was defined as the dose that would not exceed pimozide concentrations following 10 mg daily in extensive metabolizers and intermediate metabolizers (the current maximum dose in an unselected population). Results: Dose-ranging analyses revealed that 4 mg daily in CYP2D6 poor metabolizers was the maximum dose that would not result in plasma concentrations in excess of those observed in extensive metabolizer and intermediate metabolizer patients receiving 10 mg daily. CYP2D6 genotyping is now consequently recommended in the pimozide product label before exceeding 4 mg of pimozide daily in adults or 0.05 mg/kg/d in children. Previously, dose adjustment was recommended every 3 days to achieve the desired clinical response for all patients. The label was modified to subsequently reflect that pimozide doses should not be increased earlier than 14 days in patients who are known CYP2D6 poor metabolizers. Conclusions: Given the risk of increased pimozide concentrations and longer time to steady state in CYP2D6 poor metabolizers, the FDA has revised the pimozide label to provide clinicians with clearer dosing, titration, and genotype testing recommendations, The new information is intended to enhance therapeutic individualization of pimozide in pediatric and adult patients. J Clin Psychiatry 2012;73(9):1187-1190 (c) Copyright 2012 Physicians Postgraduate Press, Inc. C1 [Rogers, Hobart L.; Bhattaram, Atul; Zineh, Issam; Gobburu, Jogarao; Mathis, Mitchell; Laughren, Thomas P.; Pacanowski, Michael] US FDA, Silver Spring, MD 20993 USA. RP Rogers, HL (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 51,Room 31, Silver Spring, MD 20993 USA. EM Hobart.Rogers@fda.hhs.gov NR 19 TC 21 Z9 21 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2012 VL 73 IS 9 BP 1187 EP 1190 DI 10.4088/JCP.11m07572 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 090SN UT WOS:000315000400002 PM 23059146 ER PT J AU Merenda, C AF Merenda, Christine TI Racial/Ethnic Composition of Study Participants in FDA-Approved Oncology New Molecular Entities, 2006-2008 SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE subpopulations; drugs ID CLINICAL-TRIALS; UNITED-STATES; CANCER AB The US Food and Drug Administration (FDA) has an ongoing interest in identifying the race/ethnicity of clinical trial participants to ensure they are representative of the people who will use the products once they are approved, and differences in response to medical products have already been observed in racial/ethnic subgroups of the US population. As a result, we reviewed the racial/ethnic composition of study participants in clinical trials of FDA-approved oncology products. Oncology products were chosen because of the disparate incidence and impact of cancer in racial/ethnic communities. New Drug and Biologics Licensing Application databases were searched for new molecular entity (NME) approvals for oncologic treatment from January 1, 2006, through December 31, 2008. We then reviewed NME applications for the pivotal Phase II and III trials used for approval decisions. We then compared the racial/ethnic composition results from the recent trials with those conducted earlier. We also assessed FDA-approved labeling to determine the extent to which race-based findings were included. US participants averaged 20.3% (range, 11%-97%) of the total participants in the studies reviewed. A comparison of the racial/ethnic composition showed the participation of whites and blacks or African Americans have decreased, while that of Latinos, Asians, and Native Hawaiians/Pacific Islanders has increased. The results suggest better attention to compliance with collection and reporting, as the percentage of US study participants whose race and/or ethnicity could not be determined decreased from 31% to <1%. With respect to product labeling, the current study found 6 (60%) included race-based findings. C1 US FDA, Publ Hlth Serv, Silver Spring, MD 20993 USA. RP Merenda, C (reprint author), US FDA, Publ Hlth Serv, 10903 New Hampshire Ave,Bldg 32,Rm 5334, Silver Spring, MD 20993 USA. EM christine.merenda@fda.hhs.gov NR 15 TC 0 Z9 0 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP-OCT PY 2012 VL 104 IS 9-10 BP 430 EP 435 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 068VL UT WOS:000313394200004 PM 23342816 ER PT J AU Donovan, SM Schneeman, B Gibson, GR Sanders, ME AF Donovan, Sharon M. Schneeman, Barbara Gibson, Glenn R. Sanders, Mary Ellen TI Establishing and Evaluating Health Claims for Probiotics SO ADVANCES IN NUTRITION LA English DT Editorial Material ID US C1 [Donovan, Sharon M.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Schneeman, Barbara] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Gibson, Glenn R.] Univ Reading, Dept Food & Nutr Sci, Reading, Berks, England. [Sanders, Mary Ellen] Dairy & Food Culture Technol, Centennial, CO USA. RP Donovan, SM (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. EM sdonovan@illinois.edu OI Donovan, Sharon/0000-0002-9785-4189 NR 8 TC 5 Z9 6 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 EI 2156-5376 J9 ADV NUTR JI Adv. Nutr. PD SEP PY 2012 VL 3 IS 5 BP 723 EP 725 DI 10.3945/an.112.002592 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 066LL UT WOS:000313222200011 PM 22983853 ER PT J AU Rahman, Z Zidan, AS Samy, R Sayeed, VA Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Samy, Raghu Sayeed, Vilayat A. Khan, Mansoor A. TI Improvement of Physicochemical Properties of an Antiepileptic Drug by Salt Engineering SO AAPS PHARMSCITECH LA English DT Article DE cyclamic acid; dissolution; lamotrigine; salt; solubility ID NMR; LAMOTRIGINE; SOLUBILITY; STATE; SOLIDS; ACID; COCRYSTALS; CYCLAMATE; COMPLEXES; SPECTRA AB The focus of the present investigation was to evaluate the feasibility of using cyclamic salt of lamotrigine in order to improve its solubility and intrinsic dissolution rate (IDR). The salt was prepared by solution crystallization method and characterized chemically by fourier transform infrared spectroscopy (FTIR), proton (H-1) and carbon (C-13) nuclear magnetic resonance (liquid and solid, NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), physicochemically for solubility, IDR, solution and solid-state stability, and polymorphism by solution recrystallization and slurry conversion studies. The FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt formation. The salt formation increased lamotrigine solubility by 19-fold and IDR by 4.9-fold in water. The solution and solid-state stability were similar to parent molecule and were resistant to polymorphic transformation. In conclusion, cyclamic salt of lamotrigine provides another potential avenue for the pharmaceutical development of lamotrigine with improved physicochemical properties especially for pediatric population. It is also possible that appropriate dosage forms can be formulated with much lower drug amount and better safety profile than existing products. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; Samy, Raghu; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. RP Khan, MA (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012; OI Rahman, Ziyaur/0000-0002-0402-825X FU FDA-NIH [IAG Y1-HD-0052-01]; Oak Ridge Institute for Science and Education (ORISE) FX Part of the work was supported by FDA-NIH grant# IAG Y1-HD-0052-01. The authors would like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting the postdoctoral research. The authors also extend this acknowledgment to Dr. Robert T. Berendt (FDA). NR 39 TC 12 Z9 12 U1 0 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD SEP PY 2012 VL 13 IS 3 BP 793 EP 801 DI 10.1208/s12249-012-9800-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 070IH UT WOS:000313499300006 PM 22588676 ER PT J AU Gao, ZM Westenberger, B AF Gao, Zongming Westenberger, Benjamin TI Dissolution Testing of Acetaminophen Suspension Using Dialysis Adapter in Flow-Through Apparatus: A Technical Note SO AAPS PHARMSCITECH LA English DT Article DE dialysis adapter; dissolution testing; flow through method; USP 4 C1 [Gao, Zongming; Westenberger, Benjamin] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM Zongming.Gao@fda.hhs.gov NR 5 TC 5 Z9 6 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD SEP PY 2012 VL 13 IS 3 BP 944 EP 948 DI 10.1208/s12249-012-9820-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 070IH UT WOS:000313499300024 PM 22743842 ER PT J AU DeSilva, B Garofolo, F Rocci, M Martinez, S Dumont, I Landry, F Dicaire, C Szekely-Klepser, G Weiner, R Arnold, M Bansal, S Bateman, K Bauer, R Booth, B Davis, S Dudal, S Gouty, D Grundy, J Haidar, S Hayes, R Jemal, M Kaur, S Kelley, M Knutsson, M Le Blaye, O Lee, J Lowes, S Ma, M Mitsuoka, T Neto, JT Nicholson, R Ormsby, E Sailstad, J Stevenson, L Tang, D Welink, J Viswanathan, CT Wang, LX Woolf, E Yang, E AF DeSilva, Binodh Garofolo, Fabio Rocci, Mario Martinez, Suzanne Dumont, Isabelle Landry, France Dicaire, Catherine Szekely-Klepser, Gabriella Weiner, Russell Arnold, Mark Bansal, Surendra Bateman, Kevin Bauer, Ronald Booth, Brian Davis, Scott Dudal, Sherri Gouty, Dominique Grundy, John Haidar, Sam Hayes, Roger Jemal, Mohammed Kaur, Surinder Kelley, Marian Knutsson, Magnus Le Blaye, Olivier Lee, Jean Lowes, Steve Ma, Mark Mitsuoka, Toshinari Tavares Neto, Joao Nicholson, Robert Ormsby, Eric Sailstad, Jeffrey Stevenson, Lauren Tang, Daniel Welink, Jan Viswanathan, C. T. Wang, Laixin Woolf, Eric Yang, Eric TI 2012 White Paper on Recent Issues in Bioanalysis and Alignment of Multiple Guidelines SO BIOANALYSIS LA English DT Article ID GLOBAL CRO COUNCIL; VALIDATION GROUP WORKSHOP; LIGAND-BINDING ASSAYS; REGULATED BIOANALYSIS; INTERNAL STANDARD; RECOMMENDATIONS; STABILITY; HARMONIZATION; CALIBRATION; GUIDANCE AB Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agencies participated in the 6th Workshop on Recent Issues in Bioanalysis (WRIB). Like the previous sessions, this event was in the format of a practical, focused, highly interactive and informative workshop aiming for high-quality, improved regulatory compliance and scientific excellence. Numerous 'hot' topics in bioanalysis of both small and large molecules were shared and discussed, leading to consensus and recommendations among panelists and attendees representing the bioanalytical community. The major outcome of this year's workshop was the noticeable alignment of multiple bioanalytical guidance/guidelines from different regulatory agencies. This represents a concrete step forward in the global harmonization of bioanalytical activities. The present 2012 White Paper acts as a practical and useful reference document that provides key information and solutions on several topics and issues in the constantly evolving world of bioanalysis. C1 [Garofolo, Fabio; Martinez, Suzanne; Dumont, Isabelle; Landry, France; Dicaire, Catherine] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [DeSilva, Binodh; Arnold, Mark; Jemal, Mohammed] Bristol Myers Squibb Co, Princeton, NJ USA. [Rocci, Mario] ICON Dev Solut, Whitesboro, NY USA. [Szekely-Klepser, Gabriella] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. [Weiner, Russell] Merck Res Labs, Rahway, NJ USA. [Bansal, Surendra] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Bateman, Kevin; Woolf, Eric] Merck Res Labs, West Point, PA USA. [Bauer, Ronald] AGES, Vienna, Austria. [Booth, Brian; Haidar, Sam] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Davis, Scott; Nicholson, Robert] PPD, Richmond, VA USA. [Dudal, Sherri] Novartis Pharma Inc, Basel, Switzerland. [Gouty, Dominique] Intertek, San Diego, CA USA. [Grundy, John] Isis Pharmaceut Inc, Carlsbad, CA USA. [Hayes, Roger] MPI Res, Mattawan, MI USA. [Kaur, Surinder] Genentech Inc, San Francisco, CA 94080 USA. [Kelley, Marian] MKelley Consulting LLC, W Chester, PA USA. [Knutsson, Magnus] Ferring Pharmaceut, Copenhagen, Denmark. [Le Blaye, Olivier] ANSM, St Denis, France. [Lee, Jean; Ma, Mark] Amgen Inc, Thousand Oaks, CA 91320 USA. [Lowes, Steve] Advion BioServ Inc, Ithaca, NY USA. [Mitsuoka, Toshinari] Japan MHLW NIHS, Tokyo, Japan. [Tavares Neto, Joao] ANVISA, Brasilia, DF, Brazil. [Ormsby, Eric] Hlth Canada TPD, Ottawa, ON, Canada. [Sailstad, Jeffrey] Sailstad & Associates, Durham, NC USA. [Stevenson, Lauren] Biogen Idec Inc, Cambridge, MA USA. [Tang, Daniel] ICON Dev Solut, Shanghai, Peoples R China. [Welink, Jan] Med Evaluat Board, Utrecht, Netherlands. [Viswanathan, C. T.] CT Vishwanathan & Associates, Rockville, MD USA. [Wang, Laixin] Tandem Labs, Salt Lake City, UT USA. [Yang, Eric] GlaxoSmithKline, King Of Prussia, PA USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com OI Arnold, Mark/0000-0002-6961-433X FU US FDA (Canada); EMA (Canada); TPD (Canada); ANSM (France); MEB (The Netherlands); AN VISA (Brazil); MHWL (Japan); AGES (Austria); Waters; Pharma Medica Research; GYROS; Biotage; Tandem Labs; Intertek Pharmaceutical Services; Thermo Scientific; Worldwide Clinical Trials; mSpec Group; JCL; WIL Reseach Company; Zef Scientific; PPD; Celerion; EMD Millipore; CPR Pharma Services; ICON; Supelco Analytical; PRA International; Advion; Cerilliant; AIT Bioscience; Chemtos; XenoBiotic Laboratories; MSParts; BioPharma Services; Micro Constants; Alliance Pharma; Algorithme Pharma; iStudy Reporter Bioanalytics; Altura Analytics; AB Sciex; MPI Research; Radix Biosolutions; Nuvisan Pharma Services; Randox; Bioanalysis Journal; Peak Scientific; ICF FX The authors would like to acknowledge the US FDA, EMA, TPD (Canada), ANSM (France), MEB (The Netherlands), AN VISA (Brazil), MHWL (Japan) and AGES (Austria) for supporting this workshop. B DeSilva (Bristol-Myers Squibb [BMS]), F Garofolo (Algorithme Pharma), G Szekely-Klepser (Allergan), R Weiner (Merck) and M Rocci (ICON) for chairing the workshop. All the workshop attendees and members of the bioanalytical community who have sent comments and suggestions to complete this White Paper. Speakers/panelists: M Arnold (BMS), S Bansal (Hoffmann-La Roche), K Bateman (Merck), R Bauer (AGES), B Booth (FDA), S Davis (PPD), B DeSilva (BMS), S Dudal (Novartis Pharma), F Garofolo (Algorithme Pharma), D Gouty (Intertek), J Grundy (Isis Pharmaceutical), S Haidar (FDA), R Hayes (MPI Research), M Jemal (BMS), S Kaur (Genentech), M Kelley (MKelley Consulting LLC), M Knutsson (Ferring Pharmaceuticals), O Le Blaye (ANSM), J Lee (Amgen), S Lower (Advion), M Ma (Amgen), T Mitsuoka (Japan MHLW-NIHS), J Tavares Neto (ANVISA), R Nicholson (PPD), E Ormsby (TPD), M Rocci (ICON), J Sailstad(Sailstad and Associates), L Stevenson (Biogen Idec), G Szekely-Klepser (Allergan), D Tang (ICON), J Welink (Medicines Evaluation Board), R Weiner (Merck), CT Viswanathan (CT Vishwanathan & Associates), L Wang (Tandem Labs), E Woolf (Merck) and E Yang (GlaxoSmithKline). S Martinez, I Dumont, F Landry and C Dicaire (Algorithme Pharma) for collecting the workshop minutes and preparing the first draft of this White Paper. W Garofolo (Meeting Coordinator) for the logistic organization of the event. Workshop sustaining sponsors: Waters, Pharma Medica Research, GYROS, Biotage, Tandem Labs, Intertek Pharmaceutical Services, Thermo Scientific, Worldwide Clinical Trials, mSpec Group, JCL, WIL Reseach Company, Zef Scientific, PPD, Celerion, EMD Millipore, CPR Pharma Services, ICON, Supelco Analytical, PRA International, Advion, Cerilliant, AIT Bioscience, Chemtos, XenoBiotic Laboratories, MSParts, BioPharma Services, Micro Constants, Alliance Pharma, Algorithme Pharma, iStudy Reporter Bioanalytics, Altura Analytics, AB Sciex, MPI Research, Radix Biosolutions, Nuvisan Pharma Services, Randox, Bioanalysis Journal, Peak Scientific, ICF. Media Partner: Future Science Group. NR 32 TC 44 Z9 45 U1 1 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD SEP PY 2012 VL 4 IS 18 SI SI BP 2213 EP 2226 DI 10.4155/BIO.12.205 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 036ZI UT WOS:000311070400009 PM 23046264 ER PT J AU Pisani, SL Neese, SL Doerge, DR Helferich, WG Schantz, SL Korol, DL AF Pisani, Samantha L. Neese, Steven L. Doerge, Daniel R. Helferich, William G. Schantz, Susan L. Korol, Donna L. TI Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats SO HORMONES AND BEHAVIOR LA English DT Article DE Genistein; Estradiol; Place learning; Response learning; Memory systems; Estrogen receptor beta ID ESTROGEN-RECEPTOR-BETA; RADIAL-ARM MAZE; CENTRAL-NERVOUS-SYSTEM; MIDDLE-AGED RATS; OVARIECTOMIZED RATS; WORKING-MEMORY; SPATIAL MEMORY; SOY PHYTOESTROGENS; DIFFERENTIAL REINFORCEMENT; ENVIRONMENTAL ESTROGENS AB Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatal function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17 beta-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for 2 days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 mu g/kg) but not high dose (45 mu g/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over 2 days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor beta and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ER beta subtype and affinity for GPER. (C) 2012 Elsevier Inc. All rights reserved. C1 [Korol, Donna L.] Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA. [Pisani, Samantha L.; Neese, Steven L.; Schantz, Susan L.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Neese, Steven L.; Schantz, Susan L.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA. [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. RP Korol, DL (reprint author), Syracuse Univ, Dept Biol, 107 Coll Pl, Syracuse, NY 13244 USA. EM spisan2@illinois.edu; stlneese@illinois.edu; daniel.doerge@fda.hhs.org; helferich@illinois.edu; schantz@illinois.edu; dlkorol@syr.edu FU ODS [P50 AT006268]; NCAAM; NCI; NSF [IOB 0520876]; NIA [PO1 AG024387]; NIEHS [T32 ES007326] FX This research was supported by grant P50 AT006268 from ODS, NCAAM, and NCI; NSF IOB 0520876 to DLK, and NIA PO1 AG024387 to SLS and DLK. SLN also received support from NIEHS T32 ES007326. The authors would like to thank Ashley D. Ginsberg and Jessie W. Zhang for the experimental assistance. The views presented in this article are solely the responsibility of the authors and do not necessarily reflect those of the NCAAM, ODS, NCI, NIH, or USDA. NR 83 TC 12 Z9 12 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD SEP PY 2012 VL 62 IS 4 BP 491 EP 499 DI 10.1016/j.yhbeh.2012.08.006 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 031PJ UT WOS:000310654100018 PM 22944517 ER PT J AU Wang, H Gill, VS Irvin, KA Byrd, M Bolger, CM Zheng, J Dickey, EE Duvall, RE Jacobson, AP Hammack, TS AF Wang, Hua Gill, Vikas S. Irvin, Kari A. Byrd, Mindi Bolger, Cathryn M. Zheng, Jie Dickey, Erin E. Duvall, Robert E. Jacobson, Andrew P. Hammack, Thomas S. TI Recovery of Salmonella from Internally and Externally Contaminated Whole Tomatoes Using Several Different Sample Preparation Procedures SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID UNIVERSAL PREENRICHMENT BROTH; UNITED-STATES; RAW TOMATOES; FRESH PRODUCE; TEMPERATURE; MONTEVIDEO; OUTBREAKS; SEROVARS; JUICE; TIME AB Studies were conducted to determine the relative effectiveness of whole soak [current Bacteriological Analytical Manual-(BAM) Salmonella method], quarter, stomach, and blend methods for the recovery of Salmonella organisms from internally and externally contaminated tomatoes. Tomatoes were subjected to three inoculation methods: surface inoculation, internal inoculation by injection, and immersion with single Salmonella serovars. The inoculation levels ranged from 1 to 100 CFU/tomato for surface and injection inoculation or 1 to 100 CFU/mL for immersion inoculation. Tomatoes were held for 3 days after inoculation at 2-6 degrees C prior to initiation of analysis. Contaminated tomatoes were soaked, quartered, stomached, and blended in appropriate portions of Universal Pre-enrichment broth, and incubated for 24 h at 35 +/- 2 degrees C. The BAM Salmonella culture method was followed thereafter, and tomatoes were treated as a low-microbial-load food. The stomaching procedure was significantly (P < 0.05) more effective than the whole soak procedure for recovery of internalized Salmonella from tomatoes (by injection). The blending procedure was arithmetically superior to the stomaching procedure for detection of internalized Salmonella from tomatoes (by immersion). The blending procedure showed the same effectiveness as the whole soak procedure for the detection of Salmonella on tomato surfaces. Comparisons between test portion-to-broth ratios (weight to volume) showed that a 1:3 test portion-to-broth ratio had a better buffering capacity for blended tomatoes than a 1:1 test portion-to-broth ratio. It is recommended that the current whole soak BAM tomato sample preparation procedure be replaced with a blending procedure and a 1:3 test portion-to-broth ratio. C1 [Wang, Hua; Gill, Vikas S.; Irvin, Kari A.; Byrd, Mindi; Bolger, Cathryn M.; Zheng, Jie; Dickey, Erin E.; Duvall, Robert E.; Jacobson, Andrew P.; Hammack, Thomas S.] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, College Pk, MD 20740 USA. RP Wang, H (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, 5100 Paint Branch Pkwy,HFS 711, College Pk, MD 20740 USA. EM Hua.Wang@fda.hhs.gov NR 21 TC 2 Z9 2 U1 1 U2 12 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2012 VL 95 IS 5 BP 1452 EP 1456 DI 10.5740/jaoacint.11-463 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 031OS UT WOS:000310652300025 PM 23175979 ER PT J AU Whittaker, P AF Whittaker, Paul TI Evaluating the Use of Fatty Acid Profiles to Differentiate Human Pathogenic and Nonpathogenic Listeria Species SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID EPIDEMIC; FOOD AB Listeria monocyto genes is a Gram-positive human pathogen that is responsible for serious infections in immunocompromised individuals and pregnant women. Because of recent epidemics caused by food contaminated with L. monocytogenes, rapid methods for the detection of this pathogen in food are of interest. Capillary gas chromatography with flame ionization detection (GC-FID) was used to determine the cellular fatty acid profiles of six species of Listeria. The six different species are L. monocytogenes, L. ivanovii, L. innocua, L. welshimeri, L. seeligeri, and L. grayi. For GC-FID analysis, whole cell fatty acid methyl esters (FAMEs) from cells cultured on brain heart infusion (BHI) agar at 35 degrees C for 24 h were obtained by saponification, methylation, and extraction into hexane/methyl tert-butyl ether. A preliminary data set for 15 strains of Listeria species was prepared using fatty acid profiles from two or three replicates prepared on different days. Major fatty acids of the Listeria strains evaluated in this study were C-15:0 iso, C-15:0 ante iso, C-16:0 iso, C-16:0, C-17:0 iso, and C-17:0 ante iso. All of the major fatty acids differ significantly among these six species. The two fatty acids C-17:0 ante iso and C-15:0 ante iso showed the highest percentages, and the ratio of the two clearly showed significant differences between the human pathogen L. monocytogenes and the five nonpathogenic species. Analysis of FAMEs from Listeria strains grown on BHI agar by a GC-FID method is a sensitive procedure for identification of these organisms and differentiation between pathogenic and nonpathogenic species. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 13 TC 3 Z9 3 U1 2 U2 11 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2012 VL 95 IS 5 BP 1457 EP 1459 DI 10.5740/jaoacint.11-505 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 031OS UT WOS:000310652300026 PM 23175980 ER PT J AU Alter, HJ Mikovits, JA Switzer, WM Ruscetti, FW Lo, SC Klimas, N Komaroff, AL Montoya, JG Bateman, L Levine, S Peterson, D Levin, B Hanson, MR Genfi, A Bhat, M Zheng, HQ Wang, R Li, BJ Hung, GC Lee, LL Sameroff, S Heneine, W Coffin, J Hornig, M Lipkin, WI AF Alter, Harvey J. Mikovits, Judy A. Switzer, William M. Ruscetti, Francis W. Lo, Shyh-Ching Klimas, Nancy Komaroff, Anthony L. Montoya, Jose G. Bateman, Lucinda Levine, Susan Peterson, Daniel Levin, Bruce Hanson, Maureen R. Genfi, Afia Bhat, Meera Zheng, HaoQiang Wang, Richard Li, Bingjie Hung, Guo-Chiuan Lee, Li Ling Sameroff, Stephen Heneine, Walid Coffin, John Hornig, Mady Lipkin, W. Ian TI A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus SO MBIO LA English DT Article ID RETROVIRUS XMRV; UNITED-STATES; MOUSE DNA; BLOOD; SEQUENCES; FAILURE; ABSENCE; CELLS; CONTAMINATION; INFECTION AB The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field. C1 [Genfi, Afia; Bhat, Meera; Sameroff, Stephen; Hornig, Mady; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA. [Coffin, John] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Alter, Harvey J.; Wang, Richard] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Switzer, William M.; Zheng, HaoQiang; Heneine, Walid] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Mikovits, Judy A.] Mikovits Consulting, Oxnard, CA USA. [Ruscetti, Francis W.] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD USA. [Lo, Shyh-Ching; Li, Bingjie; Hung, Guo-Chiuan] US FDA, Tissue Safety Lab, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Klimas, Nancy] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Klimas, Nancy] Miami Vet Affairs Med Ctr, Miami, FL USA. [Montoya, Jose G.] Stanford Univ, Infect Dis Clin, Palo Alto, CA 94304 USA. [Komaroff, Anthony L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bateman, Lucinda] Fatigue Consultat Clin, Salt Lake City, UT USA. [Levine, Susan] Levine Clin, New York, NY USA. [Peterson, Daniel] Simmaron Res Inst, Incline Village, NV USA. [Levin, Bruce] Columbia Univ, Dept Biostat, New York, NY USA. [Hanson, Maureen R.; Lee, Li Ling] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. RP Lipkin, WI (reprint author), Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA. EM wil2001@columbia.edu OI Hanson, Maureen/0000-0001-8141-3058 FU National Institutes of Health [AI1057158] FX This study was funded by National Institutes of Health award AI1057158 (NBC-Lipkin). NR 39 TC 19 Z9 20 U1 3 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2012 VL 3 IS 5 AR e00266-12 DI 10.1128/mBio.00266-12 PG 7 WC Microbiology SC Microbiology GA 030QK UT WOS:000310585000015 ER PT J AU Kim, JN Kim, BS Kim, SJ Cerniglia, CE AF Kim, Jong Nam Kim, Bong-Soo Kim, Seong-Jae Cerniglia, Carl E. TI Effects of Crude Oil, Dispersant, and Oil-Dispersant Mixtures on Human Fecal Microbiota in an In Vitro Culture System SO MBIO LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SPILL; GULF; TOXICITY; SEAFOOD; CONTAMINATION; COMMUNITIES; RESPONSES AB The Deepwater Horizon oil spill of 2010 raised concerns that dispersant and dispersed oil, as well as crude oil itself, could contaminate shellfish and seafood habitats with hazardous residues that had potential implications for human health and the ecosystem. However, little is known about the effects of crude oil and dispersant on the human fecal microbiota. The aim of this research was to evaluate the potential effects of Deepwater Horizon crude oil, Corexit 9500 dispersant, and their combination on human fecal microbial communities, using an in vitro culture test system. Fecal specimens from healthy adult volunteers were made into suspensions, which were then treated with oil, dispersant, or oil-dispersant mixtures under anaerobic conditions in an in vitro culture test system. Perturbations of the microbial community, compared to untreated control cultures, were assessed using denaturing gradient gel electrophoresis (DGGE), real-time PCR, and pyrosequencing methods. DGGE and pyrosequencing analysis showed that oil-dispersant mixtures reduced the diversity of fecal microbiota from all individuals. Real-time PCR results indicated that the copy numbers of 16S rRNA genes in cultures treated with dispersed oil or oil alone were significantly lower than those in control incubations. The abundance of the Bacteroidetes decreased in crude oil-treated and dispersedoil- treated cultures, while the Proteobacteria increased in cultures treated with dispersed oil. In conclusion, the human fecal microbiota was affected differently by oil and dispersed oil, and the influence of dispersed oil was significantly greater than that of either oil or dispersant alone compared to control cultures. IMPORTANCE There have been concerns whether human health is adversely affected by exposure to spilled crude oil, which contains regulated carcinogens, such as polycyclic aromatic hydrocarbons. In this study, we determined the effect of BP Deepwater Horizon crude oil and oil dispersant on the human intestinal microbiota, since there is the potential that low-level residues of petrochemicals could contaminate seafood. The results of this study will increase our understanding of the ecophysiological changes in the microbial communities of the human gastrointestinal tract with respect to crude oil exposure. C1 [Kim, Jong Nam; Kim, Bong-Soo; Kim, Seong-Jae; Cerniglia, Carl E.] FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Cerniglia, CE (reprint author), FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM carl.cerniglia@fda.hhs.gov RI Kim, Bong-Soo/L-4779-2013 OI Kim, Bong-Soo/0000-0003-1243-8280 FU U.S. Department of Energy; Food and Drug Administration FX This research was supported in part by an appointment to the Research Participation Program (B.-S. Kim and J. N. Kim) at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the Food and Drug Administration. NR 30 TC 2 Z9 2 U1 2 U2 42 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2012 VL 3 IS 5 AR e00376-12 DI 10.1128/mBio.00376-12 PG 10 WC Microbiology SC Microbiology GA 030QK UT WOS:000310585000042 ER PT J AU Self, RL Wu, WH AF Self, Randy L. Wu, Wen-Hsin TI Determination of eight biogenic amines in selected seafood products by MSPD extraction followed by UHPLC-Orbitrap MS SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE Biogenic amines; Food safety; Orbitrap; Matrix solid-phase dispersion; Seafood; Atmospheric pressure chemical ionization; Food composition; Food analysis ID SALMON SALMO-SALAR; MASS-SPECTROMETRY; FISH SAUCE; MAHI-MAHI; FRESH; INDEX AB A quantitative method was previously explored in canned and frozen tuna utilizing matrix solid-phase dispersion for extraction of agmatine, cadaverine, histamine, phenyethylamine, putrescine, tryptamine, tyramine, and urocanic acid with separation and quantification of these compounds by ultra-high performance hydrophilic interaction chromatography (UHPLC-HILIC) with orbitrap mass spectrometric detection. In the current work, the method was extended onto analysis of biogenic amines in non-tuna food matrices known to be associated with scombroid poisoning, including canned/frozen mackerel and frozen mahi-mahi. For method applicability across a wider range of sample types, a non-scombroid species, sockeye salmon, as well as a Thai fish sauce made with anchovy, were also tested. The method was validated with respect to accuracy, repeatability, linearity, and limits of detection and quantitation for all eight analytes in each of these sample types. Recoveries fell in the 80-109% range, percent relative standard deviation ranged from 0.2 to 9.5%, and correlation coefficients for linear regressions were not less than 0.9951 for all samples and analytes. Limits of detection and quantitation were found to be appropriate for the analysis for each sample and analyte combination. Published by Elsevier Inc. C1 [Self, Randy L.; Wu, Wen-Hsin] US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Appl Technol Ctr, Bothell, WA 98021 USA. RP Wu, WH (reprint author), US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Appl Technol Ctr, 22201 23rd DR SE, Bothell, WA 98021 USA. EM cindy.wu@fda.hhs.gov NR 19 TC 7 Z9 9 U1 4 U2 55 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD SEP PY 2012 VL 27 IS 2 BP 169 EP 173 DI 10.1016/j.jfca.2012.06.002 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 024KI UT WOS:000310107700008 ER PT J AU Pereira, FC Cunha-Oliveira, T Viana, SD Travassos, AS Nunes, S Silva, C Prediger, RD Rego, AC Ali, SF Ribeiro, CAF AF Pereira, Frederico C. Cunha-Oliveira, Teresa Viana, Sofia D. Travassos, Ana S. Nunes, Sara Silva, Carlos Prediger, Rui Daniel Cristina Rego, A. Ali, Syed F. Fontes Ribeiro, Carlos Alberto TI Disruption of striatal glutamatergic/GABAergic homeostasis following acute methamphetamine in mice SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Methamphetamine; Striatum; Glutamate/GABA homeostasis; RAGE; Locomotion ID INDUCED NEUROTOXICITY; DOPAMINE TRANSPORTER; TERMINAL MARKERS; OXIDATIVE STRESS; GLUTAMINE; BRAIN; ASTROCYTES; INHIBITION; APOPTOSIS; NEURONS AB Methamphetamine leads to functional changes in basal ganglia that are linked to impairment in motor activity. Previous studies from our group and others have shown that a single high-methamphetamine injection induces striatal dopaminergic changes in rodents. However, striatal glutamatergic, GABAergic and serotoninergic changes remain elusive under this methamphetamine regimen. Moreover, nothing is known about the participation of the receptor for advanced glycation end-products (RAGE), which is overexpressed upon synaptic dysfunction and glial response, on methamphetamine-induced striatal dysfunction. The aim of this work was to provide an integrative characterization of the striatal changes in amino acids, monoamines and astroglia, as well as in the RAGE levels, and the associated motor activity profile of C57BL/6 adult mice, 72 h after a single-high dose of methamphetamine (30 mg/kg, i.p.). Our findings indicate, for the first time, that methamphetamine decreases striatal glutamine, glutamate and GABA levels, as well as glutamine/glutamate and GABA/glutamate ratios, while serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels remain unchanged. This methamphetamine regimen also produced dopaminergic terminal degeneration in the striatum, as evidenced by dopamine and tyrosine hydroxylase depletion. Consistently, methamphetamine decreased the locomotor activity of mice, in the open field test. In addition, increased levels of glutamine synthase and glial fibrillary acidic protein were observed. Nevertheless, methamphetamine failed to change RAGE levels. Our results show that acute methamphetamine intoxication induces pronounced changes in the striatal glutamatergic/GABAergic and dopaminergic homeostasis, along with astrocyte activation. These neurochemical and glial alterations are accompanied by impairment in locomotor activity. (C) 2012 Elsevier Inc. All rights reserved. C1 [Pereira, Frederico C.; Viana, Sofia D.; Travassos, Ana S.; Nunes, Sara; Silva, Carlos; Fontes Ribeiro, Carlos Alberto] Univ Coimbra, Fac Med, Inst Biomed Res Light & Image IBILI, P-3000354 Coimbra, Portugal. [Cunha-Oliveira, Teresa] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3000354 Coimbra, Portugal. [Prediger, Rui Daniel] Univ Fed Santa Catarina, Dept Farmacol, Florianopolis, SC, Brazil. [Ali, Syed F.] Natl Ctr Toxicol Research Food & Drug Adm NCTR FD, Div Neurotoxicol, Neurochem Lab, Jefferson, AR USA. RP Pereira, FC (reprint author), Univ Coimbra, Fac Med, Inst Biomed Res Light & Image IBILI, Subunit 1,Polo 3, P-3000354 Coimbra, Portugal. EM fredcp@ci.up.pt RI Prediger, Rui/C-4036-2013; Cunha-Oliveira, Teresa/A-3054-2009; Rego, Ana Cristina/L-4272-2014; OI Cunha-Oliveira, Teresa/0000-0002-7382-0339; Rego, Ana Cristina/0000-0003-0700-3776; Pereira, Frederico/0000-0002-9381-3320; Viana, Sofia/0000-0002-1316-1319 FU Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [SFRH/BPD/34711/2007]; FSE; POPH (European Union); Faculty of Medicine, University of Coimbra, Portugal [FCP011]; [PEst-C/SAU/UI3282/2011] FX TCO holds a post-doctoral fellowship from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal, ref SFRH/BPD/34711/2007), co-financed by FSE and POPH (European Union). This research was supported by PEst-C/SAU/UI3282/2011 and by FCP011 (Faculty of Medicine, University of Coimbra, Portugal). NR 46 TC 10 Z9 10 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 2012 VL 34 IS 5 BP 522 EP 529 DI 10.1016/j.ntt.2012.07.005 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 027WT UT WOS:000310385500007 PM 22884891 ER PT J AU Kondragunta, B Han, J Joshi, BH Brorson, KA Puri, RK Uplekar, S Moreira, AR Rao, G AF Kondragunta, Bhargavi Han, Jing Joshi, Bharat H. Brorson, Kurt A. Puri, Raj K. Uplekar, Shaunak Moreira, Antonio R. Rao, Govind TI Genomic analysis of a hybridoma batch cell culture metabolic status in a standard laboratory 5 L bioreactor SO BIOTECHNOLOGY PROGRESS LA English DT Article DE cell culture; genomic; time-course; sparged bioreactor; microarrays ID HAMSTER OVARY CELLS; CHO-CELLS; GENE-EXPRESSION; RECOMBINANT PROTEIN; BUTYRATE TREATMENT; MICROARRAY DATA; FLUX ANALYSIS; ANIMAL-CELLS; GROWTH-RATE; GLYCOSYLATION AB Currently, there is a gap in the knowledge of the culture responses to controlled bioreactor environment during the course of batch cell culture from early exponential phase to stationary-phase. If available, such information could be used to designate gene transcripts for predicting cell status and as a quality predictor for a controlled bioreactor. In this study, we used oligonucleotide microarrays to obtain baseline gene expression profiles during the time-course of a hybridoma batch cell culture in a 5 L bench-scale bioreactor. Gene expression changes that were up or down modulated from early-to-late in batch culture, as well as invariant gene profiles with significant expression were identified using microarray. Typical cellular functions that seemed to be correlated with transcriptomics were oxidative stress response, DNA damage response, apoptosis, and cellular metabolism. As confirmatory evidence, microarray findings were verified with a more rigorous semiquantitative gene-specific Reverse transcriptase-polymerase chain reaction (RT-PCR). The results of this study suggest that under predefined bioreactor culture conditions, significant gene changes from lag to log to stationary phase could be identified, which could then be used to track the culture state. (c) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012 C1 [Kondragunta, Bhargavi; Uplekar, Shaunak; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Uplekar, Shaunak; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Han, Jing; Joshi, Bharat H.; Puri, Raj K.] US FDA, Div Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM Raj.Puri@fda.hhs.gov; grao@umbc.edu FU Sartorius-Stedim Biotechnology; CDER/FDA Critical Path Project [1500] FX This work would not have been achieved without scientific support from Amy X Yang and Toshio Fujisawa (CBER, FDA), and Mike Hanson (UMBC). The UMBC authors gratefully acknowledge funding from Sartorius-Stedim Biotechnology. Support from CDER/FDA Critical Path Project #1500 contributed to the completion of this study. They dedicate this article to Prof. Raj Mutharsan, for his pioneering work on intra-cellular analytes measurement to assess cell physiological state. NR 45 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 2012 VL 28 IS 5 BP 1126 EP 1137 DI 10.1002/btpr.1605 PG 12 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019DV UT WOS:000309718200002 PM 22837152 ER PT J AU Kondragunta, B Joshi, BH Han, J Brorson, KA Puri, RK Moreira, AR Rao, G AF Kondragunta, Bhargavi Joshi, Bharat H. Han, Jing Brorson, Kurt A. Puri, Raj K. Moreira, Antonio R. Rao, Govind TI Bioreactor environment-sensitive sentinel genes as novel metrics for cell culture scale-down comparability SO BIOTECHNOLOGY PROGRESS LA English DT Article DE sentinel genes; scale-down; minibioreactors; time-course ID MONOCLONAL-ANTIBODY; HOUSEKEEPING GENE; EXPRESSION; METABOLISM; APOPTOSIS; SYSTEM; PLATE; GLYCOSYLATION; OPTIMIZATION; CULTIVATION AB Scale-down of bioreactors is currently done based on matching one or more measurable parameters such as kLa and P/V, which could result in insufficient process comparability. Currently, there is a lack of genomic translational studies in cell culture scale-down, which could help delineate measurable cellular attributes for improved scale-down. In this study, we scaled-down from a typical bench-scale 5-L bioreactor to a novel high-throughput 35-mL minibioreactor based on matching oxygen transfer rate, which resulted in cell growth and product-related discrepancies using Sp2/0 cells. Performing DNA microarrays on time-course samples from both systems, we identified 200 differentially expressed transcripts, presumably because of bioreactor aeration and mixing differences with scale-down. Evaluating these transcripts for bioreactor-relevant cellular functions such as oxidative stress response and DNA damage response, we chose 18 sentinel genes based on their degree of difference and functionality, which we further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Tracking the differential expression of Sod1, Apex1, and Odc1 genes, we were able to correlate sparging-related damage and poor mixing, as possible causes for physiological changes such as prolonged culture in minibioreactors. Additionally, to verify our sentinel gene findings, we performed follow-up improved scale-down studies based on gene analysis and measured transcriptomic changes. As a result, qRT-PCR-based genomic profiles and cell growth profiles showed better convergence between the improved minibioreactor conditions and the model 5-L bioreactor. Our results broadly show that based on the knowledge from transcriptomic changes of sentinel gene profiles, it is possible to improve bioreactor scale-down for more comparable processes. (c) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012 C1 [Kondragunta, Bhargavi; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Dept Chem Biochem & Environm Engn, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Joshi, Bharat H.; Han, Jing; Puri, Raj K.] US FDA, Div Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kondragunta, Bhargavi; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Rao, G (reprint author), Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. EM Raj.Puri@fda.hhs.gov; grao@umbc.edu FU PDA Fellowship; Sartorius Stedim Biotech; CDER/FDA Critical Path Project [1500] FX UMBC authors acknowledge funding in part from the PDA Fellowship and Sartorius Stedim Biotech. Special thanks to Amy Yang and Toshio Fujisawa, CBER, Shaunak Uplekar and Joao Da Silva, graduate students from the Department of Chemical and Biochemical Engineering, UMBC, for their scientific support. Support from CDER/FDA Critical Path Project # 1500 contributed to the completion of this study. NR 40 TC 4 Z9 4 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 2012 VL 28 IS 5 BP 1138 EP 1151 DI 10.1002/btpr.1606 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019DV UT WOS:000309718200003 PM 22848039 ER PT J AU Rathore, AS Mittal, S Lute, S Brorson, K AF Rathore, Anurag S. Mittal, Shachi Lute, Scott Brorson, Kurt TI Chemometrics applications in biotechnology processes: Predicting column integrity and impurity clearance during reuse of chromatography resin SO BIOTECHNOLOGY PROGRESS LA English DT Article DE chemometrics; MVDA; multivariate data analysis; bioprocessing; column integrity; impurity clearance; column reuse ID PROCESS ANALYTICAL TECHNOLOGY; PRINCIPAL COMPONENT ANALYSIS; PROTEIN-A CHROMATOGRAPHY; MULTIVARIATE DATA-ANALYSIS; ROOT CAUSE; CULTURE; IDENTIFICATION; DIAGNOSIS; DESIGN; PLS AB Separation media, in particular chromatography media, is typically one of the major contributors to the cost of goods for production of a biotechnology therapeutic. To be cost-effective, it is industry practice that media be reused over several cycles before being discarded. The traditional approach for estimating the number of cycles a particular media can be reused for involves performing laboratory scale experiments that monitor column performance and carryover. This dataset is then used to predict the number of cycles the media can be used at manufacturing scale (concurrent validation). Although, well accepted and widely practiced, there are challenges associated with extrapolating the laboratory scale data to manufacturing scale due to differences that may exist across scales. Factors that may be different include: level of impurities in the feed material, lot to lot variability in feedstock impurities, design of the column housing unit with respect to cleanability, and homogeneity of the column packing. In view of these challenges, there is a need for approaches that may be able to predict column underperformance at the manufacturing scale over the product lifecycle. In case such an underperformance is predicted, the operators can unpack and repack the chromatography column beforehand and thus avoid batch loss. Chemometrics offers one such solution. In this article, we present an application of chemometrics toward the analysis of a set of chromatography profiles with the intention of predicting the various events of column underperformance including the backpressure buildup and inefficient deoxyribonucleic acid clearance. (c) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012 C1 [Rathore, Anurag S.; Mittal, Shachi] Indian Inst Technol Delhi, Dept Chem Engn, New Delhi 110016, India. [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Silver Spring, MD 20903 USA. RP Rathore, AS (reprint author), Indian Inst Technol Delhi, Dept Chem Engn, New Delhi 110016, India. EM asrathore@biotechcmz.com FU US FDA [FDA-SOL-1091873] FX The authors acknowledge financial support from the US FDA via requisition FDA-SOL-1091873. NR 29 TC 11 Z9 11 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 2012 VL 28 IS 5 BP 1308 EP 1314 DI 10.1002/btpr.1610 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019DV UT WOS:000309718200023 PM 22888107 ER PT J AU Volokhov, DV Amselle, M Beck, BJ Popham, DL Whittaker, P Wang, H Kerrigan, E Chizhikov, VE AF Volokhov, Dmitriy V. Amselle, Megan Beck, Brian J. Popham, David L. Whittaker, Paul Wang, Hua Kerrigan, Elizabeth Chizhikov, Vladimir E. TI Lactobacillus brantae sp nov., isolated from faeces of Canada geese (Branta canadensis) SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID SEQUENCE-ANALYSIS MLSA; G+C CONTENT; API 50CH; GENES; STRAINS; GENUS; IDENTIFICATION; PREDICTION; DIVERSITY; RESISTANT AB Three strains of lactic acid bacteria (LAB) were isolated from the faeces of apparently healthy wild Canada geese (Branta canadensis) in 2010 by cultivating faecal LAB on Rogosa SL agar under aerobic conditions. These three isolates were found to share 99.90 % gene sequence similarity of their 16S rRNA, their 16S-23S intergenic transcribed spacer region (ITS), partial 23S rRNA, rpoB, rpoC, rpoA and pheS gene sequences. However, the three strains exhibited lower levels of sequence similarity of these genetic targets to all known LAB, and the phylogenetically closest species to the geese strains were Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus saniviri. In comparison to L. casei ATCC 393(T), L. paracasei ATCC 25302(T), L. rhamnosus ATCC 7469(T) and L. saniviri DSM 24301(T), the novel isolates reacted uniquely in tests for cellobiose, galactose, mannitol, citric acid, aesculin and dextrin, and gave negative results in tests for L-proline arylamidase and L-pyrrolydonyl-arylamidase, and in the Voges-Proskauer test. Biochemical tests for cellobiose, aesculin, galactose, gentiobiose, mannitol, melezitose, ribose, salicin, sucrose, trehalose, raffinose, turanose, amygdalin and arbutin could be used for differentiation between L. saniviri and the novel strains. On the basis of phenotypic and genotypic characteristics, and phylogenetic data, the three isolates represent a novel species of the genus Lactobacillus, for which the name Lactobacillus brantae sp. nov. is proposed. The type strain is SL1108(T) (=ATCC BAA-21421=LMG 26001(T)=DSM 23927(T)) and two additional strains are SL1170 and SL60106. C1 [Volokhov, Dmitriy V.; Chizhikov, Vladimir E.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Amselle, Megan; Beck, Brian J.; Kerrigan, Elizabeth] ATCC, Manassas, VA 20110 USA. [Popham, David L.] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA. [Whittaker, Paul; Wang, Hua] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov RI Popham, David/F-8066-2015 OI Popham, David/0000-0002-2614-143X NR 36 TC 1 Z9 1 U1 0 U2 11 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD SEP PY 2012 VL 62 BP 2068 EP 2076 DI 10.1099/ijs.0.033852-0 PN 9 PG 9 WC Microbiology SC Microbiology GA 023QD UT WOS:000310048600004 PM 22021580 ER PT J AU Khurana, S Frasca, D Blomberg, B Golding, H AF Khurana, Surender Frasca, Daniela Blomberg, Bonnie Golding, Hana TI AID Activity in B Cells Strongly Correlates with Polyclonal Antibody Affinity Maturation in-vivo Following Pandemic 2009-H1N1 Vaccination in Humans SO PLOS PATHOGENS LA English DT Article ID INDUCED CYTIDINE DEAMINASE; LIVED PLASMA-CELLS; INFLUENZA VACCINE; H1N1 INFLUENZA; CLASS SWITCH; AGE; MEMORY; REPERTOIRE; DIVERSITY; RESPONSES AB The role of Activation-Induced Cytidine Deaminase (AID) in somatic hypermutation and polyclonal antibody affinity maturation has not been shown for polyclonal responses in humans. We investigated whether AID induction in human B cells following H1N1pdm09 vaccination correlated with in-vivo antibody affinity maturation against hemagglutinin domains in plasma of young and elderly individuals. AID was measured by qPCR in B cells from individuals of different ages immunized with the H1N1pdm09 influenza vaccine. Polyclonal antibody affinity in human plasma for the HA1 and HA2 domains of the H1N1pdm09 hemagglutinin was measured by antibody-antigen complex dissociation rates using real time kinetics in Surface Plasmon Resonance. Results show an age-related decrease in AID induction in B cells following H1N1pdm09 vaccination. Levels of AID mRNA before vaccination and fold-increase of AID mRNA expression after H1N1pdm09 vaccination directly correlated with increase in polyclonal antibody affinity to the HA1 globular domain (but not to the conserved HA2 stalk). In the younger population, significant affinity maturation to the HA1 globular domain was observed, which associated with initial levels of AID and fold-increase in AID after vaccination. In some older individuals (>65 yr), higher affinity to the HA1 domain was observed before vaccination and H1N1pdm09 vaccination resulted in minimal change in antibody affinity, which correlated with low AID induction in this age group. These findings demonstrate for the first time a strong correlation between AID induction and in-vivo antibody affinity maturation in humans. The ability to generate high affinity antibodies could have significant impact on the elucidation of age-specific antibody responses following vaccination and eventual clinical efficacy and disease outcome. C1 [Khurana, Surender; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Frasca, Daniela; Blomberg, Bonnie] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. RP Khurana, S (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM surender.khurana@fda.hhs.gov; hana.golding@fda.hhs.gov FU NIH [AG023717, AG032576] FX This work was supported by NIH AG023717 and AG032576 (BB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 25 Z9 26 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2012 VL 8 IS 9 AR e1002920 DI 10.1371/journal.ppat.1002920 PG 7 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 020MY UT WOS:000309816500027 PM 23028320 ER PT J AU Wang, YN Lee, JY Michele, T Chowdhury, BA Gobburu, JV AF Wang, Yaning Lee, Joo Yeon Michele, Theresa Chowdhury, Badrul A. Gobburu, Jogarao V. TI Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE indacaterol; E-max model; assumption evaluation; dose selection AB Objective: Indacaterol is a long-acting beta-agonist (LABA) approved by FDA in 2011 at a dose of 75 mu g once daily for the treatment of chronic obstructive pulmonary disease (COPD). During the review process for indacaterol approval, data were reanalyzed by FDA to evaluate the validity of the model-based conclusions regarding dose selection. Methods: The same dose-response model applied by the sponsor was used to analyze a subset of the original data. Model predictions were compared with observed data to evaluate the model. Subgroups were created to visualize the relationship between key model parameters and covariates. The E-max model structure was evaluated for a meta-analysis. Results: Patient-level analyses showed that the model-based claim of additional benefit of 150 mu g over 75 mu g for more severe patients is not supported by the data. Mis-specified covariate model structures for key parameters contributed to this inconsistency. The assumed E-max model structure is not supported by the study-level data and the study-level analysis overestimates the incremental difference between two adjacent doses. Conclusions: Even though model-based drug development is highly desirable, thorough model evaluation and justification is necessary to ensure the validity of related decisions. C1 [Wang, Yaning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Michele, Theresa; Chowdhury, Badrul A.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Wang, YN (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 1252, Silver Spring, MD 20903 USA. EM Yaning.Wang@fda.hhs.gov NR 2 TC 5 Z9 5 U1 0 U2 6 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD SEP PY 2012 VL 50 IS 9 BP 622 EP 630 DI 10.5414/CP201758 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 018BI UT WOS:000309634500002 PM 22578206 ER PT J AU Wang, YN Lee, JY Michele, T Chowdhury, BA AF Wang, Yaning Lee, Joo Yeon Michele, Theresa Chowdhury, Badrul A. TI Response to comment on the report "Limitations of model-based dose selection for indacaterol in patients with chronic obstructive pulmonary disease" SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material C1 [Wang, Yaning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Michele, Theresa; Chowdhury, Badrul A.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Wang, YN (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 1252, Silver Spring, MD 20903 USA. EM Yaning.Wang@fda.hhs.gov NR 5 TC 1 Z9 1 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD SEP PY 2012 VL 50 IS 9 BP 638 EP 638 DI 10.5414/CP201758C PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 018BI UT WOS:000309634500004 ER PT J AU Saini, V Abdulrazzaq, O Bourdo, S Dervishi, E Petre, A Bairi, VG Mustafa, T Schnackenberg, L Viswanathan, T Biris, AS AF Saini, Viney Abdulrazzaq, Omar Bourdo, Shawn Dervishi, Enkeleda Petre, Anca Bairi, Venu Gopal Mustafa, Thikra Schnackenberg, Laura Viswanathan, Tito Biris, Alexandru S. TI Structural and optoelectronic properties of P3HT-graphene composites prepared by in situ oxidative polymerization SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID WALLED CARBON NANOTUBES; ORGANIC SOLAR-CELLS; PHOTOVOLTAIC DEVICES; PHOTOPHYSICAL PROPERTIES; RAMAN-SPECTROSCOPY; GRAPHENE; POLY(3-HEXYLTHIOPHENE); GRAPHITE; FILMS; 3-HEXYLTHIOPHENE AB Poly(3-hexylthiophene) (P3HT)-graphene nanocomposites were synthesized via in situ oxidative polymerization of 3-hexylthiophene monomer in the presence of graphene. The main thrust was to investigate the structural and optoelectronic properties of P3HT-graphene nanocomposites with various graphene concentrations. NMR spectroscopy was used to determine the regioregularity of the polymer composites, whereas Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study their structural and thermal properties. Moreover, cyclic voltammetry was employed to evaluate the HOMO levels of the nanocomposites, while optical spectrophotometry (UV-Vis-NIR) was utilized to determine the optical bandgap of the composites. The information from the aforementioned techniques was used to estimate the HOMO-LUMO energy levels. The results revealed changes in the optical bandgap of P3HT with increasing graphene content. Furthermore, an extensive study aiming at the effect of graphene content on the optical constants of P3HT was conducted using ellipsometry. Photoluminescence analysis of the samples showed no quenching effect of photoluminescence emission with increasing graphene content. Our studies indicate that the inclusion of graphene impacts the optoelectronic properties of P3HT, which can further be used for advanced applications, such as organic solar cells, organic light emitting diodes, organic field-effect transistors, and polymer batteries. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4751271] C1 [Saini, Viney; Abdulrazzaq, Omar; Bourdo, Shawn; Dervishi, Enkeleda; Mustafa, Thikra; Biris, Alexandru S.] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. [Petre, Anca] Univ Pau & Pays Adour, IPRA, SIAME, Pau, France. [Bairi, Venu Gopal; Viswanathan, Tito] Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. [Schnackenberg, Laura] Natl Ctr Toxicol Res, Ctr Metabol, Jefferson, AR 72079 USA. RP Saini, V (reprint author), Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. EM vxsaini@ualr.edu; asbiris@ualr.edu FU Arkansas Science & Technology Authority [08-CAT-03]; Department of Energy [DE-FG36-06GO86072]; National Science Foundation [NSF/EPS-1003970] FX The financial support from the Arkansas Science & Technology Authority (Grant No. 08-CAT-03), the Department of Energy (DE-FG36-06GO86072), and National Science Foundation (NSF/EPS-1003970) is greatly appreciated. The editorial assistance of Dr. Marinelle Ringer is also acknowledged. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 44 TC 23 Z9 23 U1 4 U2 64 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD SEP 1 PY 2012 VL 112 IS 5 AR 054327 DI 10.1063/1.4751271 PG 9 WC Physics, Applied SC Physics GA 010CN UT WOS:000309072200140 ER PT J AU Rupcich, F Badal, A Kyprianou, I Schmidt, TG AF Rupcich, Franco Badal, Andreu Kyprianou, Iacovos Schmidt, Taly Gilat TI A database for estimating organ dose for coronary angiography and brain perfusion CT scans for arbitrary spectra and angular tube current modulation SO MEDICAL PHYSICS LA English DT Article DE CT; dose; coronary angiography; brain perfusion ID MONTE-CARLO SIMULATIONS; DUAL-ENERGY CT; MULTIDETECTOR CT; IMAGE QUALITY; RADIATION; BREAST; REDUCTION; CATARACT; FEASIBILITY; FILTRATION AB Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 degrees through anthropomorphic voxelized female chest and head (0 degrees and 30 degrees tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tables of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDIvol and multiplying by a physical CTDIvol measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 degrees relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate total organ doses calculated using our database are within 1% of those calculated using Monte Carlo simulations with the same geometry and scan parameters for all organs except red bone marrow (within 6%), and within 23% of published estimates for different voxelized phantoms. Results from the example of using the database to estimate organ dose for coronary angiography CT acquisitions show 2.1%, 1.1%, and -32% change in breast dose and 2.1%, -0.74%, and 4.7% change in lung dose for reduced kVp, tube current modulated, and partial angle protocols, respectively, relative to the reference protocol. Results show -19.2% difference in dose to eye lens for a tilted scan relative to a nontilted scan. The reported relative changes in organ doses are presented without quantification of image quality and are for the sole purpose of demonstrating the use of the proposed database. Conclusions: The proposed database and calculation method enable the estimation of organ dose for coronary angiography and brain perfusion CT scans utilizing any spectral shape and angular tube current modulation scheme by taking advantage of the precalculated Monte Carlo simulation results. The database can be used in conjunction with image quality studies to develop optimized acquisition techniques and may be particularly beneficial for optimizing dual kVp acquisitions for which numerous kV, mA, and filtration combinations may be investigated. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4739243] C1 [Rupcich, Franco; Schmidt, Taly Gilat] Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. [Badal, Andreu; Kyprianou, Iacovos] US FDA, Div Imaging & Appl Math OSEL CDRH, Silver Spring, MD 20905 USA. RP Rupcich, F (reprint author), Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. EM franco.rupcich@mu.edu; Andreu.Badal-Soler@fda.hhs.gov; Iacovos.Kyprianou@fda.hhs.gov; taly.gilat-schmidt@mu.edu OI Schmidt, Taly/0000-0002-9840-0963 FU appointment to the Research Participation Program at the FDA Center for Devices and Radiological Health; National Science Foundation [OCI-0923037, CBET-0521602] FX This study was supported in part by an appointment to the Research Participation Program at the FDA Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the United States Department of Energy and the Food and Drug Administration, Office of Women's Health. Computer simulations were performed on the Marquette University Pere High Performance Computing Cluster, which was funded in part by National Science Foundation awards OCI-0923037 and CBET-0521602. The authors would like to thank Lars E. Olson, Ph.D. and David Herzfeld for their support with the high performance cluster. NR 49 TC 6 Z9 6 U1 1 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2012 VL 39 IS 9 BP 5336 EP 5346 DI 10.1118/1.4739243 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 013VR UT WOS:000309334500005 PM 22957601 ER PT J AU Kuselman, I Shpitzer, S Pennecchi, F Burns, C AF Kuselman, Ilya Shpitzer, Shamai Pennecchi, Francesca Burns, Cathy TI Investigating out-of-specification test results of mass concentration of total suspended particulates in air based on metrological concepts-a case study SO AIR QUALITY ATMOSPHERE AND HEALTH LA English DT Article DE Total suspended particulates in air; Mass concentration; Out-of-specification test results; Measurement uncertainty; Producer's and consumer's risks; Acceptance limits AB A metrological approach is used for investigating out-of-specification (OOS) test results of total suspended particulate matter (TSP) mass concentrations in ambient air. As a case study, 496 test results of mass concentration of TSP in ambient air were obtained according to methods of the Environmental Protection Agency, USA. The samples, collected in 2009, came from the same geographic proximity in three stone quarries located in Israel. Twenty of the test results were OOS test results that exceeded the upper limit specified in the national air quality regulations. Investigation of the OOS test results indicated the fact that only 10% of these results (two out of 20) can be decidedly interpreted as witnesses of violations of the national air quality regulations. The other 90% were probably metrologically related, i.e., compatible with the national air quality regulations when considering the measurement uncertainty associated with the test results. Probabilities of future OOS test results and global risks of the stone producer and the consumer, who is defined as an inhabitant near a quarry, were estimated. Acceptance limits, resembling "warning and action lines" used in quality control charts, for air test results were calculated by taking into account the measurement uncertainty. C1 [Kuselman, Ilya; Shpitzer, Shamai] Natl Phys Lab Israel INPL, IL-91904 Jerusalem, Israel. [Pennecchi, Francesca] Ist Nazl Ric Metrol INRIM, I-10135 Turin, Italy. [Burns, Cathy] US FDA, Denver, CO 80225 USA. RP Kuselman, I (reprint author), Natl Phys Lab Israel INPL, IL-91904 Jerusalem, Israel. EM ilya.kuselman@moital.gov.il RI Pennecchi, Francesca/G-9812-2015 OI Pennecchi, Francesca/0000-0003-1328-3858 FU IUPAC [2008-030-1-500]; CITAC FX This work has been supported by IUPAC (Project 2008-030-1-500) and CITAC (Minutes of the 25th CITAC Members' Meeting, Paris, 2010). NR 15 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1873-9318 J9 AIR QUAL ATMOS HLTH JI Air Qual. Atmos. Health PD SEP PY 2012 VL 5 IS 3 BP 269 EP 276 DI 10.1007/s11869-010-0103-6 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 015YA UT WOS:000309481100001 ER PT J AU Hoffmann, D Bijol, V Krishnamoorthy, A Gonzalez, VR Frendl, G Zhang, Q Goering, PL Brown, RP Waikar, SS Vaidya, VS AF Hoffmann, Dana Bijol, Vanesa Krishnamoorthy, Aparna Gonzalez, Victoria R. Frendl, Gyorgy Zhang, Qin Goering, Peter L. Brown, Ronald P. Waikar, Sushrut S. Vaidya, Vishal S. TI Fibrinogen Excretion in the Urine and Immunoreactivity in the Kidney Serves as a Translational Biomarker for Acute Kidney Injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; C-REACTIVE PROTEIN; ATHEROSCLEROTIC LESIONS; CARDIAC-SURGERY; CYSTATIN C; DISEASE; QUALIFICATION; TOXICITY; OUTCOMES AB Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AM). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AM (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AM (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AM from those without AM (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AM. (Am J Pat hot 2012, 181:818-828. http://dx.doi.org/10.1016/j.ajpath.2012.06.004) C1 [Vaidya, Vishal S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Lab Kidney Toxicol & Regenerat,Renal Div, Boston, MA 02115 USA. [Bijol, Vanesa] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Frendl, Gyorgy] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Gonzalez, Victoria R.] Natl Inst Med Sci & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City, DF, Mexico. [Zhang, Qin; Goering, Peter L.; Brown, Ronald P.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. [Vaidya, Vishal S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Vaidya, VS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Lab Kidney Toxicol & Regenerat,Renal Div, Room 562,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vvaidya@partners.org RI Ramirez, Victoria/I-8087-2012; OI Ramirez, Victoria/0000-0002-2782-1381 FU NIH [ES016723, ES017543] FX Supported in part by the NIH (Pathway to Independence grant ES016723 and Outstanding New Environmental Scientist award ES017543 to V.S.V.). NR 45 TC 12 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2012 VL 181 IS 3 BP 818 EP 828 DI 10.1016/j.ajpath.2012.06.004 PG 11 WC Pathology SC Pathology GA 012QH UT WOS:000309251100011 PM 22819533 ER PT J AU Zhang, ZW Chen, Z Troendle, JF Zhang, J AF Zhang, Zhiwei Chen, Zhen Troendle, James F. Zhang, Jun TI Causal Inference on Quantiles with an Obstetric Application SO BIOMETRICS LA English DT Article DE Double robustness; Inverse probability weighting; Missing data; Outcome regression; Propensity score; Stratification; Subclassification ID DOUBLY ROBUST ESTIMATION; PROPENSITY SCORE; INCOMPLETE DATA; MISSING DATA; MODELS; BIAS AB The current statistical literature on causal inference is primarily concerned with population means of potential outcomes, while the current statistical practice also involves other meaningful quantities such as quantiles. Motivated by the Consortium on Safe Labor (CSL), a large observational study of obstetric labor progression, we propose and compare methods for estimating marginal quantiles of potential outcomes as well as quantiles among the treated. By adapting existing methods and techniques, we derive estimators based on outcome regression (OR), inverse probability weighting, and stratification, as well as a doubly robust (DR) estimator. By incorporating stratification into the DR estimator, we further develop a hybrid estimator with enhanced numerical stability at the expense of a slight bias under misspecification of the OR model. The proposed methods are illustrated with the CSL data and evaluated in simulation experiments mimicking the CSL. C1 [Zhang, Zhiwei] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200092, Peoples R China. [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China. RP Zhang, ZW (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM zhiwei.zhang@fda.hhs.gov NR 28 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2012 VL 68 IS 3 BP 697 EP 706 DI 10.1111/j.1541-0420.2011.01712.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 011RW UT WOS:000309183600007 PM 22150612 ER PT J AU Proschan, M Brittain, E Kammerman, L AF Proschan, Michael Brittain, Erica Kammerman, Lisa TI Comment on Proschan et al. (2011), Out of the Frying Pan and in to the Fire? SO BIOMETRICS LA English DT Letter C1 [Proschan, Michael; Brittain, Erica] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Kammerman, Lisa] US FDA, Div Biometr 3, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Proschan, M (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA. EM ProschaM@niaid.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2012 VL 68 IS 3 BP 990 EP 991 PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 011RW UT WOS:000309183600038 ER PT J AU Skinner, M Valentin, JP Gintant, G Koerner, J Pettit, S Wisialowski, T AF Skinner, Matt Valentin, Jean-Pierre Gintant, Gary Koerner, John Pettit, Syril Wisialowski, Todd TI Assessing concordance of nonclinical and clinical QT data: The ILSI-HESI cardiovascular safety subcommittee initiative re-visited SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Meeting Abstract C1 [Skinner, Matt; Valentin, Jean-Pierre] AstraZeneca, Macclesfield, Cheshire, England. [Gintant, Gary] Abbott Labs, Abbott Pk, IL 60064 USA. [Koerner, John] US FDA, Silver Spring, MD USA. [Pettit, Syril] HESI, Washington, DC USA. [Wisialowski, Todd] Pfizer Inc, Groton, CT 06340 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD SEP-OCT PY 2012 VL 66 IS 2 BP 170 EP 171 DI 10.1016/j.vascn.2012.08.041 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 006IM UT WOS:000308812700054 ER PT J AU Koerner, J Darpo, B Skinner, M Vargas, HM Willard, J Pettit, S Valentin, JP AF Koerner, John Darpo, B. Skinner, M. Vargas, H. M. Willard, J. Pettit, S. Valentin, J. P. TI Assessment of the concordance between nonclinical repolarization assays and clinical measure of QT interval prolongation SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Meeting Abstract C1 [Koerner, John; Willard, J.] US FDA, Silver Spring, MD USA. [Skinner, M.; Valentin, J. P.] AstraZeneca, Macclesfield, Cheshire, England. [Vargas, H. M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Pettit, S.] Proarrhythmia Model Comm, HESI, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD SEP-OCT PY 2012 VL 66 IS 2 BP 179 EP 180 DI 10.1016/j.vascn.2012.08.073 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 006IM UT WOS:000308812700086 ER PT J AU Vargas, HM Bass, AS Koerner, J Matis-Mitchell, S Pugsley, MK Skinner, M Burnham, M Pettit, S Valentin, JP AF Vargas, Hugo M. Bass, Alan S. Koerner, John Matis-Mitchell, Sherri Pugsley, Michael K. Skinner, Matt Burnham, Matthew Pettit, Syril Valentin, Jean Pierre TI Evaluation of QTc prolongation in animal and human studies: A qualitative assessment of nonclinical and clinical concordance based on the literature SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Meeting Abstract C1 [Vargas, Hugo M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Koerner, John] US FDA, Silver Spring, MD USA. [Pugsley, Michael K.; Pettit, Syril] Johnson & Johnson PRD 6 Hlth & Environm Sci Inst, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD SEP-OCT PY 2012 VL 66 IS 2 BP 203 EP 203 DI 10.1016/j.vascn.2012.08.156 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 006IM UT WOS:000308812700169 ER PT J AU Croley, TR White, KD Callahan, JH Musser, SM AF Croley, Timothy R. White, Kevin D. Callahan, John H. Musser, Steven M. TI The Chromatographic Role in High Resolution Mass Spectrometry for Non-Targeted Analysis SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Chromatographic separation; Peak coalescence; Co-elution; Mass accuracy ID ION-CYCLOTRON RESONANCE; DESORPTION ELECTROSPRAY-IONIZATION; AMBIENT CONDITIONS; PEAK COALESCENCE; IDENTIFICATION; FOOD; QUANTIFICATION; DATABASES; ACCURACY; PRODUCTS AB Resolution improvements in time-of-flight instrumentation and the emergence of the Orbitrap mass spectrometer have researchers using high resolution mass spectrometry to determine elemental compositions and performing screening methods based on the full-scan data from these instruments. This work is focused on examining instrument performance of both a QTOF and a bench-top Orbitrap. In this study, the impact of chromatographic resolution on mass measurement accuracy, mass measurement precision, and ion suppression is examined at a fundamental level. This work was extended to a mixture of over 200 pesticides to determine how well two different software algorithms componentized and correctly identified these compounds under different sets of chromatographic conditions, where co-elution was expected to vary markedly. C1 [Croley, Timothy R.; White, Kevin D.; Callahan, John H.; Musser, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20770 USA. RP Croley, TR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 707,5100 Paint Branch Pkwy, College Pk, MD 20770 USA. EM timothy.croley@fda.hhs.gov NR 29 TC 29 Z9 29 U1 5 U2 51 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD SEP PY 2012 VL 23 IS 9 BP 1569 EP 1578 DI 10.1007/s13361-012-0392-0 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 012MD UT WOS:000309239400014 PM 22711514 ER PT J AU Anez, G Heisey, DAR Espina, LM Stramer, SL Rios, M AF Anez, German Heisey, Daniel A. R. Espina, Luz M. Stramer, Susan L. Rios, Maria TI Short Report: Phylogenetic Analysis of Dengue Virus Types 1 and 4 Circulating in Puerto Rico and Key West, Florida, during 2010 Epidemics SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID EVOLUTION; FEVER; MODELS AB We describe sequences of six strains of dengue virus (DENV): three DENV-1 isolates and two DENV-4 isolates from Puerto Rico, and a DENV-1 strain from Key West, Florida, obtained from blood donors during 2010 epidemics. Phylogenetic analysis revealed that the Puerto Rico DENV-1 strains constitute a new lineage within genotype V different from those that circulated in Puerto Rico during the past two decades. The newer Puerto Rico DENV-1 strains associated with strains from the Caribbean and South America. The DENV-1 strain from Key West, Florida clustered with a strain isolated from mosquito pools collected in that area and with a number of strains from Nicaragua and Mexico circulating during 2006-2009. The Puerto Rico DENV-4 isolates of genotype II associated with strains that have circulated on the island throughout the 1980s and 1990s and with strains from the Caribbean region and Central America. Introduction and circulation of novel DENV lineages in dengue-endemic regions have the potential to increase the severity of dengue cases. C1 [Anez, German; Rios, Maria] US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Stramer, Susan L.] Amer Red Cross, Gaithersburg, MD USA. RP Rios, M (reprint author), US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, HFM-315, Bethesda, MD 20892 USA. EM german.anez@fda.hhs.gov; daniel.heisey@fda.hhs.gov; luz.espinagomez@fda.hhs.gov; stramers@usa.redcross.org; maria.rios@fda.hhs.gov OI Anez, German/0000-0001-5361-3001 FU Office of Blood Research and Review/Center for Biologics Evaluation and Research/Food and Drug Administration (OBRR/CBER/FDA); Federal Earmark [1H75CK000159-01] FX This study was supported in part by the Office of Blood Research and Review/Center for Biologics Evaluation and Research/Food and Drug Administration (OBRR/CBER/FDA). Financial support for blood donation screening in Puerto Rico provided by Federal Earmark 1H75CK000159-01. NR 22 TC 8 Z9 8 U1 0 U2 9 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2012 VL 87 IS 3 BP 548 EP 553 DI 10.4269/ajtmh.2012.12-0091 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 004KH UT WOS:000308680100027 PM 22826483 ER PT J AU Stokes, W McFarland, R Kulpa-Eddy, J Gatewood, D Levis, R Halder, M Pulle, G Kojima, H Casey, W Gaydamaka, A Miller, T Brown, K Lewis, C Chapsal, JM Bruckner, L Gairola, S Kamphuis, E Rupprecht, CE Wunderli, P McElhinney, L De Mattia, F Gamoh, K Hill, R Reed, D Doelling, V Johnson, N Allen, D Rinckel, L Jones, B AF Stokes, William McFarland, Richard Kulpa-Eddy, Jodie Gatewood, Donna Levis, Robin Halder, Marlies Pulle, Gayle Kojima, Hajime Casey, Warren Gaydamaka, Alexander Miller, Timothy Brown, Karen Lewis, Charles Chapsal, Jean-Michel Bruckner, Lukas Gairola, Sunil Kamphuis, Elisabeth Rupprecht, Charles E. Wunderli, Peter McElhinney, Lorraine De Mattia, Fabrizio Gamoh, Koichiro Hill, Richard Reed, David Doelling, Vivian Johnson, Nelson Allen, David Rinckel, Lori Jones, Brett TI Report on the international workshop on alternative methods for human and veterinary rabies vaccine testing: State of the science and planning the way forward SO BIOLOGICALS LA English DT Article DE Rabies vaccines; Potency; Replacement; Refinement; Reduction; Implementation; In vitro ID MONOCLONAL-ANTIBODY; ANTIGENIC PROPERTIES; POTENCY TEST; ANIMAL USE; GLYCOPROTEIN; VIRUS; ELISA; CHALLENGE; MICE AB Potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. NICEATM, ICCVAM, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. Workshop participants agreed that general anesthesia should be used for intracerebral virus injections and that humane endpoints should be used routinely as the basis for euthanizing animals when conducting the mouse rabies challenge test. Workshop participants recommended as a near-term priority replacement of the mouse challenge with a test validated to ensure potency, such as the mouse antibody serum neutralization test for adjuvanted veterinary rabies vaccines for which an international collaborative study was recently completed. The workshop recommended that an in vitro antigen quantification test should be a high priority for product-specific validation of human and non-adjuvanted veterinary rabies vaccines. Finally, workshop participants recommended greater international cooperation to expedite development, validation, regulatory acceptance, and implementation of alternative test methods for rabies vaccine potency testing. C1 [Stokes, William; Casey, Warren] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program,NIH, Res Triangle Pk, NC 27709 USA. [McFarland, Richard; Levis, Robin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Kulpa-Eddy, Jodie] US Anim & Plant Hlth Inspect Serv, USDA, Vet Serv, Riverdale, MD 20737 USA. [Gatewood, Donna; Lewis, Charles; Hill, Richard] USDA, Ctr Vet Biol, Ames, IA 50010 USA. [Halder, Marlies] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, European Union Reference Lab Alternat Anim Testin, I-21027 Ispra, Varese, Italy. [Pulle, Gayle] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON K1A 0L2, Canada. [Kojima, Hajime] Natl Inst Hlth Sci, Japanese Ctr Validat Alternat Methods, Setagaya Ku, Tokyo 1585801, Japan. [Gaydamaka, Alexander] Inst Anim Hlth, Washington, DC USA. [Miller, Timothy] Benchmark Biolabs, Lincoln, NE 68528 USA. [Brown, Karen] Pair ODocs Consultants, Parkville, MO 64152 USA. [Chapsal, Jean-Michel] Sanofi Pasteur, Lyon, France. [Bruckner, Lukas] Inst Viruskrankheiten & Immunprophylaxe, CH-3147 Mittelhausern, Switzerland. [Gairola, Sunil] Serum Inst India Ltd, Pune 411028, Maharashtra, India. [Kamphuis, Elisabeth] Paul Ehrlich Inst, D-63225 Langen, Germany. [Rupprecht, Charles E.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30329 USA. [McElhinney, Lorraine] Anim Hlth & Vet Labs Agcy, Weybridge CH64 7TE, Surrey, England. [De Mattia, Fabrizio] MSD Anim Hlth, NL-5830 AA Boxmeer, Netherlands. [Gamoh, Koichiro] Minist Agr, Natl Vet Assay Lab, Kokubunji, Tokyo, Japan. [Reed, David] D E Reed & Associates, Chanhassen, MN 55317 USA. [Doelling, Vivian; Johnson, Nelson; Allen, David; Rinckel, Lori; Jones, Brett] Integrated Lab Syst Inc, Morrisville, NC 27560 USA. RP Stokes, W (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program,NIH, POB 12233,MD K2-16, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov RI McElhinney, Lorraine/C-7997-2011; APHA, Staff publications/E-6082-2010 OI McElhinney, Lorraine/0000-0002-6022-348X; FU International Cooperation on Alternative Test Method (ICATM); NICEATM-ICCVAM; European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM); Health Canada; Japanese Center for the Validation of Alternative Methods (JaCVAM) FX The authors extend their sincere appreciation to all participants in the international workshop for their contributions leading to the workshop conclusions and recommendations. The members of the Rabies Workshop Organizing Committee, ICCVAM Interagency Biologics Working Group, and NICEATM staff are acknowledged for their contributions to the planning of the workshop, and all the invited experts are acknowledged for their contributions to breakout group discussions and workshop proceedings. Participating national/international validation organizations from the International Cooperation on Alternative Test Method (ICATM) are also gratefully acknowledged for their scientific contributions and financial support, including NICEATM-ICCVAM, the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Health Canada, and the Japanese Center for the Validation of Alternative Methods (JaCVAM). Finally, the authors gratefully acknowledge Dr. Rajendra Chhabra and Dr. Michael Humble from the National Institute of Environmental Health Sciences, National Institutes of Health, USA for their review of the manuscript. NR 48 TC 13 Z9 13 U1 0 U2 17 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD SEP PY 2012 VL 40 IS 5 BP 369 EP 381 DI 10.1016/j.biologicals.2012.07.005 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 010IB UT WOS:000309087000008 PM 22884673 ER PT J AU Bonhoeffer, J Black, S Izurieta, H Zuber, P Sturkenboom, M AF Bonhoeffer, Jan Black, Steve Izurieta, Hector Zuber, Patrick Sturkenboom, Miriam TI Current status and future directions of post-marketing vaccine safety monitoring with focus on USA and Europe SO BIOLOGICALS LA English DT Article; Proceedings Paper CT Symposium on Post Licensure Evaluation of Vaccine Safety - Current Status and Future Directions CY APR 27-28, 2011 CL Barcelona, SPAIN SP Int Alliance Biol Standardizat (IABS) DE Vaccine- safety; Monitoring; Pharmacovigilance ID ADVERSE EVENTS; IMMUNIZATION SAFETY; SURVEILLANCE; DATALINK AB Vaccine safety research is a key component of public health programs. Regulatory agencies need to be able to make informed decisions. Public health authorities need to respond to vaccine concerns before they turn into large scale scares reducing vaccine uptake and derailing immunization programs. Several post-licensure vaccine safety monitoring systems have been established in the USA and Europe, and methods such as rapid cycle analysis have been developed for real-time detection and analysis of safety issues. Accurate and reliable vaccine product testing and monitoring requires high quality data of populations of 100 million and above depending on the frequency of the event, vaccine coverage, and the time pressure during which data need to be generated. This requires post-licensure safety studies utilizing large linked population based databases of exposure and outcomes. Harmonized methods for development and linkage of these databases across countries need to be further developed, validated and implemented. Concerted action between the US and Europe could move vaccine safety monitoring to today's level of requirements globally and should be pursued. Published by Elsevier Ltd on behalf of The International Alliance for Biological Standardization. C1 [Bonhoeffer, Jan] Brighton Collaborat Fdn, CH-4031 Basel, Switzerland. [Bonhoeffer, Jan] Univ Childrens Hosp Basel, Basel, Switzerland. [Black, Steve] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Izurieta, Hector] US FDA, Rockville, MD 20857 USA. [Zuber, Patrick] World Hlth Org, Geneva, Switzerland. [Sturkenboom, Miriam] Erasmus MC, Rotterdam, Netherlands. RP Bonhoeffer, J (reprint author), Brighton Collaborat Fdn, CH-4031 Basel, Switzerland. EM j.bonhoeffer@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014 NR 23 TC 8 Z9 9 U1 2 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD SEP PY 2012 VL 40 IS 5 BP 393 EP 397 DI 10.1016/j.biologicals.2012.07.007 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 010IB UT WOS:000309087000012 PM 22902972 ER PT J AU Zhao, YW Xia, QS da Costa, GG Yu, HT Cai, LN Fu, PP AF Zhao, Yuewei Xia, Qingsu da Costa, Goncalo Gamboa Yu, Hongtao Cai, Lining Fu, Peter P. TI Full Structure Assignments of Pyrrolizidine Alkaloid DNA Adducts and Mechanism of Tumor Initiation SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FORMATION IN-VIVO; METABOLIC-ACTIVATION; DIETARY-SUPPLEMENTS; MEDICINAL-PLANTS; CROSS-LINKING; RIDDELLIINE; TOXICITY; DEHYDRORETRONECINE; MONOCROTALINE; CELLS AB Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro 5 4 3 generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N-6-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N2-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined. C1 [Zhao, Yuewei; Xia, Qingsu; da Costa, Goncalo Gamboa; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. [Cai, Lining] Biotranex LLC, Monmouth Jct, NJ 08852 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov FU NCTR; U.S. Department of Energy; FDA FX This research was supported in part by appointment (Y.Z.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. NR 42 TC 24 Z9 25 U1 0 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 2012 VL 25 IS 9 BP 1985 EP 1996 DI 10.1021/tx300292h PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 005VB UT WOS:000308777100021 PM 22857713 ER PT J AU Pankewycz, O Ambrus, J Shen, L Xuan, JX Li, H Wu, J Guo, LW Feng, L Laftavi, MR AF Pankewycz, Oleh Ambrus, Julian, Jr. Shen, Long Xuan, Jingxiu Li, Hong Wu, Jing Guo, Li-Wu Feng, Lin Laftavi, Mark R. TI Inhibiting Wipf2 downregulation by transgenic expression of its 3 ' mRNA-untranslated region improves cytotoxicity and vaccination response SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Gene regulation; mRNA 3' untranslated region; T cells; Wiskott-Aldrich syndrome (WAS); WAS-like (WASL) interacting protein ID WISKOTT-ALDRICH-SYNDROME; T-CELL-ACTIVATION; ACTIN-FILAMENT SYSTEM; MICRORNA TARGETS; GENE-EXPRESSION; N-WASP; PROTEIN; RECEPTOR; MICE; CYTOSKELETON AB Lymphocyte activation results in profound changes in the abundance of mRNA transcripts many of which are downregulated. The WiskottAldrich syndrome (WAS) protein (WASP) family is critical for productive T-cell receptor signaling and actin reorganization. The WASP signal pathway includes the WAS/WAS-like (WASL) interacting protein family 2 (WIPF2) gene also known as WIRE/WICH. We show that both human WIPF2 and mouse Wipf2 are mice, alternatively spliced within the 3' untranslated region (3'UTR) resulting in two major transcripts of approximately 4.5 and 6 kb in size. Following T-cell activation, the level of human WIPF2 and mouse Wipf2 mRNA rapidly declines. In mice, this decline is accompanied by a marked reduction in WIPF2 protein levels. Transgenic expression of a 240-bp fragment derived from a highly conserved terminal 3'UTR found within the 6-kb transcript blocks Wipf2 downregulation. These effects may be mediated by competitive inhibition of microinhibitory RNA (miRNA) regulation since the 6-kb-derived transgene and the 4.5-kb transcript share functional binding sites for miRNA146a. Blocking Wipf2 gene and protein repression resulted in improved T-cell responses to antigen immunization in vivo as well as in vitro cytotoxic T-cell killing. Collectively, these data suggest that early downregulation of this immunologically relevant gene controls the intensity of selective lymphocyte functions. C1 [Pankewycz, Oleh; Xuan, Jingxiu; Feng, Lin; Laftavi, Mark R.] SUNY Buffalo, Dept Surg, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Ambrus, Julian, Jr.; Shen, Long; Wu, Jing] SUNY Buffalo, Dept Med, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Li, Hong] Sichuan Univ, Joint Res Ctr, W China Univ 2, Hosp Chengdu, Chengdu 610064, Peoples R China. [Guo, Li-Wu] US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. RP Pankewycz, O (reprint author), Eire Cty Med Ctr, Div Transplantat, Room 1062,462 Grider St, Buffalo, NY 14215 USA. EM op3@buffalo.edu FU American Diabetes Association; John R. Oishei Foundation; Kaleida Health Foundation, Buffalo, NY FX This work was supported in part by grants from the American Diabetes Association, John R. Oishei Foundation, and Kaleida Health Foundation, Buffalo, NY to OP. NR 49 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2012 VL 42 IS 9 BP 2409 EP 2418 DI 10.1002/eji.201141533 PG 10 WC Immunology SC Immunology GA 000RH UT WOS:000308404800023 PM 22674044 ER PT J AU Zaidi, MB McDermott, PF Campos, FD Chim, R Leon, M Vazquez, G Figueroa, G Lopez, E Contreras, J Estrada-Garcia, T AF Zaidi, Mussaret B. McDermott, Patrick F. Campos, Freddy D. Chim, Rodolfo Leon, Magda Vazquez, Gabriela Figueroa, Gloria Lopez, Estela Contreras, Jesus Estrada-Garcia, Teresa TI Antimicrobial-Resistant Campylobacter in the Food Chain in Mexico SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; ANTIBIOTIC-RESISTANCE; HUMANS; TRANSMISSION; PATHOGENS; CHICKENS; THAILAND; DIARRHEA; POULTRY; STRAINS AB We describe prevalence and antimicrobial susceptibility results for thermophilic Campylobacter isolates collected from humans, food, and food-animals in an integrated food chain surveillance network in Mexico. From 2003 to 2006, stool samples were collected from children with diarrhea at state sentinel hospitals. Concurrently, fecal samples from asymptomatic children in kindergartens, as well as raw chicken, pork and beef from retail outlets, and food-animal intestines from slaughterhouses were all collected in 65 cities from four different states. C. jejuni was identified with a standardized hippurate test. Hippurate negative, indoxyl acetate positive isolates were classified as Campylobacter spp. Susceptibility testing was performed by agar dilution according to Clinical and Laboratory Standards Institute guidelines. A total of 1,259 C. jejuni and 1,797 Campylobacter spp. isolates were recovered from 11,811 samples. Chicken was significantly more contaminated for both intestinal samples (93.6%) and meat products (58.3%), compared with swine (71.4%)/pork (14.6%) samples, and cattle (25.1%)/beef (5.3%) samples (p < 0.001). Campylobacter was recovered from 5.1% of children with diarrhea and from 3.2% of asymptomatic children. Chicken was significantly more likely to harbor ciprofloxacin-resistant C. jejuni (85.8%) than swine (62.5%, OR = 3.6), cattle (39.8%, OR = 9.3), or humans (58.2%, OR = 4.4). No significant differences were found for ciprofloxacin-resistant Campylobacter spp. among food-animals, but the rate in food-animals was significantly higher than in humans (84% vs. 56.7%, OR = 4.0). Swine was significantly more likely to harbor erythromycin-resistant C. jejuni (14.8%) than chicken (3.5%, OR = 4.9), cattle (1.8%, OR = 9.3), or humans (3.0%, OR = 5.7), and was associated with higher rates of erythromycin-resistant Campylobacter spp. (41.9%) than chicken (10.5%, OR = 6.1) and humans (11.9%, OR = 5.3). The high resistance rates to ciprofloxacin preclude the use of fluoroquinolones for treatment of campylobacteriosis in Mexico. Our results emphasize the need for ongoing and integrated surveillance of antimicrobial usage and antimicrobial susceptibility in humans and animals. C1 [Zaidi, Mussaret B.] Hosp Gen OHoran, Dept Invest, Microbiol Res Lab, Merida 97000, Yucatan, Mexico. [Zaidi, Mussaret B.; Campos, Freddy D.; Chim, Rodolfo] Hosp Reg Alta Especialidad Peninsula Yucatan, Infect Dis Res Unit, Merida, Mexico. [McDermott, Patrick F.] US FDA, Laurel, MD USA. [Vazquez, Gabriela; Figueroa, Gloria] Secretaria Salud Estado Michoacan, Morelia, Michoacan, Mexico. [Lopez, Estela] Serv Salud Estado San Luis Potosi, Lab Estatal Salud Publ, San Luis Potosi, Mexico. [Contreras, Jesus] Hosp Infantil Estado Sonora, Hermosillo, Sonora, Mexico. [Estrada-Garcia, Teresa] CINVESTAV IPN, Dept Mol Biomed, Mexico City, DF, Mexico. RP Zaidi, MB (reprint author), Hosp Gen OHoran, Dept Invest, Microbiol Res Lab, Av Itzaes X Jacinto Canek, Merida 97000, Yucatan, Mexico. EM mbzaidi@prodigy.net.mx FU U.S. Food and Drug Administration [FD-U-001934-03-2]; Fundacion Mexicana para la Salud, Capitulo Peninsular FX This study was financed by the U.S. Food and Drug Administration (grant FD-U-001934-03-2) and the Fundacion Mexicana para la Salud, Capitulo Peninsular. NR 34 TC 8 Z9 10 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SEP PY 2012 VL 9 IS 9 BP 841 EP 847 DI 10.1089/fpd.2012.1127 PG 7 WC Food Science & Technology SC Food Science & Technology GA 004RU UT WOS:000308699600011 PM 22870938 ER PT J AU Smith, JL Tong, MM Fux, E Anderson, DM AF Smith, Juliette L. Tong, Mengmeng Fux, Elie Anderson, Donald M. TI Toxin production, retention, and extracellular release by Dinophysis acuminata during extended stationary phase and culture decline SO HARMFUL ALGAE LA English DT Article DE Dinophysis; Dinophysistoxin; Extracellular; Okadaic acid; Pectenotoxin; Starvation ID SHELLFISH POISONING TOXINS; OKADAIC ACID; CILIATE PREY; BALTIC SEA; TOXICITY; PECTENOTOXIN-2; SURVIVAL; GROWTH; ALEXANDRIUM; DYNAMICS AB Dinophysis spp. produce diarrhetic shellfish poisoning (DSP) toxins and pectenotoxins. The extent to which the dinoflagellate cells retain their toxicity in stationary phase, a period when cells are most toxic, and their transition into cell death is not known. Here we present results on the production, recycling, retention, and release of toxins from a monoculture of Dinophysis acuminata during these two important stages. Once stationary phase was reached, cultures were divided between light and dark treatments to identify if light influenced toxin dynamics. Light was required for long-term cell maintenance (> 2 months) of D. acuminata in the absence of prey, however, in the dark, cells in stationary phase survived on reserves alone for four weeks before beginning to decline. Cells maintained relatively constant levels of intracellular OA (0.39 +/- 0.03 pg/cell, 0.44 +/- 0.05 pg/cell), DTX1 (0.45 +/- 0.09 pg/cell, 0.64 +/- 0.10 pg/cell) and PTX2 (10.4 +/- 1.4 pg/cell, 11.0 +/- 1.9 pg/cell) in the dark and light treatments, respectively, throughout stationary phase and into culture decline. Toxin production was only apparent during late exponential and early stationary growth when cells were actively dividing. In general, the concentration of dissolved (extracellular) toxin in the medium significantly increased upon culture aging and decline: cells did not appear to be actively or passively releasing toxin during stationary phase, but rather extracellular release was likely a result of cell death. Light availability did not have an apparent effect on toxin production, quotas, or intracellular vs. extracellular distribution. Together these results suggest that a bloom of D. acuminata would retain its cellular toxicity or potency as long as the population is viable, and that cells under conditions of low light (e.g., at the boundary or below euphotic zone) and/or minimal prey could maintain toxicity for extended periods. (c) 2012 Elsevier B.V. All rights reserved. C1 [Smith, Juliette L.; Tong, Mengmeng; Anderson, Donald M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Fux, Elie] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Smith, JL (reprint author), Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. EM jlsmith@whoi.edu FU NSF Grant [OCE-0850421]; Coastal Ocean Institute at the Woods Hole Oceanographic Institution; National Institute of Environmental Health Sciences [1-P50-ES012742]; National Science Foundation through the Woods Hole Center for Oceans and Human Health [OCE-0430724]; Research Participation Program for the Center for Food Safety and Applied Nutrition FX The authors would like to thank David M. Kulis, at WHOI, for his guidance regarding the culturing of Dinophysis acuminata. This work was funded by a NSF Grant OCE-0850421 to D.M.A. and a postdoctoral scholarship to J.L.S. through the Coastal Ocean Institute at the Woods Hole Oceanographic Institution. Support to D.M.A. and J.L.S. was also provided by the National Institute of Environmental Health Sciences (1-P50-ES012742) and the National Science Foundation through the Woods Hole Center for Oceans and Human Health (OCE-0430724). Support to E.F. was provided by the Research Participation Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through a contract with the U.S. Food and Drug Administration.[SS] NR 41 TC 12 Z9 12 U1 1 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD SEP PY 2012 VL 19 BP 125 EP 132 DI 10.1016/j.hal.2012.06.008 PG 8 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 009NY UT WOS:000309033700016 ER PT J AU Cao, GJ Zhao, SH Strain, E Luo, Y Timme, R Wang, C Brown, E Meng, JH Allard, M AF Cao, Guojie Zhao, Shaohua Strain, Errol Luo, Yan Timme, Ruth Wang, Charles Brown, Eric Meng, Jianghong Allard, Marc TI Draft Genome Sequences of Eight Salmonella enterica Serotype Newport Strains from Diverse Hosts and Locations SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UNITED-STATES; EVOLUTION; ILLNESS AB Salmonellosis is a major contributor to the global public health burden. Salmonella enterica serotype Newport has ranked among three Salmonella serotypes most commonly associated with food-borne outbreaks in the United States. It was thought to be polyphyletic and composed of independent lineages. Here we report draft genomes of eight strains of S. Newport from diverse hosts and locations. C1 [Timme, Ruth; Wang, Charles; Brown, Eric; Allard, Marc] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Cao, Guojie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Cao, Guojie; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr JIFSAN, College Pk, MD 20742 USA. [Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Strain, Errol; Luo, Yan] US FDA, Biostat Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Allard, M (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM marc.allard@fda.hhs.gov FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD FX The study was supported in part by funding from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD. NR 7 TC 7 Z9 7 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2012 VL 194 IS 18 BP 5146 EP 5146 DI 10.1128/JB.01171-12 PG 1 WC Microbiology SC Microbiology GA 001FO UT WOS:000308446100054 PM 22933769 ER PT J AU Johannesen, L Galeotti, L AF Johannesen, Lars Galeotti, Loriano TI Automatic ECG quality scoring methodology: mimicking human annotators SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE ECG; signal quality; noise; recording; QRS detection; electrocardiogram AB An algorithm to determine the quality of electrocardiograms (ECGs) can enable inexperienced nurses and paramedics to record ECGs of sufficient diagnostic quality. Previously, we proposed an algorithm for determining if ECG recordings are of acceptable quality, which was entered in the PhysioNet Challenge 2011. In the present work, we propose an improved two-step algorithm, which first rejects ECGs with macroscopic errors (signal absent, large voltage shifts or saturation) and subsequently quantifies the noise (baseline, powerline or muscular noise) on a continuous scale. The performance of the improved algorithm was evaluated using the PhysioNet Challenge database (1500 ECGs rated by humans for signal quality). We achieved a classification accuracy of 92.3% on the training set and 90.0% on the test set. The improved algorithm is capable of detecting ECGs with macroscopic errors and giving the user a score of the overall quality. This allows the user to assess the degree of noise and decide if it is acceptable depending on the purpose of the recording. C1 [Johannesen, Lars] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20933 USA. [Galeotti, Loriano] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20933 USA. RP Johannesen, L (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Bldg 51,RM 2168,10903 New Hampshire Ave, Silver Spring, MD 20933 USA. EM lars.johannesen@fda.hhs.gov; loriano.galeotti@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI GALEOTTI, LORIANO/0000-0002-3200-9080 NR 17 TC 16 Z9 17 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 J9 PHYSIOL MEAS JI Physiol. Meas. PD SEP PY 2012 VL 33 IS 9 BP 1479 EP 1489 DI 10.1088/0967-3334/33/9/1479 PG 11 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA 009AW UT WOS:000308998700007 PM 22902927 ER PT J AU Vieira, MDT Huang, SM AF Vieira, Manuela de Lima Toccafondo Huang, Shiew-Mei TI Botanical-Drug Interactions: A Scientific Perspective SO PLANTA MEDICA LA English DT Review DE drug-interactions; botanical products; regulatory science; clinical pharmacology ID ST-JOHNS-WORT; GINKGO-BILOBA EXTRACT; THISTLE SILYBUM-MARIANUM; TRADE HERBAL PRODUCTS; GLYCOPROTEIN-MEDIATED TRANSPORT; HUMAN CYTOCHROME-P450 ENZYMES; MECHANISM-BASED INACTIVATION; HEALTHY CHINESE VOLUNTEERS; PLATELET-ACTIVATING-FACTOR; INTESTINAL P-GLYCOPROTEIN AB There is a continued predisposition of concurrent use of drugs and botanical products. A general lack of knowledge of the interaction potential together with an under-reporting of botanical use poses a challenge for the health care providers and a safety concern for patients. Botanical-drug interactions increase the patient risk, especially with regard to drugs with a narrow therapeutic index (e.g., warfarin, cyclosporine, and digoxin). Examples of case reports and clinical studies evaluating botanical-drug interactions of commonly used botanicals in the US are presented. The potential pharmacokinetic and pharmacodynamic bases of such interactions are discussed, as well as the challenges associated with the interpretation of the available data and prediction of botanical-drug interactions. Recent FDA experiences with botanical products and interactions including labeling implications as a risk management strategy are highlighted. C1 [Vieira, Manuela de Lima Toccafondo; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Vieira, MDT (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mtoccafondo@yahoo.com FU CAPES/ Fulbright program FX The authors acknowledge the CAPES/ Fulbright program for the doctoral scholarship of M. Vieira. This work was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by Oak Ridge Institute for Science and Education through an inter-agency agreement between the US Department of Energy and US Food and Drug Administration. NR 199 TC 21 Z9 21 U1 2 U2 32 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 EI 1439-0221 J9 PLANTA MED JI Planta Med. PD SEP PY 2012 VL 78 IS 13 BP 1400 EP 1415 DI 10.1055/s-0032-1315145 PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 006CA UT WOS:000308795700002 ER PT J AU Friedrich, BM Trefry, JC Biggins, JE Hensley, LE Honko, AN Smith, DR Olinger, GG AF Friedrich, Brian M. Trefry, John C. Biggins, Julia E. Hensley, Lisa E. Honko, Anna N. Smith, Darci R. Olinger, Gene G. TI Potential Vaccines and Post-Exposure Treatments for Filovirus Infections SO VIRUSES-BASEL LA English DT Review DE filovirus; Ebola; ebolavirus; Marburg virus; marburgvirus; vaccines; post-exposure treatments; clinical trials; non-human primates; animal models ID EBOLA-VIRUS INFECTION; NIEMANN-PICK C1; ANTIBODY-DEPENDENT ENHANCEMENT; PROTECTS NONHUMAN-PRIMATES; EQUINE ENCEPHALITIS-VIRUS; RESPIRATORY SYNDROME CORONAVIRUS; ANTISENSE MORPHOLINO OLIGOMERS; ADENOVIRUS-BASED VACCINE; T-CELL RESPONSES; HEMORRHAGIC-FEVER AB Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. C1 [Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G.] USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA. [Hensley, Lisa E.] US FDA, Med Sci Countermeasures Initiat McMi, Silver Spring, MD 20901 USA. RP Olinger, GG (reprint author), USA, Med Res Inst Infect Dis, Div Virol, 1425 Porter St, Frederick, MD 21702 USA. EM brian.m.friedrich.ctr@us.army.mil; john.c.trefry.ctr@us.army.mil; julia.biggins@us.army.mil; lisa.hensley@fda.hhs.gov; anna.honko@us.army.mil; darci.smith1@us.army.mil; Gene.olinger@us.army.mil OI Olinger, Gene/0000-0001-7338-0292; Honko, Anna/0000-0001-9165-148X FU JSTO-NRC CBD postdoctoral funds from DTRA; Department of Defense Chemical and Biological Defense Program [TMTI0017_09_RD_T]; DTRA [CBCALL12-THRFDA1-2-0135] FX BMF and JCT are National Research Council (NRC) postdoctoral fellows. BMF is also funded by JSTO-NRC CBD postdoctoral funds from DTRA. ANH is partially supported by Joint Project Management Office for Transformational Medical Technologies agreement TMTI0017_09_RD_T from the Department of Defense Chemical and Biological Defense Program. GGO is supported by the DTRA grant CBCALL12-THRFDA1-2-0135. NR 176 TC 25 Z9 29 U1 0 U2 36 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD SEP PY 2012 VL 4 IS 9 BP 1619 EP 1650 DI 10.3390/v4091619 PG 32 WC Virology SC Virology GA 012XF UT WOS:000309269300014 PM 23170176 ER PT J AU Park, EJ Wu, KY Mi, ZH Dong, T Lawrence, JP Ko, CW Huang, SM Zhang, L Crentsil, V Zhang, JL Xu, NN AF Park, Eun Jung Wu, Kunyi Mi, Zenghui Dong, Ting Lawrence, John P. Ko, Chia-Wen Huang, Shiew-Mei Zhang, Lei Crentsil, Victor Zhang, Jialu Xu, Nancy N. TI A Systematic Comparison of Cockcroft-Gault and Modification of Diet in Renal Disease Equations for Classification of Kidney Dysfunction and Dosage Adjustment SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE advanced age; Cockcroft-Gault; dosing; Modification of Diet in Renal Disease; pharmacokinetics; standardized serum creatinine assay ID GLOMERULAR-FILTRATION-RATE; CREATININE CLEARANCE; IMPAIRMENT; PREVALENCE; VOLUNTEERS; METABOLISM; FORMULA; WEIGHT; ADULTS; DRUGS AB BACKGROUND: The dosing of drugs in patients with kidney dysfunction is often based on the estimates of kidney function. OBJECTIVE: To systematically compare the performance of the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations for dosage adjustment. METHODS: We assessed agreement (concordance, kappa statistics [kappa,kappa(omega)) between CG and MDRD using a Food and Drug Administration database to evaluate the effect of renal function on the pharmacokinetics of 36 approved drugs. Across the approved drugs, we compared the correlation between these 2 equations for renal drug clearance (Cl-ren) and area under the concentration-time curve. For 26 approved drugs that require renal dose adjustment, we also compared dosing regimens and expected exposure using these equations. Sensitivity analyses were performed by adjusting the MDRD estimates for individualized body surface area and/or range of serum creatinine assay calibration errors. RESULTS: In the pharmacokinetic database with 973 subjects (age 18-95 years, weight 35-153 kg, female 33%), we found that the CG and the MDRD classification of renal function generally agreed (64.2%, kappa = 0.54, kappa(omega) = 0.73). Among the subjects studied for drugs requiring renal dose adjustment, dosages in 12% were changed to a higher or lower dosing category by the MDRD compared to the CG equation. In particular, using MDRD in place of CG for dosage modification yielded higher dosing recommendations for subjects with a combination of age >80 years, weight <55 kg, and serum creatinine >0.7 and <= 1.5 mg/dL; the coefficient of determination was also higher by CG than MDRD in trials that enrolled these or similar patients. CONCLUSIONS: For patients with advanced age, low weight, and modestly elevated serum creatinine, further work is needed before the MDRD equations can replace the CG equation for dose adjustment in the labeling. C1 [Park, Eun Jung; Wu, Kunyi; Mi, Zenghui; Dong, Ting] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Lawrence, John P.; Ko, Chia-Wen; Zhang, Jialu] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Huang, Shiew-Mei; Zhang, Lei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Crentsil, Victor] US FDA, Div Psychiat Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Xu, NN (reprint author), US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM nancy.xu@fda.hhs.gov FU CDER Critical Path Program at the FDA; FDA CDER Critical Path Program; FDA Commissioner fellowship program FX This research was funded by the CDER Critical Path Program at the FDA.; We are grateful to the FDA CDER Critical Path Program for funding. This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the US Department of Energy and the FDA. This project was also supported in part by the FDA Commissioner fellowship program. NR 31 TC 20 Z9 20 U1 0 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 2012 VL 46 IS 9 BP 1174 EP 1187 DI 10.1345/aph.1Q757 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 005XS UT WOS:000308784000005 PM 22932303 ER PT J AU El Fiky, A Perreault, R Rabin, RL AF El Fiky, A. Perreault, R. Rabin, R. L. TI Type I and III interferon are attenuated in a human in vitro model of alternatively activated macrophages and is mediated by IRF4 SO CYTOKINE LA English DT Meeting Abstract CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting of the International-Society-for-Interferon-and-Cytokine-Research (ISICR) CY SEP 11-14, 2012 CL Geneva, SWITZERLAND SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR) C1 [El Fiky, A.; Perreault, R.; Rabin, R. L.] US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, Bethesda, MD 20014 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2012 VL 59 IS 3 SI SI BP 557 EP 558 DI 10.1016/j.cyto.2012.06.211 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 005FG UT WOS:000308735300189 ER PT J AU Cooper, CK Buckman-Garner, S Slack, MA Florian, JA McCune, S AF Cooper, Charles K. Buckman-Garner, ShaAvhree Slack, Mary Ann Florian, Jeffry A. McCune, Susan TI Developing Standardized Data: Connecting the Silos SO DRUG INFORMATION JOURNAL LA English DT Editorial Material DE data standards; clinical trials; clinical data C1 [Cooper, Charles K.; Buckman-Garner, ShaAvhree; Florian, Jeffry A.; McCune, Susan] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Slack, Mary Ann] US FDA, Off Planning & Informat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McCune, S (reprint author), US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,WO21 RM4526, Silver Spring, MD 20993 USA. EM Susan.McCune@fda.hhs.gov NR 7 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2012 VL 46 IS 5 BP 521 EP 522 DI 10.1177/0092861512454117 PG 2 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 999TL UT WOS:000308337800003 ER PT J AU Rosario, LA Kropp, TJ Wilson, SE Cooper, CK AF Rosario, Lilliam A. Kropp, Timothy J. Wilson, Stephen E. Cooper, Charles K. TI Join FDA/PhUSE Working Groups to Help Harness the Power of Computational Science SO DRUG INFORMATION JOURNAL LA English DT Editorial Material C1 [Rosario, Lilliam A.; Kropp, Timothy J.; Wilson, Stephen E.; Cooper, Charles K.] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rosario, LA (reprint author), US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,WO 21 RM4512, Silver Spring, MD 20993 USA. EM Lilliam.Rosario@fda.hhs.gov NR 2 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2012 VL 46 IS 5 BP 523 EP 524 DI 10.1177/0092861512456839 PG 2 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 999TL UT WOS:000308337800004 ER PT J AU Capaldi, D Ackley, K Brooks, D Carmody, J Draper, K Kambhampati, R Kretschmer, M Levin, D McArdle, J Noll, B Raghavachari, R Roymoulik, I Sharma, BP Thurmer, R Wincott, F AF Capaldi, Daniel Ackley, Kathy Brooks, Doug Carmody, Judy Draper, Ken Kambhampati, Rao Kretschmer, Matthias Levin, Daren McArdle, James Noll, Bernhard Raghavachari, Ramesh Roymoulik, Ipsita Sharma, B. P. (Bob) Thuermer, Rene Wincott, Fran TI Quality Aspects of Oligonucleotide Drug Development: Specifications for Active Pharmaceutical Ingredients SO DRUG INFORMATION JOURNAL LA English DT Article DE therapeutic oligonucleotides; active pharmaceutical ingredients; specifications; specification tests; analytical methods ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY GEL-ELECTROPHORESIS; IONIZATION MASS-SPECTROMETRY; DOUBLE-STRANDED DNA; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; NUCLEIC-ACIDS; SYNTHETIC OLIGONUCLEOTIDES; INTERFERING RNA; ANTISENSE DNA; PURIFICATION AB This article, which is the first in a planned series intended to address chemistry, manufacturing, and control (CMC) aspects of therapeutic oligonucleotides, examines the topic of specifications for active pharmaceutical ingredients (APIs). The authors attempt to present basic scientific considerations for the broadest range of oligonucleotide APIs. Tests and analytical methods suitable for the control of single- and double-stranded oligonucleotide APIs and conjugated oligonucleotide APIs are discussed. C1 [Capaldi, Daniel] Isis Pharmaceut Inc, Carlsbad, CA 92010 USA. [Ackley, Kathy] Girindus Amer Inc, Cincinnati, OH USA. [Brooks, Doug] Regado Biosci, Durham, NC USA. [Carmody, Judy] ZioPharm Oncol Inc, Boston, MA USA. [Draper, Ken] Int Sci Associates LLC, Reno, NV USA. [Kambhampati, Rao; Raghavachari, Ramesh] US FDA, Washington, DC 20204 USA. [Kretschmer, Matthias] Alnylam Pharmaceut Inc, Cambridge, MA USA. [Levin, Daren] GlaxoSmithKline, Res Triangle Pk, NC USA. [McArdle, James] McArdle & Associates, Encinitas, CA USA. [Noll, Bernhard] NB Chem De, Neuss, Germany. [Roymoulik, Ipsita] NITTO DENKO Avecia, Milford, MA USA. [Sharma, B. P. (Bob)] Geron Corp, Menlo Pk, CA USA. [Thuermer, Rene] Fed Inst Drugs & Med Devices, BfArM, Bonn, Germany. [Wincott, Fran] Wincott & Associates LLC, Boston, MA USA. RP Capaldi, D (reprint author), Isis Pharmaceut Inc, 2855 Gazelle Court, Carlsbad, CA 92010 USA. EM dcapaldi@isisph.com NR 47 TC 5 Z9 5 U1 0 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2012 VL 46 IS 5 BP 611 EP 626 DI 10.1177/0092861512445311 PG 16 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 999TL UT WOS:000308337800016 ER PT J AU Zuurbier, L Petricoin, EF Vuerhard, MJ Calvert, V Kooi, C Buijs-Gladdines, JGCAM Smits, WK Sonneveld, E Veerman, AJP Kamps, WA Horstmann, M Pieters, R Meijerink, JPP AF Zuurbier, Linda Petricoin, Emanuel F., III Vuerhard, Maartje J. Calvert, Valerie Kooi, Clarissa Buijs-Gladdines, Jessica G. C. A. M. Smits, Willem K. Sonneveld, Edwin Veerman, Anjo J. P. Kamps, Willem A. Horstmann, Martin Pieters, Rob Meijerink, Jules P. P. TI The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE pediatric T-ALL; PTEN; AKT; NOTCH1; gamma-secretase resistance; outcome ID SPORADIC BREAST-CANCER; NOTCH1 MUTATIONS; PROGNOSTIC-SIGNIFICANCE; ACTIVATION MECHANISM; FBXW7 MUTATIONS; GENE-EXPRESSION; COWDEN-SYNDROME; CHILDREN; PROTOCOL; IMPACT AB Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to gamma-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to gamma-secretase inhibitors. C1 [Zuurbier, Linda; Vuerhard, Maartje J.; Kooi, Clarissa; Buijs-Gladdines, Jessica G. C. A. M.; Smits, Willem K.; Pieters, Rob; Meijerink, Jules P. P.] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, NL-3015 GJ Rotterdam, Netherlands. [Petricoin, Emanuel F., III; Calvert, Valerie] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Petricoin, Emanuel F., III] NCI, FDA Clin Prote Program, US FDA, Bethesda, MD 20892 USA. [Veerman, Anjo J. P.; Kamps, Willem A.] DCOG, The Hague, Netherlands. [Veerman, Anjo J. P.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands. [Smits, Willem K.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Oncol, Groningen, Netherlands. [Horstmann, Martin] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany. [Horstmann, Martin] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Childrens Canc Ctr Hamburg, Inst Res, Hamburg, Germany. RP Meijerink, JPP (reprint author), Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Room Sp2456,Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM j.meijerink@erasmusmc.nl RI Meijerink, Jules/D-4393-2017 OI Meijerink, Jules/0000-0002-6860-798X FU Children Cancer Free Foundation (Stichting Kinderen Kankervrij (KiKa)); Erasmus University Trustfonds foundation; Children Cancer Free Foundation [KIKA2007-012, KIKA2008-029, AMC2008-4265] FX this work was supported by the Children Cancer Free Foundation (Stichting Kinderen Kankervrij (KiKa)) and the Erasmus University Trustfonds foundation. The Children Cancer Free Foundation grants KIKA2007-012 (L.Z. and C.K.), KIKA2008-029 (W.K.S.) and AMC2008-4265 (J.B.-G.). NR 48 TC 35 Z9 38 U1 1 U2 7 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2012 VL 97 IS 9 BP 1405 EP 1413 DI 10.3324/haematol.2011.059030 PG 9 WC Hematology SC Hematology GA 007SL UT WOS:000308908300021 PM 22491738 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Re: Zuo J, Joseph GB, Li X, et al. In vivo intervertebral disc characterization using magnetic resonance spectroscopy and T-1 rho imaging: association with discography and Oswestry Disability Index and Short Form-36 Health Survey. Spine (Phila Pa 1976) 2012;37:214-21 SO SPINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 2012 VL 37 IS 19 BP 1724 EP 1724 DI 10.1097/BRS.0b013e3182659f28 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 999YR UT WOS:000308352300027 PM 22932027 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Re: Wang Z, Kim JH, Higashino K, et al. Cartilage intermediate layer protein (CILP) regulation in intervertebral discs. The effect of age, degeneration, and bone morphogenetic protein-2. Spine (Phila Pa 1976) 2012;37:E203-8 SO SPINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 2012 VL 37 IS 19 BP 1725 EP 1725 DI 10.1097/BRS.0b013e3182659f3d PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 999YR UT WOS:000308352300028 PM 22932028 ER PT J AU Mentz, RJ Kaski, JC Dan, GA Goldstein, S Stockbridge, N Alonso-Garcia, A Ruilope, LM Martinez, FA Zannad, F Pitt, B Fiuzat, M O'Connor, CM AF Mentz, Robert J. Kaski, Juan-Carlos Dan, Gheorghe-Andrei Goldstein, Sidney Stockbridge, Norman Alonso-Garcia, Angeles Ruilope, Luis M. Martinez, Felipe A. Zannad, Faiez Pitt, Bertram Fiuzat, Mona O'Connor, Christopher M. TI Implications of geographical variation on clinical outcomes of cardiovascular trials SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; ACUTE CORONARY SYNDROMES; POINTS CONVINCE TRIAL; ATRIAL-FIBRILLATION; INTERNATIONAL DIFFERENCES; UNITED-STATES; END-POINTS; MULTILEVEL ANALYSIS; MERIT-HF AB Cardiovascular clinical trials are increasingly conducted globally as a means to reduce costs, expedite timelines, provide broad applicability, and satisfy regulatory authorities. Potential problems with trial globalization include regional differences in patient characteristics, medical practice patterns, and health policies which may influence outcomes and limit generalizability. Moreover, concerns have been raised about ethical misconduct and unsatisfactory quality oversight in regions with less trial experience and infrastructure. This article reviews geographical differences in cardiovascular trials in heart failure, acute coronary syndromes, hypertension and atrial fibrillation. It also explores potential explanations for these differences and methods to standardize the presentation of trial results. This review is based on discussions between basic scientists and clinical trialists at the 8th Global Cardio Vascular Clinical Trialists Forum 2011 in Paris, France, from December 2 to 3. (Am Heart J 2012;164:303-12.) C1 [Mentz, Robert J.; Fiuzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Kaski, Juan-Carlos] Univ London, Cardiovasc Sci Res Ctr, London, England. [Dan, Gheorghe-Andrei] Univ Med & Pharm Carol Davila, Colentina Univ Hosp, Bucharest, Romania. [Goldstein, Sidney] Henry Ford Hosp, Detroit, MI 48202 USA. [Stockbridge, Norman] US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. [Alonso-Garcia, Angeles] Hosp Univ Puerta de Hierro, Madrid, Spain. [Ruilope, Luis M.] Hosp 12 Octubre, E-28041 Madrid, Spain. [Martinez, Felipe A.] Natl Univ Cordoba, Cordoba, Argentina. [Zannad, Faiez] Ctr Invest Clin, Nancy, France. [Pitt, Bertram] Univ Michigan, Sch Med, Univ Hosp, Ann Arbor, MI USA. RP Mentz, RJ (reprint author), Duke Univ, Med Ctr, 2301 Erwin Rd, Durham, NC 27710 USA. EM robert.mentz@duke.edu FU Novartis; Forrest Laboratories; Medtronic FX FZ has received honoraria from and served on advisory boards for Pfizer. BP is a consultant to Pfizer, Merck, Novartis, Takeda, Astra Zeneca, Bayer, Lilly, BMS, Cytopherx, Amorcyte, Relypsa, BG-Medicine, Aurasense, GE-Health Care; stocks options in Relypsa, BG-Medicine, and Aurasense; grants from Novartis, Forrest Laboratories, and Medtronic. The other authors report no relevant conflicts of interest related to this work. NR 56 TC 26 Z9 26 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2012 VL 164 IS 3 BP 303 EP 312 DI 10.1016/j.ahj.2012.06.006 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 004OD UT WOS:000308690100005 PM 22980295 ER PT J AU Shapiro, MA Chen, XH AF Shapiro, Marjorie A. Chen, Xiao-Hong TI Regulatory Considerations When Developing Assays for the Characterization and Quality Control of Antibody-Drug Conjugates SO AMERICAN LABORATORY LA English DT Article ID TRASTUZUMAB C1 [Shapiro, Marjorie A.; Chen, Xiao-Hong] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Shapiro, MA (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Marjorie.Shapiro@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 5 PU AMER LABORATORY-LABCOMPARE PI SOUTHPORT PA 3530 POST ROAD, STE 206A, SOUTHPORT, CT 06890 USA SN 0044-7749 J9 AM LAB JI Am. Lab. PD SEP PY 2012 VL 44 IS 8 BP 26 EP 31 PG 6 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 005DE UT WOS:000308729900005 ER PT J AU Baldwin, RL Chelonis, JJ Prunty, PK Paule, MG AF Baldwin, Ronald L. Chelonis, John J. Prunty, Patricia K. Paule, Merle G. TI The use of an incremental repeated acquisition task to assess learning in children SO BEHAVIOURAL PROCESSES LA English DT Article DE Learning; Incremental repeated acquisition; Age; Sex; Intelligence; Children ID OPERANT TEST BATTERY; WORKING-MEMORY; DEVELOPMENTAL ASPECTS; NONHUMAN-PRIMATES; COLUMBA-LIVIA; REACTION-TIME; HOMO-SAPIENS; SELF-CONTROL; PERFORMANCE; RATS AB The development of valid animal models of learning is especially important since learning is critical for nearly all aspects of human behavior and identifying appropriate surrogates provides additional opportunity to study various aspects of learning. Examining the factors that affect learning is often complicated by the need to administer the same task repeatedly across experimental conditions. Incremental repeated acquisition (IRA) tasks have been used extensively in animal research because they circumvent this problem by requiring a subject to learn different response chains repeatedly across sessions. The present study examined the association of age, sex of the participant, and IQ on the performance of an incremental repeated acquisition task in 837 children, aged 5-13 years. This task required children to learn to press four response levers in a specific sequence that was randomly chosen. Illumination of colored indicator lights signaled position in the required response chain. Initially, for the first link, only one of the four levers was correct: a response to it resulted in the delivery of a monetary reinforcer (5 cents). After mastery of the first link (i.e. three correct presses), the children were presented with a two-link response chain: a different lever had to be pressed before pressing the previously correct lever. After mastery of the two-link chain, the response chain length was once again increased, and so on until a response chain consisting of six links was completed or until the task timed out. Older children and children with higher IQs mastered longer response chain lengths and were more accurate in performance of this learning task than younger children. In addition, older children and children with higher IQs had higher effective response rates and lower ineffective response rates. No significant effects of the sex of the participant were demonstrated for any of the variables on this task, except overall response rate. The results indicate that this test is sensitive to developmental variables in children, with the degree of sensitivity of certain dependent variables being age-dependent. Characterization of performance of this task by humans facilitates comparisons with animal models employing the same task, thus enhancing its translational utility. (C) 2012 Elsevier B.V. All rights reserved. C1 [Baldwin, Ronald L.; Chelonis, John J.; Paule, Merle G.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA. [Chelonis, John J.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. [Prunty, Patricia K.] Mt Olive Coll, Dept Psychol, Mt Olive, NC USA. RP Baldwin, RL (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, 1617,W 13th St, Little Rock, AR 72202 USA. EM baldwinronaldl@uams.edu NR 49 TC 5 Z9 5 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD SEP PY 2012 VL 91 IS 1 BP 103 EP 114 DI 10.1016/j.beproc.2012.06.004 PG 12 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 002HT UT WOS:000308523400017 PM 22710096 ER PT J AU Wagner, L Verma, A Meade, BD Reiter, K Narum, DL Brady, RA Little, SF Burns, DL AF Wagner, Leslie Verma, Anita Meade, Bruce D. Reiter, Karine Narum, David L. Brady, Rebecca A. Little, Stephen F. Burns, Drusilla L. TI Structural and Immunological Analysis of Anthrax Recombinant Protective Antigen Adsorbed to Aluminum Hydroxide Adjuvant SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LETHAL TOXIN NEUTRALIZATION; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES; SALT ADJUVANTS; GUINEA-PIGS; VACCINE; PROTEIN; STABILITY; RECEPTOR; BINDING AB New anthrax vaccines currently under development are based on recombinant protective antigen (rPA) and formulated with aluminum adjuvant. Because long-term stability is a desired characteristic of these vaccines, an understanding of the effects of adsorption to aluminum adjuvants on the structure of rPA is important. Using both biophysical and immunological techniques, we compared the structure and immunogenicity of freshly prepared rPA-Alhydrogel formulations to that of formulations stored for 3 weeks at either room temperature or 37 degrees C in order to assess the changes in rPA structure that might occur upon long-term storage on aluminum adjuvant. Intrinsic fluorescence emission spectra of tryptophan residues indicated that some tertiary structure alterations of rPA occurred during storage on Alhydrogel. Using anti-PA monoclonal antibodies to probe specific regions of the adsorbed rPA molecule, we found that two monoclonal antibodies that recognize epitopes located in domain 1 of PA exhibited greater reactivity to the stored formulations than to freshly prepared formulations. Immunogenicity of rPA-Alhydrogel formulations in mice was assessed by measuring the induction of toxin-neutralizing antibodies, as well as antibodies reactive to 12-mer peptides spanning the length of PA. Mice immunized with freshly prepared formulations developed significantly higher toxin-neutralizing antibody titers than mice immunized with the stored preparations. In contrast, sera from mice immunized with stored preparations exhibited increased reactivity to nine 12-mer peptides corresponding to sequences located throughout the rPA molecule. These results demonstrate that storage of rPA-Alhydrogel formulations can lead to structural alteration of the protein and loss of the ability to elicit toxin-neutralizing antibodies. C1 [Wagner, Leslie; Verma, Anita; Brady, Rebecca A.; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC USA. [Reiter, Karine; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA. [Little, Stephen F.] USA, Med Res Inst Infect Dis, Frederick, MD USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM drusilla.burns@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, NIH; Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, NIH, and the Center for Biologics Evaluation and Research, Food and Drug Administration. The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax PA, recombinant from B. anthracis, NR-164; anthrax LF, recombinant from B. anthracis, NR-142; J774A. 1 monocyte/macrophage (mouse) working cell bank, NR-28; and rabbit anti-PA reference serum pool, NR-3839. NR 39 TC 17 Z9 17 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD SEP PY 2012 VL 19 IS 9 BP 1465 EP 1473 DI 10.1128/CVI.00174-12 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 002AX UT WOS:000308503400017 PM 22815152 ER PT J AU Hunt, PR Olejnik, N Sprando, RL AF Hunt, Piper Reid Olejnik, Nicholas Sprando, Robert L. TI Toxicity ranking of heavy metals with screening method using adult Caenorhabditis elegans and propidium iodide replicates toxicity ranking in rat SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Alternative animal model; Caenorhabditis elegans; Toxicity ranking; Heavy metals; Propidium iodide; Liquid culture ID LIFE-SPAN; HISTOPATHOLOGICAL CHANGES; C-ELEGANS; NEMATODE; CADMIUM; GROWTH; MUTANT; MODEL; REPRODUCTION; SURVIVAL AB The utility of any model system for toxicity screening depends on the level of correlation between test responses and toxic reactions in humans. Assays in Caenorhabditis elegans can be fast and inexpensive, however few studies have been done comparing toxic responses in this easily cultured nematode with data on mammalian toxicity. Here we report that a screening assay for acute toxicity, using adult C. elegans grown in axenic liquid culture, replicated LD50 toxicity ranking in rat for five metals. This assay utilized the COPAS Biosort and propidium iodide (PI) as a fluorescent indicator of morbidity and mortality after 30-h exposures. We found that chronic toxicity assays of 2-week treatment duration, followed by analysis of PI induced red fluorescence levels, produced less consistent results than the acute assays. However, other chronic toxicity endpoints were compound and concentration specific, including changes in vulval and gonadal morphology, intestinal thickness and integrity, and the presence of retained internal eggs in post-reproductive animals. Some of these endpoints reflect similar findings in mammals, indicating that measurements of morbidity and mortality in conjunction with morphology analyses in C elegans may have the potential to predict mammalian toxic responses. Published by Elsevier Ltd. C1 [Hunt, Piper Reid; Olejnik, Nicholas; Sprando, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, Laurel, MD 20708 USA. RP Hunt, PR (reprint author), Mod 1,Room 2002,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Piper.Hunt@fda.hhs.gov; Nicholas.Olejnik@fda.hhs.gov; Sprando@fda.hhs.gov RI Hunt, Piper/G-1555-2012 OI Hunt, Piper/0000-0003-0538-7606 NR 41 TC 20 Z9 22 U1 2 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 2012 VL 50 IS 9 BP 3280 EP 3290 DI 10.1016/j.fct.2012.06.051 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 003PT UT WOS:000308624500044 PM 22771366 ER PT J AU Tobon-Velasco, JC Vazquez-Victorio, G Macias-Silva, M Cuevas, E Ali, SF Maldonado, PD Gonzalez-Trujano, ME Cuadrado, A Pedraza-Chaverri, J Santamaria, A AF Cesar Tobon-Velasco, Julio Vazquez-Victorio, Genaro Macias-Silva, Marina Cuevas, Elvis Ali, Syed F. Maldonado, Perla D. Eva Gonzalez-Trujano, Maria Cuadrado, Antonio Pedraza-Chaverri, Jose Santamaria, Abel TI S-allyl cysteine protects against 6-hydroxydopamine-induced neurotoxicity in the rat striatum: Involvement of Nrf2 transcription factor activation and modulation of signaling kinase cascades SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE SAC; 6-OHDA; Nrf2; Neuroprotection; Oxidative stress; Parkinson's disease ID ANTIOXIDANT RESPONSE ELEMENT; HEME OXYGENASE-1 EXPRESSION; INDUCED OXIDATIVE STRESS; CUL3-BASED E3 LIGASE; AGED GARLIC EXTRACT; MPTP MOUSE MODEL; FACTOR-KAPPA-B; PARKINSONS-DISEASE; LIPID-PEROXIDATION; ALLYLCYSTEINE PREVENTS AB Pharmacological activation at the basal ganglia of the transcription factor Nrf2, guardian of redox homeostasis, holds a strong promise for the slow progression of Parkinson's disease (PD). However, a potent Nrf2 activator in the brain still must be found. In this study, we have investigated the potential use of the antioxidant compound S-allyl cysteine (SAC) in the activation of Nrf2 in 6-hydoxydopamine (6-OHDA)-intoxicated rats. In the rat striatum, SAC by itself promoted the Nrf2 dissociation of Keap-1, its nuclear translocation, the subsequent association with small MafK protein, and further binding of the Nrf2/MafX complex to ARE sequence, as well as the up-regulation of Nrf2-dependent genes encoding the antioxidant enzymes HO-1, NQO-1, GR, and SOD-1. In vivo and in vitro experiments to identify signaling pathways activated by SAC pointed to Akt as the most likely kinase participating in Nrf2 activation by SAC. In PC12 cells, SAC stimulated the activation of Akt and ERK1/2 and inhibited JNK1/2/3 activation. In the rat striatum, the SAC-induced activation of Nrf2 is likely to contribute to inhibit the toxic effects of 6-OHDA evidenced by phase 2 antioxidant enzymes up-regulation, glutathione recovery, and attenuation of reactive oxygen species (ROS), nitric oxide (NO), and lipid peroxides formation. These early protective effects correlated with the long-term preservation of the cellular redox status, the striatal dopamine (DA) and tyrosine hydroxylase (TH) levels, and the improvement of motor skills. Therefore, this study indicates that, in addition to direct scavenging actions, the activation of Nrf2 by SAC might confer neuroprotective responses through the modulation of kinase signaling pathways in rodent models of PD, and suggests that this antioxidant molecule may have a therapeutic value in this human pathology. (c) 2012 Elsevier Inc. All rights reserved. C1 [Cesar Tobon-Velasco, Julio; Santamaria, Abel] SSA, Inst Nacl Neurol & Neurocirugia, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Cesar Tobon-Velasco, Julio; Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Macias-Silva, Marina; Cuevas, Elvis] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico. [Cuevas, Elvis; Ali, Syed F.; Santamaria, Abel] FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Maldonado, Perla D.] SSA, Inst Nacl Neurol & Neurocirugia, Lab Patol Vasc, Mexico City 14269, DF, Mexico. [Eva Gonzalez-Trujano, Maria] SSA, Inst Nacl Psiquiatria, Dept Invest Neurociencias, Mexico City, DF, Mexico. [Cuadrado, Antonio] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Dept Bioquim, Barcelona, Spain. [Cuadrado, Antonio] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Inst Invest Biomed Alberto Sols UAM CSIC, Barcelona, Spain. RP Santamaria, A (reprint author), SSA, Inst Nacl Neurol & Neurocirugia, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. EM pedraza@unam.mx; absada@yahoo.com OI Cuadrado, Antonio/0000-0002-3444-9012 FU PAPIIT/UNAM [IN201910, IN222909]; CONACyT [129838]; Spanish Ministry of Science and Innovation [SAF2010-17822]; CONACyT-Mexico [239757] FX This work was supported in part by PAPIIT/UNAM (IN201910) and CONACyT (129838) (J.P.-C.), PAPIIT/UNAM (IN222909) (M.M.-S.), and SAF2010-17822 from the Spanish Ministry of Science and Innovation. Julio Cesar Tobon-Velasco is scholarship holder from CONACyT-Mexico (239757). We gratefully acknowledge Dr. Maria Eugenia Gonsebatt (IIB-UNAM) for critical reading of the manuscript and stimulating discussions. We also thank Dr. Esperanza Garcia (INNN, Mexico), Dr. Sonia Galvan-Arzate (INNN, Mexico), Dr. Isabel Lastres-Becker (IIB-CIBERNED, UAM, Spain), M.Sc., Omar N. Medina-Campos (FQ-UNAM, Mexico), Dr. Ana L. Martinez (INPs, Mexico), Alicia K. Esquivel-Medina, and Alejandra E. Alvarez Mejia for technical support. The authors declare no conflict of interest. NR 85 TC 21 Z9 23 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2012 VL 53 IS 5 BP 1024 EP 1040 DI 10.1016/j.freeradbiomed.2012.06.040 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 003PV UT WOS:000308624700002 PM 22781654 ER PT J AU Hillyer, P Mane, VP Schramm, LM Puig, M Verthelyi, D Chen, A Zhao, Z Navarro, MB Kirschman, KD Bykadi, S Jubin, RG Rabin, RL AF Hillyer, Philippa Mane, Viraj P. Schramm, Lynnsie M. Puig, Montserrat Verthelyi, Daniela Chen, Aaron Zhao, Zeng Navarro, Maria B. Kirschman, Kevin D. Bykadi, Srikant Jubin, Ronald G. Rabin, Ronald L. TI Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE interferon-alpha; interferon-lambda; qRT-PCR; Toll-like receptor; dendritic cell ID REGULATORY FACTOR FAMILY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC HEPATITIS-C; REAL-TIME PCR; IFN-ALPHA; DENDRITIC CELLS; DIFFERENTIAL EXPRESSION; MOLECULAR BEACONS; I INTERFERONS; TRANSCRIPTION FACTORS AB Recent genome-wide association studies suggest distinct roles for 12 human interferon-alpha (IFN-alpha) and 3 IFN-lambda subtypes that may be elucidated by defining the expression patterns of these sets of genes. To overcome the impediment of high homology among each of the sets, we designed a quantitative real-time PCR assay that incorporates the use of molecular beacon and locked nucleic acid (LNA) probes, and in some instances, LNA oligonucleotide inhibitors. We then measured IFN subtype expression by human peripheral blood mononuclear cells and by purified monocytes, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), and monocyte-derived macrophages (MDM), and -dendritic cells (MDDC) in response to poly I:C, lipopolysaccharide (LPS), imiquimod and CpG oligonucleotides. We found that in response to poly I: C and LPS, monocytes, MDM and MDDC express a subtype pattern restricted primarily to IFN-beta and IFN-lambda 1. In addition, while CpG elicited expression of all type I IFN subtypes by pDC, imiquimod did not. Furthermore, MDM and mDC highly express IFN-lambda, and the subtypes of IFN-lambda are expressed hierarchically in the order IFN-lambda 1 followed by IFN-lambda 2, and then IFN-lambda 3. These data support a model of coordinated cell- and ligand-specific expression of types I and III IFN. Defining IFN subtype expression profiles in a variety of contexts may elucidate specific roles for IFN subtypes as protective, therapeutic or pathogenic mediators. Immunology and Cell Biology (2012) 90, 774-783; doi:10.1038/icb.2011.109; published online 17 January 2012 C1 [Rabin, Ronald L.] US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Puig, Montserrat; Verthelyi, Daniela] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Jubin, Ronald G.] PBL Interferonsource, Piscataway, NJ USA. RP Rabin, RL (reprint author), US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bldg 29,Room 203A,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM ronald.rabin@fda.hhs.gov FU CBER FDA Intramural Funds; CBER/FDA-NIAID/NIH Interagency Agreement [YI-AI-6153-01]; DHSS National Vaccine Program Office; NIH Intramural Targeted Antiviral Program FX We thank Sergei Kotenko for the cDNA for IFN-lambda 1, -lambda 2 and -lambda 3, Tammy Massie for advice on statistical analysis, Shannon Murphy for assistance with isolating the primary dendritic cells, and Raymond P Donnelly, Siobhan C Cowley, and Carl G Feng for careful review of the paper. This work was funded by CBER FDA Intramural Funds, CBER/FDA-NIAID/NIH Interagency Agreement YI-AI-6153-01, DHSS National Vaccine Program Office and NIH Intramural Targeted Antiviral Program. NR 79 TC 35 Z9 39 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD SEP PY 2012 VL 90 IS 8 BP 774 EP 783 DI 10.1038/icb.2011.109 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 004NV UT WOS:000308689300098 PM 22249201 ER PT J AU Mehta, A Jarow, JP Maples, P Sigman, M AF Mehta, Akanksha Jarow, Jonathan P. Maples, Pat Sigman, Mark TI Defining the "Normal" Postejaculate Urinalysis SO JOURNAL OF ANDROLOGY LA English DT Article DE Infertility; reproductive tract; semen; sperm; retrograde ejaculation ID POST-EJACULATORY URINE; SPERM AB Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 +/- 1.6 vs 2.0 +/- 1.4 mL, P < .001) and sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (<5 million/mL) with low semen volume (<0.5 mL), and significant sperm counts in PEU (>5 million). Although infertile men tend to have a higher proportion of their total sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management. C1 [Mehta, Akanksha; Sigman, Mark] Brown Univ, Warren Alpert Med Sch, Div Urol, Providence, RI 02905 USA. [Jarow, Jonathan P.] US FDA, Off New Drugs, Silver Spring, MD USA. [Maples, Pat] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. RP Sigman, M (reprint author), Brown Univ, Warren Alpert Med Sch, Div Urol, 2 Dudley St,Suite 175-185, Providence, RI 02905 USA. EM msigman@lifespan.org FU NICHD [U54 HD 055740] FX Supported by NICHD U54 HD 055740. NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD SEP-OCT PY 2012 VL 33 IS 5 BP 917 EP 920 DI 10.2164/jandrol.111.015974 PG 4 WC Andrology SC Endocrinology & Metabolism GA 005XD UT WOS:000308782500022 PM 22282438 ER PT J AU Rosenzweig, S Sadat, M Moir, S Lusso, P Kaplan, G Wolfe, L Memoli, M He, M Hussein, N Nievas, E Mitchell, R Garofalo, M Ireland, D Grunes, C Cimbro, R Chun, TW Bristol, T Adams, D Marciano, B Calvo, K Stoddard, J Justement, S Jaques, J Chiorini, J Priel, DL Kuhns, D DiPasquale, G Verthelyi, D AF Rosenzweig, S. Sadat, M. Moir, S. Lusso, P. Kaplan, G. Wolfe, L. Memoli, M. He, M. Hussein, N. Nievas, E. Mitchell, R. Garofalo, M. Ireland, D. Grunes, C. Cimbro, R. Chun, T-W. Bristol, T. Adams, D. Marciano, B. Calvo, K. Stoddard, J. Justement, S. Jaques, J. Chiorini, J. Priel, D. Long Kuhns, D. DiPasquale, G. Verthelyi, D. TI GENETIC DEFECTS IN MOGS ASSOCIATE SEVERE HYPOGAMMAGLOBULINEMIA WITH NATURAL RESISTANCE TO VIRAL INFECTIONS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [Rosenzweig, S.; Sadat, M.; Hussein, N.; Nievas, E.; Mitchell, R.] NIAID, Infect Dis Susceptibil Unit, LHD, NIH, Bethesda, MD 20892 USA. [Kaplan, G.; Ireland, D.; Grunes, C.; Jaques, J.; Verthelyi, D.] US FDA, Bethesda, MD 20014 USA. [Wolfe, L.; Adams, D.] NHGRI, NIH, Bethesda, MD 20892 USA. [He, M.] Emory Univ, Atlanta, GA 30322 USA. [Calvo, K.; Stoddard, J.] NIH, CC, Bethesda, MD 20892 USA. [Chiorini, J.; DiPasquale, G.] NIDCR, NIH, Bethesda, MD USA. [Priel, D. Long; Kuhns, D.] SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 25 EP 25 PG 1 WC Immunology SC Immunology GA 005CU UT WOS:000308728900043 ER PT J AU Keller, B Salzer, U Drager, R Schlesier, M Ragheb, JA Gutenberger, S Rakhmanov, M Warnatz, K AF Keller, B. Salzer, U. Draeger, R. Schlesier, M. Ragheb, J. A. Gutenberger, S. Rakhmanov, M. Warnatz, K. TI DECREASED CALCIUM SIGNALING IN CD4 T CELLS OF CVID IA PATIENTS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID) CY OCT 03-06, 2012 CL Florence, ITALY SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI) C1 [Keller, B.; Salzer, U.; Draeger, R.; Schlesier, M.; Gutenberger, S.; Rakhmanov, M.; Warnatz, K.] Univ Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany. [Schlesier, M.] Univ Med Ctr, Dept Rheumathol & Clincal Immunol, Freiburg, Germany. [Ragheb, J. A.] US FDA, Immunol Lab, Div Therapeut Prot, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2012 VL 32 SU 1 BP 308 EP 309 PG 2 WC Immunology SC Immunology GA 005CU UT WOS:000308728900630 ER PT J AU Strauss, DG AF Strauss, David G. TI Importance of defining left bundle branch block SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Editorial Material ID INTRAVENTRICULAR-CONDUCTION DISTURBANCES; CARDIAC RESYNCHRONIZATION THERAPY; VENTRICULAR CONDUCTION; MYOCARDIAL SCAR; MORPHOLOGY C1 US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM david.strauss@fda.hhs.gov NR 14 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2012 VL 45 IS 5 BP 505 EP 507 DI 10.1016/j.jelectrocard.2012.06.023 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 003OO UT WOS:000308621400018 PM 22920786 ER PT J AU Schramm, LM Kirschman, KD Heuer, M Chen, AA Verthelyi, D Puig, M Rabin, RL AF Schramm, Lynnsie M. Kirschman, Kevin D. Heuer, Melissa Chen, Aaron A. Verthelyi, Daniela Puig, Montserrat Rabin, Ronald L. TI High-Throughput Quantitative Real-Time Polymerase Chain Reaction Array for Absolute and Relative Quantification of Rhesus Macaque Types I, II, and III Interferon and Their Subtypes SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; LOCKED NUCLEIC-ACID; ALPHA; RESPONSES; INFECTION; VACCINES; RECEPTOR AB Rhesus macaques provide a valuable research and preclinical model for cancer and infectious diseases, as nonhuman primates share immune pathways with humans. Interferons (IFNs) are key cytokines in both innate and adaptive immunity, so a detailed analysis of gene expression in peripheral blood and tissues may shed insight into immune responses. Macaques have 18 IFN genes, of which 14 encode for 13 distinct IFN-alpha subtypes, and one for IFN-beta. Here, we developed a high-throughput array to evaluate each of the IFN-alpha subtypes, as well as IFN-beta, IFN-gamma and 2 subtypes of IFN-lambda. With this array, expression of each IFN species may be quantified as relative to a reference (housekeeping) gene (Delta Cq) or fitted to its own 4-point standard curve for absolute quantification (copy number per mass unit RNA). After validating the assay with IFN complementary DNA, we determined the IFN expression profile of peripheral blood mononuclear cells from 3 rhesus macaques in response to TLR agonists, and demonstrated that the profiles are consistent among animals. Furthermore, because the IFN expression profiles differ depending on the TLR stimuli, they suggest different biological functions for many of the IFN species measured, including individual subtypes of IFN-alpha. C1 [Schramm, Lynnsie M.; Kirschman, Kevin D.; Heuer, Melissa; Chen, Aaron A.; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasite & Allergen Prod, Off Vaccine Res & Regulat, Bethesda, MD 20892 USA. [Verthelyi, Daniela; Puig, Montserrat] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20014 USA. RP Rabin, RL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasite & Allergen Prod, Off Vaccine Res & Regulat, Bldg 29,Rm 203A 9000 Rockville Pike, Bethesda, MD 20892 USA. EM montserrat.puig@fda.hhs.gov; ronald.rabin@fda.hhs.gov FU FDA Intramural Funds, CBER/FDA-NIAID/NIH [YI-AI-6153-01]; DHSS National Vaccine Program Office; NIH Intramural Targeted Antiviral Program; Research Participation Program at the Center for Biologics Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration FX The authors thank Harold Dickensheets for reviewing the article. In addition, we thank Lewis Shankle and the Animal Care Facility staff for their expert care of the nonhuman primates included in this study. The assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Food and Drug Administration at large. This work was funded by FDA Intramural Funds, CBER/FDA-NIAID/NIH interagency agreement YI-AI-6153-01, DHSS National Vaccine Program Office, and NIH Intramural Targeted Antiviral Program. This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through and interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 29 TC 2 Z9 2 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD SEP PY 2012 VL 32 IS 9 BP 407 EP 415 DI 10.1089/jir.2012.0015 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 005JJ UT WOS:000308746400003 PM 22817480 ER PT J AU Zhang, Q da Costa, GG Von Tungeln, LS Jacob, CC Brown, RP Goering, PL AF Zhang, Qin da Costa, Goncalo Gamboa Von Tungeln, Linda S. Jacob, Cristina C. Brown, Ronald P. Goering, Peter L. TI Urinary Biomarker Detection of Melamine- and Cyanuric Acid-Induced Kidney Injury in Rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE kidney injury; obstructive nephropathy; nephrotoxicity biomarker; melamine; cyanuric acid ID SPRAGUE-DAWLEY RATS; MONOCLONAL-ANTIBODIES; PAPILLARY ANTIGENS; RENAL TOXICITY; F344 RATS; NEPHROTOXICITY; EXPOSURE; CATS; IDENTIFICATION; GENTAMICIN AB Oral coexposure of rats to melamine (MEL) and cyanuric acid (CYA) results in a dose-dependent increase in the formation of MEL-CYA crystals in the kidney. The aim of this study was to determine if urinary biomarkers of acute kidney injury could be used to noninvasively detect renal damage associated with crystal formation in the kidneys of MEL- and CYA-exposed rats. Urine was obtained on days 0 (predose), 2, 4, 14, and 28 from male and female Fischer 344 rats fed a diet supplemented with 0, 120, 180, or 240 ppm each of MEL and CYA. A number of urinary protein biomarkers (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, osteopontin, albumin, alpha-GST, GST-Yb1, renal papillary antigen 1 [RPA-1], and clusterin) were measured using a multiplex assay system. The results showed that RPA-1 (distal tubule and collecting duct injury biomarker) was elevated on day 28 at the 120 ppm dose and higher in male rats and at the 180 ppm dose and higher in female rats; however, other urinary protein biomarkers were significantly elevated only at the 240 ppm dose. Significant elevation in blood urea nitrogen and serum creatinine levels, and severe renal damage evidenced by histopathology, were observed after 28 days of exposure to the highest dose, despite the fact that MEL-CYA crystals were observable at the 120 and 180 ppm doses. These data indicate that RPA-1 may serve as a noninvasive urinary biomarker for the detection and monitoring of obstructive nephropathy associated with MEL-CYA exposure. C1 [Zhang, Qin; Brown, Ronald P.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [da Costa, Goncalo Gamboa; Von Tungeln, Linda S.; Jacob, Cristina C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 64,Rm 4064, Silver Spring, MD 20993 USA. EM peter.goering@fda.hhs.gov RI Jacob, Cristina/A-3885-2015 OI Jacob, Cristina/0000-0003-2652-3865 FU U.S. Food and Drug Administration; National Toxicology Program at the National Institute of Environmental Health Sciences [FDA IAG 224-07-0007, NIH Y1ES1027] FX U.S. Food and Drug Administration and the National Toxicology Program at the National Institute of Environmental Health Sciences [FDA IAG 224-07-0007, NIH Y1ES1027]. NR 32 TC 4 Z9 4 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2012 VL 129 IS 1 BP 1 EP 8 DI 10.1093/toxsci/kfs182 PG 8 WC Toxicology SC Toxicology GA 998JN UT WOS:000308234000002 PM 22610612 ER PT J AU Mahajan, B Zheng, H Pham, PT Sedegah, MY Majam, VF Akolkar, N Rios, M Ankrah, I Madjitey, P Amoah, G Addison, E Quakyi, IA Kumar, S AF Mahajan, Babita Zheng, Hong Phuong Thao Pham Sedegah, Mary Y. Majam, Victoria F. Akolkar, Namita Rios, Maria Ankrah, Isaac Madjitey, Parnor Amoah, George Addison, Ebenezer Quakyi, Isabella A. Kumar, Sanjai TI Polymerase chain reaction-based tests for pan-species and species-specific detection of human Plasmodium parasites SO TRANSFUSION LA English DT Article ID HUMAN MALARIA PARASITE; UNITED-STATES; FALCIPARUM INFECTIONS; DNA ISOLATION; BLOOD-CLOTS; AMPLIFICATION; EPIDEMIOLOGY; KNOWLESI; SUDAN; AREA AB BACKGROUND: There is still a need to improve the sensitivity of polymerase chain reaction (PCR) tests for malaria to detect submicroscopic asexual stage Plasmodium infections during the early phase and chronic, asymptomatic phase of infection when the parasite burden is very low. STUDY DESIGN AND METHODS: The inhibitory effect of hemoglobin (Hb) on PCR limits the volume of blood that can be used in the PCR-based detection of intraerythrocytic Plasmodium parasites. We lysed red blood cells with saponin to reduce the Hb concentration in extracted nucleic acid and, as a result, significantly increased the volume of blood that can be tested by PCR. The analytical sensitivity of the PCR was determined using whole blood spiked with ring-stage Plasmodium falciparum parasites, and its clinical sensitivity by testing blood filmpositive and blood filmnegative samples from individuals living in an endemic area in Ghana. RESULTS: We have developed a pan-Plasmodium PCR that detects all five human Plasmodium species with the highest analytical sensitivity of two P. falciparum parasites/mL of whole blood and species-specific PCR tests that distinguished between the five human Plasmodium species. Pan-Plasmodium PCR detected 78 of 78 (100%) blood filmpositive and 19 of 101 (18.81%) blood filmnegative samples from asymptomatic individuals living in Ghana. Pan-Plasmodium PCR was equally sensitive with samples collected as anticoagulated whole blood and clotted blood and in blood collected by finger stick into capillaries. CONCLUSION: We have developed PCR tests with the highest reported sensitivity to date for pan-Plasmodium diagnosis and species-specific diagnosis and detected blood filmnegative asymptomatic infections in individuals living in malaria-endemic countries. C1 [Kumar, Sanjai] US FDA, Lab Emerging Pathogens, DETTD, OBRR,CBER, Rockville, MD 20852 USA. Univ Ghana, Sch Publ Hlth, Coll Hlth Sci, Legon, Accra, Ghana. RP Kumar, S (reprint author), US FDA, Lab Emerging Pathogens, DETTD, OBRR,CBER, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Sanjai.kumar@fda.hhs.gov FU Multilateral Initiatives on Malaria (MIM) through the UNICEF/UNDP/WHO Special Programme for Research and Training in Tropical Diseases (TDR) [A30033] FX We thank David Asher, MD, FDA, for reviewing the paper. Prof. Isabella Quakyi received financial support from the Multilateral Initiatives on Malaria (MIM) Project A30033 through the UNICEF/UNDP/WHO Special Programme for Research and Training in Tropical Diseases (TDR). NR 26 TC 18 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 IS 9 BP 1949 EP 1956 DI 10.1111/j.1537-2995.2011.03541.x PG 8 WC Hematology SC Hematology GA 000OY UT WOS:000308397400015 PM 22320188 ER PT J AU Menis, M Izurieta, HS Anderson, SA Kropp, G Holness, L Gibbs, J Erten, T Worrall, CM MaCurdy, TE Kelman, JA Ball, R AF Menis, Mikhail Izurieta, Hector S. Anderson, Steven A. Kropp, Garner Holness, Leslie Gibbs, Jonathan Erten, Tugce Worrall, Christopher M. MaCurdy, Thomas E. Kelman, Jeffrey A. Ball, Robert TI Outpatient transfusions and occurrence of serious noninfectious transfusion-related complications among US elderly, 2007-2008: utility of large administrative databases in blood safety research SO TRANSFUSION LA English DT Article ID ACUTE LUNG INJURY; RBC STORAGE VARIABLES; ADDITIVE SOLUTION; CELL; TRANSPLANTATION; LEUKOREDUCTION; PATHOGENESIS; IRRADIATION; EXPERIENCE; COMPONENTS AB BACKGROUND: Transfusion-related acute lung injury (TRALI) and hemolytic transfusion reactions account for significant transfusion-related morbidity and mortality in the United States. Our study evaluated types and quantities of transfused components as well as occurrence of TRALI, ABO, and Rh incompatibilities among the US elderly in the institutional outpatient setting during 2007 to 2008. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized the Centers for Medicare & Medicaid Services' large administrative databases. Transfusions were identified by recorded procedure and revenue center codes, while complications were ascertained via ICD-9-CM diagnosis codes. The study quantified blood use based on revenue center units. RESULTS: Among 26,054,242 and 25,662,864 Medicare elderly in 2007 and 2008, a total of 241,055 (0.9%) and 251,284 (1.0%) had outpatient transfusions. Leukoreduced red blood cells (LR-RBCs) was the most frequently transfused single blood component (60.1 and 61.3%, respectively) each year. Likewise, LR-RBCs and LR pheresis platelets (LR-PLTs) was the most frequent component combination (2.4 and 2.6%, respectively). TRALI rate comparison for RBCs and PLTs versus RBCs only showed higher rate for RBCs and PLTs (p = 0.033). In 2007 and 2008, ABO incompatibility rate comparison for irradiated (IR) LR-RBCs versus LR-RBCs showed higher rates for IR LR-RBCs (rate ratio [RR] 37.4, 95% confidence interval [CI] 10.6-132.6; and RR 31.3, 95% CI 11.6-84.4, respectively). CONCLUSION: This study shows potential usefulness of Medicare databases in assessment of blood utilization, transfusion-related complications, and risk factors among US elderly in the outpatient setting. It suggests limitations (e.g., need for several years of data to better assess rare complications) and importance of databases as hypothesis-generating tool to supplement blood safety research. C1 [Menis, Mikhail] US FDA, Analyt Epidemiol Branch, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Acumen LLC, Burlingame, CA USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Menis, M (reprint author), US FDA, Analyt Epidemiol Branch, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 225, Rockville, MD 20852 USA. EM Mikhail.Menis@fda.hhs.gov FU internal FDA funds FX This research was supported through internal FDA funds. NR 53 TC 9 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 IS 9 BP 1968 EP 1976 DI 10.1111/j.1537-2995.2011.03535.x PG 9 WC Hematology SC Hematology GA 000OY UT WOS:000308397400017 PM 22313096 ER PT J AU Chen, WJ Petrick, NA Sahiner, B AF Chen, Weijie Petrick, Nicholas A. Sahiner, Berkman TI Hypothesis Testing in Noninferiority and Equivalence MRMC ROC Studies SO ACADEMIC RADIOLOGY LA English DT Article DE MRMC; ROC; noninferiority; hypothesis testing ID DORFMAN-BERBAUM-METZ; NON-INFERIORITY; DIAGNOSTIC-ACCURACY; MULTIREADER ROC; CURVES; SYSTEMS; READERS; AREAS AB Rationale and Objectives: Conventional multireader multicase receiver operating characteristic (MRMC ROC) methodologies use hypothesis testing to test differences in diagnostic accuracies among several imaging modalities. The general MRMC-ROC analysis framework is designed to show that one modality is statistically different among a set of competing modalities (ie, the superiority setting). In practice, one may wish to show that the diagnostic accuracy of a modality is noninferior or equivalent, in a statistical sense, to that of another modality instead of showing its superiority (a higher bar). The purpose of this article is to investigate the appropriate adjustments to the conventional MRMC ROC hypothesis testing methodology for the design and analysis of noninferiority and equivalence hypothesis tests. Materials and Methods: We present three methodological adjustments to the updated and unified Obuchowski-Rockette (OR)/Dorfman-Berbaum-Metz (DBM) MRMC ROC method for use in statistical noninferiority/equivalence testing: 1) the appropriate statement of the null and alternative hypotheses; 2) a method for analyzing the experimental data; and 3) a method for sizing MRMC noninferiority/equivalence studies. We provide a clinical example to further illustrate the analysis of and sizing/power calculation for noninferiority MRMC ROC studies and give some insights on the interplay of effect size, noninferiority margin parameter, and sample sizes. Results: We provide detailed analysis and sizing computation procedures for a noninferiority MRMC ROC study using our method adjusted from the updated and unified OR/DBM MRMC method. Likewise, we show that an equivalence hypothesis test is identical to performing two simultaneous noninferiority tests (ie, either modality is noninferior to the other). Conclusion: Conventional MRMC ROC methodology developed for superiority studies can and should be adjusted appropriately for the design and analysis of a noninferiority/equivalence hypothesis testing. In addition, the confidence interval of the difference in diagnostic accuracies is important information and should generally accompany the statistical analysis and any conclusions drawn from the hypothesis testing. C1 [Chen, Weijie; Petrick, Nicholas A.; Sahiner, Berkman] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov NR 22 TC 8 Z9 8 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2012 VL 19 IS 9 BP 1158 EP 1165 DI 10.1016/j.acra.2012.04.011 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 993MR UT WOS:000307864300017 PM 22717591 ER PT J AU Cohen, PA Goday, A Swann, JP AF Cohen, Pieter A. Goday, Alberto Swann, John P. TI The Return of Rainbow Diet Pills SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID UNITED-STATES; BRAZIL; FENPROPOREX; SUPPLEMENT; DRUGS AB The US Food and Drug Administration (FDA) has recently warned consumers about the risks of weight loss supplements adulterated with multiple pharmaceutical agents. Some of these supplements combine potent anorectics, such as amphetamines derivatives, with benzodiazepines, beta-blockers, and other medications to suppress the anorectics' adverse effects. These weight loss supplements represent the most recent generation of rainbow diet pills, named for their bright and varied colors, which date back more than 70 years. Beginning in the 1940s, several US pharmaceutical firms aggressively promoted rainbow pills to physicians and patients. By the 1960s the pills had caused dozens of deaths before the FDA began removing them from the US market. We used a variety of original resources to trace these deadly pills from their origins in the United States to their popularity in Spain and Brazil to their reintroduction to the United States as weight loss dietary supplements. (Am J Public Health. 2012;102:1676-1686. doi:10.2105/AJPH.2012.300655) C1 [Cohen, Pieter A.] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Pieter A.] Cambridge Hlth Alliance, Somerville, MA USA. [Goday, Alberto] Hosp del Mar, Dept Endocrinol, Barcelona, Spain. [Goday, Alberto] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Swann, John P.] US FDA, Hist Off, Silver Spring, MD USA. RP Cohen, PA (reprint author), 236 Highland Ave, Somerville, MA 02143 USA. EM pcohen@challiance.org NR 82 TC 9 Z9 9 U1 2 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2012 VL 102 IS 9 BP 1676 EP 1686 DI 10.2105/AJPH.2012.300655 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 994EJ UT WOS:000307913400011 PM 22813089 ER PT J AU Tembhare, PR Marti, G Wiestner, A Degheidy, H Farooqui, M Kreitman, RJ Jasper, GA Yuan, CM Liewehr, D Venzon, D Stetler-Stevenson, M AF Tembhare, Prashant R. Marti, Gerald Wiestner, Adrian Degheidy, Heba Farooqui, Mohammed Kreitman, Robert J. Jasper, Gregory A. Yuan, Constance M. Liewehr, David Venzon, David Stetler-Stevenson, Maryalice TI QUANTIFICATION OF EXPRESSION OF ANTIGENS TARGETED BY ANTIBODY BASED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 27th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 05-09, 2012 CL New Orleans, LA SP Int Clin Cytometry Soc C1 [Tembhare, Prashant R.; Jasper, Gregory A.; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Marti, Gerald; Degheidy, Heba] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Wiestner, Adrian; Farooqui, Mohammed] NHLBI, NIH, Bethesda, MD USA. [Kreitman, Robert J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liewehr, David; Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2012 VL 82B IS 5 MA P39 BP 340 EP 340 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 001MU UT WOS:000308465600050 ER PT J AU Petrochenko, PE Zhang, Q Wildt, B Betz, MW Goering, PL Wang, HR Sun, T Narayan, RJ AF Petrochenko, Peter E. Zhang, Qin Wildt, Bridget Betz, Martha W. Goering, Peter L. Wang, Haorong Sun, Ted Narayan, Roger J. TI In Vitro Cytotoxicity of Rare Earth Oxide Nanoparticles for Imaging Applications SO INTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY LA English DT Article ID RAW 264.7 MACROPHAGES; QUANTUM DOTS; LUMINESCENCE PROPERTIES; CARBON NANOTUBES; PARTICLES; EMISSION; ADHESION; PVP AB The in vitro cytotoxicity and cellular uptake of commercially available doped YVO4 were evaluated in RAW 264.7 macrophages using the MTT assay. The results indicated that 2050nm diameter samarium-doped YVO4 showed significant toxicity at concentrations of 25 mu g/mL and higher; samples of the same material functionalized with COOH showed less cytotoxicity. At concentrations of 25100 mu g/mL, 2050nm erbium-doped YVO4 showed less toxicity compared with 2050nm samarium-doped YVO4. Ten nanometer samples showed no toxicity at concentrations of 100600 mu g/mL. The cytotoxicity of rare earth nanoparticles in macrophages is dependent, at least in part, on size and surface functionalization. C1 [Petrochenko, Peter E.; Zhang, Qin; Wildt, Bridget; Betz, Martha W.; Goering, Peter L.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Petrochenko, Peter E.; Narayan, Roger J.] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC 27965 USA. [Petrochenko, Peter E.; Narayan, Roger J.] N Carolina State Univ, Raleigh, NC 27965 USA. [Wang, Haorong; Sun, Ted] Sun Innovat Inc, Fremont, CA 94539 USA. RP Petrochenko, PE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM roger_narayan@msn.com RI Narayan, Roger/J-2789-2013 OI Narayan, Roger/0000-0002-4876-9869 FU NSF/FDA [1041375] FX Peter E. Petrochenko is supported in part by an NSF/FDA Scholar-in-Residence Award #1041375. The authors would also like to acknowledge Sun Innovations for providing samples of rare earth metal nanoparticles that were used in the study. NR 41 TC 5 Z9 5 U1 0 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1546-542X J9 INT J APPL CERAM TEC JI Int. J. Appl. Ceram. Technol. PD SEP-OCT PY 2012 VL 9 IS 5 BP 881 EP 892 DI 10.1111/j.1744-7402.2012.02784.x PG 12 WC Materials Science, Ceramics SC Materials Science GA 001EW UT WOS:000308444200001 ER PT J AU Fiorentino, R Liu, GM Pariser, AR Mulberg, AE AF Fiorentino, Robert Liu, Gumei Pariser, Anne R. Mulberg, Andrew E. TI Cross-sector sponsorship of research in eosinophilic esophagitis: A collaborative model for rational drug development in rare diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Clinical outcome assessment; eosinophilic esophagitis; the International Gastrointestinal Eosinophil Researchers; US Food and Drug Administration; Study Endpoints and Labeling Development ID PLACEBO-CONTROLLED TRIAL; CLINICAL-RESEARCH; CHILDREN; ADULTS AB Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives. (J Allergy Clin Immunol 2012;130:613-6.) C1 [Fiorentino, Robert; Mulberg, Andrew E.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Gastroenterol & Inborn Errors Prod, Silver Spring, MD 20993 USA. [Liu, Gumei; Pariser, Anne R.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rare Dis Program, Silver Spring, MD 20993 USA. RP Mulberg, AE (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Gastroenterol & Inborn Errors Prod, 10903 New Hampshire Ave,Bldg 22,Rm 5114, Silver Spring, MD 20993 USA. EM Andrew.mulberg@fda.hhs.gov NR 19 TC 24 Z9 24 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2012 VL 130 IS 3 BP 613 EP 616 DI 10.1016/j.jaci.2012.07.011 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 001LZ UT WOS:000308463500006 PM 22857796 ER PT J AU Sauna, ZE Ameri, A Kim, B Yanover, C Viel, KR Rajalingam, R Cole, SA Howard, TE AF Sauna, Z. E. Ameri, A. Kim, B. Yanover, C. Viel, K. R. Rajalingam, R. Cole, S. A. Howard, T. E. TI Observations regarding the immunogenicity of BDD-rFVIII derived from a mechanistic personalized medicine perspective SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID RECOMBINANT FACTOR-VIII; HEMOPHILIA-A; INHIBITORS; PROTEIN C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Sauna, Z. E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ameri, A.] Georgia Hlth Sci Univ, Div Hematol & Oncol, Dept Pediat, Augusta, GA USA. [Kim, B.] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Viel, K. R.] Histonis Inc, Atlanta, GA USA. [Rajalingam, R.] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geen Sch Med, Immunogenet Ctr, Los Angeles, CA USA. [Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Howard, T. E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Room 1258, Los Angeles, CA 90073 USA. EM tom.howard@va.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU NHLBI NIH HHS [1RC2-HL101851, HL-71130, HL-72533] NR 17 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2012 VL 10 IS 9 BP 1961 EP 1965 DI 10.1111/j.1538-7836.2012.04830.x PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 999FI UT WOS:000308294400032 PM 22734827 ER PT J AU Ferlin, KM Kaplan, DS Fisher, JP AF Ferlin, K. M. Kaplan, D. S. Fisher, J. P. TI Chondrocyte adhesion and phenotype maintenance in 2D and 3D substrates SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD SEP PY 2012 VL 6 SU 1 SI SI BP 350 EP 350 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 999LG UT WOS:000308313003103 ER PT J AU Maher, C Hu-Primmer, J MacGill, T Courtney, B Borio, L AF Maher, Carmen Hu-Primmer, Jean MacGill, Tracy Courtney, Brooke Borio, Luciana TI Meeting the challenges of medical countermeasure development SO MICROBIAL BIOTECHNOLOGY LA English DT Review AB Despite substantial investments since the events of 2001, much work remains to prepare the nation for a chemical, biological, radiological or nuclear (CBRN) attack or to respond to an emerging infectious disease threat. Following a 2010 review of the US Public Health Emergency Medical Countermeasures Enterprise, FDA launched its Medical Countermeasures initiative (MCMi) to facilitate the development and availability of medical products to counter CBRN and emerging disease threats. As a regulatory agency, FDA has a unique and critical part to play in this national undertaking. Using a three-pillar approach, FDA is addressing key challenges associated with the regulatory review process for medical countermeasures; gaps in regulatory science for MCM development and evaluation; and issues related to the legal, regulatory and policy framework for an effective public health response. Filling the gaps in the MCM Enterprise is a huge national undertaking, requiring the collaboration of all stakeholders, including federal partners, current and prospective developers of medical countermeasures, relevant research organizations, and state and local responders. Especially critical to success are an appreciation of the long timelines, risks and high costs associated with developing medical countermeasures and the systems to deliver them and the requisite support of all stakeholders, including national leadership. C1 [Maher, Carmen; Hu-Primmer, Jean; MacGill, Tracy; Courtney, Brooke; Borio, Luciana] Med Countermeasures Initiat MCMi, FDA, Silver Spring, MD USA. RP Maher, C (reprint author), Med Countermeasures Initiat MCMi, FDA, Silver Spring, MD USA. EM Carmen.Maher@fda.hhs.gov NR 15 TC 2 Z9 2 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7907 J9 MICROB BIOTECHNOL JI Microb. Biotechnol. PD SEP PY 2012 VL 5 IS 5 SI SI BP 588 EP 593 DI 10.1111/j.1751-7915.2012.00362.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 995WS UT WOS:000308046100003 PM 22925432 ER PT J AU Mullard, A McClellan, M AF Mullard, Asher McClellan, Mark TI AN AUDIENCE WITH ... Mark McClellan SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 [McClellan, Mark] Brookings Inst, Ctr Hlth Care Reform, Washington, DC 20036 USA. [McClellan, Mark] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2012 VL 11 IS 9 BP 668 EP 668 DI 10.1038/nrd3837 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 003BE UT WOS:000308582300012 ER PT J AU Anez, G Heisey, DA Espina, LM Stramer, SL Rios, M AF Anez, G. Heisey, D. A. Espina, L. M. Stramer, S. L. Rios, M. TI Phylogenetic Analysis of Dengue Virus Types 1 and 4 Circulating in Blood Donors from Puerto Rico and Key West, Florida, During 2010 Epidemics SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Anez, G.; Heisey, D. A.; Espina, L. M.; Rios, M.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA. EM German.Anez@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 14A EP 14A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600010 ER PT J AU Bosch-Marce, M Seetharaman, S Kurtz, J Wagner, SJ Mohan, KV Atreya, CD AF Bosch-Marce, M. Seetharaman, S. Kurtz, J. Wagner, S. J. Mohan, K. V. Atreya, C. D. TI Evaluation of In Vitro Properties of Leukoreduced Whole Blood-derived Platelets Treated with Antimicrobial Peptides SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Bosch-Marce, M.; Mohan, K. V.; Atreya, C. D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Seetharaman, S.; Kurtz, J.; Wagner, S. J.] Amer Red Cross, Blood Components Dept, Rockville, MD USA. EM marta.boschmarce@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 71A EP 71A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600153 ER PT J AU Gelderman, MP Farrell, JA Yazer, MH Waters, JH Vostal, JG AF Gelderman, M. P. Farrell, J. A. Yazer, M. H. Waters, J. H. Vostal, J. G. TI Impact of Rejuvenation on Physical Stress Resistance of Male and Pre-menopausal Female Red Blood Cells During Storage SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Gelderman, M. P.; Farrell, J. A.; Vostal, J. G.] US FDA, Lab Cellular Hematol DH, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Yazer, M. H.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Yazer, M. H.] Univ Pittsburgh, Inst Transfus Med, Pittsburgh, PA USA. [Waters, J. H.] Univ Pittsburgh, Dept Anesthesia, Pittsburgh, PA USA. EM monique.gelderman-fuhrmann@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 79A EP 79A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600172 ER PT J AU Illoh, O Holness, L Davey, R AF Illoh, O. Holness, L. Davey, R. TI Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors: Summary of a Workshop SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Illoh, O.; Holness, L.; Davey, R.] US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. EM Orieji.Illoh@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 92A EP 93A PG 2 WC Hematology SC Hematology GA 000PH UT WOS:000308398600207 ER PT J AU Menis, M Anderson, SA Holness, L Kropp, G Wang, EL Johnson, C Worrall, CM Kelman, JA Ball, R Izurieta, H AF Menis, M. Anderson, S. A. Holness, L. Kropp, G. Wang, E. L. Johnson, C. Worrall, C. M. Kelman, J. A. Ball, R. Izurieta, H. TI Transfusion-Associated Circulatory Overload (TACO) Among Inpatient US Elderly as Recorded in Medicare Administrative Databases During 2011 SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Menis, M.; Anderson, S. A.; Holness, L.; Ball, R.; Izurieta, H.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Kropp, G.; Wang, E. L.; Johnson, C.] Acumen LLC, Burlingame, CA USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicare Serv, Baltimore, MD USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicaid Serv, Baltimore, MD USA. EM Mikhail.Menis@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 169A EP 169A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600412 ER PT J AU Illoh, O Holness, L Barash, F Haddad, S Espinola, R Mullersman, J Cannon, S AF Illoh, O. Holness, L. Barash, F. Haddad, S. Espinola, R. Mullersman, J. Cannon, S. TI Anaphylactic Transfusion Reactions: A Six-year Review of Fatalities Reported to the FDA SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Illoh, O.; Holness, L.; Haddad, S.; Espinola, R.] US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. [Barash, F.; Mullersman, J.] US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA. [Cannon, S.] US FDA, Off Compliance & Biol Qual, Rockville, MD 20857 USA. EM Orieji.Illoh@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 171A EP 171A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600417 ER PT J AU Menis, M Izurieta, H Anderson, SA Kropp, G Johnson, C Wang, EL Golding, B Worrall, CM Forshee, R Kelman, JA AF Menis, M. Izurieta, H. Anderson, S. A. Kropp, G. Johnson, C. Wang, E. L. Golding, B. Worrall, C. M. Forshee, R. Kelman, J. A. TI Use of Immune Globulins Among the US Elderly as Recorded in Medicare Databases During a Five-Year Period, 2007-2011 SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Menis, M.; Izurieta, H.; Anderson, S. A.; Golding, B.; Forshee, R.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Kropp, G.; Johnson, C.; Wang, E. L.] Acumen LLC, Burlingame, CA USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicare Serv, Baltimore, MD USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicaid Serv, Baltimore, MD USA. EM Mikhail.Menis@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 193A EP 193A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600475 ER PT J AU Grigorenko, E Fisher, C Patel, S Tibbets, C Kourout, M Purkayastha, A Nakhasi, HL Duncan, RC AF Grigorenko, E. Fisher, C. Patel, S. Tibbets, C. Kourout, M. Purkayastha, A. Nakhasi, H. L. Duncan, R. C. TI Evaluation of New Technology Multiplex Nucleic Acid Tests for Emerging and Blood Borne Pathogens SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Fisher, C.; Kourout, M.; Nakhasi, H. L.; Duncan, R. C.] US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Grigorenko, E.; Patel, S.] Life Technol Corp, Beverly, MA USA. [Tibbets, C.; Purkayastha, A.] TessArae LLC, Potomac Falls, VA USA. EM Elena.Grigorenko@lifetech.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 213A EP 214A PG 2 WC Hematology SC Hematology GA 000PH UT WOS:000308398600527 ER PT J AU McDowell, K Nag, N Beren, J Asher, D Gregori, L AF McDowell, K. Nag, N. Beren, J. Asher, D. Gregori, L. TI Development of vCJD-Infected Blood Reference Materials SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [McDowell, K.; Nag, N.; Beren, J.; Asher, D.; Gregori, L.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Kristy.McDowell@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 213A EP 213A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600526 ER PT J AU Grinev, A Chancey, C Chizhikov, V Rios, M AF Grinev, A. Chancey, C. Chizhikov, V. Rios, M. TI Next Generation Microarray-based Assay Allows for Rapid Detection of West Nile Virus Genetic Variants SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Grinev, A.; Chancey, C.; Chizhikov, V.; Rios, M.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM andriyan.grinev@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 222A EP 222A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600549 ER PT J AU Chancey, C Teixeira-Carvalho, A Anez, G Espina, LM Rios, M AF Chancey, C. Teixeira-Carvalho, A. Anez, G. Espina, L. M. Rios, M. TI Flow Cytometry Shows Biochemical Variations and Structural Changes in RBC Upon Binding of West Nile and Dengue Viruses SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Chancey, C.; Teixeira-Carvalho, A.; Anez, G.; Espina, L. M.; Rios, M.] US FDA, DETTD, CBER, Bethesda, MD 20014 USA. [Teixeira-Carvalho, A.] Fiocruz MS, CPqRR, Belo Horizonte, MG, Brazil. EM caren.chancey@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 226A EP 226A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600561 ER PT J AU Wang, X Tan, J Zhang, P Zhao, J Hewlett, I AF Wang, X. Tan, J. Zhang, P. Zhao, J. Hewlett, I. TI Influenza A Virus (H5N1) Can Be Transmitted Through Blood Transfusion in Ferrets SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Wang, X.; Tan, J.; Zhang, P.; Zhao, J.; Hewlett, I.] US FDA, CBEER DETTD, Bethesda, MD 20014 USA. EM xue.wang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 226A EP 227A PG 2 WC Hematology SC Hematology GA 000PH UT WOS:000308398600562 ER PT J AU Espinola, R O'Callaghan, S Weir, L Mercado, TC Illoh, O Davey, R AF Espinola, R. O'Callaghan, S. Weir, L. Mercado, T. C. Illoh, O. Davey, R. TI Quarantine Release Errors (QREs) in Blood Establishments: Summary of a Public Workshop SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 06-09, 2012 CL Boston, MA SP AABB, CTTXPO C1 [Espinola, R.; O'Callaghan, S.; Weir, L.; Mercado, T. C.; Illoh, O.; Davey, R.] US FDA, Off Blood Res & Review, Div Blood Applicat, Rockville, MD 20857 USA. [Espinola, R.; O'Callaghan, S.; Weir, L.; Mercado, T. C.; Illoh, O.; Davey, R.] US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM ricardo.espinola@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2012 VL 52 SU 3 SI SI BP 269A EP 269A PG 1 WC Hematology SC Hematology GA 000PH UT WOS:000308398600673 ER PT J AU Marshall, V Gruber, M AF Marshall, Valerie Gruber, Marion TI Influenza immunization during pregnancy: US regulatory perspective SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Food and Drug Administration; influenza vaccine; labeling; pregnancy ID MATERNAL IMMUNIZATION; YOUNG INFANTS; VACCINATION; ANTIBODY; WOMEN; MOTHER; SAFETY AB Maternal immunization with inactivated influenza vaccines is an important public health strategy to protect mothers and young infants from the serious complications of influenza. Although not contraindicated in pregnant women, currently US-licensed influenza vaccines are not specifically labeled for use during pregnancy. Several postmarketing initiatives are ongoing to obtain maternal and infant safety and immunogenicity data on US-licensed inactivated influenza vaccines used in pregnant women. The Food and Drug Administration is revising its pregnancy labeling regulations to improve the characterization and communication of risks of drugs and biologics used during pregnancy. To obtain a specifically labeled indication for use of an influenza vaccine during pregnancy, adequate and well-controlled prelicensure studies are needed to obtain data on the product's safety and effectiveness and to demonstrate protection of the mother and/or infant against influenza illness. C1 [Marshall, Valerie; Gruber, Marion] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. RP Marshall, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. NR 24 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2012 VL 207 IS 3 SU S BP S57 EP S62 DI 10.1016/j.ajog.2012.06.075 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997SC UT WOS:000308185400011 PM 22920061 ER PT J AU Orzechowski, KL Swain, MD Robl, MG Tinaza, CA Swaim, HL Jones, YL Myers, MJ Yancy, HF AF Orzechowski, Krystyna L. Swain, Marla D. Robl, Martin G. Tinaza, Constante A. Swaim, Heidi L. Jones, Yolanda L. Myers, Michael J. Yancy, Haile F. TI Neurotoxic effects of ivermectin administration in genetically engineered mice with targeted insertion of the mutated canine ABCB1 gene SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID TRANSPORTING P-GLYCOPROTEINS; BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; BREED DISTRIBUTION; DELETION MUTATION; KNOCKOUT MICE; MDR1; TOXICITY; DOGS; SENSITIVITY AB Objective-To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. Animals-14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Procedures-Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. Results-After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. Conclusions and Clinical Relevance-The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1-1 Delta mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process. (Am J Vet Res 2012;73:1477-1484) C1 [Orzechowski, Krystyna L.; Swain, Marla D.; Swaim, Heidi L.; Jones, Yolanda L.; Myers, Michael J.; Yancy, Haile F.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Robl, Martin G.; Tinaza, Constante A.] US FDA, Off Appl Res & Safety Assessments, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Yancy, HF (reprint author), US FDA, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM haile.yancy@fda.hhs.gov NR 37 TC 3 Z9 3 U1 1 U2 8 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD SEP PY 2012 VL 73 IS 9 BP 1477 EP 1484 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 994EK UT WOS:000307913500019 PM 22924731 ER PT J AU James, LP Senior, J AF James, L. P. Senior, J. TI Gastrohepatology: Tools, Targets, and Trajectories SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID C VIRUS-INFECTION AB Gastrointestinal (GI) and hepatic conditions are a leading source of healthcare utilization today. A significant segment of the over-the-counter and prescription drug market comprises drugs used to alleviate symptoms localized to the alimentary tract. The discovery of new mechanisms of disease pathogenesis will inform the future development of targeted therapeutics for conditions managed by gastroenterologists and hepatologists. Newly approved drugs and evolving mechanistic targets offer a promising trajectory to both clinicians and patients with GI and liver disorders. C1 [James, L. P.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [James, L. P.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Senior, J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP James, LP (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. EM jameslaurap@uams.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2012 VL 92 IS 3 BP 267 EP 271 DI 10.1038/clpt.2012.123 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994PU UT WOS:000307944100001 PM 22910480 ER PT J AU Lee, SC Apparaju, S Kim, I Estes, K Jappar, D Bashaw, ED AF Lee, S-C Apparaju, S. Kim, I. Estes, K. Jappar, D. Bashaw, E. D. TI Clinical Pharmacology Considerations in Development of Gastrohepatology Products SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID HEALTHY-VOLUNTEERS AB Clinical pharmacology has a key role in advancing candidate drugs from bench to bedside. A thorough understanding of underlying pharmacokinetic (PK) and pharmacodynamic (PD) processes is essential to inform the next steps in any drug development program with the goal of personalized medicine. Development of gastrohepatology drug products faces unique clinical pharmacology challenges that require collaborative efforts from academia, the pharmaceutical industry, and regulatory agencies. RP Lee, SC (reprint author), US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM suechih.lee@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2012 VL 92 IS 3 BP 281 EP 283 DI 10.1038/clpt.2012.121 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994PU UT WOS:000307944100007 PM 22910484 ER PT J AU Senior, JR AF Senior, J. R. TI Alanine Aminotransferase: A Clinical and Regulatory Tool for Detecting Liver Injury-Past, Present, and Future SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SERUM TRANSAMINASE ACTIVITY; ADVERSE DRUG-REACTIONS; CAUSALITY ASSESSMENT; HEPATOTOXICITY; DISEASE; TRIALS; POPULATION; VALIDATION; DIAGNOSIS; BLOOD AB Assay of the serum activity of the enzyme alanine aminotransferase (ALT) has become the primary screening tool for detecting acute liver injury. But what does an elevated value mean? Not what it is too often mistakenly believed to indicate. It is not a test of liver function. It does not necessarily predict worse effects to come (in a given person). It is not a valid measure of severity of liver injury or dysfunction. It is too unspecific to be reliable in screening for relatively rare effects on the liver. Although these are substantial limitations, ALT is a very useful biomarker if understood and used properly. It is important to consider how and why these erroneous concepts came to have such wide acceptance, and how elevations of ALT activity for evaluating patients and subjects under study might be interpreted better. C1 US FDA, Off Pharmacovigilance & Epidemiol, Ctr Drug Evaluat & Res, Fed Res Ctr White Oak, Silver Spring, MD USA. RP Senior, JR (reprint author), US FDA, Off Pharmacovigilance & Epidemiol, Ctr Drug Evaluat & Res, Fed Res Ctr White Oak, Silver Spring, MD USA. EM john.senior@fda.hhs.gov NR 51 TC 30 Z9 30 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2012 VL 92 IS 3 BP 332 EP 339 DI 10.1038/clpt.2012.108 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994PU UT WOS:000307944100014 PM 22871997 ER PT J AU Sauna, ZE Ameri, A Kim, B Yanover, C Viel, KR Rajalingam, R Cole, SA Howard, TE AF Sauna, Z. E. Ameri, A. Kim, B. Yanover, C. Viel, K. R. Rajalingam, R. Cole, S. A. Howard, T. E. TI A view of the Aledort-Iorio Debate concerning the immunogenicity of B-Domain-deleted and full-length recombinant FVIII products from a mechanistic personalized medicine perspective SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Sauna, Z. E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ameri, A.] Georgia Hlth Sci Univ, Div Hematol & Oncol, Dept Pediat, Augusta, GA USA. [Kim, B.; Howard, T. E.] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA. [Kim, B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Viel, K. R.] Histonis Inc, Atlanta, GA USA. [Rajalingam, R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, UCLA Immunogenet Ctr, Los Angeles, CA 90095 USA. [Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2012 VL 18 IS 5 BP 830 EP 830 PG 1 WC Hematology SC Hematology GA 993ZT UT WOS:000307900700054 ER PT J AU Plaut, RD Kelly, VK Lee, GM Stibitz, S Merkel, TJ AF Plaut, Roger D. Kelly, Vanessa K. Lee, Gloria M. Stibitz, Scott Merkel, Tod J. TI Dissemination Bottleneck in a Murine Model of Inhalational Anthrax SO INFECTION AND IMMUNITY LA English DT Article ID AEROSOL CHALLENGE MODEL; BACILLUS-ANTHRACIS; SALMONELLA-TYPHIMURIUM; FLUORESCENT PROTEIN; INDEPENDENT ACTION; FATAL INFECTIONS; SINGLE ORGANISM; PATHOLOGY; SPORES; PATHOGENESIS AB Inhalational anthrax is caused by the sporulating bacterium Bacillus anthracis. A current model for progression in mammalian hosts includes inhalation of bacterial spores, phagocytosis of spores in the nasal mucosa-associated lymphoid tissue (NALT) and lungs by macrophages and dendritic cells, trafficking of phagocytes to draining lymph nodes, germination of spores and multiplication of vegetative bacteria in the NALT and lymph nodes, and dissemination of bacteria via the bloodstream to multiple organs. In previous studies, the kinetics of infection varied greatly among mice, leading us to hypothesize the existence of a bottleneck past which very few spores (perhaps only one) progress to allow the infection to proceed. To test this hypothesis, we engineered three strains of B. anthracis Sterne, each marked with a different fluorescent protein, enabling visual differentiation of strains grown on plates. Mice were infected with a mixture of the three strains, the infection was allowed to proceed, and the strains colonizing the organs were identified. Although the inoculum consisted of approximately equal numbers of each of the three strains, the distal organs were consistently colonized by a majority of only one of the three strains, with the dominant strain varying among animals. Such dominance of one strain over the other two was also found at early time points in the cervical lymph nodes but not in the mediastinal lymph nodes. These results support the existence of a bottleneck in the infectious process. C1 [Plaut, Roger D.; Kelly, Vanessa K.; Lee, Gloria M.; Stibitz, Scott; Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Merkel, TJ (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM tod.merkel@fda.hhs.gov RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X FU NIH NIAID Middle Atlantic Regional Center of Excellence [U54 AI057168] FX This work was supported by NIH NIAID Middle Atlantic Regional Center of Excellence grant U54 AI057168. NR 36 TC 14 Z9 14 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2012 VL 80 IS 9 BP 3189 EP 3193 DI 10.1128/IAI.00515-12 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 993ON UT WOS:000307869100020 PM 22753373 ER PT J AU Toomey, VM Nickum, EA Flurer, CL AF Toomey, Valerie M. Nickum, Elisa A. Flurer, Cheryl L. TI Cyanide and Amygdalin as Indicators of the Presence of Bitter Almonds in Imported Raw Almonds SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; bitter almonds; amygdalin; cyanide; liquid chromatography-mass spectrometry; ultraviolet-visible spectrophotometry ID ACID-HYDROLYSIS; PLANTS; LEAVES AB Consumer complaints received by the U.S. Food and Drug Administration in August 2010 about raw organic almonds tasting bitter opened an investigation into the presence of bitter almonds in the imported product. Bitter almonds (Prunus amygdalus) contain the cyanogenic glucoside amygdalin, which hydrolyzes to produce cyanide. Ultravioletvisible spectrophotometry was used to detect and quantitate cyanide, and liquid chromatography-mass spectrometry was utilized to detect amygdalin in the submitted samples. Control bitter almonds were found to contain 1.4 mg cyanide/g and an estimated level of 2025 mg amygdalin/g. The questioned samples contained between 14 and 42 mu g cyanide/g and were positive for the presence of amygdalin. Sweet almonds were found to be negative for both compounds, at levels of detection of 4 mu g cyanide/g and 200 mu g amygdalin/g. C1 [Toomey, Valerie M.; Nickum, Elisa A.; Flurer, Cheryl L.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM cheryl.flurer@fda.hhs.gov NR 12 TC 3 Z9 4 U1 3 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 2012 VL 57 IS 5 BP 1313 EP 1317 DI 10.1111/j.1556-4029.2012.02138.x PG 5 WC Medicine, Legal SC Legal Medicine GA 000MX UT WOS:000308391500025 PM 22564183 ER PT J AU Brzezinski, JL Craft, DL AF Brzezinski, Jennifer L. Craft, David L. TI Characterization of Microorganisms Isolated from Counterfeit Toothpaste SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; toothpaste; counterfeit drug; bacteria; Colgate; enterobacteriaceae AB The appearance of potentially counterfeit Colgate toothpaste on the American market prompted a criminal investigation by the United States Food and Drug Administration (FDA), including the collection of c. 60,000 tubes of toothpaste from retail outlets and product distributors. Microbiological testing was performed based on the FDA Bacteriological Analytical Manual, which determined the presence and number of bacteria present in the products. Bacteria were isolated from each Colgate variety; up to 2 X 106 cfu/g were isolated from some of the product units. Using conventional microscopic and biochemical bacterial identification methods, most of the bacteria isolated from these samples were Gram-negative rods of several genera, including Pseudomonas, Serratia, and Klebsiella. Most of the organisms isolated represent opportunistic pathogens, and therefore, counterfeit Colgate toothpaste containing high levels of bacteria pose a human health hazard. C1 [Brzezinski, Jennifer L.; Craft, David L.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Brzezinski, JL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM jennifer.brzezinski@fda.hhs.gov NR 5 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 2012 VL 57 IS 5 BP 1365 EP 1367 DI 10.1111/j.1556-4029.2012.02130.x PG 3 WC Medicine, Legal SC Legal Medicine GA 000MX UT WOS:000308391500035 PM 22509777 ER PT J AU Kelly, KA Miller, DB Bowyer, JF O'Callaghan, JP AF Kelly, Kimberly A. Miller, Diane B. Bowyer, John F. O'Callaghan, James P. TI Chronic exposure to corticosterone enhances the neuroinflammatory and neurotoxic responses to methamphetamine SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glucocorticoids; methamphetamine; microglial activation; neuroinflammation; neurotoxicity; stress ID FIBRILLARY ACIDIC PROTEIN; NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; MICROGLIAL ACTIVATION; NEURONAL DEGENERATION; DOPAMINERGIC NEUROTOXICITY; SUBSTITUTED AMPHETAMINES; PARKINSONS-DISEASE; STRIATAL GLUTAMATE; GENE-EXPRESSION AB J. Neurochem. (2012) 122, 9951009. Abstract Up-regulation of proinflammatory cytokines and chemokines in brain (neuroinflammation) accompanies neurological disease and neurotoxicity. Previously, we documented a striatal neuroinflammatory response to acute administration of a neurotoxic dose of methamphetamine (METH), i.e. one associated with evidence of dopaminergic terminal damage and activation of microglia and astroglia. When we used minocycline to suppress METH-induced neuroinflammation, indices of dopaminergic neurotoxicity were not affected, but suppression of neuroinflammation was incomplete. Here, we administered the classic anti-inflammatory glucocorticoid, corticosterone (CORT), in an attempt to completely suppress METH-related neuroinflammation. METH alone caused large increases in striatal proinflammatory cytokine/chemokine mRNA and subsequent astrocytic hypertrophy, microglial activation, and dopaminergic nerve terminal damage. Pre-treatment of mice with acute CORT failed to prevent neuroinflammatory responses to METH. Surprisingly, when mice were pre-treated with chronic CORT in the drinking water, an enhanced striatal neuroinflammatory response to METH was observed, an effect that was accompanied by enhanced METH-induced astrogliosis and dopaminergic neurotoxicity. Chronic CORT pre-treatment also sensitized frontal cortex and hippocampus to mount a neuroinflammatory response to METH. Because the levels of chronic CORT used are associated with high physiological stress, our data suggest that chronic CORT therapy or sustained physiological stress may sensitize the neuroinflammatory and neurotoxicity responses to METH. C1 [Kelly, Kimberly A.; Miller, Diane B.; O'Callaghan, James P.] NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. [Bowyer, John F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP O'Callaghan, JP (reprint author), NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. EM jdo5@cdc.gov RI Kelly, Kimberly/J-9834-2012; O'Callaghan, James/O-2958-2013; Miller, Diane/O-2927-2013 OI Kelly, Kimberly/0000-0002-1146-3137; FU Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health FX Intramural funds from the Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NR 83 TC 28 Z9 28 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2012 VL 122 IS 5 BP 995 EP 1009 DI 10.1111/j.1471-4159.2012.07864.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 994YA UT WOS:000307969700013 PM 22776046 ER PT J AU Argaw, T Wilson, CA AF Argaw, Takele Wilson, Carolyn A. TI Detailed Mapping of Determinants within the Porcine Endogenous Retrovirus Envelope Surface Unit Identifies Critical Residues for Human Cell Infection within the Proline-Rich Region SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RECEPTOR-BINDING DOMAIN; HOST-RANGE; VIRAL ENTRY; SUBGROUP-B; GLYCOPROTEIN; PROTEIN; TROPISM; GENE AB Replication-competent porcine endogenous retroviruses (PERVs) are either human cell tropic (PERV-A and PERV-B) or non-human cell tropic (PERV-C). We previously demonstrated that PERV in vitro cell tropism is modulated by 2 residues within the C terminus of SU and that the PERV receptor binding domain (RBD) extends beyond the variable regions A and B (VRA and VRB, respectively), to include the proline rich-region (PRR) of SU (M. Gemeniano et al., Virology 346:108-117, 2000; T. Argaw et al., J. Virol. 82:7483-7489, 2008). The present study aimed to identify the specific elements within the PERV RBD that interact with the C-terminal elements of SU to facilitate human cell infection. We constructed a series of chimeric and mutated envelopes between PERV-A and PERV-C and using pseudotyped retroviral vectors to map the human cell tropism-determining sequences within the PERV RBD. We show that the PRR from PERV-A is both necessary and sufficient to allow human cell infection when substituted into the homologous region of the PERV-C envelope carrying two C-terminal amino acid substitutions shown to influence human cell tropism, Q374R and I412V (PERV-Crv). Furthermore, substitution of a single amino acid residue in the PRR of the non-human-tropic PERV-Crv envelope allows vectors carrying this envelope to infect human cells. Receptor interference assays showed that these modified PERV-C envelopes do not bind either of the human PERV-A receptors, suggesting the presence of a distinct human PERV-C receptor. Finally, vectors carrying these modified PERV-C envelopes infect primary human endothelial cells, a cell type likely to be exposed to PERV in clinical use of certain porcine xenotransplantation products. C1 [Argaw, Takele; Wilson, Carolyn A.] US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wilson, CA (reprint author), US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Carolyn.wilson@fda.hhs.gov FU Howard Hughes Medical Institute NR 29 TC 6 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2012 VL 86 IS 17 BP 9096 EP 9104 DI 10.1128/JVI.00738-12 PG 9 WC Virology SC Virology GA 990JW UT WOS:000307627800016 PM 22696659 ER PT J AU Krishnaiah, YSR Khan, MA AF Krishnaiah, Yellela S. R. Khan, Mansoor A. TI Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Review DE Colorectal cancer; colon-specific drug delivery; oral; targeted; treatment; prevention ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INFLAMMATORY-BOWEL-DISEASE; IN-VIVO EVALUATION; FAMILIAL ADENOMATOUS POLYPOSIS; GASTROINTESTINAL PH PROFILES; ULCERATIVE-COLITIS; GUAR GUM; CYCLOOXYGENASE-2 INHIBITOR; DOSAGE FORMS; 5-AMINOSALICYLIC ACID AB Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC. C1 [Krishnaiah, Yellela S. R.; Khan, Mansoor A.] US FDA, CDER, OPS, OTR,Div Prod Qual Res, Silver Spring, MD 20993 USA. RP Krishnaiah, YSR (reprint author), US FDA, CDER, OPS, OTR,Div Prod Qual Res, 10903 New Hampshire Ave,White Oak Bldg 64, Silver Spring, MD 20993 USA. EM krishnaiah.yellela@fda.hhs.gov NR 226 TC 14 Z9 16 U1 3 U2 44 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1083-7450 EI 1097-9867 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD SEP-OCT PY 2012 VL 17 IS 5 BP 521 EP 540 DI 10.3109/10837450.2012.696268 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995HF UT WOS:000307998100001 PM 22681390 ER PT J AU Krishnaiah, YSR Nada, A AF Krishnaiah, Yellela S. R. Nada, Aly TI Enantioselective penetration enhancing effect of carvone on the in vitro transdermal permeation of nicorandil SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE Transdermal; carvone; enantiomers; in vitro permeation; enantioselective; rat epidermis ID HUMAN STRATUM-CORNEUM; RAT ABDOMINAL SKIN; PERCUTANEOUS-ABSORPTION ENHANCEMENT; MOLECULARLY IMPRINTED POLYMER; THERAPEUTIC SYSTEM; HUMAN VOLUNTEERS; RACEMIC PROPRANOLOL; COMPOSITE MEMBRANE; HAIRLESS MOUSE; HPMC GEL AB The objective was to investigate the difference in penetration enhancing effect of R-carvone, S-carvone and RS-carvone on the in vitro transdermal drug permeation. In vitro permeation studies were carried out across neonatal rat epidermis from 2% w/v HPMC (hydroxypropyl methylcellulose) gel containing 4% w/v of nicorandil (a model drug) and a selected concentration (12% w/v) of either R-carvone, S-carvone or RS-carvone against a control. The stratum corneum (SC) of rats was treated with vehicle (70% v/v ethanol-water) or ethanolic solutions of 12% w/v R-carvone, S-carvone or RS-carvone. The enhancement ratio (ER) of R-carvone, S-carvone and RS-carvone when compared to control was about 37.1, 31.2 and 29.9, respectively indicating enantioselective penetration enhancing effect of carvone enantiomers. Furthermore, there was a significant decrease in the lag time required to produce a steady-state flux of nicorandil with S-carvone when compared to R-carvone and RS-carvone. DSC and FT-IR studies indicate that the investigated enantiomers of carvone exhibit a difference in their ability to affect the cellular organization of SC lipids and proteins thereby showing enantioselective transdermal drug permeation. It was concluded that R-carvone exhibited a higher penetration enhancing activity on transdermal permeation of nicorandil when compared to its S-isomer or racemic mixture. C1 [Krishnaiah, Yellela S. R.] Nova SE Univ, Coll Pharm, Ft Lauderdale, FL 33314 USA. [Krishnaiah, Yellela S. R.; Nada, Aly] Kuwait Univ, Fac Pharm, Dept Pharmaceut, Kuwait, Kuwait. RP Krishnaiah, YSR (reprint author), US FDA, Div Prod Qual & Res, CDER, OPS,OTR, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM krishnaiah.yellela@fda.hhs.gov RI Krishaiah, Yellela/B-1124-2011 OI Krishaiah, Yellela/0000-0002-4844-911X FU Kuwait University [PP02/05] FX This work was supported by Kuwait University Research Grant No. PP02/05. NR 57 TC 2 Z9 3 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD SEP-OCT PY 2012 VL 17 IS 5 BP 574 EP 582 DI 10.3109/10837450.2011.557729 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995HF UT WOS:000307998100005 PM 21428701 ER PT J AU Xiong, Y Zhou, ZH Notkins, AL AF Xiong, Y. Zhou, Z. -H. Notkins, A. L. TI Pictorial Demonstration of the Simultaneous Binding of Multiple Unrelated Antigens to Individual Polyreactive Antibody-Producing B Cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Letter ID MONOCLONAL AUTOANTIBODIES; REPERTOIRE; ORGANS; REACT C1 [Xiong, Y.; Notkins, A. L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Zhou, Z. -H.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov FU Intramural NIH HHS [ZIA DE000423-25] NR 7 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD SEP PY 2012 VL 76 IS 3 BP 342 EP 343 DI 10.1111/j.1365-3083.2012.02746.x PG 2 WC Immunology SC Immunology GA 996MV UT WOS:000308094200018 PM 22703112 ER PT J AU Grim, CJ Kothary, MH Gopinath, G Jarvis, KG Beaubrun, JJG McClelland, M Tall, BD Franco, AA AF Grim, C. J. Kothary, M. H. Gopinath, G. Jarvis, K. G. Beaubrun, J. Jean-Gilles McClelland, M. Tall, B. D. Franco, A. A. TI Identification and Characterization of Cronobacter Iron Acquisition Systems SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ENTEROBACTER-SAKAZAKII INFECTIONS; BIDIRECTIONAL PROMOTER REGION; ESCHERICHIA-COLI O157-H7; CITRATE TRANSPORT-SYSTEM; POWDERED INFANT FORMULA; SALMONELLA-ENTERICA; OUTER-MEMBRANE; YERSINIA-ENTEROCOLITICA; SHIGELLA-DYSENTERIAE; RECEPTOR PROTEINS AB Cronobacter spp. are emerging pathogens that cause severe infantile meningitis, septicemia, or necrotizing enterocolitis. Contaminated powdered infant formula has been implicated as the source of Cronobacter spp. in most cases, but questions still remain regarding the natural habitat and virulence potential for each strain. The iron acquisition systems in 231 Cronobacter strains isolated from different sources were identified and characterized. All Cronobacter spp. have both the Feo and Efe systems for acquisition of ferrous iron, and all plasmid-harboring strains (98%) have the aerobactin-like siderophore, cronobactin, for transport of ferric iron. All Cronobacter spp. have the genes encoding an enterobactin-like siderophore, although it was not functional under the conditions tested. Furthermore, all Cronobacter spp. have genes encoding five receptors for heterologous siderophores. A ferric dicitrate transport system (fec system) is encoded specifically by a subset of Cronobacter sakazakii and C. malonaticus strains, of which a high percentage were isolated from clinical samples. Phylogenetic analysis confirmed that the fec system is most closely related to orthologous genes present in human-pathogenic bacterial strains. Moreover, all strains of C. dublinensis and C. muytjensii encode two receptors, FcuA and Fct, for heterologous siderophores produced by plant pathogens. Identification of putative Fur boxes and expression of the genes under iron-depleted conditions revealed which genes and operons are components of the Fur regulon. Taken together, these results support the proposition that C. sakazakii and C. malonaticus may be more associated with the human host and C. dublinensis and C. muytjensii with plants. C1 [Grim, C. J.; Kothary, M. H.; Gopinath, G.; Jarvis, K. G.; Beaubrun, J. Jean-Gilles; Tall, B. D.; Franco, A. A.] US FDA, CFSAN, Laurel, MD USA. [Jarvis, K. G.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [McClelland, M.] Vaccine Res Inst San Diego, San Diego, CA USA. RP Franco, AA (reprint author), US FDA, CFSAN, Laurel, MD USA. EM augusto.franco-mora@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629; McClelland, Michael/0000-0003-1788-9347 FU Department of Energy FX We thank the Department of Energy for financial support. NR 84 TC 17 Z9 18 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2012 VL 78 IS 17 BP 6035 EP 6050 DI 10.1128/AEM.01457-12 PG 16 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 990DS UT WOS:000307611800008 PM 22706064 ER PT J AU Vallejos, JR Micheletti, M Brorson, KA Moreira, AR Rao, G AF Vallejos, Jose R. Micheletti, Martina Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Optical sensor enabled rocking T-flasks as novel upstream bioprocessing tools SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE disposable bioreactors; optical sensors; T-flasks; mass transfer; scale-down; seed train ID CELL-CULTURE PROCESS; LIQUID MASS-TRANSFER; MICROTITER PLATES; BIOREACTOR SYSTEM; OXYGEN-TRANSFER; SULFITE OXIDATION; SHAKE FLASKS; GROWTH; MICROBIOREACTOR; CULTIVATION AB During the past decade, novel disposable cell culture vessels (generally referred to as Process Scouting Devices or PSDs) have become increasingly popular for laboratory scale studies and seed culture generation. However, the lack of engineering characterization and online monitoring tools for PSDs makes it difficult to elucidate their oxygen transfer capabilities. In this study, a mass transfer characterization (kLa) of sensor enabled static and rocking T-flasks is presented and compared with other non-instrumented PSDs such as CultiFlask 50 (R), spinner flasks, and SuperSpinner D 1000 (R). We have also developed a mass transfer empirical correlation that accounts for the contribution of convection and diffusion to the volumetric mass transfer coefficient (kLa) in rocking T-flasks. We also carried out a scale-down study at matched kLa between a rocking T75-flask and a 10?L (2?L filling volume) wave bioreactor (Cultibag (R)) and we observed similar DO and pH profiles as well as maximum cell density and protein titer. However, in this scale-down study, we also observed a negative correlation between cell growth and protein productivity between the rocking T-flask and the wave bioreactor. We hypothesize that this negative correlation can be due to hydrodynamic stress difference between the rocking T-flask and the Cultibag. As both cell culture devices share key similarities such as type of agitation (i.e., rocking), oxygen transfer capabilities (i.e., kLa) and disposability, we argue that rocking T-flasks can be readily integrated with wave bioreactors, making the transition from research-scale to manufacturing-scale a seamless process. Biotechnol. Bioeng. 2012;109: 22952305. (c) 2012 Wiley Periodicals, Inc. C1 [Vallejos, Jose R.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Ctr Adv Sensor Technol, Dept Chem Biochem & Environm Engn, Baltimore, MD 21250 USA. [Micheletti, Martina] UCL, Adv Ctr Biochem Engn, Dept Biochem Engn, London, England. [Brorson, Kurt A.] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rao, G (reprint author), Univ Maryland, Ctr Adv Sensor Technol, Dept Chem Biochem & Environm Engn, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM grao@umbc.edu FU Sartorius-Stedim Biotech FX Contract grant sponsor: Sartorius-Stedim Biotech NR 31 TC 3 Z9 3 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD SEP PY 2012 VL 109 IS 9 BP 2295 EP 2305 DI 10.1002/bit.24508 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 978QE UT WOS:000306759500014 PM 22473759 ER PT J AU Liu, J Florian, J Birnkrant, D Murray, J Jadhav, PR AF Liu, Jiang Florian, Jeffry Birnkrant, Debra Murray, Jeffrey Jadhav, Pravin R. TI Interferon Responsiveness Does Not Change in Treatment-Experienced Hepatitis C Subjects: Implications for Drug Development and Clinical Decisions SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GENOTYPE 1 INFECTION; PLUS RIBAVIRIN; PEGYLATED INTERFERON; RANDOMIZED-TRIAL; VIRUS-INFECTION; HCV INFECTION; RETREATMENT; THERAPY; PEGINTERFERON; TELAPREVIR AB Background. The purpose of this research was to compare interferon (IFN) responsiveness in treatment-naive and pegylated interferon a-ribavirin (P/R)-experienced subjects and to understand the implications of comparability in IFN responsiveness across treatment courses on drug development and clinical decision making. Methods. Data from 3750 subjects treated with P/R in 8 trials were reviewed. The change in hepatitis C virus (HCV) RNA at week 4 in response to P/R was compared according to end-of-study (EOS) status (responder, relapser, partial and null responder) for treatment-naive subjects and the previous P/R response status (known as prior relapsers, prior partial responders, and prior null responders at the baseline) for P/R-experienced subjects. Results. In subjects receiving a first course of P/R treatment (treatment-naive subjects), HCV RNA change after 4 weeks of P/R was correlated with EOS status on a P/R regimen. Importantly, for the first time, we have quantitatively demonstrated that IFN responsiveness in P/R-experienced subjects administered a second course of P/R treatment was similar to the IFN responsiveness in the treatment-naive subjects with corresponding EOS status. Conclusions. We contend that P/R-experienced subjects are represented within treatment-naive subjects. There are 2 important implications of this finding: (1) from a drug development perspective, a successful direct antiviral plus P/R therapy (IFN-based triple therapy) trial in P/R-experienced subjects may serve as supportive evidence in treatment-naive subjects; and (2) from a clinical decision perspective, previous P/R exposure should not alter new treatment decisions involving IFN-based triple therapy, as the IFN responsiveness to a second course of IFN is comparable. C1 [Liu, Jiang; Florian, Jeffry; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. [Birnkrant, Debra; Murray, Jeffrey] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Silver Spring, MD USA. RP Jadhav, PR (reprint author), 10903 New Hampshire Ave,Rm 3160,Bldg 51, Silver Spring, MD 20993 USA. EM pravinj@gmail.com NR 31 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2012 VL 55 IS 5 BP 639 EP 644 DI 10.1093/cid/cis510 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 988NR UT WOS:000307498300005 PM 22652581 ER PT J AU Fishman, JA Greenwald, MA Grossi, PA AF Fishman, Jay A. Greenwald, Melissa A. Grossi, Paolo A. TI Transmission of Infection With Human Allografts: Essential Considerations in Donor Screening SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ORGAN TRANSPLANT RECIPIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; WEST-NILE-VIRUS; MUSCULOSKELETAL TISSUE DONORS; TRANSMITTED VIRAL-INFECTIONS; UNITED-STATES; LIVER-TRANSPLANTATION; DISEASE TRANSMISSION; BLOOD-DONORS AB Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70 000 organs, 100 000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation. C1 [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, MGH Transplantat Ctr,Med Sch, Transplant Infect Dis Program,Infect Dis Div, Boston, MA USA. [Greenwald, Melissa A.] US FDA, US PHS, Div Human Tissues,Ctr Biol Evaluat & Res, Reprod Branch Off Cellular Tissue & Gene Therapie, Rockville, MD 20857 USA. [Grossi, Paolo A.] Univ Insubria, Dept Infect Dis, Varese, Italy. [Grossi, Paolo A.] Natl Ctr Transplantat, Rome, Italy. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org RI GROSSI, PAOLO/A-6158-2013; Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 62 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2012 VL 55 IS 5 BP 720 EP 727 DI 10.1093/cid/cis519 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 988NR UT WOS:000307498300017 PM 22670038 ER PT J AU Moallem, U Vyas, D Teter, BB Delmonte, P Zachut, M Erdman, RA AF Moallem, U. Vyas, D. Teter, B. B. Delmonte, P. Zachut, M. Erdman, R. A. TI Transfer rate of alpha-linolenic acid from abomasally infused flaxseed oil into milk fat and the effects on milk fatty acid composition in dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE alpha-linolenic acid; flaxseed oil ID EXTRUDED LINSEED; HOLSTEIN COWS; FISH-OIL; PROFILE; PLASMA; BIOHYDROGENATION; PERFORMANCE; SECRETION; RESPONSES; HULLS AB The objectives of the present study were to evaluate the transfer efficiency of a-linolenic acid (ALA) from the abomasum into milk fat, its interaction with milk fat content and yield, and the relationship between ALA and C16:0 in milk fat. Three rumen-fistulated multiparous Holstein cows at midlactation were used in a 3 x 3 Latin square design. Treatments consisted of abomasal infusion of (1) 110 mL of water/d (control), (2) 110 mL of flaxseed oil/d (low flaxseed oil, LFO), and (3) 220 mL of flaxseed oil/d (high flaxseed oil, HFO). Experimental periods were continued for 2 wk and fat supplements were infused abomasally during the last 7 d of each period. Average dry matter intake and milk yield were not affected by oil infusion. Milk fat and lactose content tended to be greater with flaxseed infusion compared with the control. Plasma ALA was 2.9- and 4.0-fold greater with LFO and HFO, respectively. The apparent transfer efficiency of ALA to milk was 44.8 and 45.7% with LFO and HFO, respectively. The C16:0 content in milk fat was decreased by 3.59 and 5.25 percentage units, whereas the ALA content was increased by 1.68 and 3.09 percentage units with LFO and HFO, respectively. Similarly, C18:2n-6 was increased by 0.95 and 1.31 percentage units with LFA and HFO, respectively, without changes in other fatty acids (FA). Total polyunsaturated FA was 4.4 and 2.7% lower in the HFO and LFO, respectively, than in the control. Furthermore, C16:0 content in the milk fat was reduced to a greater extent than the increase in ALA content, as a 1.68 and 3.09 percentage unit increase occurred in ALA compared with a 3.6 and 5.25 percentage unit decrease in C16:0 for LFO and HFO, respectively, such that a negative correlation existed between ALA and C16:0 (r = -0.72). In conclusion, abomasal infusion of flaxseed oil dramatically increased the ALA content in plasma and milk fat. Because the replacement of C16:0 with ALA and C18:2n-6 occurred without changes in other FA presumed to be synthesized de novo in the mammary gland, this suggests that the preformed C16:0 was replaced, rather than being caused, by an overall suppression of de novo FA synthesis in the mammary gland. C1 [Moallem, U.; Zachut, M.] Agr Res Org, Volcani Ctr, Inst Anim Sci, Dept Dairy Cattle, IL-50250 Bet Dagan, Israel. [Vyas, D.; Teter, B. B.; Erdman, R. A.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Delmonte, P.] Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Moallem, U (reprint author), Agr Res Org, Volcani Ctr, Inst Anim Sci, Dept Dairy Cattle, POB 6, IL-50250 Bet Dagan, Israel. EM uzim@volcani.agri.gov.il OI Vyas, Diwakar/0000-0002-7657-0267 NR 28 TC 3 Z9 3 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD SEP PY 2012 VL 95 IS 9 BP 5276 EP 5284 DI 10.3168/jds.2012-5415 PG 9 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 990IC UT WOS:000307623200056 PM 22916932 ER PT J AU Feingold, B Brooks, MM Zeevi, A Ohmann, EL Burckart, GJ Ferrell, RE Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, JK Naftel, DC Webber, SA AF Feingold, Brian Brooks, Maria M. Zeevi, Adriana Ohmann, Erin L. Burckart, Gilbert J. Ferrell, Robert E. Chinnock, Richard Canter, Charles Addonizio, Linda Bernstein, Daniel Kirklin, James K. Naftel, David C. Webber, Steven A. TI Renal function and genetic polymorphisms in pediatric heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE pediatrics; heart transplantation; genetic polymorphism; cytochrome P450; TGF-betal; renal function ID SINGLE NUCLEOTIDE POLYMORPHISMS; HEME OXYGENASE; RISK-FACTORS; FAS LIGAND; FAILURE; NEPHROTOXICITY; DISEASE; IMPACT; DYSFUNCTION; REJECTION AB BACKGROUND: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. METHODS: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2). RESULTS: Mean age at transplantation was 6.2 +/- 6.1 years. Mean follow-up was 5.1 +/- 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGF beta 1, CYP3A5, ABCB1, and ACE. CONCLUSIONS: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGF beta 1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation. J Heart Lung Transplant 2012;31:1003-8 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Feingold, Brian] UPMC, Childrens Hosp Pittsburgh, Fac Pavil, Pittsburgh, PA 15224 USA. [Brooks, Maria M.; Zeevi, Adriana; Ferrell, Robert E.] Univ Pittsburgh, Pittsburgh, PA USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Chinnock, Richard] Loma Linda Univ, Loma Linda, CA 92350 USA. [Canter, Charles] Washington Univ, Sch Med, St Louis, MO USA. [Addonizio, Linda] Columbia Univ, New York, NY USA. [Bernstein, Daniel] Stanford Univ, Palo Alto, CA 94304 USA. [Kirklin, James K.; Naftel, David C.] Univ Alabama Birmingham, Birmingham, AL USA. RP Feingold, B (reprint author), UPMC, Childrens Hosp Pittsburgh, Fac Pavil, 4401 Penn Ave,5th Flr, Pittsburgh, PA 15224 USA. EM brian.feingold@chp.edu OI Chinnock, Richard/0000-0002-9814-1762; Brooks, Maria/0000-0002-2030-7873 FU National Institutes of Health [KL2 RR-024154, KL2 TR-000146]; National Heart Lung Blood Institute, National Institutes of Health [5P50 HL 07432-05] FX Dr. Feingold's effort on this project was supported by the National Institutes of Health through Grants KL2 RR-024154 and KL2 TR-000146. This project was also supported by the National Heart Lung Blood Institute, National Institutes of Health (5P50 HL 07432-05). The content is solely the responsibility of the authors and does not necessarily represent the views of the National Heart Lung Blood Institute or the National Institutes of Health. NR 36 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2012 VL 31 IS 9 BP 1003 EP 1008 DI 10.1016/j.healun.2012.05.010 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 996UL UT WOS:000308120200011 PM 22789135 ER PT J AU Kolibab, K Derrick, SC Jacobs, WR Morris, SL AF Kolibab, Kristopher Derrick, Steven C. Jacobs, William R. Morris, Sheldon L. TI Characterization of an intracellular ATP assay for evaluating the viability of live attenuated mycobacterial vaccine preparations SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE BCG vaccine; ATP assay; Attenuated live vaccines; Tuberculosis; Viability ID FIREFLY LUCIFERASE ASSAY; ADENOSINE-TRIPHOSPHATE; BCG VACCINES; TUBERCULOSIS; EXTRACTION; METAANALYSIS; IMPROVEMENT; STRAINS; CELLS AB The viability of BCG vaccine has traditionally been monitored using a colony-forming unit (CFU) assay. Despite its widespread use, results from the CFU assay can be highly variable because of the characteristic clumping of mycobacteria, their requirement for complex growth media, and the three week incubation period needed to cultivate slow-growing mycobacteria. In this study, we evaluated whether an ATP luminescence assay (which measures intracellular ATP content) could be used to rapidly estimate the viability of lyophilized and/or frozen preparations of six different BCG vaccine preparations - Danish, Tokyo, Russia, Brazil, Tice, and Pasteur - and two live attenuated mycobacterial vaccine candidates - a Delta lysA Delta panCD M. tuberculosis strain and a Delta mmaA4 BCG vaccine mutant. For every vaccine tested, a significant correlation was observed between intracellular ATP concentrations and the number of viable attenuated bacilli. However, the extractable intracellular ATP levels detected per cell among the different live vaccines varied suggesting that validated ATP luminescence assays with specific appropriate standards must be developed for each individual live attenuated vaccine preparation. Overall, these data indicate that the ATP luminescence assay is a rapid, sensitive, and reliable alternative method for quantifying the viability of varying live attenuated mycobacterial vaccine preparations. Published by Elsevier B.V. C1 [Kolibab, Kristopher; Derrick, Steven C.; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. [Jacobs, William R.] Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA. RP Morris, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov NR 27 TC 4 Z9 5 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 EI 1872-8359 J9 J MICROBIOL METH JI J. Microbiol. Methods PD SEP PY 2012 VL 90 IS 3 BP 245 EP 249 DI 10.1016/j.mimet.2012.05.015 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 990ED UT WOS:000307612900017 PM 22652432 ER PT J AU Burckart, GJ Green, DJ AF Burckart, Gilbert J. Green, Dionna J. TI The personalized medicine revolution: Getting it right for children SO PEDIATRIC TRANSPLANTATION LA English DT Editorial Material C1 [Burckart, Gilbert J.; Green, Dionna J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. EM gilbert.burckart@fda.hhs.gov NR 7 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD SEP PY 2012 VL 16 IS 6 BP 530 EP 532 DI 10.1111/j.1399-3046.2011.01638.x PG 3 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 983GD UT WOS:000307106800023 PM 22225514 ER PT J AU Benz, RD Cross, KP Bower, DA Judson, PN Barber, CG Nath, S AF Benz, R. D. Cross, K. P. Bower, D. A. Judson, P. N. Barber, C. G. Nath, S. TI ToxML: A Common Exchange Standard for Raw and Summarized Genetic Toxicology Data and Data Analysis Results SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Benz, R. D.] US FDA CDER OPS OTR DDSR, Silver Spring, MD USA. [Cross, K. P.; Bower, D. A.] Leadscope Inc, Columbus, OH USA. [Judson, P. N.] Judson Consulting Serv, Harrogate, England. [Barber, C. G.] Lhasa Ltd, Leeds, W Yorkshire, England. [Nath, S.] PointCross Life Sci, Foster City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S45 EP S45 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300132 ER PT J AU Bhalli, J Shaddock, J Pearce, M Ding, W Dobrovolsky, V Heflich, R AF Bhalli, J. Shaddock, J. Pearce, M. Ding, W. Dobrovolsky, V Heflich, R. TI Genotoxicity of Aristolochic Acids in F344 Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Bhalli, J.; Shaddock, J.; Pearce, M.; Ding, W.; Dobrovolsky, V; Heflich, R.] US FDA, Div Genet & Mol Toxicol, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S55 EP S55 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300170 ER PT J AU Bishop, ME Ding, W Lyn-Cook, LE Pearce, MG Manjanatha, MG AF Bishop, M. E. Ding, W. Lyn-Cook, L. E. Pearce, M. G. Manjanatha, M. G. TI Evaluation of In Vivo Genotoxicity of Estragole by Comet Assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Bishop, M. E.; Ding, W.; Lyn-Cook, L. E.; Pearce, M. G.; Manjanatha, M. G.] US FDA, Jefferson Labs, Natl Ctr Toxicol Res, Jefferson, AR USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S55 EP S55 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300171 ER PT J AU Butler, K Rajani, A Elespuru, R AF Butler, K. Rajani, A. Elespuru, R. TI Genotoxicity and Uptake of Titanium Dioxide Nanoparticles in Salmonella typhimurium SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Butler, K.] NCI, Bethesda, MD 20892 USA. [Butler, K.; Rajani, A.; Elespuru, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S58 EP S58 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300184 ER PT J AU Chen, T Yan, J Chen, X AF Chen, T. Yan, J. Chen, X. TI Development of a microRNA Assay to Evaluate Genotoxicity of Agents SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Chen, T.; Yan, J.; Chen, X.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S30 EP S30 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300070 ER PT J AU Cross, KP Benz, RD Stavitskaya, L Kruhlak, NL AF Cross, K. P. Benz, R. D. Stavitskaya, L. Kruhlak, N. L. TI Identifying Structure-Activity Cliffs in a Salmonella QSAR Model for Predicting the Potential Mutagenicity of Genotoxic Drug Impurities and Other Organic Molecules SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Cross, K. P.] Leadscope Inc, Columbus, OH USA. [Benz, R. D.; Stavitskaya, L.; Kruhlak, N. L.] US FDA CDER OPS OTR DDSR, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S44 EP S44 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300129 ER PT J AU Dobrovolsky, V Heflich, R Ferguson, S AF Dobrovolsky, V Heflich, R. Ferguson, S. TI Pig-a Mutant RBCs in Rats Treated with ENU In Utero SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Dobrovolsky, V; Heflich, R.; Ferguson, S.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S54 EP S54 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300169 ER PT J AU Elespuru, R Rajani, A Butler, K AF Elespuru, R. Rajani, A. Butler, K. TI Miniaturized Bacterial Mutagenicity Assays Designed to Use Less Test Agent SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Elespuru, R.; Rajani, A.; Butler, K.] US FDA CDRH, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S45 EP S45 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300131 ER PT J AU Guo, X Lin, H Dial, S Richter, P Moore, M Mei, N AF Guo, X. Lin, H. Dial, S. Richter, P. Moore, M. Mei, N. TI Mutagenic Potency of Four Chemicals Contained in Cigarette Smoke SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Guo, X.; Lin, H.; Dial, S.; Moore, M.; Mei, N.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Richter, P.] Ctr Tobacco Prod, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S54 EP S54 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300166 ER PT J AU Mei, N McDaniel, LP Guo, XQ Chen, T AF Mei, N. McDaniel, L. P. Guo, X. Q. Chen, T. TI Mutagenicity and DNA Adduct Formation by Aristolochic Acid in the Spleen of Big Blue Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Mei, N.; McDaniel, L. P.; Guo, X. Q.; Chen, T.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S50 EP S50 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300151 ER PT J AU Mendrick, DL AF Mendrick, D. L. TI 'Omic Biomarkers SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Mendrick, D. L.] US FDA, Div Syst Biol, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S18 EP S18 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300024 ER PT J AU Myers, MB McKim, KL Wang, Y McKinzie, PB Meng, F Parsons, BL AF Myers, M. B. McKim, K. L. Wang, Y. McKinzie, P. B. Meng, F. Parsons, B. L. TI Normal and Pathological Levels of KRAS Mutation: Information with Implications for Personalized Cancer Treatment SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Myers, M. B.; McKim, K. L.; Wang, Y.; McKinzie, P. B.; Meng, F.; Parsons, B. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S62 EP S62 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300200 ER PT J AU Parsons, BL Manjanatha, MG Myers, MB Mckim, KL Wang, Y Gollapudi, BB Moore, N Haber, LT Moore, MM AF Parsons, B. L. Manjanatha, M. G. Myers, M. B. Mckim, K. L. Wang, Y. Gollapudi, B. B. Moore, N. Haber, L. T. Moore, M. M. TI Induction of cII and K-Ras Mutation in Lung DNA of Big Blue Mice Exposed to Ethylene Oxide by Inhalation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Parsons, B. L.; Manjanatha, M. G.; Myers, M. B.; Mckim, K. L.; Wang, Y.; Moore, M. M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Gollapudi, B. B.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Moore, N.] Dow Europe GmbH, Horgen, Switzerland. [Haber, L. T.] TERA NA, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S62 EP S62 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300199 ER PT J AU Petibone, D Kulkarni, R Chang, CW Chen, J Churchwell, M Morris, S AF Petibone, D. Kulkarni, R. Chang, C-W Chen, J. Churchwell, M. Morris, S. TI Evaluation of p53 Genotype on Gene Expression and O-6-ethylguanine Levels in the Cerebrum from Male C57BL/6 Mice Exposed to ENU SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Petibone, D.; Kulkarni, R.; Morris, S.] Div Genet & Mol Toxicol, Jefferson, AR USA. [Chang, C-W; Chen, J.] Div Personalized Med & Nutr, Jefferson, AR USA. [Churchwell, M.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S52 EP S52 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300161 ER PT J AU Schisler, M Gollapudi, B McDaniel, P Moore, M AF Schisler, M. Gollapudi, B. McDaniel, P. Moore, M. TI Reevaluation of the Mouse Lymphoma Forward Mutation Assay (MLA) Results on 342 Chemicals from the US National Toxicology Program's (NTP) Database SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 43rd Annual Meeting of the Environmental-Mutagen-Society (EMS) CY SEP 08-12, 2012 CL Bellevue, WA SP Environm Mutagen Soc (EMS) C1 [Schisler, M.; Gollapudi, B.] Dow Chem Co USA, Midland, MI 48674 USA. [McDaniel, P.; Moore, M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2012 VL 53 SU 1 BP S56 EP S56 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 993YM UT WOS:000307896300176 ER PT J AU Cheng, TF Choudhuri, S Muldoon-Jacobs, K AF Cheng, Tsu-Fan Choudhuri, Supratim Muldoon-Jacobs, Kristi TI Epigenetic targets of some toxicologically relevant metals: a review of the literature SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE gene expression; epigenetics; DNA methylation; histone modification; noncoding RNA; inorganic heavy metals; organic metals ID INDUCED MALIGNANT-TRANSFORMATION; HISTONE ACETYLTRANSFERASE ACTIVITY; GENE-EXPRESSION CHANGES; C-TERMINAL TAIL; DNA METHYLATION; ORGANOTIN COMPOUNDS; INDUCED CARCINOGENESIS; MEDICAGO-TRUNCATULA; ALZHEIMERS-DISEASE; DEMETHYLASE JMJD1A AB The term epigenetics was coined in the context of developmental studies, but the meaning of the term has evolved over time. Epigenetic modulators of gene expression are now known to include DNA methylation, chromatin modifications and noncoding RNAs. The observation that epigenetic changes can be transmitted transgenerationally makes the science of epigenetics very relevant to the field of environmental and molecular toxicology. Heavy metals constitute an important class of environmental contaminants that have been known to influence gene expression directly by binding various metal response elements in the target gene promoters. Recent research suggests that metals can also influence gene expression through epigenetic mechanisms; this adds a new twist to the complexity of metal-mediated gene expression. Here, we review recent studies that investigate the epigenetic, gene expression, and biological effects of various inorganic and organic forms of heavy metals, such as cadmium, arsenic, nickel, chromium, methylmercury, lead, copper and organotin compounds. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Cheng, Tsu-Fan; Muldoon-Jacobs, Kristi] US FDA, Ctr Food Safety & Appl Nutr, OFAS, DFCN, College Pk, MD 20740 USA. [Choudhuri, Supratim] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Notice Review, College Pk, MD 20740 USA. RP Muldoon-Jacobs, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OFAS, DFCN, HFS 275 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Kristi.jacobs@fda.hhs.gov NR 105 TC 51 Z9 51 U1 1 U2 79 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP PY 2012 VL 32 IS 9 BP 643 EP 653 DI 10.1002/jat.2717 PG 11 WC Toxicology SC Toxicology GA 979GP UT WOS:000306805800001 PM 22334439 ER PT J AU Sahu, SC Amankwa-Sakyi, M O'Donnell, MW Sprando, RL AF Sahu, Saura C. Amankwa-Sakyi, Margaret O'Donnell, Michael W., Jr. Sprando, Robert L. TI Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE usnic acid; dietary supplement; hepatotoxicity; liver toxicity; liver cells; HepG2 cells; gene expression profiles ID PRIMARY HUMAN HEPATOCYTES; HUMAN HEPATOMA-CELL; OXIDATIVE STRESS; IN-VITRO; RAT HEPATOCYTES; GENE-EXPRESSION; VALPROIC ACID; MITOCHONDRIAL-FUNCTION; DIETARY-SUPPLEMENT; MECHANISTIC ASSAYS AB Usnic acid, a natural botanical product, is a constituent of some dietary supplements used for weight loss. It has been associated with clinical hepatotoxicity leading to liver failure in humans. The present study was undertaken for metabolism and toxicity evaluations of usnic acid in human hepatoblastoma HepG2 cells in culture. The cells were treated with the vehicle control and usnic acid at concentrations of 0100?mu m for 24?h at 37?degrees C in 5% CO2. Following the treatment period, the cells were evaluated by biochemical and toxicogenomic endpoints of toxicity that included cytochrome P450 activity, cytotoxicity, oxidative stress, mitochondrial dysfunction and changes in pathway focused gene expression profiles. Usnic acid exposure resulted in increased P450 activity, cytotoxicity, oxidative stress and mitochondrial dysfunction in HepG2 cells. The pathway-focused gene expression analysis resulted in significantly altered expression of six genes out of a total of 84 genes examined. Of the six altered genes, three genes were up-regulated and three genes down-regulated. A marked up-regulation of one gene CCL21 associated with inflammation, one gene CCNC associated with proliferation and carcinogenesis and one gene UGT1A4 associated with metabolism as well as DNA damage and repair were observed in the usnic acid-treated cells compared with the vehicle control. Also a marked down-regulation of one gene CSF2 associated with inflammation and two genes (CYP7A1 and CYP2E1) associated with oxidative metabolic stress were observed in the usnic acid-treated cells compared with the control. The biomarkers used in this study demonstrate the toxicity of usnic acid in human hepatoblastoma HepG2 cells, suggesting an oxidative mechanism of action. Published 2011. This article is a US Government work and is in the public domain in the USA. C1 [Sahu, Saura C.; Sprando, Robert L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Amankwa-Sakyi, Margaret; O'Donnell, Michael W., Jr.] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM saura.sahu@fda.hhs.gov NR 91 TC 14 Z9 14 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP PY 2012 VL 32 IS 9 BP 722 EP 730 DI 10.1002/jat.1721 PG 9 WC Toxicology SC Toxicology GA 979GP UT WOS:000306805800008 PM 21953288 ER PT J AU Sahu, SC O'Donnell, MW Sprando, RL AF Sahu, Saura C. O'Donnell, Michael W., Jr. Sprando, Robert L. TI Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE usnic acid; LPS; dietary supplement; food contaminant; hepatotoxicity; liver toxicity; liver cells; HepG2 cells; gene expression profiles ID PRIMARY HUMAN HEPATOCYTES; DNA ADDUCT FORMATION; HUMAN HEPATOMA-CELL; GENE-EXPRESSION; IN-VITRO; OXIDATIVE STRESS; RAT HEPATOCYTES; MITOCHONDRIAL-FUNCTION; DIETARY-SUPPLEMENT; MECHANISTIC ASSAYS AB Usnic acid (UA), a natural botanical product, is a constituent of some dietary supplements used for weight loss. It has been associated with clinical hepatotoxicity leading to liver failure in humans. The present study was undertaken to evaluate the interactive toxicity, if any, of UA with lipopolysaccarides (LPS), a potential contaminant of food, at low non-toxic concentrations. The human hepatoblastoma HepG2 cells were treated with the vehicle control and test agents, separately and in a binary mixture, for 24 h at 37 0C in 5% CO2. After the treatment period, the cells were evaluated by the traditional biochemical endpoints of toxicity in combination with the toxicogenomic endpoints that included cytotoxicity, oxidative stress, mitochondrial injury and changes in pathway-focused gene expression profiles. Compared with the controls, low non-toxic concentrations of UA and LPS separately showed no effect on the cells as determined by the biochemical endpoints. However, the simultaneous mixed exposure of the cells to their binary mixture resulted in increased cytotoxicity, oxidative stress and mitochondrial injury. The pathway-focused gene expression analysis resulted in the altered expression of several genes out of 84 genes examined. Most altered gene expressions induced by the binary mixture of UA and LPS were different from those induced by the individual constituents. The genes affected by the mixture were not modulated by either UA or LPS. The results of the present study suggest that the interactions of low nontoxic concentrations of UA and LPS produce toxicity in HepG2 cells. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Sahu, Saura C.; Sprando, Robert L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [O'Donnell, Michael W., Jr.] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM saura.sahu@fda.hhs.gov NR 85 TC 10 Z9 11 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP PY 2012 VL 32 IS 9 BP 739 EP 748 DI 10.1002/jat.2768 PG 10 WC Toxicology SC Toxicology GA 979GP UT WOS:000306805800010 PM 22777745 ER PT J AU Mehta, A Mohr, BA AF Mehta, Aashish Mohr, Belinda Acuna TI Economic Liberalization and Rising College Premiums in Mexico: A Reinterpretation SO WORLD DEVELOPMENT LA English DT Article DE skill premium; employment composition; trade liberalization; services; Latin America; Mexico ID FOREIGN DIRECT-INVESTMENT; WAGE INEQUALITY; TRADE LIBERALIZATION; RELATIVE WAGES; DEMAND; MAQUILADORAS; EMPLOYMENT; GROWTH; SKILL; GLOBALIZATION AB Mexico's college premium rose in the 1990s. Studies employing structural decomposition analyses treat the college premium as the relative price of "skilled" to "unskilled" workers. They find that reallocations of labor across industries and occupations cannot account for rising college premiums, and often attribute them to widely observed trade-induced increases in skills demand within the manufacturing sector. In contrast, using a reduced-form decomposition that moves beyond a binary definition of skill and allows for inter-occupation wage differentials, we show that employment shifts across occupations and industries can account for the increase in the college premium. We link the rising premium, and differences in its trajectory by gender and cohort, to the growth of specific professions that produce services, not manufactured goods. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mehta, Aashish] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Mohr, Belinda Acuna] US FDA, Ctr Food Safety, Rockville, MD 20857 USA. RP Mehta, A (reprint author), Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. NR 43 TC 2 Z9 2 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-750X J9 WORLD DEV JI World Dev. PD SEP PY 2012 VL 40 IS 9 BP 1908 EP 1920 DI 10.1016/j.worlddev.2012.04.007 PG 13 WC Economics; Planning & Development SC Business & Economics; Public Administration GA 978UN UT WOS:000306771400014 ER PT J AU Imes, DL Wictum, EJ Allard, MW Sacks, BN AF Imes, Donna L. Wictum, Elizabeth J. Allard, Marc W. Sacks, Benjamin N. TI Identification of single nucleotide polymorphisms within the mtDNA genome of the domestic dog to discriminate individuals with common HVI haplotypes SO FORENSIC SCIENCE INTERNATIONAL-GENETICS LA English DT Article DE Canis lupus familiaris; Dog; HVI; Mitochondrial; mtDNA ID MITOCHONDRIAL-DNA; CONTROL REGION; INFORMATIVE SNPS; TANDEM REPEATS; SEQUENCE; ASSAY; HAIR; HAPLOGROUPS; NETWORKS; MULTIPLE AB We sequenced the entire similar to 16 kb canine mitochondrial genome (mtGenome) of 100 unrelated domestic dogs (Canis lupus familiaris) and compared these to 246 published sequences to assess hypervariable region I (HVI) haplotype frequencies. We then used all available sequences to identify informative single nucleotide polymorphisms (SNPs) outside of the control region for use in further resolving mtDNA haplotypes corresponding to common HVI haplotypes. Haplotype frequencies in our data set were highly correlated with previous ones (e.g., F-ST = 0.02, r = 0.90), suggesting the total data set reasonably reflected the broader dog population. A total of 128 HVI haplotypes was represented. The 10 most common HVI haplotypes (n = 184 dogs) represented 53.3% of the sample. We identified a total 71 SNPs in the mtGenomes (external to the control region) that resolved the 10 most common HVI haplotypes into 63 mtGenome subhaplotypes. The random match probability of the dataset based solely on the HVI sequence was 4%, whereas the random match probability of the mtGenome subhaplotypes was <1%. Thus, the panel of 71 SNPs identified in this study represents a useful forensic tool to further resolve the identity of individual dogs from mitochondrial DNA (mtDNA). (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Imes, Donna L.; Wictum, Elizabeth J.; Sacks, Benjamin N.] Univ Calif Davis, Vet Genet Lab, Forens Unit, Davis, CA 95616 USA. [Imes, Donna L.; Sacks, Benjamin N.] Univ Calif Davis, Canid Divers & Conservat Lab, Ctr Vet Genet, Davis, CA 95616 USA. [Allard, Marc W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Sacks, Benjamin N.] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. RP Sacks, BN (reprint author), Univ Calif Davis, Vet Genet Lab, Forens Unit, 1 Shields Ave,Old Davis Rd, Davis, CA 95616 USA. EM donna.imes@gmail.com; bethw@ucdavis.edu; mwallard@gmail.com; bnsacks@ucdavis.edu FU Forensic Sciences Masters Program; Veterinary Genetics Laboratory FX We thank S. Fain of the USFWS Forensic Laboratory for wolf samples, and C. Penedo, N. C. Pedersen, L. A. Lyons, T. Kun, C. Lindquist, G. Byrns, M. Christiansen-Weller, L. Brault, S. Bricker, A. Del Valle and the UC Davis, Veterinary Genetics Laboratory for dog samples, technical support, training, and use of space and equipment. Funding was provided by the Forensic Sciences Masters Program and Veterinary Genetics Laboratory. NR 46 TC 17 Z9 17 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1872-4973 J9 FORENSIC SCI INT-GEN JI Forensic Sci. Int.-Genet. PD SEP PY 2012 VL 6 IS 5 BP 630 EP 639 DI 10.1016/j.fsigen.2012.02.004 PG 10 WC Genetics & Heredity; Medicine, Legal SC Genetics & Heredity; Legal Medicine GA 973KE UT WOS:000306358200028 PM 22436122 ER PT J AU Adams, WP Lee, SL Plourde, R Lionberger, RA Bertha, CM Doub, WH Bovet, JM Hickey, AJ AF Adams, Wallace P. Lee, Sau L. Plourde, Robert Lionberger, Robert A. Bertha, Craig M. Doub, William H. Bovet, Jean-Marc Hickey, Anthony J. TI Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers SO AAPS JOURNAL LA English DT Article DE device modifications; dry powder inhaler; formulation; generic; in vitro performance ID COMPUTATIONAL FLUID-DYNAMICS; SIZE; DISPERSION; DESIGN; UNIFORMITY; PARTICLES AB The study examined the sensitivity of DPI in vitro performance to formulation and device changes. Rotahaler/Rotacaps was selected as the reference DPI drug product, and Aerolizer was selected as the test device. Since the test device was recognized to have much greater efficiency of dispersion, simple modifications to both formulation and device were made in an effort to provide a closer match to the in vitro performance of the reference product. The modifications included varying the drug and lactose particle sizes and/or lactose fine particle content in the test formulations, as well as lowering the specific resistance of the test device. These modifications were intended to address variables important for drug product performance for a defined experimental design and were not intended to mimic the extensive formulation and device design strategies that are employed in an industrial setting. Formulation and device modifications resulted in a modified test product that approached the reference product in the in vitro performance. C1 [Lee, Sau L.; Lionberger, Robert A.] US FDA, CDER OPS Off Gener Drugs, Rockville, MD 20855 USA. [Plourde, Robert] Catalent Pharma Solut, Morrisville, NC USA. [Bertha, Craig M.] US FDA, CDER OPS Off New Drug Qual Assessment, Silver Spring, MD USA. [Doub, William H.] US FDA, CDER OPS Div Pharmaceut Anal, St Louis, MO USA. [Bovet, Jean-Marc; Hickey, Anthony J.] Cirrus Pharmaceut Inc, Durham, NC USA. [Hickey, Anthony J.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Lee, SL (reprint author), US FDA, CDER OPS Off Gener Drugs, Rockville, MD 20855 USA. EM sau.lee@fda.hhs.gov NR 28 TC 12 Z9 12 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2012 VL 14 IS 3 BP 400 EP 409 DI 10.1208/s12248-012-9352-7 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 962DO UT WOS:000305519900004 PM 22476943 ER PT J AU Cardot, JM Davit, BM AF Cardot, J. -M. Davit, B. M. TI In vitro-In Vivo Correlations: Tricks and Traps SO AAPS JOURNAL LA English DT Article DE biowaiver; in vitro-in vivo correlation (IVIVC); predictability; prediction; time scaling ID ORAL-DRUG ABSORPTION; IVIVC; LEVEL; MODEL; DISSOLUTION; FORMULATION; SYSTEM AB In vitro-in vivo correlation (IVIVC) is a biopharmaceutical tool recommended to be used in development of formulation. When validated, it can speed up development of formulation, be used to fix dissolution limits and also as surrogate of in vivo study. However, as do all tools, it presents limitations and traps. The aim of the present paper is to investigate five common traps which could limit either the setting or use of IVIVC (1) using mean or individual values; (2) correction of absolute bioavailability; (3) correction of lag time and time scaling; (4) flip-flop model; and (5) predictability corrections. C1 [Cardot, J. -M.] Auvergne Univ, UFR Pharm, ERT CIDAM, Dept Biopharmaceut, F-63001 Clermont Ferrand, France. [Davit, B. M.] US FDA, Div Bioequivalence 2, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cardot, JM (reprint author), Auvergne Univ, UFR Pharm, ERT CIDAM, Dept Biopharmaceut, 28 Pl H Dunant,BP 38, F-63001 Clermont Ferrand, France. EM j-michel.cardot@u-clermont1.fr NR 38 TC 21 Z9 22 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2012 VL 14 IS 3 BP 491 EP 499 DI 10.1208/s12248-012-9359-0 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 962DO UT WOS:000305519900014 PM 22547350 ER PT J AU Awotwe-Otoo, D Agarabi, C Keire, D Lee, S Raw, A Yu, L Habib, MJ Khan, MA Shah, RB AF Awotwe-Otoo, David Agarabi, Cyrus Keire, David Lee, Sau Raw, Andre Yu, Lawrence Habib, Muhammad J. Khan, Mansoor A. Shah, Rakhi B. TI Physicochemical Characterization of Complex Drug Substances: Evaluation of Structural Similarities and Differences of Protamine Sulfate from Various Sources SO AAPS JOURNAL LA English DT Article DE circular dichroism; differential scanning calorimetry; Fourier-transform infrared spectroscopy; nuclear magnetic resonance; peptide; protamine sulfate; thermogravimetric analysis ID PROTEIN SECONDARY STRUCTURE; NMR CHEMICAL-SHIFTS; SCANNING CALORIMETRY; CIRCULAR-DICHROISM; PURIFICATION; SEQUENCES; TESTIS AB The purpose of this study was to characterize and evaluate differences of protamine sulfate, a highly basic peptide drug, obtained from five different sources, using orthogonal thermal and spectroscopic analytical methods. Thermogravimetric analysis and modulated differential scanning calorimetry showed that all five protamine sulfate samples had different moisture contents and glass transition and melting temperatures when temperature was modulated from 25 to 270A degrees C. Protamine sulfate from source III had the highest residual moisture content (4.7 A +/- 0.2%) at 105A degrees C, resulting in the lowest glass transition (109.7A degrees C) and melting (184.2A degrees C) temperatures compared with the other four sources. By Fourier-transform infrared (FTIR) spectroscopy, the five sources of protamine sulfate had indistinguishable spectra, and the spectra were consistent with a predominantly random coil conformation in solution and a minor population in a beta-sheet conformation (similar to 12%). Circular dichroism spectropolarimetry confirmed the FTIR results with prominent minima at 206 nm observed for all five sources. Finally, proton (H-1) nuclear magnetic resonance spectroscopy showed that all five protamine sulfate sources had identical spectra with backbone amide chemical shifts between 8.20 and 8.80 ppm, consistent with proteins with predominantly random coil conformation. In conclusion, thermal analyses showed differences in the thermal behavior of the five sources of protamine sulfate, while spectroscopic analyses showed the samples had a predominantly random coil conformation with a small amount of beta-sheet present. C1 [Awotwe-Otoo, David; Agarabi, Cyrus; Khan, Mansoor A.; Shah, Rakhi B.] US FDA, Div Prod Qual Res, OTR, OPS,CDER, Silver Spring, MD USA. [Keire, David] US FDA, Div Pharmaceut Anal, OTR, OPS,CDER, St Louis, MO 63101 USA. [Lee, Sau; Raw, Andre; Yu, Lawrence] US FDA, Off Gener Drugs, OTR, OPS,CDER, Silver Spring, MD USA. [Habib, Muhammad J.] Howard Univ, Coll Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. RP Shah, RB (reprint author), US FDA, Div Prod Qual Res, OTR, OPS,CDER, 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD USA. EM rakhi.shah@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 29 TC 9 Z9 9 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2012 VL 14 IS 3 BP 619 EP 626 DI 10.1208/s12248-012-9375-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 962DO UT WOS:000305519900029 PM 22678712 ER PT J AU Beaubrun, JJG Cheng, CM Chen, KS Ewing, L Wang, H Agpaoa, MC Huang, MCJ Dickey, E Du, JM Williams-Hill, DM Hamilton, B Micallef, SA Goldstein, RER George, A Joseph, SW Sapkota, AR Jacobson, AP Tall, BD Kothary, MH Dudley, K Hanes, DE AF Beaubrun, Junia Jean-Gilles Cheng, Chorng-Ming Chen, Kai-Shun Ewing, Laura Wang, Hua Agpaoa, Maria C. Huang, Mei-Chiung J. Dickey, Erin Du, Jamie M. Williams-Hill, Donna M. Hamilton, Brittany Micallef, Shirley A. Goldstein, Rachel E. Rosenberg George, Ashish Joseph, Sam W. Sapkota, Amy R. Jacobson, Andrew P. Tall, Ben D. Kothary, Mahendra H. Dudley, Kim Hanes, Darcy E. TI The evaluation of a PCR-based method for identification of Salmonella enterica serotypes from environmental samples and various food matrices SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella spp.; Molecular serotyping ID MULTIPLEX PCR AB The most commonly used method for serotyping Salmonella spp. is based on the Kaufmann-White scheme, and is composed of serological reactions using antibodies to LPS agglutinins. The multiplex PCR used in this investigation was established by Kim et al. to serotype the 30 most common clinical Salmonella serotypes, as determined by CDC. The PCR assay consists of two five-plex reactions and a single two-plex PCR reaction, based on six genetic loci from Salmonella enterica serotype Typhimurium and four loci from S. enterica serotype Typhi. In this investigation, we further evaluated the method for serotyping Salmonella spp. using a reference collection, environmental samples collected from a Mid-Atlantic region tomato farm study, four food matrices spiked with different Salmonella serotypes and a proficiency test. The PCR assay was first evaluated using DNA isolated from pure cultures of isolates obtained from various clinical and environmental samples, and then DNA isolated from broth cultures of food matrices of "Red round" and Roma tomatoes, Romaine lettuce, green onions and Serrano peppers spiked with serotypes Newport, Typhimurium, Javiana and Saintpaul, respectively. The results showed that the PCR assay correctly serotyped Salmonella spp. from the clinical, environmental, spiked food matrices, and proficiency test samples. These findings are significant because the PCR assay was successful in the identification of Salmonella in the spiked samples in a broth culture containing other non-salmonella organism. This method may be a useful resource for the food safety community. Published by Elsevier Ltd. C1 [Beaubrun, Junia Jean-Gilles] US FDA, MOD Facil 1, Virulence Mech Branch HFS 025,Ctr Food Safety & A, Div Virulence Assessment,Off Appl Res & Safety As, Laurel, MD 20708 USA. [Cheng, Chorng-Ming; Chen, Kai-Shun; Agpaoa, Maria C.; Huang, Mei-Chiung J.; Du, Jamie M.; Williams-Hill, Donna M.] US FDA, Off Regulatory Affairs, Irvine, CA 92612 USA. [Wang, Hua; Dickey, Erin; Jacobson, Andrew P.] US FDA, College Pk, MD 20740 USA. [Micallef, Shirley A.; Goldstein, Rachel E. Rosenberg; George, Ashish; Joseph, Sam W.; Sapkota, Amy R.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Hamilton, Brittany] Howard Univ, Washington, DC 20050 USA. RP Beaubrun, JJG (reprint author), US FDA, MOD Facil 1, Virulence Mech Branch HFS 025,Ctr Food Safety & A, Div Virulence Assessment,Off Appl Res & Safety As, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM junia.jean-gillesbeaubrun@fda.hhs.gov RI Sapkota, Amy/A-6046-2011; OI Tall, Ben/0000-0003-0399-3629 NR 13 TC 7 Z9 8 U1 4 U2 21 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD SEP PY 2012 VL 31 IS 2 BP 199 EP 209 DI 10.1016/j.fm.2012.03.016 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 953UI UT WOS:000304898300009 PM 22608224 ER PT J AU Kim, SHJ Jackson, AJ Hur, R Hunt, CA AF Kim, Sean H. J. Jackson, Andre J. Hur, Rim Hunt, C. Anthony TI Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products SO THEORETICAL BIOLOGY AND MEDICAL MODELLING LA English DT Article ID HIGHLY VARIABLE DRUGS; ABSORPTION; BIOEQUIVALENCE; MODELS; FORMULATIONS; DISPOSITION; PREDICTION; SYSTEMS AB Objective: Develop and validate particular, concrete, and abstract yet plausible in silico mechanistic explanations for large intra- and interindividual variability observed for eleven bioequivalence study participants. Do so in the face of considerable uncertainty about mechanisms. Methods: We constructed an object-oriented, discrete event model called SUBJECT (we use small caps to distinguish computational objects from their biological counterparts). It maps abstractly to a dissolution test system and study subject to whom product was administered orally. A SUBJECT comprises four interconnected grid spaces and event mechanisms that map to different physiological features and processes. DRUGS move within and between spaces. We followed an established, Iterative Refinement Protocol. Individualized mechanisms were made sufficiently complicated to achieve prespecified Similarity Criteria, but no more so. Within SUBJECTS, the DISSOLUTION space is linked to both a product-SUBJECT Interaction Space and the GI TRACT. The GI TRACT and Interaction Space connect to PLASMA, from which DRUG is eliminated. Results: We discovered parameterizations that enabled the eleven SUBJECT simulation results to achieve the most stringent Similarity Criteria. Simulated profiles closely resembled those with normal, odd, and double peaks. We observed important subject-by-formulation interactions within SUBJECTS. Conclusion: We hypothesize that there were interactions within bioequivalence study participants corresponding to the subject-by-formulation interactions within SUBJECTS. Further progress requires methods to transition currently abstract SUBJECT mechanisms iteratively and parsimoniously to be more physiologically realistic. As that objective is achieved, the approach presented is expected to become beneficial to drug development (e.g., controlled release) and to a reduction in the number of subjects needed per study plus faster regulatory review. C1 [Kim, Sean H. J.; Hur, Rim; Hunt, C. Anthony] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Jackson, Andre J.] US FDA, Off Clin Pharmacol, Washington, DC 20204 USA. RP Hunt, CA (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. EM a.hunt@ucsf.edu FU CDH Research Foundation; Alternatives Research and Development Foundation FX This research was supported in part by the CDH Research Foundation and the Alternatives Research and Development Foundation. The funding bodies had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 33 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4682 J9 THEOR BIOL MED MODEL JI Theor. Biol. Med. Model. PD AUG 31 PY 2012 VL 9 AR 39 DI 10.1186/1742-4682-9-39 PG 17 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 083XF UT WOS:000314498500001 PM 22938185 ER PT J AU Au, P Hursh, DA Lim, A Moos, MC Oh, SS Schneider, BS Witten, CM AF Au, Patrick Hursh, Deborah A. Lim, Agnes Moos, Malcolm C., Jr. Oh, Steven S. Schneider, Bruce S. Witten, Celia M. TI FDA Oversight of Cell Therapy Clinical Trials SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material C1 [Au, Patrick; Hursh, Deborah A.; Lim, Agnes; Moos, Malcolm C., Jr.; Oh, Steven S.; Schneider, Bruce S.; Witten, Celia M.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Au, P (reprint author), US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM pakwai.au@fda.hhs.gov RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 3 TC 7 Z9 8 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 29 PY 2012 VL 4 IS 149 AR 149fs31 DI 10.1126/scitranslmed.3004131 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 001WT UT WOS:000308491600002 PM 22932219 ER PT J AU Wang, JH Roderiquez, G Norcross, MA AF Wang, Jinhai Roderiquez, Gregory Norcross, Michael A. TI Control of Adaptive Immune Responses by Staphylococcus aureus through IL-10, PD-L1, and TLR2 SO SCIENTIFIC REPORTS LA English DT Article ID LEUKOCYTE ANTIGEN-DR; TH17 CELL-DIFFERENTIATION; MYD88-DEFICIENT MICE; LIPOTEICHOIC ACID; APOPTOTIC CELLS; SEPTIC PATIENTS; HUMAN MONOCYTES; T-CELLS; EXPRESSION; INFECTIONS AB Microbes induce innate immune responses in hosts. It is critical to know how different microbes control adaptive responses through innate pathways. The impact of gram-positive bacteria on the innate and adaptive responses is unclear. Herein we report that Staphylococcus aureus induces IL-10, Th17-inducing cytokines IL-6 and IL-23, chemokines, and regulates dendritic cell markers. S. aureus inhibits T-cell IL-2 responses through modulation of HLA-DR, CD86 and PD-L1. IFN-gamma, Src kinase inhibitors, or TLR2 antibodies prevented the down-modulation of HLA-DR by S. aureus. Our data demonstrate that innate TLR signaling induces multi-dimensional inhibition of adaptive immune responses, which may contribute to the lack of protective immunity to bacteria or microbe tolerance. IL-10 and PD-L1 antagonists may boost immunity to vaccines for S. aureus and other microbes. C1 [Wang, Jinhai; Roderiquez, Gregory; Norcross, Michael A.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM jinhai.wang@fda.hhs.gov; Michael.norcross@fda.hhs.gov NR 45 TC 23 Z9 26 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD AUG 28 PY 2012 VL 2 AR 606 DI 10.1038/srep00606 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 997CD UT WOS:000308140900004 PM 22930672 ER PT J AU Nagarkatti, R Bist, V Sun, S de Araujo, FF Nakhasi, HL Debrabant, A AF Nagarkatti, Rana Bist, Vaibhav Sun, Sirena de Araujo, Fernanda Fortes Nakhasi, Hira L. Debrabant, Alain TI Development of an Aptamer-Based Concentration Method for the Detection of Trypanosoma cruzi in Blood SO PLOS ONE LA English DT Article ID IN-VITRO SELECTION; CHAGAS-DISEASE PATIENTS; RNA APTAMERS; AFRICAN TRYPANOSOMES; PCR; POLYMERASE; SURFACE; ASSAY; LIGANDS; SAMPLES AB Trypanosoma cruzi, a blood-borne parasite, is the etiological agent of Chagas disease. T. cruzi trypomastigotes, the infectious life cycle stage, can be detected in blood of infected individuals using PCR-based methods. However, soon after a natural infection, or during the chronic phase of Chagas disease, the number of parasites in blood may be very low and thus difficult to detect by PCR. To facilitate PCR-based detection methods, a parasite concentration approach was explored. A whole cell SELEX strategy was utilized to develop serum stable RNA aptamers that bind to live T. cruzi trypomastigotes. These aptamers bound to the parasite with high affinities (8-25 nM range). The highest affinity aptamer, Apt68, also demonstrated high specificity as it did not interact with the insect stage epimastigotes of T. cruzi nor with other related trypanosomatid parasites, L. donovani and T. brucei, suggesting that the target of Apt68 was expressed only on T. cruzi trypomastigotes. Biotinylated Apt68, immobilized on a solid phase, was able to capture live parasites. These captured parasites were visible microscopically, as large motile aggregates, formed when the aptamer coated paramagnetic beads bound to the surface of the trypomastigotes. Additionally, Apt68 was also able to capture and aggregate trypomastigotes from several isolates of the two major genotypes of the parasite. Using a magnet, these parasite-bead aggregates could be purified from parasite-spiked whole blood samples, even at concentrations as low as 5 parasites in 15 ml of whole blood, as detected by a real-time PCR assay. Our results show that aptamers can be used as pathogen specific ligands to capture and facilitate PCR-based detection of T. cruzi in blood. C1 [Nagarkatti, Rana; Bist, Vaibhav; Sun, Sirena; de Araujo, Fernanda Fortes; Nakhasi, Hira L.; Debrabant, Alain] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Nagarkatti, R (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM alain.debrabant@fda.hhs.gov FU FDA under FDA Critical Path Initiative FX This work was supported by FDA internal funding under the FDA Critical Path Initiative. No external funding sources were used for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 12 Z9 13 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 22 PY 2012 VL 7 IS 8 AR e43533 DI 10.1371/journal.pone.0043533 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 999CI UT WOS:000308286300063 PM 22927983 ER PT J AU Banerjee, S Siburt, CJP Abraham, B Jia, YP Wood, F Todd, M Alayash, AI Bonaventura, C Crumbliss, AL AF Banerjee, Sambuddha Siburt, Claire J. Parker Abraham, Bindu Jia, Yiping Wood, Francine Todd, Mollan Alayash, Abdu I. Bonaventura, Celia Crumbliss, Alvin L. TI Protection provided by haptoglobin (Hp) and alpha hemoglobin stabilizing protein (AHSP) toward cell free hemoglobin and a-hemoglobin subunit: A common strategy to insulate heme induced toxicity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Banerjee, Sambuddha; Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke UniversityNC, Dept Chem, Durham, NC 27708 USA. [Abraham, Bindu; Jia, Yiping; Wood, Francine; Todd, Mollan; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Bonaventura, Celia] Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC USA. EM sb218@duke.edu NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 88-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800658 ER PT J AU Buhse, L Gryniewicz-Ruzicka, CM Dunn, JD Arzhantsev, S Spencer, JA Rodriguez, J Westenberger, BJ Kauffman, JF AF Buhse, Lucinda Gryniewicz-Ruzicka, Connie M. Dunn, Jamie D. Arzhantsev, Sergey Spencer, John A. Rodriguez, Jason Westenberger, Benjamin J. Kauffman, John F. TI Rapid screening methods for pharmaceutical surveillance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Buhse, Lucinda; Gryniewicz-Ruzicka, Connie M.; Dunn, Jamie D.; Arzhantsev, Sergey; Spencer, John A.; Rodriguez, Jason; Westenberger, Benjamin J.; Kauffman, John F.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM Lucinda.Buhse@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 29-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802111 ER PT J AU Cormier, EP AF Cormier, Elizabeth Pollina TI Chemists, chemistry, and the FDA: Building quality into drug manufacturing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Cormier, Elizabeth Pollina] US FDA, Rockville, MD 20855 USA. EM elizabeth.cormier@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 396-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621801892 ER PT J AU DeGrasse, J AF DeGrasse, Jeffrey TI Sticky DNA: The use of DNA aptamers for the rapid and robust detection of pathogens, proteins, and small molecules in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [DeGrasse, Jeffrey] US FDA, Div Analyt Chem, College Pk, MD 20740 USA. EM JEFFREY.DEGRASSE@FDA.HHS.GOV NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 16-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800082 ER PT J AU Doell, DL Folmer, DE Lee, HS Carberry, SE AF Doell, Diana L. Folmer, Daniel E. Lee, Hyoung S. Carberry, Susan E. TI Exposure assessment of 4-methylimidazole (4-MEI) from caramel coloring for the US population SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Doell, Diana L.; Folmer, Daniel E.; Lee, Hyoung S.; Carberry, Susan E.] US FDA, College Pk, MD 20740 USA. EM Diana.Doell@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 156-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800210 ER PT J AU Duncan, TV AF Duncan, Timothy V. TI Using nanotechnology to make foods safer: Nanoparticles as sensors for small molecules, protein toxins, and foodborne pathogens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Duncan, Timothy V.] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. EM timothy.duncan@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 15-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800081 ER PT J AU Girard, L Smith, S Lopez, M Kijak, P Feng, SX AF Girard, Lauren Smith, Shani Lopez, Mayda Kijak, Phil Feng, Shixia TI Determination and confirmation of oxytetracycline, chlortetracycline, and tetracycline in bovine kidney by LC-MS/MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Girard, Lauren; Smith, Shani; Lopez, Mayda; Kijak, Phil; Feng, Shixia] US FDA, CVM, Laurel, MD 20708 USA. EM Lauren.Girard@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 126-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800182 ER PT J AU Handy, SM Deeds, J AF Handy, Sara M. Deeds, Jonathan TI DNA-based species identification in support of food safety at the FDA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Handy, Sara M.; Deeds, Jonathan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM sara.handy@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 17-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800083 ER PT J AU Hatwell, KR Mihalov, JJ Bailey, AB AF Hatwell, Karen R. Mihalov, Jeremy J. Bailey, Allan B. TI Assessing exposure to BPA for infants, toddlers, and adults SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Hatwell, Karen R.; Bailey, Allan B.] US FDA, Div Food Contact Notificat, College Pk, MD 20740 USA. [Mihalov, Jeremy J.] US FDA, Div Biotechnol & GRAS Notice Review, College Pk, MD 20740 USA. EM karen.hatwell@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 140-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800196 ER PT J AU Hatwell, KR Turowski, PN Bailey, AB AF Hatwell, Karen R. Turowski, Petra N. Bailey, Allan B. TI Assessing the exposure to organotin compounds from food contact applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Hatwell, Karen R.; Turowski, Petra N.; Bailey, Allan B.] US FDA, Div Food Contact Notificat, College Pk, MD 20740 USA. EM karen.hatwell@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 141-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800197 ER PT J AU Jackson, LS AF Jackson, Lauren S. TI Detection of food allergens: Current analytical methods and future needs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Jackson, Lauren S.] US FDA, Div Food Proc Sci & Technol, CFSAN, Bedford Pk, IL 60501 USA. EM Lauren.Jackson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 197-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800241 ER PT J AU Jayasuriya, H Amarasinghe, K Chu, PS Reimschuessel, R Hasbrouck, N Evans, E Chattopadhaya, C AF Jayasuriya, Hiranthi Amarasinghe, Kande Chu, Pak S. Reimschuessel, Renate Hasbrouck, Nicholas Evans, Eric Chattopadhaya, Chaitali TI Discovery of a novel glucuronide metabolite of methyltestosterone in tilapia bile by liquid chromatography/quadrupole-time of flight mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Jayasuriya, Hiranthi; Amarasinghe, Kande; Chu, Pak S.; Reimschuessel, Renate; Hasbrouck, Nicholas; Evans, Eric; Chattopadhaya, Chaitali] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM hiranthi100@live.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 204-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800454 ER PT J AU Jin, TC Wang, Y Chen, YW Albillos, SM Kothary, MH Fu, TJ Tankersley, B McHugh, TH Zhang, YZ AF Jin, Tengchuan Wang, Yang Chen, Yu-Wei Albillos, Silvia M. Kothary, Mahendra H. Fu, Tong-Jen Tankersley, Boyce McHugh, Tara H. Zhang, Yu-Zhu TI Purification and characterization of convicilin, a vicilin-like globulin, from Korean pine (Pinus koraiensis) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [McHugh, Tara H.; Zhang, Yu-Zhu] USDA, ARS PWA WRRC, Albany, CA 94710 USA. [Jin, Tengchuan; Wang, Yang; Chen, Yu-Wei; Zhang, Yu-Zhu] IIT, Dept Biol & Chem Sci, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Albillos, Silvia M.] IIT, Natl Ctr Food Safety & Technol, Bedford, IL 60501 USA. [Tankersley, Boyce] Chicago Bot Garden, Glencoe, IL 60022 USA. EM yuzhu.zhang@ars.usda.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 219-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800263 ER PT J AU Jitian, S Yang, HHW Weisz, A AF Jitian, Simion Yang, H. -H. Wendy Weisz, Adrian TI Determination of 1,3,6-pyrenetrisulfonic acid trisodium salt and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt in the color additive D&C Green No. 8 (Pyranine) using high-performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Jitian, Simion] Tech Univ Timisoara, Fac Engn Hunedoara, RO-1900 Timisoara, Romania. [Yang, H. -H. Wendy; Weisz, Adrian] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 103-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800873 ER PT J AU Johnston, JJ Zhou, T AF Johnston, John J. Zhou, Tong TI Inter-agency risk communication: Inorganic arsenic residues in poultry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Johnston, John J.] US Food Safety & Inspect Serv, Off Publ Hlth Sci, Off Assistant Administrator, USDA, Washington, DC 20250 USA. [Zhou, Tong] US FDA, Off New Anim Drug Evaluat, Div Human Food Safety, Ctr Vet Med, Rockville, MD 20855 USA. EM John.Johnston@fsis.usda.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 267-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800516 ER PT J AU Lunn, G AF Lunn, George TI Analytical procedures and the regulation of new drug development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Lunn, George] US FDA, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. EM george.lunn@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 30-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802112 ER PT J AU MacMahon, S Begley, TH Diachenko, GW AF MacMahon, Shaun Begley, Timothy H. Diachenko, Gregory W. TI LC-MS detection of process-induced contaminants in edible oils SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [MacMahon, Shaun; Begley, Timothy H.; Diachenko, Gregory W.] US FDA, College Pk, MD 20740 USA. EM shaun.macmahon@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 19-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800085 ER PT J AU Mindak, WR AF Mindak, William R. TI Arsenic in juice - are the results reliable? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Mindak, William R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM william.mindak@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 78-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800141 ER PT J AU Nazumudeen, F Cox, S Chauca, H Obando, J Svoronos, P AF Nazumudeen, Fathima Cox, Shelema Chauca, Hendri Obando, Jose Svoronos, Paris TI Identification of mycotoxin and chemotherapeutics by FDA Northeast Region Laboratory SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Nazumudeen, Fathima; Svoronos, Paris] CUNY Queensborough Community Coll, Dept Chem, Bayside, NY 11364 USA. [Cox, Shelema; Chauca, Hendri; Obando, Jose] Food & Drug Adm Northeast Reg, Jamaica, NY 11433 USA. EM fthm.nazumudeen@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 267-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621801774 ER PT J AU Novais, DA Harjivan, SG Wanke, R Pinheiro, PF Santos, PP Beland, FA Marques, MM Antunes, AMM AF Novais, David A. Harjivan, Shrika G. Wanke, Riccardo Pinheiro, Pedro F. Santos, Pedro P. Beland, Frederick A. Matilde Marques, M. Antunes, Alexandra M. M. TI Oxidation of phenolic nevirapine metabolites to a reactive quinone - a plausible pathway to toxicity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Novais, David A.; Harjivan, Shrika G.; Wanke, Riccardo; Pinheiro, Pedro F.; Santos, Pedro P.; Matilde Marques, M.; Antunes, Alexandra M. M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1096 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 70-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621808691 ER PT J AU Nyman, PJ Begley, TH AF Nyman, Patricia J. Begley, Timothy H. TI Determination of volatile organic compounds (VOCs) in food by vacuum distillation sampling and gas chromatography/mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Nyman, Patricia J.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM patricia.nyman@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 41-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800106 ER PT J AU Phillips, KS Hitchins, V Patwardhan, D AF Phillips, K. Scott Hitchins, Victoria Patwardhan, Dinesh TI Contact lens materials and multipurpose solutions: Lessons learned from laboratory research SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Phillips, K. Scott; Patwardhan, Dinesh] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Hitchins, Victoria] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Kenneth.Phillips@fda.hhs.gov RI phillips, kenneth/F-7560-2014 OI phillips, kenneth/0000-0002-6552-0694 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 12-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802095 ER PT J AU Silverstein, JS Casey, BJ Dair, BJ Kofinas, P AF Silverstein, Joshua S. Casey, Brendan J. Dair, Benita J. Kofinas, Peter TI Protein adsorption on nanopatterned block copolymers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Silverstein, Joshua S.; Kofinas, Peter] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Silverstein, Joshua S.; Casey, Brendan J.; Dair, Benita J.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20993 USA. EM joshua.silverstein@fda.hhs.gov RI Kofinas, Peter/A-8204-2012 OI Kofinas, Peter/0000-0001-6657-3037 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 615-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802787 ER PT J AU Srinivasan, J AF Srinivasan, Jannavi TI Crop composition: A key component in the safety assessment of a new plant variety SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Srinivasan, Jannavi] US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. EM Jannavi.Srinivasan@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 288-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800537 ER PT J AU Tkachenko, V Williams, AJ Borodina, Y Switzer, F Peryea, T Callahan, L AF Tkachenko, Valery Williams, Antony J. Borodina, Yulia Switzer, Frank Peryea, Tyler Callahan, Larry TI How can the International Chemical Identifier (InChI) be extended to non-trivial chemicals? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Tkachenko, Valery; Williams, Antony J.] Royal Soc Chem, Wake Forest, NC 27587 USA. [Borodina, Yulia; Switzer, Frank; Peryea, Tyler; Callahan, Larry] FDA, Silver Spring, MD 20993 USA. EM tkachenkov@rsc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 139-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802200 ER PT J AU Tolleson, WH Triplett, OA Nguyen, KT AF Tolleson, William H. Triplett, Odbert A. Nguyen, Kiet T. TI Effect of pH on the thermal stability of ricin evaluated using differential scanning calorimetry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Tolleson, William H.; Triplett, Odbert A.; Nguyen, Kiet T.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM william.tolleson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 28-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800094 ER PT J AU Tsai, DH Elzey, S DelRio, FW Keene, AM Tyner, KM Clogston, JD MacCuspie, RI Guha, S Zachariah, MR Hackley, VA AF Tsai, De-Hao Elzey, Sherrie DelRio, Frank W. Keene, Athena M. Tyner, Katherine M. Clogston, Jeffrey D. MacCuspie, Robert I. Guha, Suvajyoti Zachariah, Michael R. Hackley, Vincent A. TI Tumor necrosis factor interaction with gold nanoparticles SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Tsai, De-Hao; Elzey, Sherrie; DelRio, Frank W.; MacCuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena M.; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Clogston, Jeffrey D.] NCI Frederick, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. EM dhtsai@nist.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 493-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621802673 ER PT J AU Tyburczy, C Mossoba, MM Delmonte, P Fardin-Kia, AR Rader, JI AF Tyburczy, Cynthia Mossoba, Magdi M. Delmonte, Pierluigi Fardin-Kia, Ali Reza Rader, Jeanne I. TI Evaluation of low trans fat edible oils by Fourier transform infrared spectroscopy and gas chromatography: A comparison of regulatory methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Tyburczy, Cynthia; Mossoba, Magdi M.; Delmonte, Pierluigi; Fardin-Kia, Ali Reza; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM cynthia.tyburczy@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 18-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621800084 ER PT J AU Wang, SG Zhao, YW Xia, QS da Costa, AG Cai, LN Fu, PP AF Wang, Shuguang Zhao, Yuewei Xia, Qingsu da Costa, Alo Gamboa Cai, Lining Fu, Peter P. TI Reactions of dehydropyrrolizidine alkaloids with valine and hemoglobin SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Wang, Shuguang; Zhao, Yuewei; Xia, Qingsu; da Costa, Alo Gamboa; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Cai, Lining] Biotranex LLC, Monmouth Jct, NJ 08852 USA. EM Shuguang.Wang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 229-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621804446 ER PT J AU Witkowski, MR AF Witkowski, Mark R. TI Pharmaceutical forensics: The use of a multidisciplinary approach in the detection of counterfeit pharmaceuticals SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Witkowski, Mark R.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM mark.witkowski@wl.com NR 0 TC 0 Z9 0 U1 3 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 2-SOCED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621808619 ER PT J AU Xia, QS Zhao, YW da Costa, GG Yu, HT Cai, LN Fu, PP AF Xia, Qingsu Zhao, Yuewei da Costa, Goncalo Gamboa Yu, Hongtao Cai, Lining Fu, Peter P. TI Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor induction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc C1 [Xia, Qingsu; Zhao, Yuewei; da Costa, Goncalo Gamboa; Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. [Cai, Lining] Biotranex LLC, Monmouth Jct, NJ 08852 USA. EM qingsu.xia@fda.hhs.gov; peter.fu@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2012 VL 244 MA 57-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 220XX UT WOS:000324621808678 ER PT J AU Khare, S Lawhon, SD Drake, KL Nunes, JES Figueiredo, JF Rossetti, CA Gull, T Everts, RE Lewin, HA Galindo, CL Garner, HR Adams, LG AF Khare, Sangeeta Lawhon, Sara D. Drake, Kenneth L. Nunes, Jairo E. S. Figueiredo, Josely F. Rossetti, Carlos A. Gull, Tamara Everts, Robin E. Lewin, Harris A. Galindo, Cristi L. Garner, Harold R. Adams, Leslie Garry TI Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance SO PLOS ONE LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; INFLAMMATORY BOWEL DISEASES; SUBSP-PARATUBERCULOSIS; CROHNS-DISEASE; JOHNES-DISEASE; SSP PARATUBERCULOSIS; BOVINE MONOCYTES; GAMMA-INTERFERON; DENDRITIC CELLS; PEYERS-PATCHES AB Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch. C1 [Khare, Sangeeta; Lawhon, Sara D.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Adams, Leslie Garry] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Pathobiol, College Stn, TX USA. [Drake, Kenneth L.] Seralogix Ltd, Austin, TX USA. [Everts, Robin E.; Lewin, Harris A.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA. [Galindo, Cristi L.; Garner, Harold R.] Univ Texas SW Med Sch, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX USA. RP Khare, S (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM gadams@cvm.tamu.edu RI Lawhon, Sara/G-5147-2011 OI Lawhon, Sara/0000-0001-9154-8909 FU U.S. Department of Agriculture Cooperative State Research, Education and Extension Service-National Research Initiative-Coordinated Agricultural Project-Johne's Disease Integrated Program [2004-35605-14243, Q6286224133]; Texas AM University; Texas A&M University Life Sciences Task Force; National Institutes of Health (U.S.) NIH-NIAID [AI060933]; NIH NIAID SBIR [2R44AI058362-02, R43AI084223-01] FX The study was supported by funds to Sangeeta Khare from the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service-National Research Initiative-Coordinated Agricultural Project-Johne's Disease Integrated Program (2004-35605-14243 sub-award Q6286224133) and Animal Health formula funds through Texas A&M University. This study was also supported by funds awarded to Leslie Garry Adams from the Texas A&M University Life Sciences Task Force. Sara D. Lawhon was supported by National Institutes of Health (U.S.) NIH-NIAID AI060933. The computational analysis work was supported in part by NIH NIAID SBIR grants 2R44AI058362-02 and R43AI084223-01 awarded to Kenneth L. Drake. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 87 TC 20 Z9 20 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 17 PY 2012 VL 7 IS 8 AR e42127 DI 10.1371/journal.pone.0042127 PG 34 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996DG UT WOS:000308063700011 PM 22912686 ER PT J AU Pripuzova, N Wang, R Tsai, S Li, BJ Hung, GC Ptak, RG Lo, SC AF Pripuzova, Natalia Wang, Richard Tsai, Shien Li, Bingjie Hung, Guo-Chiuan Ptak, Roger G. Lo, Shyh-Ching TI Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens SO PLOS ONE LA English DT Article ID DISEASES (RAPID)-BIOACTIVE AMPLIFICATION; RELIABLE ASSAY PROTOCOL; B-VIRUS DNA; WEST-NILE-VIRUS; RAPID DETECTION; PROBING BAP; HIV TYPE-1; GROUP-O; IDENTIFICATION; QUANTIFICATION AB Background: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. Findings: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100-1,000 geq/ml of plasma of HIV-1 subtypes (A - G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. Conclusions: The viral array described here demonstrated adequate performance in the testing of donors' clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development. C1 [Pripuzova, Natalia; Tsai, Shien; Li, Bingjie; Hung, Guo-Chiuan; Lo, Shyh-Ching] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapy,Ctr Biol Evalu, Bethesda, MD 20014 USA. [Wang, Richard] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD USA. RP Pripuzova, N (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapy,Ctr Biol Evalu, Bethesda, MD 20014 USA. EM ShyhChing.Lo@fda.hhs.gov NR 43 TC 5 Z9 5 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 17 PY 2012 VL 7 IS 8 AR e43246 DI 10.1371/journal.pone.0043246 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 996DG UT WOS:000308063700066 PM 22912836 ER PT J AU Yin, JJ Liu, J Ehrenshaft, M Roberts, JE Fu, PP Mason, RP Zhao, BZ AF Yin, Jun-Jie Liu, Jun Ehrenshaft, Marilyn Roberts, Joan E. Fu, Peter P. Mason, Ronald P. Zhao, Baozhong TI Phototoxicity of nano titanium dioxides in HaCaT keratinocytes-Generation of reactive oxygen species and cell damage SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE TiO2 nanoparticles; Phototoxicity; Reactive oxygen species (ROS); Lipid peroxidation; Human HaCaT keratinocytes; ESR; Oximetry; Immuno-spin trapping ID PROTEIN RADICAL FORMATION; SINGLET OXYGEN; PHOTOCATALYTIC ACTIVITY; TIO2 NANOPARTICLES; OXIDATIVE STRESS; IN-VITRO; TOXICITY; EPR; UVA; CYTOTOXICITY AB Nano-sized titanium dioxide (TiO2) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO2 nanoparticles (nano-TiO2) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO2 particles caused phototoxicity, as determined by the MIS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO2 dose-dependent. The smaller the particle size of the nano-TiO2 the higher the cell damage. The rutile form of nano-TiO2 showed less phototoxicity than anatase nano-TiO2. The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance (ESR) oximetry and immuno-spin trapping as unique probing methods, we demonstrated that UVA irradiation of nano-TiO2 can induce significant cell damage, mediated by lipid and protein peroxidation. These overall results suggest that nano-TiO2 is phototoxic to human skin keratinocytes, and that this phototoxicity is mediated by ROS generated during UVA irradiation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Liu, Jun; Zhao, Baozhong] Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Roberts, Joan E.] Fordham Univ, New York, NY 10023 USA. [Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Zhao, BZ (reprint author), Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. EM zhaobz@nanoctr.cn RI Zhao, Baozhong/B-5865-2011; Yin, Jun Jie /E-5619-2014 FU FY11 FDA Nanotechnology CORES Program; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (JJ Yin) and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors are indebted to Dr. Jianxun Xu for his help in SEM image analysis, Dr. Zhanjun Gu, Yeteng Zhong for their help in XRD analysis, and Dr. Ann Motten, NIEHS, for critical reading of the manuscript. NR 42 TC 57 Z9 60 U1 4 U2 56 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 15 PY 2012 VL 263 IS 1 BP 81 EP 88 DI 10.1016/j.taap.2012.06.001 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 984RK UT WOS:000307208900011 PM 22705594 ER PT J AU Peters, SM Yancy, H Deaver, C Jones, YL Kenyon, E Chiesa, OA Esparza, J Screven, R Lancaster, V Stubbs, JT Yang, MC Wiesenfeld, PL Myers, MJ AF Peters, Sharla M. Yancy, Haile Deaver, Christine Jones, Yolanda L. Kenyon, Elizabeth Chiesa, Oscar A. Esparza, Juan Screven, Rudell Lancaster, Vicki Stubbs, John T., III Yang, Maocheng Wiesenfeld, Paddy L. Myers, Michael J. TI In vivo characterization of inflammatory biomarkers in swine and the impact of flunixin meglumine administration SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Inflammation; Biomarkers; Non-steroidal anti-inflammatory drugs; Swine ID ACUTE-PHASE-REACTANT; DENDRITIC CELL MATURATION; MYCOBACTERIUM-TUBERCULOSIS; MONOCYTE DIFFERENTIATION; ANTIGEN PRESENTATION; KAPPA-B; ASPIRIN; CD1; VITRO; PHARMACOKINETICS AB Non-steroidal anti-inflammatory drugs (NSAID) are a family of chemicals that function to reduce pain, fever, and inflammation, and they are commonly used in people and animals for this purpose. Currently there are no NSAIDs approved for the management of inflammation in swine due to a lack of validated animal models and suitable biomarkers to assess efficacy. A previous in vitro study examining biomarkers of inflammation identified fourteen genes that were significantly altered in response to Escherichia coli lipopolysaccharide (LPS)-induced inflammation. In the present study, five of those fourteen genes were tested in vivo to determine if the same effects observed in vitro were also observed in vivo. Plasma levels of prostaglandin E-2 (PGE(2)), an essential mediator of fever and inflammation, were also determined. Two groups of swine were stimulated with LPS with the second group also treated with flunixin meglumine. Blood was collected at 0, 1, 3, 6, 8, 24, and 48 h post LPS-stimulation. The RNA was extracted from the blood and quantitative real-time-PCR (qRT-PCR) was utilized to determine the expression patterns of CD1, CD4, serum amyloid A2 (SAA2), Caspase 1, and monocyte chemoattractant protein 1 (MCP-1). The LPS-stimulated animals demonstrated a statistically significant alteration in expression of SAA2 and CD1 at 3 h post-stimulation. Flunixin meglumine treated animals' demonstrated reduced expression of CD1 in comparison to the LPS-stimulated swine at 24 and 48 h post LPS-stimulation. Flunixin meglumine treated animals exhibited reduced expression of SAA2 at 48 h post-stimulation compared to LPS-stimulated swine. Swine treated with LPS demonstrated statistically significant increases in plasma PGE(2) at 1 h post-stimulation. Swine treated with flunixin meglumine had no increase in plasma PGE(2) levels at any time. These results demonstrate that PGE(2) production, along with two out of five genes (SAA2 and CD1) have the potential to serve as early biomarkers of inflammation as well as indicators of NSAID efficacy. Published by Elsevier B.V. C1 [Peters, Sharla M.; Yancy, Haile; Deaver, Christine; Jones, Yolanda L.; Kenyon, Elizabeth; Chiesa, Oscar A.; Esparza, Juan; Screven, Rudell; Yang, Maocheng; Myers, Michael J.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Lancaster, Vicki] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. [Peters, Sharla M.; Stubbs, John T., III] Howard Univ, Dept Microbiol, Washington, DC 20059 USA. [Wiesenfeld, Paddy L.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.myers@fda.hhs.gov NR 32 TC 5 Z9 5 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD AUG 15 PY 2012 VL 148 IS 3-4 BP 236 EP 242 DI 10.1016/j.vetimm.2012.05.001 PG 7 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 009MR UT WOS:000309030400003 PM 22648045 ER PT J AU Bailey, AM AF Bailey, Alexander M. TI IS MY PRODUCT CAPABLE OF TUMOR FORMATION? SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID STEM-CELLS C1 US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Bailey, AM (reprint author), US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM alexander.bailey@fda.hhs.gov NR 9 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 15 PY 2012 VL 4 IS 147 AR 147fs28 DI 10.1126/scitranslmed.3003685 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 994UR UT WOS:000307958800001 PM 22896673 ER PT J AU Abzug, MJ Qin, M Levin, MJ Fenton, T Beeler, JA Bellini, WJ Audet, S Sowers, SB Borkowsky, W Nachman, SA Pelton, SI Rosenblatt, HM AF Abzug, Mark J. Qin, Min Levin, Myron J. Fenton, Terence Beeler, Judy A. Bellini, William J. Audet, Susette Sowers, Sun Bae Borkowsky, William Nachman, Sharon A. Pelton, Stephen I. Rosenblatt, Howard M. CA Int Maternal Pediat Adolescent AID TI Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZAMBIAN CHILDREN; RUBELLA REVACCINATION; UNINFECTED CHILDREN; BOOSTER VACCINATION; NEUTRALIZATION TEST; VARICELLA VACCINE; ANTIBODY-RESPONSE; TYPE-1 INFECTION; IMMUNIZATION AB Background. Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). Methods. HIV-infected children 2 to < 19 years old receiving HAART and with HIV loads < 30 000 copies/mL, CD4% >= 15, and >= 1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. Results. At entry, 52% of 193 subjects were seroprotected (PRN >= 120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load <= 400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Conclusions. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. C1 [Abzug, Mark J.; Levin, Myron J.] Childrens Hosp Colorado, Aurora, CO 80045 USA. [Abzug, Mark J.; Levin, Myron J.] Univ Colorado, Sch Med, Aurora, CO USA. [Qin, Min] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Beeler, Judy A.; Audet, Susette] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Bellini, William J.; Sowers, Sun Bae] Ctr Dis Control, Div Viral Dis, Atlanta, GA 30333 USA. [Borkowsky, William] NYU, Sch Med, New York, NY USA. [Borkowsky, William] Bellevue Hosp Ctr, New York, NY 10016 USA. [Nachman, Sharon A.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Pelton, Stephen I.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Pelton, Stephen I.] Boston Med Ctr, Boston, MA USA. [Rosenblatt, Howard M.] Baylor Coll Med, Houston, TX 77030 USA. [Rosenblatt, Howard M.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Abzug, MJ (reprint author), Childrens Hosp Colorado, Box B055,13123 E 16th Ave, Aurora, CO 80045 USA. EM mark.abzug@childrenscolorado.org OI Pelton, Stephen/0000-0003-4862-5344; Bonagura, Vincent/0000-0002-0681-2099 FU Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases (NIAID) [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group [1 U01 AI068616]; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group; NICHD [N01-DK-9-001/HHSN267200800001C]; General Clinical Research Center Units; National Center for Research Resources, National Institutes of Health (NIH) [MO1-RR00069]; NIAID [U01 AI068632]; National Institute of Mental Health (NIMH) [AI068632] FX This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases (NIAID) cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group. Support of the sites was provided by the NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). This work was also supported in part by the General Clinical Research Center Units funded by the National Center for Research Resources, National Institutes of Health (NIH; including MO1-RR00069, General Clinical Research Centers Program).; Merck and Co. provided study vaccine used in P1061s. Overall support for the IMPAACT group was provided by the NIAID (U01 AI068632), the NICHD, and the National Institute of Mental Health (NIMH; AI068632). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 41 TC 20 Z9 20 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2012 VL 206 IS 4 BP 512 EP 522 DI 10.1093/infdis/jis386 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 977MQ UT WOS:000306667000009 PM 22693229 ER PT J AU Wales, SQ Ngo, D Hida, K Kulka, M AF Wales, Samantha Q. Ngo, Diana Hida, Kaoru Kulka, Michael TI Temperature and density dependent induction of a cytopathic effect following infection with non-cytopathic HAV strains SO VIROLOGY LA English DT Article DE Hepatitis A; Cytopathic effect; Apoptosis; RNase L ID HEPATITIS-A-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; RIBOSOMAL-RNA CLEAVAGE; CELL-LINE FRHK-4; MRC-5 CELLS; GROWTH-CHARACTERISTICS; PERSISTENT INFECTION; SERIAL PASSAGE; PLAQUE-ASSAY; CULTURE AB Hepatitis A virus infection and growth in cultured cells is protracted, cell-type restricted, and generally not accompanied by the appearance of a cytopathic effect, with the exception of some culture-adapted strains. We demonstrate that the non-cytopathic HAV strain HM175/clone 1 can be induced to exhibit a cytopathic phenotype in both persistently or acutely infected cells under co-dependent conditions of lower incubation temperature ( < 34 degrees C) and reduced cell density in both monkey (FRhK-4) and human (A549) cells. This phenotype is not virus-strain restricted, as it was also observed in cells infected with HAV strains, HAS-15 and LSH/S. Cytopathic effect was accompanied by rRNA cleavage, indicating activation of the RNase L pathway, viral negative strand synthesis, caspase-3 activation, and apoptosis. The results indicate that a cytopathic phenotype may be present in some HAV strains that can be induced under appropriate conditions, suggesting the potential for development of a plaque assay for this virus. Published by Elsevier Inc. C1 [Wales, Samantha Q.; Ngo, Diana; Hida, Kaoru; Kulka, Michael] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Kulka, M (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM samantha.wales@fda.hhs.gov; diana.ngo@fda.hhs.gov; kaoru.hida@fda.hhs.gov; michael.kulka@fda.hhs.gov FU FDA Commissioner's Fellowship Program FX We thank Dr. Christopher A. Elkins for critically reading the manuscript, Dr. Efstathia Papafragkou for her invaluable help and advice regarding RT-qPCR, and Mr. Mark Mammel for HAV phylogenic analysis and determination of the LSH/S genotype. We also want to thank Dr. Biswendu Goswami (FDA, retired) for his helpful advice and suggestions during the initiation of this investigation. His contributions to our laboratory will truly be missed. This study was funded by the Center for Food Safety and Applied Nutrition. K.H. was funded under the FDA Commissioner's Fellowship Program. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 64 TC 4 Z9 4 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2012 VL 430 IS 1 BP 30 EP 42 DI 10.1016/j.virol.2012.04.010 PG 13 WC Virology SC Virology GA 960IK UT WOS:000305381000004 PM 22608060 ER PT J AU Virnik, K Ni, YS Berkower, I AF Virnik, Konstantin Ni, Yisheng Berkower, Ira TI Live attenuated rubella viral vectors stably express HIV and SIV vaccine antigens while reaching high titers SO VACCINE LA English DT Article DE Live viral vectors; Rubella vaccine strain RA27/3; Stable expression; HIV MPER; SIV Gag; Vaccine antigen ID IMMUNODEFICIENCY-VIRUS TYPE-1; EQUINE ENCEPHALITIS-VIRUS; PROXIMAL EXTERNAL REGION; CLASS-I MOLECULE; HUMAN MONOCLONAL-ANTIBODY; NONSTRUCTURAL PROTEIN; RHESUS MACAQUES; NEUTRALIZING ANTIBODY; NEF GENE; REPLICATION AB Live attenuated viruses make potent and effective vaccines. Despite the urgent need for an HIV vaccine, this approach has not been feasible, since it has not been possible to attenuate the virus reliably and guarantee vaccine safety. Instead, live viral vectors have been proposed that could present HIV vaccine antigens in the most immunogenic way, in the context of an active infection. We have adapted the rubella vaccine strain RA27/3 as a vector to express HIV and SIV antigens, and tested the effect of insert size and composition on vector stability and viral titer. We have identified an acceptor site in the rubella nonstructural gene region, where foreign genes can be expressed as a fusion protein with the non-structural protein P150 without affecting essential viral functions. The inserts were expressed as early genes of rubella, under control of the rubella genomic promoter. At this site, HIV and SIV antigens were expressed stably for at least seven passages, as the rubella vectors reached high titers. Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge. Published by Elsevier Ltd. C1 [Virnik, Konstantin; Ni, Yisheng; Berkower, Ira] US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov FU Intramural NIH HHS [Z99 OD999999] NR 49 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 10 PY 2012 VL 30 IS 37 BP 5453 EP 5458 DI 10.1016/j.vaccine.2012.06.074 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 991JR UT WOS:000307697800002 PM 22776214 ER PT J AU Basu, S Hassenplug, JC AF Basu, Saptarshi Hassenplug, John C. TI Patient Access to Medical Devices - A Comparison of U.S. and European Review Processes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Basu, Saptarshi; Hassenplug, John C.] US FDA, Off Commissioner, Off Planning, White Oak, MD USA. RP Basu, S (reprint author), US FDA, Off Commissioner, Off Planning, White Oak, MD USA. NR 6 TC 22 Z9 22 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 9 PY 2012 VL 367 IS 6 BP 485 EP 488 DI 10.1056/NEJMp1204170 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 986AE UT WOS:000307310800001 PM 22852882 ER PT J AU Wu, HQ Khan, M AF Wu, Huiquan Khan, Mansoor TI THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications SO JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE Terahertz spectroscopy; Pharmaceutical development; Process Analytical Technology (PAT); Chemometrics; Pharmaceutical manufacturing process; First principles modeling ID TIME-DOMAIN SPECTROSCOPY; TERAHERTZ PULSED SPECTROSCOPY; DENSITY-FUNCTIONAL THEORY; LIQUID WATER; QUALITY; DYNAMICS; QUANTIFICATION; CRYSTALLINITY; MONOHYDRATE; VALIDATION AB As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted. Published by Elsevier B.V. C1 [Wu, Huiquan; Khan, Mansoor] Ctr Drug Evaluat & Res, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,US Food & Drug Adm, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), Ctr Drug Evaluat & Res, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,US Food & Drug Adm, HFD-940,Bldg 64,White Oak Campus,10903 New Hampsh, Silver Spring, MD 20993 USA. EM Huiquan.wu@fda.hhs.gov FU FDA CDER Regulatory Science and Review (RSR) [RSR-04-16] FX H. Wu gratefully acknowledges: (1) the scientific discussions on THz technology with Dr. Edwin Heilweil at the National Institute of Science and Technology (NIST), Gaithersburg, Maryland, USA: (2) the original FDA PAT Policy and Research Team, the FDA CDER Regulatory Science and Review (RSR) Funding Support (RSR-04-16) and Interagency Agreement between the FDA and NIST (IAG No 224-04-3008); (3) the original invitation from Dr. Henry Mantsch and Dr. Dieter Naumann, and extended invitation from the Special Issue editor Prof. Austin Barnes. The prompt internal review and approval from Dr. Vincent Vilker, Director, Office of Testing and Research (OTR), CDER, FDA are acknowledged. NR 60 TC 13 Z9 13 U1 3 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-2860 J9 J MOL STRUCT JI J. Mol. Struct. PD AUG 8 PY 2012 VL 1020 BP 112 EP 120 DI 10.1016/j.molstruc.2012.04.019 PG 9 WC Chemistry, Physical SC Chemistry GA 969HO UT WOS:000306046500016 ER PT J AU Hsu, WL Tse, KP Liang, SR Chien, YC Su, WH Yu, KJ Cheng, YJ Tsang, NM Hsu, MM Chang, KP Chen, IH Chen, TI Yang, CS Goldstein, AM Chen, CJ Chang, YS Hildesheim, A AF Hsu, Wan-Lun Tse, Ka-Po Liang, Sharon Chien, Yin-Chu Su, Wen-Hui Yu, Kelly J. Cheng, Yu-Juen Tsang, Ngan-Ming Hsu, Mow-Ming Chang, Kai-Ping Chen, I-How Chen, Tzu-I Yang, Czau-Siung Goldstein, Alisa M. Chen, Chien-Jen Chang, Yu-Sun Hildesheim, Allan TI Evaluation of Human Leukocyte Antigen-A (HLA-A), Other Non-HLA Markers on Chromosome 6p21 and Risk of Nasopharyngeal Carcinoma SO PLOS ONE LA English DT Article ID CLASS-I; SUSCEPTIBILITY; TAIWAN; ASSOCIATION; HAPLOTYPES; ALLELES AB Background: The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region. Methods: To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3). Findings: After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A). Conclusion: Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk. C1 [Hsu, Wan-Lun; Chen, Tzu-I; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Tse, Ka-Po; Chang, Yu-Sun] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Genome Med Core, Tao Yuan, Taiwan. [Liang, Sharon; Yu, Kelly J.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Liang, Sharon] US FDA, Rockville, MD 20857 USA. [Chien, Yin-Chu] China Med Univ Hosp, Mol & Genom Epidemiol Res Ctr, Taichung, Taiwan. [Su, Wen-Hui] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Mol Epidemiol Core, Tao Yuan, Taiwan. [Su, Wen-Hui] Chang Gung Univ, Grad Inst Biomed Sci, Dept Biomed Sci, Tao Yuan, Taiwan. [Yu, Kelly J.] NCI, Canc Prevent Div, Rockville, MD USA. [Cheng, Yu-Juen; Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan. [Tsang, Ngan-Ming] Chang Gung Mem Hosp Lin Kou, Dept Radiat Oncol, Tao Yuan, Taiwan. [Hsu, Mow-Ming] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. [Chang, Kai-Ping; Chen, I-How] Chang Gung Mem Hosp Lin Kou, Dept Otolaryngol, Tao Yuan, Taiwan. [Yang, Czau-Siung] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 10764, Taiwan. RP Hsu, WL (reprint author), Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. EM ysc@mail.cgu.edu.tw RI Chen, Chien-Jen/C-6976-2008; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Institutes of Health, USA; Ministry of Education, Taiwan FX The study was supported by the intramural funds from the National Institutes of Health, USA and The Top University Project of Ministry of Education, Taiwan (to Chang Gung University). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 0 Z9 0 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 7 PY 2012 VL 7 IS 8 AR e42767 DI 10.1371/journal.pone.0042767 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 987SL UT WOS:000307437900053 PM 22880099 ER PT J AU McBurney, RN Hines, WM VonTungeln, LS Schnackenberg, LK Beger, RD Moland, CL Han, T Fuscoe, JC Chang, CW Chen, JJ Su, ZQ Fan, XH Tong, WD Booth, SA Balasubramanian, R Courchesne, PL Campbell, JM Graber, A Guo, Y Juhasz, P Li, TY Lynch, MD Morel, NM Plasterer, TN Takach, EJ Zeng, CH Beland, FA AF McBurney, Robert N. Hines, Wade M. VonTungeln, Linda S. Schnackenberg, Laura K. Beger, Richard D. Moland, Carrie L. Han, Tao Fuscoe, James C. Chang, Ching-Wei Chen, James J. Su, Zhenqiang Fan, Xiao-Hui Tong, Weida Booth, Shelagh A. Balasubramanian, Raji Courchesne, Paul L. Campbell, Jennifer M. Graber, Armin Guo, Yu Juhasz, Peter Li, Tricia Y. Lynch, Moira D. Morel, Nicole M. Plasterer, Thomas N. Takach, Edward J. Zeng, Chenhui Beland, Frederick A. TI The Liver Toxicity Biomarker Study Phase I: Markers for the Effects of Tolcapone or Entacapone SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver toxicity; entacapone; tolcapone; biomarkers; treatment duration effects ID UNDERSTAND MECHANISMS; MESSENGER-RNA; TOXICOGENOMICS; IDENTIFICATION; PROTEIN AB The Liver Toxicity Biomarker Study is a systems toxicology approach to discover biomarkers that are indicative of a drug's potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a "toxic" drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a "clean" drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug-vehicle or drug-drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the study are detecting substantial "off-target" markers for the two drugs. An additional interesting finding was the modest overlap of the marker data sets for 3-day exposure and 28-day exposure, indicating that the molecular changes in liver and plasma caused by short-and long-term drug treatments do not share common characteristics. C1 [McBurney, Robert N.; Hines, Wade M.; Booth, Shelagh A.; Balasubramanian, Raji; Courchesne, Paul L.; Campbell, Jennifer M.; Graber, Armin; Guo, Yu; Juhasz, Peter; Li, Tricia Y.; Lynch, Moira D.; Morel, Nicole M.; Plasterer, Thomas N.; Takach, Edward J.; Zeng, Chenhui] BG Med Inc, Waltham, MA USA. [VonTungeln, Linda S.; Schnackenberg, Laura K.; Beger, Richard D.; Moland, Carrie L.; Han, Tao; Fuscoe, James C.; Chang, Ching-Wei; Chen, James J.; Su, Zhenqiang; Fan, Xiao-Hui; Tong, Weida; Beland, Frederick A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol HFT 110, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 FU Mitsubishi Chemical Holdings Corporation; Eisai Co. Ltd.; Daiichi Sankyo Co. Ltd.; UCB Pharma; Orion Pharma; Johnson and Johnson Inc.; Pfizer Inc. FX The authors thank Ralph Patton, Toxicologic Pathology Associates, NCTR, for conducting the clinical chemistry measurements and William M. Witt, Toxicologic Pathology Associates, NCTR, for performing the histopathological analyses. The authors also thank Dr. Paul Watkins for chairing the Scientific Advisory Committee and for his comments on the manuscript and Drs. Neil Kaplowitz and John Senior for their advice and counsel. The work described in this article was conducted under a CRADA between the U.S. Food and Drug Administration and BG Medicine Inc. Funds to conduct the work were provided to BG Medicine by Mitsubishi Chemical Holdings Corporation, Eisai Co. Ltd., Daiichi Sankyo Co. Ltd., UCB Pharma, Orion Pharma, Johnson and Johnson Inc., and Pfizer Inc. In addition, the authors thank the following companies for technology support: Applied Biosystems Inc., Affymetrix Inc., and TIBCO Software Inc. The views expressed in this article do not necessarily represent those of the U.S. Food and Drug Administration. NR 11 TC 7 Z9 7 U1 0 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2012 VL 40 IS 6 BP 951 EP 964 DI 10.1177/0192623312444026 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 119DG UT WOS:000317076800010 PM 22573522 ER PT J AU McKenna, MT Wang, SJ Nguyen, TB Burns, JE Petrick, N Summers, RM AF McKenna, Matthew T. Wang, Shijun Nguyen, Tan B. Burns, Joseph E. Petrick, Nicholas Summers, Ronald M. TI Strategies for improved interpretation of computer-aided detections for CT colonography utilizing distributed human intelligence SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Computed tomography colonography; Observer performance study; Crowdsourcing; Distributed human intelligence; Video analysis ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONIC POLYP DETECTION; OBSERVER PERFORMANCE; COLORECTAL NEOPLASIA; STOOL AB Computer-aided detection (CAD) systems have been shown to improve the diagnostic performance of CT colonography (CTC) in the detection of premalignant colorectal polyps. Despite the improvement, the overall system is not optimal. CAD annotations on true lesions are incorrectly dismissed, and false positives are misinterpreted as true polyps. Here, we conduct an observer performance study utilizing distributed human intelligence in the form of anonymous knowledge workers (KWs) to investigate human performance in classifying polyp candidates under different presentation strategies. We evaluated 600 polyp candidates from 50 patients, each case having at least one polyp >= 6 mm, from a large database of CTC studies. Each polyp candidate was labeled independently as a true or false polyp by 20 KWs and an expert radiologist. We asked each labeler to determine whether the candidate was a true polyp after looking at a single 3D-rendered image of the candidate and after watching a video fly-around of the candidate. We found that distributed human intelligence improved significantly when presented with the additional information in the video fly-around. We noted that performance degraded with increasing interpretation time and increasing difficulty, but distributed human intelligence performed better than our CAD classifier for "easy" and "moderate" polyp candidates. Further, we observed numerous parallels between the expert radiologist and the KWs. Both showed similar improvement in classification moving from single-image to video interpretation. Additionally, difficulty estimates obtained from the KWs using an expectation maximization algorithm correlated well with the difficulty rating assigned by the expert radiologist. Our results suggest that distributed human intelligence is a powerful tool that will aid in the development of CAD for CTC. (c) 2012 Published by Elsevier B.V. C1 [McKenna, Matthew T.; Wang, Shijun; Nguyen, Tan B.; Burns, Joseph E.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Burns, Joseph E.] Univ Calif Irvine, Med Ctr, Dept Radiol Sci, Orange, CA 92868 USA. [Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU National Institutes of Health, Clinical Center; US Food and Drug Administration FX The intramural research programs of the National Institutes of Health, Clinical Center, and the US Food and Drug Administration supported this work. We thank Perry J. Pickhardt, M.D., J. Richard Choi, ScD, MD and William Schindler, DO, for supplying CTC data. The mention of commercial entities, or commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such entities or products by the Department of Health and Human Services. NR 37 TC 6 Z9 6 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD AUG PY 2012 VL 16 IS 6 BP 1280 EP 1292 DI 10.1016/j.media.2012.04.007 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 018VH UT WOS:000309694100016 PM 22705287 ER PT J AU Graham, DJ Williams, JR Hsueh, YH Calia, K Levenson, M Pinheiro, SP MaCurdy, TE Worrall, C Kelman, JA AF Graham, David J. Williams, James R. Hsueh, Ya-Hui Calia, Katlyn Levenson, Mark Pinheiro, Simone P. MaCurdy, Thomas E. Worrall, Chris Kelman, Jeffrey A. TI Risk of Acute Myocardial Infarction (AMI), Stroke, and Death in Parkinson's Disease (PD) Patients Treated with Entacapone (Entac) or Other Adjunctive Therapies (AT) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Graham, David J.; Williams, James R.; Hsueh, Ya-Hui; Levenson, Mark; Pinheiro, Simone P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Calia, Katlyn; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Palo Alto, CA 94304 USA. [Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 47 BP 24 EP 24 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701047 ER PT J AU Li, Q Andrade, SE Cooper, WO Davis, RL Dublin, S Hammad, TA Pawloski, PA Pinheiro, SP Raebel, MA Scott, PE Smith, DH Dashevsky, I Haffenreffer, K Johnson, KE Toh, SD AF Li, Qian Andrade, Susan E. Cooper, William O. Davis, Robert L. Dublin, Sascha Hammad, Tarek A. Pawloski, Pamala A. Pinheiro, Simone P. Raebel, Marsha A. Scott, Pamela E. Smith, David H. Dashevsky, Inna Haffenreffer, Katherine Johnson, Karin E. Toh, Sengwee D. TI Validating a Gestational Length Algorithm Based on Administrative Health Plan Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Li, Qian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine; Toh, Sengwee D.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine; Toh, Sengwee D.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Davis, Robert L.] SE Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Dublin, Sascha; Johnson, Karin E.] Grp Hlth Res Inst, Seattle, WA USA. [Hammad, Tarek A.; Pinheiro, Simone P.; Scott, Pamela E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Smith, David H.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 65 BP 33 EP 33 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701065 ER PT J AU Edlavitch, SA Dal Pan, GJ Raine, JM Leufkens, B Avorn, J AF Edlavitch, Stanley A. Dal Pan, Gerald J. Raine, June M. Leufkens, Bert Avorn, Jerry TI Improving the Science of Regulatory Decision-Making - Advances in 2011/2012 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Edlavitch, Stanley A.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol OSE, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Raine, June M.] Vigilance, Med & Healthcare Prod Regulatory Agcy, Risk Management Medicines, London, England. [Leufkens, Bert] Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands. [Avorn, Jerry] Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 77 BP 39 EP 39 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701077 ER PT J AU Sturmer, T Funk, MJ Davis, KJ Graham, DJ Andrews, E Hallas, J AF Stuermer, Til Funk, Michele Jonsson Davis, Kourtney J. Graham, David J. Andrews, Elizabeth Hallas, Jesper TI Medicare Part D Data: Will the US Population-Based Data Be Advancing Pharmacoepidemiology and Public Health? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Stuermer, Til; Funk, Michele Jonsson] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Davis, Kourtney J.] GlaxoSmithKline, Epidemiol, Res Triangle Pk, NC USA. [Graham, David J.] US FDA, OSE, Rockville, MD 20857 USA. [Andrews, Elizabeth] RTI Int, Pharmacoepidemiol & Risk Management, Res Triangle Pk, NC USA. [Hallas, Jesper] Univ So Denmark, Dept Clin Pharmacol, Odense, Denmark. RI Jonsson Funk, Michele/F-6885-2011 OI Jonsson Funk, Michele/0000-0002-3756-7540 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 78 BP 39 EP 40 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701078 ER PT J AU Marinac-Dabic, D Sedrakyan, A Steinbuch, M Jalbert, J Crowley, J Labek, G Ritchey, MB Setoguchi, S AF Marinac-Dabic, Danica Sedrakyan, Art Steinbuch, Michael Jalbert, Jessica Crowley, Jay Labek, Gerold Ritchey, Mary Beth Setoguchi, Soko TI Unique Device Identification System (UDIS): Implications for Postmarketing Safety and Effectiveness Assessment in the United States and Europe SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Marinac-Dabic, Danica; Crowley, Jay; Ritchey, Mary Beth] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Sedrakyan, Art] Weill Cornell Med Coll, New York, NY USA. [Sedrakyan, Art] New York Presbyterian Hosp, New York, NY USA. [Steinbuch, Michael] Johnson & Johnson Med Device & Diagnost, Cincinnati, OH USA. [Jalbert, Jessica] Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02115 USA. [Labek, Gerold] Innsbruck Med Univ, Innsbruck, Austria. [Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 79 BP 40 EP 40 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701079 ER PT J AU Tu, CM Taylor, K Chai, G AF Tu, Chi-Ming Taylor, Kellie Chai, Grace TI Use of Brand Names of Discontinued Brand Drug Products by Prescribers When Generic Equivalents Exist SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Tu, Chi-Ming; Taylor, Kellie] US FDA, Div Medicat Error Prevent & Anal, CDER, OSE,OMEPRM, Silver Spring, MD USA. [Chai, Grace] US FDA, Div Epidemiol, CDER, OSE,OMEPRM, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 124 BP 61 EP 61 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701123 ER PT J AU Reichman, ME Graham, DJ Wernecke, M Southworth, MR Lam, C Worrall, CM Levenson, M MaCurdy, TE Houstoun, M Zornberg, G Zhang, RM Kelman, JA AF Reichman, Marsha E. Graham, David J. Wernecke, Michael Southworth, Mary Ross Lam, Chelsea Worrall, Chris M. Levenson, Mark MaCurdy, Thomas E. Houstoun, Monika Zornberg, Gwen Zhang, Rongmei Kelman, Jeffrey A. TI Patterns of Drug Use by Initiators of Dabigatran and Warfarin: Uptake and Persistence SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Reichman, Marsha E.; Graham, David J.; Houstoun, Monika; Zornberg, Gwen] FDA CDER OSE, Silver Spring, MD USA. [Wernecke, Michael; Lam, Chelsea] Acumen LLC, Burlingame, CA USA. [Southworth, Mary Ross] FDA CDER OND, Silver Spring, MD USA. [Worrall, Chris M.; Kelman, Jeffrey A.] CMS CM, Washington, DC USA. [Levenson, Mark; Zhang, Rongmei] FDA CDER OTS OB, Silver Spring, MD USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 141 BP 68 EP 69 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701138 ER PT J AU Funch, D Gardstein, B Chan, KA Maloney, E Mosholder, AD AF Funch, Donnie Gardstein, Betsey Chan, K. Arnold Maloney, Elizabeth Mosholder, Andrew D. TI Oseltamivir Treatment and Adverse Outcomes and Influenza-Related Complications in Children and Adults SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Funch, Donnie; Gardstein, Betsey; Chan, K. Arnold] OptumInsight, Epidemiol, Life Sci, Waltham, MA USA. [Chan, K. Arnold] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Maloney, Elizabeth; Mosholder, Andrew D.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 194 BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701187 ER PT J AU Stojanovic, D Schelfhout, J Houtchens, A Crane, HM Brown, E Kim, N Kitahata, MM Kauf, TL Delaney, JAC AF Stojanovic, Danijela Schelfhout, Jonathan Houtchens, Amy Crane, Heidi M. Brown, Elizabeth Kim, Nina Kitahata, Mari M. Kauf, Teresa L. Delaney, Joseph A. C. TI Changes in Platelet Counts over Time in HIV and Hepatitis C Virus (HCV) Co-Infected Patients SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Stojanovic, Danijela; Schelfhout, Jonathan; Houtchens, Amy; Kauf, Teresa L.; Delaney, Joseph A. C.] Univ Florida, Gainesville, FL USA. [Houtchens, Amy] US FDA, CDER, Silver Spring, MD USA. [Crane, Heidi M.; Kim, Nina; Kitahata, Mari M.] Univ Washington, Coll Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 231 BP 109 EP 109 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701223 ER PT J AU Hampp, C Borders-Hemphill, V Moeny, DG Wysowski, DK AF Hampp, Christian Borders-Hemphill, Vicky Moeny, David G. Wysowski, Diane K. TI Utilization of Antidiabetic Drugs among US Children and Adolescents, 2002-2011 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hampp, Christian; Borders-Hemphill, Vicky; Moeny, David G.; Wysowski, Diane K.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 284 BP 133 EP 133 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701273 ER PT J AU McMahon, AW Treadway, S Weinel, P Cope, JU Flack, MN Rich, S Murphy, D AF McMahon, Ann W. Treadway, Suzanne Weinel, Pamela Cope, Judith U. Flack, Marilyn N. Rich, Suzanne Murphy, Dianne TI Off-Label Use of Octreotide in Infants SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [McMahon, Ann W.; Weinel, Pamela; Cope, Judith U.; Murphy, Dianne] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. [Treadway, Suzanne] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Flack, Marilyn N.; Rich, Suzanne] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 311 BP 146 EP 146 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701299 ER PT J AU Graham, DJ Ding, X Saneinejad, S Zhou, EH Calia, K Levenson, M Gelperin, K Rose, M Hammad, TA MaCurdy, TE Worrall, C Kelman, JA AF Graham, David J. Ding, Xiao Saneinejad, Shahin Zhou, Esther H. Calia, Katlyn Levenson, Mark Gelperin, Kate Rose, Martin Hammad, Tarek A. MaCurdy, Thomas E. Worrall, Chris Kelman, Jeffrey A. TI Cardiovascular Risk of Olmesartan (Olm) Compared with Other Angiotensin-II Receptor Blockers (ARBs) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Graham, David J.; Ding, Xiao; Zhou, Esther H.; Levenson, Mark; Gelperin, Kate; Rose, Martin; Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Saneinejad, Shahin; Calia, Katlyn; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Palo Alto, CA 94304 USA. [Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 345 BP 162 EP 162 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701333 ER PT J AU Toh, D Reichman, ME Houstoun, M Southworth, MR Ding, X Hernandez, AF Levenson, M Li, LL Shoaibi, A Zornberg, G Hennessy, S AF Toh, Darren Reichman, Marsha E. Houstoun, Monika Southworth, Marry Ross Ding, Xiao Hernandez, Adrian F. Levenson, Mark Li, Lingling Shoaibi, Azadeh Zornberg, Gwen Hennessy, Sean TI Angioedema Events and Use of Drugs That Act on the Renin-Angiotensin-Aldosterone System (RAAS) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Toh, Darren; Li, Lingling] Harvard Univ, Sch Med, Boston, MA USA. [Toh, Darren; Li, Lingling] Harvard Univ, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Reichman, Marsha E.; Houstoun, Monika; Southworth, Marry Ross; Ding, Xiao; Levenson, Mark; Shoaibi, Azadeh; Zornberg, Gwen] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hernandez, Adrian F.; Hennessy, Sean] Duke Univ, Sch Med, Durham, NC USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 346 BP 162 EP 163 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701334 ER PT J AU Bobo, WV Cooper, WO Stein, CM Olfson, M Graham, D Daugherty, J Fuchs, CD Ray, WA AF Bobo, William V. Cooper, William O. Stein, Charles M. Olfson, Mark Graham, David Daugherty, James Fuchs, Catherine D. Ray, Wayne A. TI Antipsychotics and the Risk of Type 2 Diabetes in Children and Youth SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bobo, William V.; Fuchs, Catherine D.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Stein, Charles M.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Olfson, Mark] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Graham, David] US FDA, Silver Spring, MD USA. [Daugherty, James; Ray, Wayne A.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 353 BP 166 EP 166 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701341 ER PT J AU Liu, W Bird, ST Etminan, M Delaney, JAC Knox, C AF Liu, Wei Bird, Steven T. Etminan, Mahyar Delaney, Joseph A. C. Knox, Caitlin TI Drospirenone vs. Other Progestin-Based Combined Oral Contraceptives and the Risk of Incident Ulcerative Colitis: A Comparative Safety Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Liu, Wei; Bird, Steven T.; Delaney, Joseph A. C.; Knox, Caitlin] Univ Florida, Gainesville, FL USA. [Bird, Steven T.] US FDA, Silver Spring, MD USA. [Etminan, Mahyar] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 363 BP 170 EP 171 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701351 ER PT J AU Chen, RT Bonhoeffer, J Zuber, P Sturkenboom, M Velozzi, C Izurieta, H Greenberg, M Black, S Verstraeten, T AF Chen, Robert T. Bonhoeffer, Jan Zuber, Patrick Sturkenboom, Miriam Velozzi, Claudia Izurieta, Hector Greenberg, Michael Black, Steven Verstraeten, Thomas TI Global Collaborations in Vaccine Safety, Present and Future SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Chen, Robert T.; Velozzi, Claudia] Ctr Dis Control & Prevent, Atlanta, GA USA. [Bonhoeffer, Jan] Brighton Collaborat Fdn, Basel, Switzerland. [Zuber, Patrick] WHO, CH-1211 Geneva, Switzerland. [Sturkenboom, Miriam] Erasmus MC, Rotterdam, Netherlands. [Izurieta, Hector] US FDA, Rockville, MD 20857 USA. [Greenberg, Michael] Sanofi Pasteur, Lyon, France. [Black, Steven] Univ Cinncinatti, Cincinnati, OH USA. [Verstraeten, Thomas] P95, Louvain, Belgium. RI Bonhoeffer, Jan/E-5903-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 414 BP 196 EP 196 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701402 ER PT J AU Kettermann, AE Chen, JP Yang, L AF Kettermann, Anna E. Chen, Jiping Yang, Ling TI Analyses of the Effect of Tobacco Smoking on Physiological Measures SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kettermann, Anna E.; Chen, Jiping; Yang, Ling] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 422 BP 200 EP 200 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701410 ER PT J AU West, SL Squiers, L McCormack, L Southwell, BG Brouwer, ES Boudewyns, V Sullivan, H O'Donoghue, A AF West, Suzanne L. Squiers, Linda McCormack, Lauren Southwell, Brian G. Brouwer, Emily S. Boudewyns, Vanessa Sullivan, Helen O'Donoghue, Amie TI Communicating Quantitative Benefit and Risk Summaries in Promotional Labeling or Print Advertising: A Literature Review SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [West, Suzanne L.; Squiers, Linda; McCormack, Lauren; Southwell, Brian G.; Brouwer, Emily S.; Boudewyns, Vanessa] RTI Int, Res Triangle Pk, NC USA. [West, Suzanne L.; Brouwer, Emily S.] Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Sullivan, Helen; O'Donoghue, Amie] US FDA, Silver Spring, MD USA. RI Boudewyns, Vanessa/G-5713-2013 OI Boudewyns, Vanessa/0000-0002-1777-290X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 464 BP 220 EP 220 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701452 ER PT J AU Zhou, EH Gelperin, K Graham, DJ Levenson, M Rose, M Hsueh, YH Hammad, TA AF Zhou, Esther H. Gelperin, Kate Graham, David J. Levenson, Mark Rose, Martin Hsueh, Ya-Hui Hammad, Tarek A. TI Risk of Acute Myocardial Infarction (AMI), Stroke, or Death in GPRD Patients Treated with Olmesartan (Olm) or Other Angiotensin Receptor Blockers (ARBs) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhou, Esther H.; Gelperin, Kate; Graham, David J.; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Levenson, Mark; Hsueh, Ya-Hui] US FDA, Off Biostat, Silver Spring, MD USA. [Rose, Martin] US FDA, Off New Drug, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 543 BP 254 EP 255 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701524 ER PT J AU Toh, D Reichman, ME Houstoun, M Ding, X Fireman, B Gravel, E Hernandez, AF Li, LL Moyneur, E Shoaibi, A Southworth, MR Zornberg, G Hennessy, S AF Toh, Darren Reichman, Marsha E. Houstoun, Monika Ding, Xiao Fireman, Bruce Gravel, Eric Hernandez, Adrian F. Li, Lingling Moyneur, Erick Shoaibi, Azadeh Southworth, Mary Ross Zornberg, Gwen Hennessy, Sean TI Confounding Adjustment in a Distributed Data System without Sharing of Individual-Level Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Toh, Darren; Li, Lingling] Harvard Univ, Sch Med, Boston, MA USA. [Toh, Darren; Li, Lingling] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Reichman, Marsha E.; Houstoun, Monika; Ding, Xiao; Shoaibi, Azadeh; Southworth, Mary Ross; Zornberg, Gwen] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Fireman, Bruce] Kaiser Permanente No Calif, Oakland, CA USA. [Gravel, Eric; Moyneur, Erick] StatLog Consulting Inc, Quebec City, PQ, Canada. [Hernandez, Adrian F.] Duke Univ, Sch Med, Durham, NC USA. [Hennessy, Sean] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 553 BP 259 EP 260 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701534 ER PT J AU Zornberg, GL Senior, JR Graham, DJ Kim, C Wernecke, M Seeff, LB Racoosin, JA Avigan, MI Reichman, ME MaCurdy, TE Lam, C Southworth, MR Houstoun, M Levenson, M Shoaibi, A Wu, E Worrall, C Kelman, JA AF Zornberg, Gwen L. Senior, John R. Graham, David J. Kim, Clara Wernecke, Michael Seeff, Leonard B. Racoosin, Judy A. Avigan, Mark I. Reichman, Marsha E. MaCurdy, Thomas E. Lam, Chelsea Southworth, Mary Ross Houstoun, Monika Levenson, Mark Shoaibi, Azadeh Wu, Eileen Worrall, Chris Kelman, Jeffrey A. TI Severe Liver Injury (SLI) among Dronedarone, Amiodarone or Sotalol Initiators SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zornberg, Gwen L.; Senior, John R.; Graham, David J.; Seeff, Leonard B.; Avigan, Mark I.; Reichman, Marsha E.; Houstoun, Monika; Wu, Eileen] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat Res, Silver Spring, MD USA. [Kim, Clara; Levenson, Mark] US FDA, Off Biometr, OTS, Ctr Drug Evaluat Res, Silver Spring, MD USA. [Wernecke, Michael; MaCurdy, Thomas E.; Lam, Chelsea] Acumen LLC, Burlingame, CA USA. [Racoosin, Judy A.; Southworth, Mary Ross] US FDA, Off New Drugs, Ctr Drug Evaluat Res, Silver Spring, MD USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. [Shoaibi, Azadeh] US FDA, Off Med Policy, Ctr Drug Evaluat Res, Silver Spring, MD USA. [Worrall, Chris; Kelman, Jeffrey A.] CMS SafeRx, Ctr Medicare Medicaid Serv, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 557 BP 261 EP 262 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701538 ER PT J AU Hampp, C Borders-Hemphill, V Moeny, DG Wysowski, DK AF Hampp, Christian Borders-Hemphill, Vicky Moeny, David G. Wysowski, Diane K. TI Utilization of Antidiabetic Drugs among U.S: Adults, 2002-2011 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hampp, Christian; Borders-Hemphill, Vicky; Moeny, David G.; Wysowski, Diane K.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 602 BP 282 EP 282 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701582 ER PT J AU Wu, E Borders-Hemphill, V Chen, M Mehta, H Lu, S AF Wu, Eileen Borders-Hemphill, Vicky Chen, Min Mehta, Hina Lu, Susan TI Dronedarone Associated Pulmonary Toxicity and Prior Amiodarone Exposure: A Pharmacovigilance Analysis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Wu, Eileen; Borders-Hemphill, Vicky; Chen, Min; Mehta, Hina; Lu, Susan] Food & Drug Adm, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 624 BP 292 EP 292 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701602 ER PT J AU Bird, ST Munoz, M Winterstein, A Cooper-Dehoff, R Delaney, JAC AF Bird, Steven T. Munoz, Monica Winterstein, Almut Cooper-Dehoff, Rhonda Delaney, Joseph A. C. TI Trends in Utilization of Medications with Adverse Metabolic Effects in a Managed Care Population between 1999 and 2008 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bird, Steven T.; Munoz, Monica; Winterstein, Almut; Cooper-Dehoff, Rhonda; Delaney, Joseph A. C.] Univ Florida, Gainesville, FL USA. [Bird, Steven T.; Munoz, Monica] US FDA, CDER UF Acad Collaborat Program, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 643 BP 300 EP 300 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701619 ER PT J AU Sansing, VV Aggrey, G Hefflin, B AF Sansing, Veronica V. Aggrey, George Hefflin, Brockton TI Estimates of Invasive Home-Use Medical Device Adverse Events Resulting in Hospitalization SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Sansing, Veronica V.; Aggrey, George; Hefflin, Brockton] US FDA, Div Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 677 BP 315 EP 315 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701650 ER PT J AU Dublin, S Johnson, K Beaton, S Cheetham, TC Scott, PE Toh, SD Cooper, WO Davis, RL Li, DK Pawloski, P Raebel, M Smith, DH Hammad, TA Andrade, SE AF Dublin, Sascha Johnson, Karin Beaton, Sarah Cheetham, T. C. Scott, Pamela E. Toh, Sengwee D. Cooper, William O. Davis, Robert L. Li, De-Kun Pawloski, Pamala Raebel, Marsha Smith, David H. Hammad, Tarek A. Andrade, Susan E. TI Methods for Linking Mothers and Infants within Health Plans for Studies of Medication Safety in Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Dublin, Sascha; Johnson, Karin] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Beaton, Sarah] LCF Res, Hlth Serv Res, Albuquerque, NM USA. [Cheetham, T. C.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Scott, Pamela E.; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Li, De-Kun] Kaiser Permanente, Div Res, Oakland, CA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Pawloski, Pamala] HealthPartners Res Fdn, Minneapolis, MN USA. [Raebel, Marsha] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Smith, David H.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Toh, Sengwee D.] Harvard Univ, Sch Med, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Andrade, Susan E.] Fallon Community Hlth Plan Worcester, Fallon Clin, Meyers Primary Care Inst, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 692 BP 321 EP 322 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701664 ER PT J AU Kuyateh, F Margulis, AV Ding, YL Abou-Ali, A Callaham, M Hammad, TA AF Kuyateh, Fatmatta Margulis, Andrea V. Ding, Yulan Abou-Ali, Adel Callaham, Marian Hammad, Tarek A. TI Validation of Congenital Cardiac Malformations in the General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kuyateh, Fatmatta; Ding, Yulan; Abou-Ali, Adel; Callaham, Marian; Hammad, Tarek A.] US FDA, CDER, Silver Spring, MD USA. [Margulis, Andrea V.] FDA, CDER ORISE, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013; Margulis, Andrea/G-2833-2013 OI Margulis, Andrea/0000-0001-7388-6082 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 723 BP 336 EP 337 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701695 ER PT J AU Martin, DB Hopstadius, J Strandell, J Ball, R Labadie, J AF Martin, David B. Hopstadius, Johan Strandell, Johanna Ball, Robert Labadie, Jerry TI Disproportionality Analysis of Vaccine Reports - A Comparison of VAERS and VigiBase SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Martin, David B.; Ball, Robert] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Hopstadius, Johan; Strandell, Johanna; Labadie, Jerry] Uppsala Monitoring Ctr, WHO Collaborating Ctr Int Drug Monitoring, Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 774 BP 359 EP 359 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701743 ER PT J AU Dodd, CN Izurieta, H Zuber, P Romio, S Sturkenboom, M Hua, W Bonhoeffer, J Weibel, D Vellozzi, C Deceuninck, G Umapathi, T Buttery, J Macartney, K Richardson, V Crawford, N Black, S AF Dodd, Caitlin N. Izurieta, Hector Zuber, Patrick Romio, Silvana Sturkenboom, Miriam Hua, Wei Bonhoeffer, Jan Weibel, Daniel Vellozzi, Claudia Deceuninck, Genevieve Umapathi, Thirugnanam Buttery, Jim Macartney, Kristine Richardson, Vesta Crawford, Nigel Black, Steven CA Global GBS-H1N1 Working Grp TI International Collaborative Case Series Safety Monitoring for Pandemic 2009 H1N1 Vaccines: Estimation of the Risk of Guillain-Barre Syndrome SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Dodd, Caitlin N.; Black, Steven] Cincinnati Childrens Hosp, Global Child Hlth Ctr, Cincinnati, OH USA. [Izurieta, Hector; Hua, Wei] US FDA, Analyt Epidemiol Branch, Div Epidemiol, OBE CBER, Rockville, MD 20857 USA. [Romio, Silvana; Sturkenboom, Miriam; Weibel, Daniel] Erasmus Univ, Dept Med Informat, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Zuber, Patrick] WHO, Dept Immunizat Vaccines & Biol IVB, CH-1211 Geneva, Switzerland. [Vellozzi, Claudia] Ctr Dis Control, Atlanta, GA 30333 USA. [Bonhoeffer, Jan; Global GBS-H1N1 Working Grp] Brighton Collaborat, Basel, Switzerland. [Deceuninck, Genevieve] Quebec Univ Hosp, Res Ctr, Publ Hlth Res Unit, Quebec City, PQ, Canada. [Umapathi, Thirugnanam] Natl Neurosci Inst, Singapore, Singapore. [Buttery, Jim] Monash Univ, Dept Paediat, Murdoch Childrens Res Inst, Melbourne, Vic 3004, Australia. [Macartney, Kristine] Childrens Hosp, Westmead, NSW, Australia. [Richardson, Vesta] Natl Ctr Child & Adolescent Hlth, Mexico City, DF, Mexico. RI Bonhoeffer, Jan/E-5903-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 778 BP 361 EP 362 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701747 ER PT J AU Margulis, AV Kang, EM Hammad, TA AF Margulis, Andrea V. Kang, Elizabeth M. Hammad, Tarek A. TI Patterns of Antidepressant and Antipsychotic Use during Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Margulis, Andrea V.; Kang, Elizabeth M.; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. RI Margulis, Andrea/G-2833-2013 OI Margulis, Andrea/0000-0001-7388-6082 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 800 BP 371 EP 371 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701767 ER PT J AU Bobo, WV Davis, RL Toh, SD Li, DK Andrade, SE Cheetham, TC Pawloski, P Dublin, S Pinheiro, S Hammad, T Scott, PE Epstein, RA Arbogast, PG Morrow, JA Dudley, JA Lawrence, JM Avalos, LA Cooper, WO AF Bobo, William V. Davis, Robert L. Toh, Sengwee D. Li, De-Kun Andrade, Susan E. Cheetham, T. Craig Pawloski, Pamala Dublin, Sascha Pinheiro, Simone Hammad, Tarek Scott, Pamela E. Epstein, Richard A. Arbogast, Patrick G. Morrow, James A. Dudley, Judith A. Lawrence, Jean M. Avalos, Lyndsay A. Cooper, William O. TI Antiepileptic Drug Use among Pregnant Women in the US, 2001-2007: A MEPREP Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bobo, William V.; Epstein, Richard A.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Toh, Sengwee D.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Li, De-Kun; Avalos, Lyndsay A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Andrade, Susan E.] Fallon Clin Inc, Meyers Primary Care Inst, Worcester, MA USA. [Andrade, Susan E.] Fallon Commuln Hlth Plan, Worcester, MA USA. [Cheetham, T. Craig; Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Pawloski, Pamala] Hlth Partners Fdn, Minneapolis, MN USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Pinheiro, Simone; Hammad, Tarek; Scott, Pamela E.] US FDA, Silver Spring, MD USA. [Arbogast, Patrick G.; Morrow, James A.; Dudley, Judith A.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 802 BP 372 EP 372 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701769 ER PT J AU Toh, D Li, Q Cheetham, C Cooper, WO Davis, RL Dublin, S Hammad, TA Li, DK Pawloski, PA Pinheiro, SP Raebel, MA Scott, PE Smith, DH Bobo, WV Lawrence, JM Dashevsky, I Haffenreffer, K Avalos, LA Andrade, SE AF Toh, Darren Li, Qian Cheetham, Craig Cooper, William O. Davis, Robert L. Dublin, Sascha Hammad, Tarek A. Li, De-Kun Pawloski, Pamala A. Pinheiro, Simone P. Raebel, Marsha A. Scott, Pamela E. Smith, David H. Bobo, William V. Lawrence, Jean M. Dashevsky, Inna Haffenreffer, Katherine Avalos, Lyndsay A. Andrade, Susan E. TI Prevalence and Trends in the Use of Antipsychotics during Pregnancy in the US, 2001-2007 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Toh, Darren; Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Univ, Sch Med, Boston, MA USA. [Toh, Darren; Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Cheetham, Craig; Lawrence, Jean M.] Kaiser Permanente So Calif, Pasadena, CA USA. [Cooper, William O.; Bobo, William V.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Atlanta, GA USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Hammad, Tarek A.; Pinheiro, Simone P.; Scott, Pamela E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Li, De-Kun; Avalos, Lyndsay A.] Kaiser Permanente No Calif, Oakland, CA USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Andrade, Susan E.] Meyers Primary Care Inst, Worcester, MA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 808 BP 375 EP 375 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701775 ER PT J AU Moro, PL Museru, OI Broder, K Zheteyeva, Y Tepper, N Revzina, N McCullum, I Lewis, P Arana, J Barash, F Kissin, D Vellozzi, C AF Moro, Pedro L. Museru, Oidda I. Broder, Karen Zheteyeva, Yenlik Tepper, Naomi Revzina, Natalia McCullum, Isaac Lewis, Paige Arana, Jorge Barash, Faith Kissin, Dmitry Vellozzi, Claudia TI Outcomes of Infants Born to Pregnant Women Who Received Influenza A (H1N1) 2009 Live Attenuated Monovalent Vaccine: Enhanced Surveillance Using the Vaccine Adverse Event Reporting System (VAERS) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Moro, Pedro L.; Museru, Oidda I.; Broder, Karen; Zheteyeva, Yenlik; McCullum, Isaac; Lewis, Paige; Arana, Jorge; Vellozzi, Claudia] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. [Tepper, Naomi; Revzina, Natalia; Kissin, Dmitry] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Barash, Faith] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 826 BP 383 EP 383 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701792 ER PT J AU Abou-Ali, A Kang, EM Pinheiro, SP Hammad, TA AF Abou-Ali, Adel Kang, Elizabeth M. Pinheiro, Simone P. Hammad, Tarek A. TI Validation of Glaucoma Diagnosis in the UK General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Abou-Ali, Adel; Kang, Elizabeth M.; Pinheiro, Simone P.; Hammad, Tarek A.] US FDA, CDER, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 850 BP 394 EP 394 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701815 ER PT J AU Kang, EM Abou-Ali, A Pinheiro, SP Hammad, TA AF Kang, Elizabeth M. Abou-Ali, Adel Pinheiro, Simone P. Hammad, Tarek A. TI Validation of Cataract Diagnosis in the UK General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kang, Elizabeth M.; Abou-Ali, Adel; Pinheiro, Simone P.; Hammad, Tarek A.] US FDA, CDER, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 849 BP 394 EP 394 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701814 ER PT J AU Munoz, MA Stojanovic, D Etminan, M Winterstein, AG Delaney, JAC AF Munoz, Monica A. Stojanovic, Danijela Etminan, Mahyar Winterstein, Almut G. Delaney, Joseph A. C. TI Trends in Use of Benzodiazepines, Opioids, Tramadol, and Z-Drugs from 1998 to 2008 in a Managed Care Population SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Munoz, Monica A.; Stojanovic, Danijela; Winterstein, Almut G.; Delaney, Joseph A. C.] Univ Florida, Gainesville, FL USA. [Munoz, Monica A.] US FDA, Silver Spring, MD USA. [Etminan, Mahyar] Univ British Columbia, Pharmaceut Outcomes Programme, Vancouver, BC V5Z 1M9, Canada. RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2012 VL 21 SU 3 SI SI MA 920 BP 426 EP 426 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 996YU UT WOS:000308131701883 ER PT J AU Harris, C Dallas, C Rollor, E White, C Blount, B Valentin-Blasini, L Fisher, J AF Harris, Curtis Dallas, Cham Rollor, Edward, III White, Catherine Blount, Benjamin Valentin-Blasini, Liza Fisher, Jeffrey TI Radioactive Iodide (I-131(-)) Excretion Profiles in Response to Potassium Iodide (KI) and Ammonium Perchlorate (NH4ClO4) Prophylaxis SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE perchlorate; iodide; radioiodide; thyroid ID THYROID-GLAND; MALE-RAT; THYROXINE AB Radioactive iodide (I-131(-)) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish I-131(-) urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered I-131(-) and 3 hours later dosed with either saline, 30 mg/kg of NH4ClO4 or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH4ClO4 treated animals excreted significantly more I-131(-) compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T-4) was administered daily over a 3 day period. During the first 6-12 hour after I-131(-) dosing, rats administered NH4ClO4 excreted significantly more I-131(-) than the other treatment groups. T-4 treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after I-131(-) administration. We speculate that the T-4 treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to I-131(-) compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland. C1 [Harris, Curtis; Dallas, Cham; Rollor, Edward, III; White, Catherine] Univ Georgia, Coll Publ Hlth, Inst Hlth Management & Mass Destruct Def, Athens, GA 30603 USA. [Blount, Benjamin; Valentin-Blasini, Liza] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. [Fisher, Jeffrey] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Harris, C (reprint author), Univ Georgia, Coll Publ Hlth, Inst Hlth Management & Mass Destruct Def, Athens, GA 30603 USA. EM charris@ihmd.uga.edu; cdallas@ihmd.uga.edu; erollor@ihmd.uga.edu; cwhite@rx.uga.edu; bkb3@cdc.gov; lbv5@cdc.gov; jeffrey.fisher@fda.hhs.gov NR 26 TC 0 Z9 0 U1 0 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD AUG PY 2012 VL 9 IS 8 BP 2936 EP 2948 DI 10.3390/ijerph9082936 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 998MB UT WOS:000308242300025 PM 23066407 ER PT J AU McEvoy, BW Tiwari, RC AF McEvoy, Bradley W. Tiwari, Ram C. TI Discussion of "Multivariate Bayesian Logistic Regression for Analysis of Clinical Trial Safety Issues" by W. DuMouchel SO STATISTICAL SCIENCE LA English DT Editorial Material DE Meta-analysis; drug safety; hierarchical Bayesian model; data-mining; sparse data C1 [McEvoy, Bradley W.] US FDA, Div Biometr 7, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McEvoy, BW (reprint author), US FDA, Div Biometr 7, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Bradley.McEvoy@fda.hhs.gov; Ram.Tiwari@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 3 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD AUG PY 2012 VL 27 IS 3 BP 340 EP 343 DI 10.1214/12-STS381A PG 4 WC Statistics & Probability SC Mathematics GA 012QZ UT WOS:000309252900002 ER PT J AU Troendle, JF Yu, KF Westfall, PH Pennello, G Schisterman, EF AF Troendle, James F. Yu, Kai F. Westfall, Peter H. Pennello, Gene Schisterman, Enrique F. TI Comparing the Expected Misclassification Cost for Two Classifiers Based on Estimates From the Same Sample SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Likelihood ratio test; Multinomial; Power; Type I error; Wald-type test ID DIAGNOSTIC-TESTS; PREDICTION; VALUES; RISK AB In this article, we consider the problem of comparing two binary classifiers evaluated on the same sample. McNemar's test can be used to compare overall predictive accuracy. However, to evaluate the classifiers in a clinically relevant manner, expected misclassification cost should be accounted for. We show that a Wald-type test can be constructed for this purpose. We further derive a likelihood ratio test for comparison of two classifiers based on expected misclassification cost. The null distribution of the test statistic is approximated by simulation from strategically chosen parameter values. The properties of the tests are examined through simulation of correlated classification indicators. The Wald-type test has approximate Type I error control while maintaining a power advantage over the likelihood ratio test and is therefore recommended for most applications. If conservative error control is desired, the likelihood ratio test calibrated from several strategically chosen parameter values is recommended. The methods are illustrated on a prospective cohort study of coronary heart disease and also on a case-control study of preeclampsia. An interval of misclassification cost ratios for which the Wald test rejects the null hypothesis of equal expected misclassification cost is reported. Full simulation results are available as supplementary tables (S1-S6) in the online supplementary materials. C1 [Troendle, James F.] NHLBI, Off Biostat Res, NIH, DHHS, Bethesda, MD 20892 USA. [Yu, Kai F.] Tsinghua Univ, Dept Math Sci, Beijing 100084, Peoples R China. [Yu, Kai F.] Tsinghua Univ, Math Sci Ctr, Beijing 100084, Peoples R China. [Westfall, Peter H.] Texas Tech Univ, Rawls Coll Business, Area Informat Syst & Quantitat Sci ISQS, Lubbock, TX 79409 USA. [Pennello, Gene] US FDA, Diagnost Devices Branch, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM jt3t@nih.gov; kfyu@math.tsinghua.edu.cn; peter.westfall@ttu.edu; gene.pennello@fda.hhs.gov; schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH) FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov). NR 24 TC 0 Z9 0 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD AUG PY 2012 VL 4 IS 3 BP 301 EP 312 DI 10.1080/19466315.2012.695263 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 019PC UT WOS:000309750800009 ER PT J AU Heger, NE Hall, SJ Sandrof, MA McDonnell, EV Hensley, JB McDowel, EN Martin, KA Gaido, KW Johnson, KJ Boekelheide, K AF Heger, Nicholas E. Hall, Susan J. Sandrof, Moses A. McDonnell, Elizabeth V. Hensley, Janan B. McDowel, Erin N. Martin, Kayla A. Gaido, Kevin W. Johnson, Kamin J. Boekelheide, Kim TI Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE animal model; fetal testis; human; mouse; multinucleated germ cells; phthalate; rat; seminiferous cords; testicular dysgenesis; xenotransplant ID TESTICULAR DYSGENESIS SYNDROME; IN-UTERO EXPOSURE; DOSE-DEPENDENT ALTERATIONS; GERM-CELL DEVELOPMENT; LEYDIG TUMOR-CELLS; N-BUTYL PHTHALATE; DI(N-BUTYL) PHTHALATE; GENE-EXPRESSION; RAT TESTIS; MONO-(2-ETHYLHEXYL) PHTHALATE AB BACKGROUND: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. OBJECTIVES: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. METHODS: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. RESULTS: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. CONCLUSIONS: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. C1 [Heger, Nicholas E.; Hall, Susan J.; Sandrof, Moses A.; McDonnell, Elizabeth V.; Boekelheide, Kim] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Hensley, Janan B.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [McDowel, Erin N.; Martin, Kayla A.; Johnson, Kamin J.] Alfred I duPont Hosp Children, Wilmington, DE USA. [Gaido, Kevin W.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Boekelheide, K (reprint author), Brown Univ, Dept Pathol & Lab Med, Box G-E5, Providence, RI 02912 USA. EM kim_boekelheide@brown.edu FU Brown University Institutional Funds; National Institute of Environmental Health Sciences [R01ES011803, R01-ES01727, 5P20-ES018169, R21-ES013020, T32-ES7272]; U.S. Environmental Protection Agency [RD 83459401-1]; American Chemistry Council; American Chemistry Council (ACC); ACC FX This work was supported by Brown University Institutional Funds, the National Institute of Environmental Health Sciences (R01ES011803 to K.W.G.; R01-ES01727, 5P20-ES018169, and R21-ES013020 to K.B.; and T32-ES7272 to N.E.H.), the U.S. Environmental Protection Agency (RD 83459401-1 to K.B.), and the American Chemistry Council (K.B.).; This work was supported, in part, by seed funding provided to K.B. by the American Chemistry Council (ACC), a nonprofit trade association representing the chemical industry and phthalate manufacturers. The ACC had no control over the work performed or publication of this report and did not fund any of the work with human tissue. The Hamner Institutes for Health Sciences is a not-for-profit basic research institute and receives support from the ACC. K.W.G. and J.H. were employed by The Hamner while some of the work was being performed. K.B. occasionally serves as an expert consultant for chemical and pharmaceutical companies. The other authors declare they have no actual or potential competing financial interests. NR 46 TC 41 Z9 42 U1 1 U2 26 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2012 VL 120 IS 8 BP 1137 EP 1143 DI 10.1289/ehp.1104711 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 985JN UT WOS:000307260500025 PM 22511013 ER PT J AU Tyburczy, C Mossoba, MM Fardin-Kia, AR Rader, JI AF Tyburczy, Cynthia Mossoba, Magdi M. Fardin-Kia, Ali Reza Rader, Jeanne I. TI Evaluation of low trans fat edible oils by attenuated total reflection-Fourier transform infrared spectroscopy and gas chromatography: a comparison of analytical approaches SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 7th international conference on instrumental methods of analysis - modern trends and applications CY SEP 18-22, 2011 CL Chania, GREECE DE Trans fat; Attenuated total reflection; Fourier-transform infrared spectroscopy; Gas chromatography; Edible oils ID ACID DETERMINATION; SEPARATION; STABILITY; COLUMN; FOODS AB Current interest by the food industry in exploring reformulation options that lower the content of trans fat in edible fats and oils requires methods to accurately measure low levels of trans fat. In the present study, the quantitation of trans fat in 25 edible fat and oil samples was evaluated using two current analytical approaches, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), and gas chromatography with flame ionization detection (GC-FID) according to Official Methods of the American Oil Chemists' Society. Significant differences between the ATR-FTIR and reference GC-FID quantitations were found for samples with a trans fat content < 2% of total fat. These discrepancies could be explained, in part, by the presence of certain oil constituents (e.g., vitamins, carotenoids, high levels of saturated fat) that produced absorbance bands at or near 966 cm(-1) in the ATR-FTIR spectra, a region that was previously identified as being characteristic of isolated trans double bonds. Results demonstrate that the natural content of such oil constituents could result in significant overestimations of trans fat when ATR-FTIR is used to analyze edible fats and oils with a trans fat content < 2% of total fat. C1 [Tyburczy, Cynthia; Mossoba, Magdi M.; Fardin-Kia, Ali Reza; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Tyburczy, C (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM cynthia.tyburczy@fda.hhs.gov FU Center for Food Safety and Applied Nutrition FX The authors would like to acknowledge Pierluigi Delmonte (U.S. Food and Drug Administration) and John K. G. Kramer (NIR Technologies, Inc) for their insightful comments and suggestions during the preparation of this manuscript, and also Joseph Lucania and Jeffrey Christenson (Harrick Scientific Products, Inc.) for kindly providing the heated, seven-reflection ConcentratIR (R) ATR accessory. This project was supported in part by appointments of CT and ARF-K to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 32 TC 7 Z9 7 U1 4 U2 29 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 EI 1618-2650 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD AUG PY 2012 VL 404 IS 3 BP 809 EP 819 DI 10.1007/s00216-012-6189-y PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 985GR UT WOS:000307251900024 PM 22736229 ER PT J AU Pariser, AR Slack, DJ Bauer, LJ Warner, CA Tracy, LA AF Pariser, Anne R. Slack, Daniel J. Bauer, Larry J. Warner, Catherine A. Tracy, LaRee A. TI Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010 SO DRUG DISCOVERY TODAY LA English DT Review ID ORPHAN DRUGS AB New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development. C1 [Pariser, Anne R.; Slack, Daniel J.; Bauer, Larry J.; Warner, Catherine A.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Tracy, LaRee A.] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Pariser, AR (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM anne.pariser@fda.hhs.gov NR 26 TC 14 Z9 14 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG PY 2012 VL 17 IS 15-16 BP 898 EP 904 DI 10.1016/j.drudis.2012.04.011 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995XO UT WOS:000308048800013 PM 22564486 ER PT J AU Hoffmann, M Monday, SR Allard, MW Strain, EA Whittaker, P Naum, M McCarthy, PJ Lopez, JV Fischer, M Brown, EW AF Hoffmann, Maria Monday, Steven R. Allard, Marc W. Strain, Errol A. Whittaker, Paul Naum, Marianna McCarthy, Peter J. Lopez, Jose V. Fischer, Markus Brown, Eric W. TI Vibrio caribbeanicus sp nov., isolated from the marine sponge Scleritoderma cyanea SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID MULTILOCUS SEQUENCE-ANALYSIS; LENGTH DIFFERENCE TEST; DNA HYBRIDIZATION; RENATURATION RATES; ESCHERICHIA-COLI; RECOMBINATION; INCONGRUENCE; EVOLUTION; IDENTIFICATION; SYSTEMATICS AB A Gram-negative, oxidase-positive, catalase-negative, facultatively anaerobic, motile, curved rod-shaped bacterium, strain N384(T), was isolated from a marine sponge (Scleritoderma cyanea; phylum Porifera) collected from a depth of 795 feet (242 m) off the west coast of Curacao. On the basis of 16S rRNA gene sequencing, strain N384(T) was shown to belong to the genus Vibrio, most closely related to Vibrio brasiliensis LMG 20546(T) (98.8 % similarity), Vibrio nigripulchritudo ATCC 27043(T) (98.5%), Vibrio tubiashii ATCC 19109(T) (98.6%) and V. sinaloensis DSM 21326(T) (98.2 %). The DNA G + C content of strain N384(T) was 41.6 mol%. An analysis of concatenated sequences of five genes (gyrB, rpoA, pyrH, mreB and ftsZ; 4068 bp) demonstrated a clear separation between strain N384(T) and its closest neighbours and clustered strain N384(T) into the 'Orientalis' clade of vibrios. Phenotypically, the novel species belonged to the arginine dihydrolase-positive, lysine decarboxylase- and ornithine decarboxylase-negative (A+/L-/O-) cluster. The novel species was also differentiated on the basis of fatty acid composition, specifically that the proportions of iso-C-13:0, iso-C-15:0, C-15:0, iso-C-16:0, C-16:0, iso-C-17:0, C-17:1 omega 8c and C-17:0 were significantly different from those found in V. brasiliensis and V. sinaloensis. The results of DNA-DNA hybridization, average nucleotide identity and physiological and biochemical tests further allowed differentiation of this strain from other described species of the genus Vibrio. Collectively, these findings confirm that strain N384(T) represents a novel Vibrio species, for which the name Vibrio caribbeanicus sp. nov. is proposed, with the type strain N384(T) (=ATCC BAA-2122(T)=DSM 23640(T)). C1 [Hoffmann, Maria; Monday, Steven R.; Allard, Marc W.; Strain, Errol A.; Whittaker, Paul; Naum, Marianna; Brown, Eric W.] US FDA, College Pk, MD 20740 USA. [Hoffmann, Maria; Fischer, Markus] Univ Hamburg, Dept Chem, Inst Food Chem, D-20146 Hamburg, Germany. [McCarthy, Peter J.] Florida Atlantic Univ, Oceanog Inst, Ctr Marine Biomed & Biotechnol Res, Harbor Branch, Ft Pierce, FL 34946 USA. [Lopez, Jose V.] Nova SE Univ, Oceanog Ctr, Dania, FL 33004 USA. RP Hoffmann, M (reprint author), US FDA, Paint Branch Pkwy, College Pk, MD 20740 USA. EM maria.hoffman@fda.hhs.gov; eric.brown@fda.hhs.gov RI Fischer, Markus/G-9477-2012; OI McCarthy, Peter/0000-0002-2396-7463 FU Research Fellowship Program for the Center for Food Safety and Applied Nutrition FX The authors would like to thank Dr Ben Tall for his work producing the electron micrographs. The authors also acknowledge Guojie Cao and Charles Wang for their assistance with shotgun genome sequencing. This project was supported by an appointment of M. H. to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities. This is Harbor Branch Oceanographic Institute contribution number 1841. NR 47 TC 22 Z9 22 U1 3 U2 18 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 EI 1466-5034 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD AUG PY 2012 VL 62 BP 1736 EP 1743 DI 10.1099/ijs.0.032375-0 PN 8 PG 8 WC Microbiology SC Microbiology GA 006VZ UT WOS:000308849000003 PM 21930677 ER PT J AU Reich, C Ryan, PB Stang, PE Rocca, M AF Reich, Christian Ryan, Patrick B. Stang, Paul E. Rocca, Mitra TI Evaluation of alternative standardized terminologies for medical conditions within a network of observational healthcare databases SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Terminology standards; Coding scheme; Vocabulary; Taxonomy; Mapping; ICD-9-CM ID COMMON DATA MODEL; SAFETY SURVEILLANCE; INFORMATICS ASSOCIATION; LANGUAGE SYSTEM; FRAMEWORK AB Large electronic databases of health care information, such as administrative claims and electronic health records, are available and are being used in a number of public health settings, including drug safety surveillance. However, because of a lack of standardization, clinical terminologies may differ across databases. With the aid of existing resources and expert coders, we have developed mapping tables to convert ICD-9-CM diagnosis codes used in some existing databases to SNOMED-CT and MedDRA. In addition, previously developed definitions for specific health outcomes of interest were mapped to the same standardized vocabularies. We evaluated how vocabulary mapping affected (1) the retention of clinical data from two test databases, (2) the semantic space of outcome definitions, (3) the prevalence of each outcome in the test databases, and (4) the reliability of analytic methods designed to detect drug-outcome associations in the test databases. Although vocabulary mapping affected the semantic space of some outcome definitions, as well as the prevalence of some outcomes in the test databases, it had only minor effects on the analysis of drug-outcome associations. Furthermore, both SNOMED-CT and MedDRA were viable for use as standardized vocabularies in systems designed to perform active medical product surveillance using disparate sources of observational data. (c) 2012 Elsevier Inc. All rights reserved. C1 [Reich, Christian; Ryan, Patrick B.; Stang, Paul E.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD 20814 USA. [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Rocca, Mitra] US FDA, Off Translat Sci, CDER, Silver Spring, MD 20933 USA. RP Reich, C (reprint author), Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, 9650 Rockville Pike, Bethesda, MD 20814 USA. EM reich@omop.org; ryan@omop.org; PStang@its.jnj.com; mitra.rocca@fda.hhs.gov FU Foundation for the National Institutes of Health FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithlaine, Johnson & Johnson, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi, Schering-Plough Corporation, and Takeda. Assistance with writing and manuscript preparation was provided by Ken Scholz, PhD, with financial support from the Foundation for the National Institutes of Health. NR 24 TC 16 Z9 16 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD AUG PY 2012 VL 45 IS 4 SI SI BP 689 EP 696 DI 10.1016/j.jbi.2012.05.002 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 998RN UT WOS:000308258200011 PM 22683994 ER PT J AU Yoshitomi, KJ Jinneman, KC Zapata, R Weagant, SD Fedio, WM AF Yoshitomi, Ken J. Jinneman, Karen C. Zapata, Ruben Weagant, Stephen D. Fedio, Willis M. TI Detection and Isolation of Low Levels of E. coli O157:H7 in Cilantro by Real-Time PCR, Immunomagnetic Separation, and Cultural Methods with and without an Acid Treatment SO JOURNAL OF FOOD SCIENCE LA English DT Article DE cilantro; detection; Escherichia coli O157:H7; immunomagnetic separation; real-time PCR ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; FRESH-CUT CILANTRO; O157-H7 INFECTIONS; GROUND-BEEF; PACIFIC-NORTHWEST; BOVINE FECES; RAW-MILK; OUTBREAK; CONSUMPTION; ENRICHMENT AB Leafy greens such as cilantro, contaminated with Escherichia coli O157:H7, have been implicated in cases of human illnesses. High levels of microflora in fresh cilantro make recovery of low numbers of E. coli O157:H7 difficult. To improve upon current methods, immunomagnetic separation (IMS) techniques in combination with real-time PCR (RTiPCR) and selective enrichment protocols were examined. Rinsates were prepared from cilantro samples inoculated with low (similar to 0.02 CFU/g) and slightly higher (similar to 0.05 CFU/g) levels of E. coli O157:H7. Rinsate portions were enriched in modified buffered peptone water with pyruvate (mBPWp) for 5 h at 37 degrees C. After 5 h, selective agents were added to samples and further incubated at 42 degrees C overnight. Detection and recovery were attempted at 5 and 24 h with and without IMS. IMS beads were screened by RTiPCR for simultaneous detection of stx1, stx2, and uidA SNP. Additionally, broth cultures and IMS beads were streaked onto selective agar plates (Rainbow (R) agar, R & F (R) E. coli O157 Chromogenic medium, TC-SMAC and CHROMagar (TM) 0157) for isolation of E. coli O157:H7. Both broth cultures and IMS beads were also acid treated in Trypticase Soy Broth pH 2 prior to plating to selective media to improve upon cultural recovery. Although E. coli O157 strains were detected in most samples by PCR after 5 h enrichment, cultural recovery was poor. However, after 24 h enrichment, both PCR and cultural recovery were improved. Acidification of the broths and the IMS beads prior to plating greatly improved recovery from 24 h enrichment broths by suppressing the growth of competing microorganisms. Practical Application: Detection and recovery of Escherichia coli O157:H7 in fresh produce matrices (e.g., cilantro) can be complicated by high background microflora present in these foods. Rapid detection by molecular methods combined with effective enrichment and isolation procedures such as using immunomagnetic separation (IMS) techniques can quickly identify potential hazards to public health. Additional techniques such as acidification of enrichment broths can exploit acid resistance characteristics of pathogens such as E. coli O157:H7, facilitating their isolation in complex food matrices. C1 [Zapata, Ruben; Fedio, Willis M.] New Mexico State Univ, Ctr Anim Hlth Food Safety & Biosecur, Food Safety Lab, Las Cruces, NM 88003 USA. [Yoshitomi, Ken J.; Jinneman, Karen C.] US FDA, Pacific Reg Lab, Bothell, WA 98021 USA. [Weagant, Stephen D.] US FDA, Poulsbo, WA 98370 USA. RP Fedio, WM (reprint author), New Mexico State Univ, Ctr Anim Hlth Food Safety & Biosecur, Food Safety Lab, Las Cruces, NM 88003 USA. EM wfedio@nmsu.edu NR 51 TC 9 Z9 10 U1 1 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2012 VL 77 IS 8 BP M481 EP M489 DI 10.1111/j.1750-3841.2012.02813.x PG 9 WC Food Science & Technology SC Food Science & Technology GA 986ZI UT WOS:000307385800029 PM 22860597 ER PT J AU Contreras, CA Ochoa, TJ Ruiz, J Lacher, DW Durand, D DebRoy, C Lanata, CF Cleary, TG AF Contreras, C. A. Ochoa, T. J. Ruiz, J. Lacher, D. W. Durand, D. DebRoy, C. Lanata, C. F. Cleary, T. G. TI Genetic diversity of locus of enterocyte effacement genes of enteropathogenic Escherichia coli isolated from Peruvian children SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; DNA MICROARRAY ANALYSIS; PATHOGENICITY ISLAND; SUBVERSIVE ELEMENTS; STRAINS; VIRULENCE; DIARRHEA; EAE; ADHERENCE; PCR AB The aim of this study was to determine the frequency and allele associations of locus of enterocyte effacement encoded esp and tir genes among 181 enteropathogenic Escherichia coli (EPEC) strains (90 diarrhoea-associated and 91 controls) isolated from Peruvian children under 18 months of age. We analysed espA, espB, espD and tir alleles by PCR-RFLP. EPEC strains were isolated with higher frequency from healthy controls (91/424, 21.7%) than from diarrhoeal samples (90/936, 9.6%) (P<0.001); 28.9% of diarrhoeal and 17.6% of control samples were typical EPEC (tEPEC). The distribution of espA alleles (alpha, beta, beta2 and gamma) and espD alleles (alpha, beta, gamma and a new variant, espD-N1) between tEPEC and atypical EPEC (aEPEC) was significantly different (P<0.05). espD-alpha was more common among acute episodes (P<0.05). espB typing resulted in five alleles (alpha, beta, gamma and two new sub-alleles, espB-alpha2 and espB-alpha3), while tir-beta and tir-gamma2 were the most common intimin receptor subtypes. Seventy-two combinations of espA, espB, espD and tir alleles were found; the most prevalent combination was espA-beta, espB-beta, espD-beta, tir-beta (34/181 strains), which was more frequent among tEPEC strains (P<0.05). Our findings indicate that there is a high degree of heterogeneity among EPEC strains isolated from Peruvian children and that aEPEC and tEPEC variants cluster. C1 [Contreras, C. A.; Ochoa, T. J.; Durand, D.] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. [Ochoa, T. J.; Cleary, T. G.] Univ Texas Sch Publ Hlth, Houston, TX USA. [Ruiz, J.] Hosp Clin Inst Invest Biomed August Pi & Sunyer, Ctr Recerca Salut Int Barcelona, Barcelona, Spain. [Ruiz, J.] CIBERESP, Barcelona, Spain. [Lacher, D. W.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [DebRoy, C.] Penn State Univ, Dept Vet & Biomed Sci, E Coli Reference Ctr, University Pk, PA 16802 USA. [Lanata, C. F.] Inst Invest Nutr, Lima, Peru. [Lanata, C. F.] Univ Peruana Ciencias Aplicadas, Lima, Peru. RP Ochoa, TJ (reprint author), Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. EM Theresa.J.Ochoa@uth.tmc.edu RI Ruiz, Joaquin/D-2704-2013 OI Ruiz, Joaquin/0000-0002-4431-2036 FU National Institutes of Health, USA, Public Health Service [1K01TW007405, R01-HD051716]; Agencia Espanola de Cooperacion Internacional (AECID), Spain, Programa de Cooperacion Interuniversitaria e Investigacion Cientifica con Iberoamerica [D/019499/08, D/024648/09, D/030509/10]; Fondo de Investigaciones Sanitarias, Spain [CP05/0130] FX This work was partially funded by the National Institutes of Health, USA, Public Health Service awards 1K01TW007405 (T.J.O) and R01-HD051716 (T.G.C); Agencia Espanola de Cooperacion Internacional (AECID), Spain, Programa de Cooperacion Interuniversitaria e Investigacion Cientifica con Iberoamerica (D/019499/08, D/024648/09 and D/030509/10); and Fondo de Investigaciones Sanitarias, Spain [J.R. has a Miguel Servet fellowship (CP05/0130)]. NR 30 TC 3 Z9 3 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD AUG PY 2012 VL 61 IS 8 BP 1114 EP 1120 DI 10.1099/jmm.0.045443-0 PG 7 WC Microbiology SC Microbiology GA 992QG UT WOS:000307794200012 PM 22493278 ER PT J AU Baiter, S Miller, DL Schueler, BA AF Baiter, Stephen Miller, Donald L. Schueler, Beth A. TI Radiation Dose Measurements and Monitoring for Fluoroscopically Guided Interventional Procedures SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID SKIN; GUIDELINES; MANAGEMENT C1 [Baiter, Stephen] Columbia Univ, Dept Med & Radiol, New York, NY 10021 USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Schueler, Beth A.] Mayo Clin, Rochester, MN USA. RP Baiter, S (reprint author), Columbia Univ, Dept Med & Radiol, 630 W 168th St, New York, NY 10021 USA. EM sb2455@columbia.edu NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2012 VL 9 IS 8 BP 595 EP 597 DI 10.1016/j.jacr.2012.05.001 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988XY UT WOS:000307526000020 ER PT J AU Miller, DL O'Grady, NP AF Miller, Donald L. O'Grady, Naomi P. TI Guidelines for the Prevention of Intravascular Catheter-related Infections: Recommendations Relevant to Interventional Radiology for Venous Catheter Placement and Maintenance SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; COAGULASE-NEGATIVE STAPHYLOCOCCI; PULMONARY-ARTERY CATHETERS; DOUBLE-BLIND TRIAL; TUNNELED INFUSION CATHETERS; LUMEN SUBCLAVIAN CATHETERS; ANTIBIOTIC-LOCK TECHNIQUE; CRITICALLY-ILL PATIENTS C1 [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Miller, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 66,Room 4553,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donald.miller@fda.hhs.gov FU Intramural NIH HHS [Z99 CL999999] NR 130 TC 22 Z9 34 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2012 VL 23 IS 8 BP 997 EP 1006 DI 10.1016/j.jvir.2012.04.023 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 980AI UT WOS:000306865600003 PM 22840801 ER PT J AU Balsam, J Bruck, HA Kostov, Y Rasooly, A AF Balsam, Joshua Bruck, Hugh Alan Kostov, Yordan Rasooly, Avraham TI Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE Webcam; Image stacking; CMOS; CCD; LED; Fluorescence; Fluorometer; Global health ID STAPHYLOCOCCAL-ENTEROTOXIN-B; LENSLESS DIGITAL HOLOGRAPHY; ARRAY BIOSENSOR; CARBON NANOTUBES; SENSOR ARRAY; MOBILE PHONE; SYSTEM; CHIP; IMMUNOASSAY; MICROSCOPY AB Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. 1. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices. 2. We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images. and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 mu M to 1000 mu M. in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is similar to 1000 mu M, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 mu M, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings. Published by Elsevier B.V. C1 [Balsam, Joshua; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Balsam, Joshua; Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA. [Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU National Cancer Institute, Cancer Diagnosis Program; FDA's Center for Devices and Radiological Health, Office of Science and Engineering, Division of Biology FX Funded by the National Cancer Institute, Cancer Diagnosis Program and the FDA's Center for Devices and Radiological Health, Office of Science and Engineering, Division of Biology. NR 44 TC 13 Z9 13 U1 3 U2 34 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD AUG-SEP PY 2012 VL 171 BP 141 EP 147 DI 10.1016/j.snb.2012.02.003 PG 7 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 002XQ UT WOS:000308572700013 PM 23990697 ER PT J AU Kikwai, L Tran, D Hauck, WW Shah, VP Stippler, ES AF Kikwai, Loice Tran, Daren Hauck, Walter W. Shah, Vinod P. Stippler, Erika S. TI Effect of Various Operational Parameters on Drug Release from a 1% Hydrocortisone Semisolid Dosage Form Using the Vertical Diffusion Cell Apparatus SO DISSOLUTION TECHNOLOGIES LA English DT Article ID PRODUCTS AB The purpose of this study was to identify operational parameters of the vertical diffusion cell (VDC) apparatus that have an influence on results of drug release testing from semisolid dosage forms, which are one of three types of topically applied products (see USP General Chapter Topical and Transdermal Drug Products-Product Quality Tests < 3 >). The VDC apparatus operates using a static diffusion cell, a synthetic membrane, and an appropriate receptor medium. A cream formulation containing 1% hydrocortisone was used for the current study. The operational parameters investigated were stirring rate, mixing helix, stirring while sampling, medium degassing, membrane wetting with Ethomeen (a surfactant), and membrane wetting time. Stat-Ease design of experiment software was used to create partial factorial experimental designs to evaluate these parameters. The effects of the operational parameters were evaluated using mean drug release rate (slope, mu g/cm(2)/min(1/2)) and the standard deviation (SD) of six individual release rates for each experimental setup. Results of the study indicate that one parameter, the presence of Ethomeen for wetting the membrane, had a large and significant effect on both drug release rates and SD. Two parameters, stirring while sampling and mixing helix, had a significant impact on the drug release rate when Ethomeen was not used. Two parameters, medium degassing and stirring while sampling, had significant effects on the variability of the results (SD). Additionally, instrument-specific parameters (e.g., mixing helix) also contributed significantly to the variability of drug release rates. C1 [Tran, Daren; Hauck, Walter W.; Shah, Vinod P.; Stippler, Erika S.] US Pharmacopeial Convent Inc, Rockville, MD USA. [Kikwai, Loice] US FDA, Rockville, MD 20857 USA. RP Stippler, ES (reprint author), US Pharmacopeial Convent Inc, Rockville, MD USA. EM ess@usp.org NR 5 TC 2 Z9 2 U1 0 U2 2 PU DISSOLUTION TECHNOLOGIES, INC PI HOCKESSIN PA 9 YORKRIDGE TRAIL, HOCKESSIN, DE 19707-9633 USA SN 1521-298X J9 DISSOLUT TECHNOL JI Dissolut. Technol. PD AUG PY 2012 VL 19 IS 3 BP 6 EP 13 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007NQ UT WOS:000308895400001 ER PT J AU Mewton, N Strauss, DG Rizzi, P Verrier, RL Tereshchenko, LG Nearing, B Marchlinski, FE Cox, C Spooner, PM Lima, JAC AF Mewton, N. Strauss, D. G. Rizzi, P. Verrier, R. L. Tereshchenko, L. G. Nearing, B. Marchlinski, F. E. Cox, C. Spooner, P. M. Lima, J. A. C. TI Screening for arrhythmogenic myocardial substrate by 12-lead ECG, high resolution ECG and T-wave alternans in patients with low to intermediate sudden cardiac death risk SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 25-29, 2012 CL Munchen, GERMANY SP European Soc Cardiol (ESC) C1 [Mewton, N.] Cardiol Hosp Louis Pradel, Hosp Civils Lyon, Bron, France. [Strauss, D. G.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Rizzi, P.; Tereshchenko, L. G.; Spooner, P. M.; Lima, J. A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. [Verrier, R. L.; Nearing, B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Marchlinski, F. E.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Cox, C.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2012 VL 33 SU 1 BP 823 EP 823 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995MO UT WOS:000308012406107 ER PT J AU Heflin, LE Gibbs, VK Powell, ML Makowsky, R Lawrence, AL Lawrence, JM AF Heflin, Laura E. Gibbs, Victoria K. Powell, Mickie L. Makowsky, Robert Lawrence, Addison L. Lawrence, John M. TI EFFECT OF DIET QUALITY ON NUTRIENT ALLOCATION TO THE TEST AND ARISTOTLE'S LANTERN IN THE SEA URCHIN LYTECHINUS VARIEGATUS (LAMARCK, 1816) SO JOURNAL OF SHELLFISH RESEARCH LA English DT Article DE Aristotle's lantern; sea urchin; growth allometry; Lytechinus variegatus ID PHENOTYPIC PLASTICITY; RESOURCE-ALLOCATION; STRONGYLOCENTROTUS-DROEBACHIENSIS; BODY COMPONENTS; FOOD LIMITATION; RELATIVE SIZE; GROWTH-RATES; ECHINOIDEA; ECHINODERMATA; EVOLUTION AB Small, adult (19.50 +/- 2.01g wet weight) Lytechinus variegatus (Lamarck, 1816) were fed 8 formulated diets with different protein (12-36% dry weight as fed) and carbohydrate (21-39% dry weight) levels. Each sea urchin (n = 8 per treatment) was fed a daily ration of 1.5% of the average body weight of all individuals for 9 wk. Akaike information criterion (AIC) scores were used to compare 6 different dietary composition hypotheses for 8 growth measurements. For each physical growth response, different mathematical models representing a priori hypotheses were compared using the AIC score. The AIC is one of many information-theoretical approaches that allows for direct comparison of nonnested models with varying numbers of parameters. Dietary protein level and protein:energy ratio were the best models for prediction of test diameter increase. Dietary protein level was the best model of test with spines wet weight gain and test with spines dry matter production. When the Aristotle's lantern was corrected for size of the test, there was an inverse relationship with dietary protein level. Log-transformed lantern to test with spines index was also best associated with the dietary protein model. Dietary carbohydrate level was a poor predictor for growth parameters. However, the protein X carbohydrate interaction model was the best model of organic content (percent dry weight) of the test without spines. These data suggest that there is a differential allocation of resources when dietary protein is limiting and the test, but not the Aristotle's lantern, is affected by availability of dietary nutrients. C1 [Heflin, Laura E.; Powell, Mickie L.] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA. [Gibbs, Victoria K.] Villanova Univ, Villanova, PA 19085 USA. [Makowsky, Robert] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lawrence, Addison L.] Texas A&M Univ, AgriLife Res Mariculture Lab, Port Aransas, TX 78343 USA. [Lawrence, John M.] Univ S Florida, Dept Integrat Biol, Tampa, FL 33620 USA. RP Heflin, LE (reprint author), Univ Alabama Birmingham, Dept Biol, 1720 2nd Ave S,CH 374, Birmingham, AL 35294 USA. EM leheflin@uab.edu OI Gibbs, Victoria/0000-0001-6557-8194 FU University of Alabama at Birmingham, U.S. Department of Commerce [NA07OAR4170449]; [T32 HL072757] FX We thank Jeff Barry, Patty Waits Beasley, and the rest of the staff at the Texas AgriLlFE Research Mariculture Laboratory for providing technical support and facilities for this study. We thank Dorothy Moseley and Warren Jones for technical assistance. This report was prepared by S. A. W. under award NA07OAR4170449 from the University of Alabama at Birmingham, U.S. Department of Commerce. R. M. was funded through postdoctoral training grant T32 HL072757. The statements, findings, conclusions, and recommendations are those of the authors and do not necessarily reflect the views of NOAA or the U.S. Department of Commerce. NR 42 TC 2 Z9 2 U1 1 U2 15 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2012 VL 31 IS 3 BP 867 EP 874 DI 10.2983/035.031.0335 PG 8 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 998QF UT WOS:000308254800035 PM 25431520 ER PT J AU Miller, SA Coelho, SG Miller, SW Yamaguchi, Y Hearing, VJ Beer, JZ AF Miller, Sharon A. Coelho, Sergio G. Miller, Scott W. Yamaguchi, Yuji Hearing, Vincent J. Beer, Janusz Z. TI Evidence for a new paradigm for ultraviolet exposure: a universal schedule that is skin phototype independent SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE exposure schedule; indoor tanning; skin phototype; ultraviolet ID DNA-DAMAGE; PIGMENTATION; RADIATION; ERYTHEMA; KINETICS; SPECTRUM; INTERVAL AB Background: The Food and Drug Administration has published guidelines for manufacturer-recommended exposure schedules for ultraviolet (UV) tanning, intended to limit acute and delayed damage from UV exposure. These guidelines recommend that exposure schedules be adjusted for skin phototype. However, it has been shown that the dose necessary to produce tanning is similar for phototypes 2-4. Methods: We observed tanning in phototypes 2 and 3 from repeated UV exposures over a 5-week period. Pigmentation was evaluated visually, instrumentally, and through Fontana-Masson staining of biopsies. Results: The resultant pigmentation was equal or greater in phototype 3 compared with phototype 2 - both visually and instrumentally - measured on day 31 of the exposure protocol. The amount of melanin measured in biopsies taken 24 h postexposure was also greater in phototype 3 compared with phototype 2. Conclusion: Published data on tanning in phototypes 4 and 5 support our findings that higher phototypes can develop pigmentation more efficiently than lower phototypes. Therefore, a universal exposure schedule (based on sensitivity of phototype 2) can be used for all phototypes that are expected to engage in indoor tanning. This approach will result in a reduction of the UV burden for skin phototypes 3 and above. C1 [Miller, Sharon A.; Miller, Scott W.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Coelho, Sergio G.; Yamaguchi, Yuji; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 1114, Silver Spring, MD 20993 USA. EM sharona.miller@fda.hhs.gov FU US FDA Office of Women's Health; National Cancer Institute, National Institute of Health FX This research was supported by the US FDA Office of Women's Health and in part by the Intramural Research Program of the National Cancer Institute, National Institute of Health. The authors wish to express their sincere appreciation to Dr Katalin S. Korossey for her dermatological support and numerous valuable suggestions and to Judith Kniskern, RN, for her excellent handling of the human subjects and records. NR 29 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD AUG PY 2012 VL 28 IS 4 BP 187 EP 195 DI 10.1111/j.1600-0781.2012.00666.x PG 9 WC Dermatology SC Dermatology GA 004ZT UT WOS:000308720800003 PM 23017171 ER PT J AU Jackson, LS Voss, KA Ryu, D AF Jackson, L. S. Voss, K. A. Ryu, D. TI Effects of different extrusion conditions on the chemical and toxicological fate of fumonisin B-1 in maize: a short review SO WORLD MYCOTOXIN JOURNAL LA English DT Review DE reduction; toxicity; N-(deoxy-D-fructos-1-yl)-fumonisin B-1 ID SINGLE-SCREW EXTRUSION; NEURAL-TUBE DEFECTS; IN-VIVO TOXICITY; CORN-BASED FOODS; FUSARIUM-MONILIFORME; MASS-SPECTROMETRY; ESOPHAGEAL CANCER; GLUCOSE REACTION; REACTION-PRODUCT; TORTILLA CHIPS AB Fumonisin B-1 (FB1) is a common mycotoxin found in maize and maize-based food products. Although FB1 is relatively heat stable and survives most thermal processes, extrusion cooking has been shown to be effective at reducing levels of the toxin in contaminated maize. This review summarises studies on the chemical and toxicological fate of FB1 in maize extruded under different conditions. Overall, these studies indicate that stability of FB1 depends on the extrusion conditions, e. g. temperature and screw speed, and that the presence of reducing sugars augment apparent loss of the toxin. The chemical fate of FB1 was investigated by measuring FB1, hydrolysed FB1, and N-substituted FB1 compounds with a mass balance approach while the relative toxicity was determined by rat feeding trials. FB1 in contaminated grits was reduced by 21-37% and 77-87% in the absence and presence of 10% (w/w) glucose, respectively, during single-screw extrusion. Greater reductions of 64-72% and 89-94% were achieved by twin-screw extrusion. Mass balance analysis showed that most of the FB1 in grits extruded without glucose was recovered as FB1, whereas the FB1-glucose reaction product, N-(deoxy-D-fructos-1-yl)-fumonisin B-1 was the prevalent form after extrusion with glucose. 23 to 38% of FB1 in extruded grits with and without added glucose was bound to component(s) of the maize grits. Only 37-46% of FB1 present in unextruded grits could be recovered as one of the fumonisin species (hydrolysed FB1, N-substituted FB1 compounds) or as matrix-bound forms in extruded grits. Reduced FB1 concentrations in extruded grits and the even lower concentrations in grits extruded with glucose resulted in a dose-dependent reduction of toxicity as shown by the less severe apoptotic lesions and sphingolipid effects that were found in the kidneys of rats. In summary, extrusion processing, especially with glucose supplementation, is potentially useful to reduce FB1 concentrations and toxicity of contaminated maize. C1 [Jackson, L. S.] US FDA, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Voss, K. A.] USDA ARS, Toxicol & Mycotoxin Res Unit, Athens, GA 30605 USA. [Ryu, D.] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. RP Jackson, LS (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM dryu@twu.edu NR 52 TC 7 Z9 9 U1 3 U2 14 PU WAGENINGEN ACADEMIC PUBLISHERS PI WAGENINGEN PA PO BOX 220, WAGENINGEN, 6700 AE, NETHERLANDS SN 1875-0710 J9 WORLD MYCOTOXIN J JI World Mycotoxin J. PD AUG PY 2012 VL 5 IS 3 BP 251 EP 260 DI 10.3920/WMJ2012.1431 PG 10 WC Food Science & Technology; Mycology; Toxicology SC Food Science & Technology; Mycology; Toxicology GA 995SB UT WOS:000308031500006 ER PT J AU Blumenthal, GM Cortazar, P Zhang, JJ Tang, SH Sridhara, R Murgo, A Justice, R Pazdur, R AF Blumenthal, Gideon M. Cortazar, Patricia Zhang, Jenny J. Tang, Shenghui Sridhara, Rajeshwari Murgo, Anthony Justice, Robert Pazdur, Richard TI FDA Approval Summary: Sunitinib for the Treatment of Progressive Well-Differentiated Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors SO ONCOLOGIST LA English DT Article DE Sunitinib; Pancreatic neuroendocrine tumor ID ISLET-CELL-CARCINOMA; CLINICAL-TRIALS; SURVIVAL; STREPTOZOCIN; FLUOROURACIL AB On May 20, 2011, the U.S. Food and Drug Administration (FDA) approved sunitinib malate capsules (Sutent (R); Pfizer, Inc., New York) for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable locally advanced or metastatic disease. In a phase III randomized trial, 171 patients received either sunitinib (37.5 mg) or placebo once daily. The progression-free survival (PFS) interval was the primary efficacy endpoint. Secondary endpoints included the overall survival (OS) time, objective response rate (ORR), patient-reported outcomes, and safety. Based on early results favoring sunitinib, the independent data monitoring committee recommended trial termination prior to the prespecified interim analysis. This premature analysis may have led to an overestimate of the treatment effect. In the FDA analysis of investigator-assessed PFS times, the median values for the sunitinib and placebo arms were 10.2 months and 5.4 months, respectively. The ORRs were 9.3% and 0% in the sunitinib and placebo arms, respectively. The OS data were not mature at the time of approval and were confounded by 69% crossover. Common adverse reactions in patients receiving sunitinib included diarrhea, nausea, asthenia, fatigue, neutropenia, hypertension, and palmar-plantar erythrodysesthesia syndrome. Two patients on sunitinib died as a result of cardiac failure. The Oncologic Drugs Advisory Committee voted eight to two that, despite residual uncertainty about the magnitude of the PFS effect because of early trial termination, sunitinib demonstrated a favorable benefit-risk profile in pNET patients. The FDA concurred with the committee's assessment and granted sunitinib regular approval for this rare malignancy with few available therapies. The Oncologist 2012;17:1108-1113 C1 [Blumenthal, Gideon M.; Cortazar, Patricia; Zhang, Jenny J.; Tang, Shenghui; Sridhara, Rajeshwari; Murgo, Anthony; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Blumenthal, GM (reprint author), US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM gideon.blumenthal@fda.hhs.gov NR 12 TC 33 Z9 34 U1 0 U2 10 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD AUG PY 2012 VL 17 IS 8 BP 1108 EP 1113 DI 10.1634/theoncologist.2012-0044 PG 6 WC Oncology SC Oncology GA 996WS UT WOS:000308126100014 PM 22836448 ER PT J AU Buehler, PW Baek, JH Lisk, C Connor, I Sullivan, T Kominsky, D Majka, S Stenmark, KR Nozik-Grayck, E Bonaventura, J Irwin, DC AF Buehler, Paul W. Baek, Jin Hyen Lisk, Christina Connor, Ian Sullivan, Tim Kominsky, Douglas Majka, Susan Stenmark, Kurt R. Nozik-Grayck, Eva Bonaventura, Joe Irwin, David C. TI Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE hypoxia; hemolytic; hemolysis; pulmonary hypertension ID SICKLE-CELL-DISEASE; NITRIC-OXIDE BIOAVAILABILITY; ARTERIAL-HYPERTENSION; ENDOTHELIAL-CELLS; KAPPA-B; HEMOLYSIS; TEMPOL; RAT; DYSFUNCTION; NITROXIDES AB Buehler PW, Baek JH, Lisk C, Connor I, Sullivan T, Kominsky D, Majka S, Stenmark KR, Nozik-Grayck E, Bonaventura J, Irwin DC. Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism. Am J Physiol Lung Cell Mol Physiol 303: L312-L326, 2012. First published June 22, 2012; doi:10.1152/ajplung.00074.2012.-Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia the potential for exacerbation of PAH and vascular remodeling is likely more pronounced. We hypothesized that Hb may contribute to hypoxia-driven PAH collectively as a prooxidant, inflammatory, and nitric oxide (NO) scavenger. Using programmable micropump technology, we exposed male Sprague-Dawley rats housed under room air or hypoxia to 12 or 30 mg per day Hb for 3, 5, and 7 wk. Blood pressure, cardiac output, right ventricular hypertrophy, and indexes of pulmonary vascular remodeling were evaluated. Additionally, markers of oxidative stress, NO bioavailability and inflammation were determined. Hb increased pulmonary arterial (PA) pressure, pulmonary vessel wall stiffening, and right heart hypertrophy with temporal and dose dependence in both room air and hypoxic cohorts. Hb induced a modest increase in plasma oxidative stress markers (malondialdehyde and 4-hydroxynonenal), no change in NO bioavailability, and increased lung ICAM protein expression. Treatment with the antioxidant Tempol attenuated Hb-induced pulmonary arterial wall thickening, but not PA pressures or ICAM expression. Chronic exposure to low plasma Hb concentrations (range = 3-10 mu M) lasting up to 7 wk in rodents induces pulmonary vascular disease via inflammation and to a lesser extent by Hb-mediated oxidation. Tempol demonstrated a modest effect on the attenuation of Hb-induced pulmonary vascular disease. NO bioavailability was found to be of minimal importance in this model. C1 [Buehler, Paul W.; Baek, Jin Hyen] US FDA, Lab Biochem & Vasc Biol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Lisk, Christina; Connor, Ian; Sullivan, Tim; Majka, Susan; Irwin, David C.] Univ Colorado Denver & Hlth Sci Ctr, Cardiovasc Pulm Res Grp, Div Cardiol, Sch Med, Aurora, CO USA. [Stenmark, Kurt R.; Nozik-Grayck, Eva] Univ Colorado Denver & Hlth Sci Ctr, Cardiovasc Pulm Res Grp, Sch Med, Aurora, CO USA. [Kominsky, Douglas] Univ Colorado Denver & Hlth Sci Ctr, Mucosal Inflammat Res Grp, Sch Med, Aurora, CO USA. [Bonaventura, Joe] Duke Univ Med Ctr, Dept Cell Biol, Durham, NC USA. RP Irwin, DC (reprint author), 12700 E 19th Ave,Res Bldg 2,Rm 8121, Aurora, CO 80045 USA. EM david.irwin@ucdenver.edu FU American Physiological Society; National Heart, Lung, and Blood Institute [5P01HL014985-38] FX This study was supported in part by the Giles F. Filley award from the American Physiological Society and National Heart, Lung, and Blood Institute Grant 5P01HL014985-38. NR 40 TC 12 Z9 12 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2012 VL 303 IS 4 BP L312 EP L326 DI 10.1152/ajplung.00074.2012 PG 15 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 995KJ UT WOS:000308006600005 PM 22728465 ER PT J AU Ali, SF AF Ali, S. F. TI Amphetamine-like stimulants hit the headlines SO ARCHIVES OF TOXICOLOGY LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Syed.ali@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD AUG PY 2012 VL 86 IS 8 BP 1153 EP 1154 DI 10.1007/s00204-012-0880-9 PG 2 WC Toxicology SC Toxicology GA 981EJ UT WOS:000306949300001 PM 22710401 ER PT J AU Hellberg, RS DeWitt, CAM Morrissey, MT AF Hellberg, Rosalee S. DeWitt, Christina A. Mireles Morrissey, Michael T. TI Risk-Benefit Analysis of Seafood Consumption: A Review SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review ID CORONARY-HEART-DISEASE; POLYUNSATURATED FATTY-ACIDS; POLYCHLORINATED-BIPHENYLS PCBS; PRENATAL METHYLMERCURY EXPOSURE; POLYBROMINATED DIPHENYL ETHERS; SEYCHELLES CHILD-DEVELOPMENT; SUDDEN CARDIAC DEATH; MATERNAL FISH INTAKE; IN-UTERO EXPOSURE; QUANTITATIVE-ANALYSIS AB Seafood, defined here as marine and freshwater fish and shellfish, is recognized as a healthy food choice because it is a low-fat protein source that provides long-chain omega-3 fatty acids important for early development along with eye and heart health. However, seafood is also known to contain certain contaminants, such as methylmercury and persistent organic pollutants, which can have harmful effects on human health and development. In order to limit exposure to contaminants while maximizing the benefits of seafood consumption, a number of quantitative and qualitative risk-benefit analyses have been conducted for seafood consumption. This review paper provides a brief background on risk-benefit analysis of foods, followed by a discussion of the risks and benefits associated with fish consumption. Next, risk-benefit analyses are reviewed in an historical context. While risk-benefit analysis consists of three main elements (that is, assessment, management, and communication), this review will primarily focus on risk-benefit assessments. Overall, most studies have found that the benefits far outweigh the risks among the general population, especially when a variety of fish is consumed at least twice per week. However, for certain populations (for example, pregnant women and young children) a more targeted approach is warranted in order to ensure that these groups consume fish that are low in contaminants but high in omega-3 fatty acids. The potentially harmful unintended consequences of risk-benefit communication on the general population and certain groups are also discussed. C1 [Morrissey, Michael T.] Oregon State Univ, Food Innovat Ctr, Portland, OR 97209 USA. [Hellberg, Rosalee S.] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. [DeWitt, Christina A. Mireles] Oregon State Univ, Seafood Res & Educ Ctr, Astoria, OR 97103 USA. RP Morrissey, MT (reprint author), Oregon State Univ, Food Innovat Ctr, 1207 NW Naito Pkwy, Portland, OR 97209 USA. EM michael.morrissey@oregonstate.edu FU National Food Safety Initiative of the National Inst. of Food and Agriculture, U.S. Dept. of Agriculture [2007-5110-03815] FX This work was partially supported by a grant from the National Food Safety Initiative (Grant Nr 2007-5110-03815) of the National Inst. of Food and Agriculture, U.S. Dept. of Agriculture. NR 194 TC 12 Z9 13 U1 8 U2 75 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD AUG PY 2012 VL 11 IS 5 BP 490 EP 517 DI 10.1111/j.1541-4337.2012.00200.x PG 28 WC Food Science & Technology SC Food Science & Technology GA 993XL UT WOS:000307893200005 ER PT J AU Chen, JJ Shen, HCJ Rosado, LAR Zhang, YQ Di, X Zhang, BL AF Chen, Jun-Jie Shen, H-C Jennifer Rosado, Leslie A. Rivera Zhang, Yaqin Di, Xu Zhang, Baolin TI Mislocalization of death receptors correlates with cellular resistance to their cognate ligands in human breast cancer cells SO ONCOTARGET LA English DT Article DE death receptors; cellular localization; targeted cancer therapy; drug resistance ID TUMOR-NECROSIS-FACTOR; INHIBITS APOPTOSIS; DECOY RECEPTORS; TRAIL; THERAPY; COMPARTMENTALIZATION; LOCALIZATION; APO2L/TRAIL; ENDOCYTOSIS; EXPRESSION AB Multiple clinical trials are ongoing to evaluate the potential antitumor activity of human TNF variants, Fas ligand (FasL), TNF-related apoptosis inducing ligand (TRAIL) and its agonistic antibodies. These drug products act through the death receptors (DRs) TNF receptor 1 (TNFR1), Fas/CD95, DR4 (TRAIL-R1) and/or DR5 (TRAIL-R2), respectively. Therefore, characterization of the level and localization of DR expression in cancer cells is important for DR-targeted therapy. In this study, we examined the subcellular distribution of the four DRs in a panel of 10 human breast cancer cell lines by western blots and flow cytometry and 50 human breast tumors by immunohistochemistry. Despite their total protein expressions, the DRs were found to be absent on the surface of some cell lines. Consistent with this result, all four DRs were found to be mostly expressed in the cytoplasm and/or the nucleus of primary breast tumors (n=50). We further determined the growth inhibition activity (GI50) of the death ligands, recombinant human TNF alpha, FasL and TRAIL, and found a correlation with the subcellular localization of the corresponding DRs. These results demonstrate an aberrant expression of the death receptors in breast cancer cells, and suggest that the lack of surface DRs appears to be predictive of tumor resistance to DR-targeted therapies. C1 [Chen, Jun-Jie; Shen, H-C Jennifer; Rosado, Leslie A. Rivera; Zhang, Yaqin; Di, Xu; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Zhang, BL (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM Baolin.zhang@fda.hhs.gov FU FDA Critical Path funding; NCI/FDA Interagency Oncology Task Fellowship (IOTF) Program FX We thank Dr. John Gillespie from Pathology Consultant Services for analysis and scoring of the tissue microarrays, and helpful discussions on breast tissue pathology. This research was supported in part by FDA Critical Path funding and the NCI/FDA Interagency Oncology Task Fellowship (IOTF) Program. NR 37 TC 16 Z9 18 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG PY 2012 VL 3 IS 8 BP 833 EP 842 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 997ZD UT WOS:000308206100012 PM 22909995 ER PT J AU Pan, HM Feng, JH He, GX Cerniglia, CE Chen, HZ AF Pan, Hongmiao Feng, Jinhui He, Gui-Xin Cerniglia, Carl E. Chen, Huizhong TI Evaluation of impact of exposure of Sudan azo dyes and their metabolites on human intestinal bacteria SO ANAEROBE LA English DT Article DE Sudan azo dye; Human intestinal bacteria; Metabolite; Cell growth; Cell viability ID FMN-DEPENDENT AZOREDUCTASE; OXIDATIVE DNA-DAMAGE; ENTEROCOCCUS-FAECALIS; PARA RED; MOLECULAR CHARACTERIZATION; SALMONELLA-MICROSOME; CYTOCHROME-P450 1A1; MICROFLORA; REDUCTION; MUTAGENICITY AB Sudan azo dyes are banned for food usage in most countries, but they are illegally used to maintain or enhance the color of food products due to low cost, bright staining, and wide availability of the dyes. In this report, we examined the toxic effects of these azo dyes and their potential reduction metabolites on 11 prevalent human intestinal bacterial strains. Among the tested bacteria, cell growth of 2, 3, 5, 5, and 1 strains was inhibited by Sudan I, II, III, IV, and Para Red, respectively. At the tested concentration of 100 mu M, Sudan I and II inhibited growth of Clostridium perfringens and Lactobacillus rhamnosus with decrease of growth rates from 14 to 47%. Sudan II also affected growth of Enterococcus faecalis. Growth of Bifidobacterium catenulatum, C. perfringens, E. faecalis, Escherichia coli, and Peptostreptococcus magnus was affected by Sudan III and IV with decrease in growth rates from 11 to 67%. C. perfringens was the only strain in which growth was affected by Para Red with 47 and 26% growth decreases at 6 and 10 h, respectively. 1-Amino-2-naphthol, a common metabolite of the dyes, was capable of inhibiting growth of most of the tested bacteria with inhibition rates from 8 to 46%. However, the other metabolites of the dyes had no effect on growth of the bacterial strains. The dyes and their metabolites had less effect on cell viability than on cell growth of the tested bacterial strains. Clostridium indolis and Clostridium ramosum were the only two strains with about a 10 % decrease in cell viability in the presence of Sudan azo dyes. The present results suggested that Sudan azo dyes and their metabolites potentially affect the human intestinal bacterial ecology by selectively inhibiting some bacterial species, which may have an adverse effect on human health. Published by Elsevier Ltd. C1 [Pan, Hongmiao; Feng, Jinhui; Cerniglia, Carl E.; Chen, Huizhong] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [He, Gui-Xin] Univ Massachusetts, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. RP Chen, HZ (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU National Center for Toxicological Research, United States Food and Drug Administration; Oak Ridge Institute for Science and Education; U.S. Department of Energy; U.S. Food and Drug Administration FX This study was funded by National Center for Toxicological Research, United States Food and Drug Administration, and supported in part by appointments (H.P and J. F) to the Postgraduate Research Fellowship Program by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 53 TC 17 Z9 20 U1 1 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD AUG PY 2012 VL 18 IS 4 BP 445 EP 453 DI 10.1016/j.anaerobe.2012.05.002 PG 9 WC Microbiology SC Microbiology GA 991GC UT WOS:000307688500011 PM 22634331 ER PT J AU Woodcock, J AF Woodcock, J. TI The Future of Orphan Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Janet.Woodcock@fda.hhs.gov NR 3 TC 9 Z9 9 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2012 VL 92 IS 2 BP 146 EP 148 DI 10.1038/clpt.2012.89 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 976PH UT WOS:000306596300007 PM 22814657 ER PT J AU Moore, PW Haggerty, DA Cresswell, A Cantilena, L Donovan, JW Burkhart, KK AF Moore, Philip W. Haggerty, David A. Cresswell, Amanda Cantilena, Louis Donovan, J. Ward Burkhart, Keith K. TI Long term cohort of patients with Lamotrigine toxicity SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract DE Lamotrigine; Pharmacokinetics; Toxicity C1 [Moore, Philip W.; Haggerty, David A.; Cresswell, Amanda; Cantilena, Louis; Donovan, J. Ward] PinnacleHlth Toxicol Ctr, Harrisburg, PA USA. [Burkhart, Keith K.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD AUG PY 2012 VL 50 IS 7 MA 38 BP 590 EP 591 PG 2 WC Toxicology SC Toxicology GA 985WB UT WOS:000307300100046 ER PT J AU Schier, JG Sejvar, JJ Lutterloh, EC Likaka, A Katsoudas, E Karaseva, YD Barr, BT Redwood, Y Monroe, S AF Schier, Joshua G. Sejvar, James J. Lutterloh, Emily C. Likaka, Andrew Katsoudas, Eugenia Karaseva, Yelena D. Barr, Beth T. Redwood, Yanique Monroe, Stephan TI Consumption of pesticide-treated wheat seed by a rural population in Malawi SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract DE Pesticide; Food poisoning; Environmental C1 [Schier, Joshua G.; Redwood, Yanique] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. [Sejvar, James J.; Monroe, Stephan] CDC, Natl Ctr Emerging & Zoonot Dis, Atlanta, GA 30333 USA. [Lutterloh, Emily C.] Kentucky Dept Publ Hlth, Frankfort, KS USA. [Likaka, Andrew] Malawi Minist Hlth, Lilongwe, Malawi. [Katsoudas, Eugenia; Karaseva, Yelena D.] US FDA, NE Reg Lab, US Dept HHS, Jamaica, NY USA. [Barr, Beth T.] Ctr Dis Control & Prevent, Global AIDS Program, Ctr Global Hlth, Lilongwe, Malawi. RI Schier, Joshua/F-9861-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD AUG PY 2012 VL 50 IS 7 MA 200 BP 663 EP 664 PG 2 WC Toxicology SC Toxicology GA 985WB UT WOS:000307300100208 ER PT J AU Wang, YY Arlt, VM Roufosse, CA McKim, KL Myers, MB Phillips, DH Parsons, BL AF Wang, Yiying Arlt, Volker M. Roufosse, Candice A. McKim, Karen L. Myers, Meagan B. Phillips, David H. Parsons, Barbara L. TI ACB-PCR measurement of H-ras codon 61 CAA -> CTA mutation provides an early indication of aristolochic acid I carcinogenic effect in tumor target tissues SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE ras mutation; DNA adduct; carcinogenesis; mode of action; tissue specificity; aristolochic acid; allele-specific competitive blocker polymerase chain reaction (ACB-PCR) ID BALKAN ENDEMIC NEPHROPATHY; DNA-ADDUCTS; MUTANT FRACTION; UROTHELIAL CANCER; ENVIRONMENTAL CARCINOGEN; MOUSE MODEL; RISK-FACTOR; RATS; TP53; GENE AB Aristolochic acid (AA) is a strong cytotoxic nephrotoxin and carcinogen, which induces forestomach and kidney tumors in mice and is associated with development of urothelial cancer in humans. This study sought to gain mechanistic insight into AAI-induced carcinogenesis through analysis of a tumor-relevant endpoint. Female Hupki mice were treated daily with 5 mg AAI/kg body weight by gavage for 3, 12, or 21 days. Histopathology and DNA adduct analysis confirmed kidney and forestomach as target tissues for AAI-induced toxicity. H-ras codon 61 CAA?CTA mutations were measured in mouse kidney and forestomach, as well as liver and glandular stomach (nontarget organs) by allele-specific competitive blocker-PCR (ACB-PCR), because A?T transversion is the predominant mutation induced by AA and this particular mutation was found previously in AA-induced rodent forestomach tumors. Treatment-related differences were observed, with the H-ras mutant fraction (MF) of mouse kidney and forestomach exposed to 5 mg AAI/kg body weight for 21 days significantly higher than that of vehicle-treated controls (Fisher's exact test, P < 0.05). Statistically significant correlations between dA-AAI adduct levels (measured previously in the same animals) and induced H-ras MFs were evident in forestomach of mice treated for 21 days (linear regression, P < 0.05). The significant increase in H-ras MF in kidney and forestomach, along with the correlation between DNA adducts, histopathology, and oncogene mutation, provide definitive evidence that AA induces tumors through a directly mutagenic mode of action. Thus, measurement of tumor-associated mutations is a useful tool for elucidating the mechanisms underlying the tissuespecificity of carcinogenesis. Environ. Mol. Mutagen. 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Wang, Yiying; McKim, Karen L.; Myers, Meagan B.; Parsons, Barbara L.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Arlt, Volker M.; Phillips, David H.] Kings Coll London, Analyt & Environm Sci Div, MRC HPA Ctr Environm & Hlth, London SE1 9NH, England. [Roufosse, Candice A.] Imperial Coll Healthcare NHS Trust, Dept Histopathol, Hammersmith Hosp, London W12 0HS, England. RP Parsons, BL (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov OI Phillips, David/0000-0001-8509-3485; Arlt, Volker Manfred/0000-0003-4314-9318 FU Association for International Cancer Research (AICR); Cancer Research UK; NCTR; U.S. Department of Energy; U.S. Food and Drug Administration (FDA) FX Grant sponsors: Association for International Cancer Research (AICR) and Cancer Research UK.; The authors thank Drs. Mei and Manjanatha for their critical review of this manuscript. This work was supported by an appointment (YW) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration (FDA). The contents of this manuscript do not necessarily reflect the views or polices of the U.S. FDA nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. NR 40 TC 11 Z9 12 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2012 VL 53 IS 7 BP 495 EP 504 DI 10.1002/em.21710 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 986RQ UT WOS:000307362500002 PM 22729866 ER PT J AU Gonzalez-Escalona, N Brown, EW Zhang, GD AF Gonzalez-Escalona, Narjol Brown, Eric W. Zhang, Guodong TI Development and evaluation of a multiplex real-time PCR (qPCR) assay targeting ttrRSBCA locus and invA gene for accurate detection of Salmonella spp. in fresh produce and eggs SO FOOD RESEARCH INTERNATIONAL LA English DT Article DE Salmonella; Produce; Real-time PCR; qPCR; Food safety; Eggs ID MEDIATED ISOTHERMAL AMPLIFICATION; POLYMERASE-CHAIN-REACTION; RAPID DETECTION; MESSENGER-RNA; MULTICENTER VALIDATION; BIOLOGICAL SAMPLES; MAMMALIAN-CELLS; UNITED-STATES; TYPHIMURIUM; QUANTIFICATION AB Contamination of foods, especially produce and eggs, with Salmonella spp. is a major concern for public health. Therefore the development of a rapid method for Salmonella detection in those two important food commodities is urgently needed. The main objective of our study was to develop and evaluate a multiplex TaqMan-based real time PCR assay for detection of Salmonella spp. targeting invA gene and ttrRSBCA locus. The detection limit of this assay, 13 copies of genomic invA gene and ttrRSBCA locus, was determined by 10-fold dilutions of DNA from S. Typhimurium (strain SARA9). Inclusivity and exclusivity of the assay were assessed using 101 Salmonella spp. (including all Salmonella species and subspecies) and 48 non-S. enterica strains, respectively. Samples of cilantro (coriander leaves), lettuce, parsley, spinach, tomatoes and jalapeno peppers were seeded with four different Salmonella serovars at levels of 1-20 (low level) and 10(5) (high level) CFU/25 g. The inoculated samples were assayed according to the FDA Salmonella culture method in the Bacteriological Analytical Manual (BAM). Eggs were seeded with two different S. Enteritidis strains at the level used for the produce samples and were assayed according to the USDA Laboratory Guidebook Salmonella culture method. The contaminated samples were analyzed with the multiplex TaqMan-based assay developed in this study. Comparable results were obtained by the qPCR and the two bacteriological methods. Levels as low as 2 CFU/25 g for produce were detected with the qPCR method according to the BAM and 5 CFU/100 g for eggs were detected with the qPCR method according to the USDA Laboratory Guidebook. False negatives (inhibition of PCR reaction) were ruled out through the use of a DNA internal amplification control (IAC). The qPCR multiplex assay developed in this study allows rapid and accurate detection of Salmonella spp. in six high-risk produce commodities and eggs, and has the potential to be used with other food matrices. Published by Elsevier Ltd. C1 [Gonzalez-Escalona, Narjol; Brown, Eric W.; Zhang, Guodong] US FDA, CFSAN, College Pk, MD 20740 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, CFSAN, 5100 Paint Branch Pkwy,HFS 712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU FDA Foods Program Intramural Funds FX This project was supported by the FDA Foods Program Intramural Funds. NR 44 TC 10 Z9 12 U1 0 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0963-9969 J9 FOOD RES INT JI Food Res. Int. PD AUG PY 2012 VL 48 IS 1 BP 202 EP 208 DI 10.1016/j.foodres.2012.03.009 PG 7 WC Food Science & Technology SC Food Science & Technology GA 987PR UT WOS:000307430100025 ER PT J AU Arya, V Robertson, SM Struble, KA Murray, JS AF Arya, Vikram Robertson, Sarah M. Struble, Kimberly A. Murray, Jeffrey S. TI Scientific Considerations for Pharmacoenhancers in Antiretroviral Therapy SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material DE Ritonavir; pharmacoenhancer; protease inhibitor; pharmacokinetics; drug-drug interactions; metabolism ID HEALTHY-VOLUNTEERS; PROTEASE INHIBITORS; P-GLYCOPROTEIN; HIV-INFECTION; RITONAVIR; TRANSPORT; PHARMACOKINETICS; COMBINATION; TIPRANAVIR; SAQUINAVIR C1 [Arya, Vikram; Robertson, Sarah M.] US FDA, Div Clin Pharmacol 4, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Struble, Kimberly A.; Murray, Jeffrey S.] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Arya, V (reprint author), 10903 New Hampshire Ave,Bldg 51,Room 2128, Silver Spring, MD 20993 USA. EM vikram.arya@fda.hhs.gov NR 20 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2012 VL 52 IS 8 BP 1128 EP 1133 DI 10.1177/0091270011410569 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 979UD UT WOS:000306844400001 PM 21712496 ER PT J AU Mahmood, I AF Mahmood, I. TI Allometric extrapolation of factors VII, VIII and IX clearance in children from adults SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE allometry; children; clearance; efficacy; pharmacokinetics; safety ID RECOMBINANT FACTOR VIIA; DRUG CLEARANCE; POPULATION PHARMACOKINETICS; BODY-WEIGHT; INFANTS; PREDICTION; AGE; DISPOSITION; ONTOGENY; PATHWAYS AB . Background: There are situations where a pharmacokinetic (PK) study may not be possible in children, especially in neonates and infants. Under these circumstances, one would like to extrapolate PK parameters from adults or older children to neonates and infants. Allometric scaling is a method which can be used for PK extrapolation from adults to children. Objectives: The objective of this study was to evaluate the predictive performance of an allometric model for the prediction of clearance of three coagulation factors in children from adult clearance. Methods: Clearance values for three coagulation factors (rVIIa, rVIII and rIX) for adults and children were obtained from the literature. The allometric model was developed from adult data and then the model was used to predict clearance of the coagulation factors in individual child. The predicted clearance value was then compared with the observed clearance value in that child. Results: The results of the study indicated that the CL of the three coagulation factors tested in this study could be predicted with accuracy (= 30% prediction error) in most of the children from the allometric model developed from adults. Conclusions: The study indicated that allometric scaling could be applied to predict the CL of coagulation factors in children from adults with accuracy. The predicted clearance can then be used to select a dose to initiate a clinical trial (pharmacokinetics, safety and efficacy) in children. C1 Food & Drug Adm, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), Food & Drug Adm, OBRR, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 18 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2012 VL 10 IS 8 BP 1609 EP 1613 DI 10.1111/j.1538-7836.2012.04787.x PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 989HW UT WOS:000307551900019 PM 22612736 ER PT J AU Fox, DA Grandjean, P de Groot, D Paule, MG AF Fox, Donald A. Grandjean, Philippe de Groot, Didima Paule, Merle G. TI Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies SO NEUROTOXICOLOGY LA English DT Article DE Methylmercury; Lead; Ketamine; Development; Aging; Behavior; Metabolic syndrome; Obesity; Neurodegeneration ID DEVELOPING RAT-BRAIN; CENTRAL-NERVOUS-SYSTEM; OPERANT TEST BATTERY; B-WAVE AMPLITUDES; LEAD-EXPOSURE; NEURODEGENERATIVE DISEASE; METHYLAZOXYMETHANOL TREATMENT; EVOLUTIONARY PERSPECTIVE; NEUROBEHAVIORAL FUNCTION; NEURONAL MIGRATION AB To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the development of metabolic-related diseases and neurotoxicity later in life. The four speakers at this symposium presented their research results on different neurotoxic chemicals relating to the developmental origins of health and adult disease (DOHaD). Philippe Grandjean presented epidemiological data on children exposed to inorganic mercury and methylmercury, and discussed the behavioral outcome measures as they relate to age and stage of brain development. Donald A. Fox presented data that low-dose human equivalent gestational lead exposure produces late-onset obesity only in male mice that is associated with neurodegeneration. Didima de Groot presented results on prenatal exposure of rats to methylazoxymethanol and discussed the results in light of the etiology of western Pacific amyotrophic lateral sclerosis and Parkinson-dementia complex. Merle G. Paule addressed the long-term changes in learning, motivation and short-term memory in aged Rhesus monkeys following acute 24 h exposure to ketamine during early development. Overall, these presentations addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, nonmonotonic dose-response effects and neurotoxic risk assessment. The results indicate that developmental neurotoxicity results in permanent changes, thus emphasizing the need to prevent such toxicity. (C) 2011 Elsevier Inc. All rights reserved. C1 [Fox, Donald A.] Univ Houston, Coll Optometry, Houston, TX 77004 USA. [Fox, Donald A.] Univ Houston, Dept Biol & Biochem, Houston, TX USA. [Fox, Donald A.] Univ Houston, Dept Pharmaceut Sci, Houston, TX USA. [Grandjean, Philippe] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Grandjean, Philippe] Univ So Denmark, Dept Environm Med, Odense, Denmark. [de Groot, Didima] TNO, Qual & Safety Res Grp, NL-3700 AJ Zeist, Netherlands. [Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Fox, DA (reprint author), Univ Houston, Coll Optometry, 4901 Calhoun Rd, Houston, TX 77004 USA. EM dafox@uh.edu; pgrandjean@health.sdu.dk; didima.degroot@tno.nl; merle.paule@fda.hhs.gov OI Grandjean, Philippe/0000-0003-4046-9658 FU America Chemistry Council [NTX0001]; Dutch Ministries of Health, Welfare and Sports; Dutch Ministry of Social Affairs; NICHD; CDER/FDA; NCTR/FDA; [RO1 ES09797]; [RO1ES012482]; [EY07551] FX Supported in part by Grants RO1 ES09797 (PG), RO1ES012482 (DAF), Core Grant EY07551 (DAF), America Chemistry Council Project ID: NTX0001 (DdG); Dutch Ministries of Health, Welfare and Sports (DdG), Dutch Ministry of Social Affairs (DdG), NICHD (MGP), CDER/FDA (MGP), and NCTR/FDA (MGP). The authors also acknowledge the financial support of the local organizers. The findings and conclusions in the report by MG Paule are those of the author and do not necessarily represent the views of the FDA. NR 92 TC 25 Z9 26 U1 3 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD AUG PY 2012 VL 33 IS 4 SI SI BP 810 EP 816 DI 10.1016/j.neuro.2011.12.016 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 990FU UT WOS:000307617200026 PM 22245043 ER PT J AU Chung, CS Yamini, S AF Chung, Carolyn S. Yamini, Sedigheh TI FDA's Health Claim Review: Whey-protein Partially Hydrolyzed Infant Formula and Atopic Dermatitis SO PEDIATRICS LA English DT Review DE whey-protein partially hydrolyzed infant formula; atopic dermatitis; evidence-based review; qualified health claim ID HIGH-RISK INFANTS; NUTRITIONAL INTERVENTION; ANAPHYLACTIC REACTIONS; MILK FORMULAS; FOOD ALLERGY; PREVENTION; DISEASE; CHILDREN; AGE; PROPHYLAXIS AB In this review, we explain how the US Food and Drug Administration (FDA) used its evidence-based review system to evaluate the scientific evidence for a qualified health claim for 100% whey-protein partially hydrolyzed infant formula (W-PHF) and reduced risk of atopic dermatitis (AD). The labeling of health claims, including qualified health claims, on conventional foods and dietary supplements require premarket approval by the FDA. Health claims characterize the relationship between a substance (food or food component) and disease (eg, cancer or cardiovascular disease) or health-related condition (eg, hypertension). To determine whether sufficient evidence exists to support the qualified health claim, the FDA evaluated human intervention studies that evaluated the role of W-PHF in reducing the risk of AD. The FDA concluded there is little to very little evidence, respectively, to support a qualified health claim concerning the relationship between intake of W-PHF and a reduced risk of AD in partially breastfed and exclusively formula-fed infants throughout the first year after birth and up to 3 years of age. In addition, the FDA required a warning statement be displayed along with the health claim to indicate to consumers that partially hydrolyzed infant formulas are not hypoallergenic and should not be fed to infants who are allergic to milk or to infants with existing milk allergy symptoms. Pediatrics 2012;130:e408-e414 C1 [Chung, Carolyn S.; Yamini, Sedigheh] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chung, CS (reprint author), US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM carolyn.chung@fda.hhs.gov NR 44 TC 18 Z9 18 U1 2 U2 21 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2012 VL 130 IS 2 BP E408 EP E414 DI 10.1542/peds.2012-0333 PG 7 WC Pediatrics SC Pediatrics GA 983MI UT WOS:000307123000021 PM 22778306 ER PT J AU Ceridono, M Tellner, P Bauer, D Barroso, J Alepee, N Corvi, R De Smedt, A Fellows, MD Gibbs, NK Heisler, E Jacobs, A Jirova, D Jones, D Kandarova, H Kasper, P Akunda, JK Krul, C Learn, D Liebsch, M Lynch, AM Muster, W Nakamura, K Nash, JF Pfannenbecker, U Phillips, G Robles, C Rogiers, V De Water, FV Liminga, UW Vohr, HW Wattrelos, O Woods, J Zuang, V Kreysa, J Wilcox, P AF Ceridono, Mara Tellner, Paer Bauer, Daniel Barroso, Joao Alepee, Nathalie Corvi, Raffaella De Smedt, Ann Fellows, Mick D. Gibbs, Neil K. Heisler, Eckhard Jacobs, Abigail Jirova, Dagmar Jones, David Kandarova, Helena Kasper, Peter Akunda, Jacqueline Kinyamu Krul, Cyrille Learn, Douglas Liebsch, Manfred Lynch, Anthony M. Muster, Wolfgang Nakamura, Kazuichi Nash, J. Frank Pfannenbecker, Uwe Phillips, Gareth Robles, Catherine Rogiers, Vera De Water, Femke Van Liminga, Ulla Wandel Vohr, Hans-Werner Wattrelos, Olivier Woods, Julie Zuang, Valerie Kreysa, Joachim Wilcox, Phil TI The 3T3 neutral red uptake phototoxicity test: Practical experience and implications for phototoxicity testing - The report of an ECVAM-EFPIA workshop SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID VALIDATION; CHEMICALS; ASSAY; MODEL AB This is the report from the "ECVAM-EFPIA workshop on 3T3 NRU Phototoxicity Test: Practical Experience and Implications for Phototoxicity Testing", jointly organized by ECVAM and EFPIA and held on the 25-27 October 2010 in Somma Lombardo, Italy. The European Centre for the Validation of Alternative Methods (ECVAM) was established in 1991 within the European Commission Joint Research, based on a Communication from the European Commission (1991). The main objective of ECVAM is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine and replace the use of laboratory animals. The European Federation of Pharmaceuticals Industries and Association (EFPIA) represent the pharmaceutical industry operating in Europe. Through its direct membership of 31 national associations and 40 leading pharmaceutical companies, EFPIA is the voice on the EU scene of 2200 companies committed to researching, developing and bringing to patients new medicines that improve health and the quality of life around the world. The workshop, co-chaired by Joachim Kreysa (ECVAM) and Phil Wilcox (GSK, EFPIA) involved thirty-five experts from academia, regulatory authorities and industry, invited to contribute with their experiences in the field of phototoxicology. The main objectives of the workshop were: - to present 'in use' experience of the pharmaceutical industry with the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU-PT), - to discuss why it differs from the results in the original validation exercise, - to discuss technical issues and consider ways to improve the usability of the 3T3 NRU-PT for (non-topical) pharmaceuticals, e.g., by modifying the threshold of chemical light absorption to trigger photo-toxicological testing, and by modifying technical aspects of the assay, or adjusting the criteria used to classify a positive response. During the workshop, the assay methodology was reviewed by comparing the OECD Test Guideline (TG 432) with the protocols used in testing laboratories, data from EFPIA and JPMA 'surveys' were presented and possible reasons for the outcomes were discussed. Experts from cosmetics and pharmaceutical industries reported on their experience with the 3T3 NRU-PT and evidence was presented for phototoxic clinical symptoms that could be linked to certain relevant molecules. Brainstorming sessions discussed if the 3T3 NRU-PT needed to be improved and whether alternatives to the 3T3 NRU-PT exist. Finally, the viewpoint from EU and US regulators was presented. In the final session, the conclusions of the meeting were summarized, with action points. It was concluded that the 3T3 NRU-PT identifies phototoxicological hazards with a 100% sensitivity, and thus is accepted as the tier one test that correctly identifies the absence of phototoxic potential. Consequently, positive results in the 3T3 NRU-PT often do not translate into a clinical phototoxicity risk. Possible ways to improve the practical use of this assay include: (i) adaptation of changed UV/vis-absorption criteria as a means to reduce the number of materials tested, (ii) reduction of the highest concentration to be tested, and (iii) consideration of modifying the threshold criteria for the prediction of a positive call in the test. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ceridono, Mara; Barroso, Joao; Corvi, Raffaella; Zuang, Valerie; Kreysa, Joachim] European Commiss Joint Res Ctr, Ispra, Italy. [Tellner, Paer] EFPIA, Brussels, Belgium. [Bauer, Daniel] Novartis, Basel, Switzerland. [Alepee, Nathalie] LOreal, Paris, France. [De Smedt, Ann] Janssen Res & Dev, Beerse, Belgium. [Gibbs, Neil K.] Univ Manchester, Manchester, Lancs, England. [Heisler, Eckhard] Evon Stockhausen GmbH, Krefeld, Germany. [Jacobs, Abigail] US FDA, Silver Spring, MD USA. [Jirova, Dagmar] Natl Inst Publ Hlth, Prague, Czech Republic. [Jones, David] MHRA, London, England. [Kandarova, Helena] MatTek In Vitro Life Sci Labs, Bratislava, Slovakia. [Kasper, Peter] Fed Inst Drugs & Med Devices BfArM, Bonn, Germany. [Akunda, Jacqueline Kinyamu] Eli Lilly, Indianapolis, IN USA. [Krul, Cyrille] TNO, NL-3700 AJ Zeist, Netherlands. [Learn, Douglas] Charles River Labs, Horsham, PA USA. [Liebsch, Manfred] BfR Fed Inst Risk Assessment, Ctr Documentat & Evaluat Alternat Anim Expt ZEBET, Berlin, Germany. [Lynch, Anthony M.; Wilcox, Phil] GlaxoSmithKline, Ware, Herts, England. [Muster, Wolfgang] Hoffmann La Roche AG, Basel, Switzerland. [Nakamura, Kazuichi] Shionogi & Co Ltd, Tokyo, Japan. [Nash, J. Frank] Procter & Gamble Co, Cincinnati, OH USA. [Pfannenbecker, Uwe] Beiersdorf AG, Hamburg, Germany. [Phillips, Gareth] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. [Robles, Catherine] Sanofi Aventis R&D, Montpellier, France. [Rogiers, Vera] Vrije Univ Brussel, Brussels, Belgium. [De Water, Femke Van] Merck Sharp & Dohme Ltd, Schaijk, Netherlands. [Liminga, Ulla Wandel] Med Prod Agcy, Uppsala, Sweden. [Vohr, Hans-Werner] Bayer Pharma AG, Wuppertal, Germany. [Wattrelos, Olivier] Biol Servier, Gidy, France. [Woods, Julie] Univ Dundee, Photobiol Unit, Dundee, Scotland. RP Tellner, P (reprint author), Leopold Plaza Bldg,Rue Trone 108,Boite 1, B-1050 Brussels, Belgium. EM par.tellner@efpia.eu OI Kandarova, Helena/0000-0002-6926-1343 NR 15 TC 21 Z9 21 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2012 VL 63 IS 3 BP 480 EP 488 DI 10.1016/j.yrtph.2012.06.001 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 980IC UT WOS:000306885800015 PM 22687423 ER PT J AU Mazur, CS Marchitti, SA Dimova, M Kenneke, JF Lumen, A Fisher, J AF Mazur, Christopher S. Marchitti, Satori A. Dimova, Mira Kenneke, John F. Lumen, Annie Fisher, Jeff TI Human and Rat ABC Transporter Efflux of Bisphenol A and Bisphenol A Glucuronide: Interspecies Comparison and Implications for Pharmacokinetic Assessment SO TOXICOLOGICAL SCIENCES LA English DT Article DE metabolism; xenobiotic transporters; physiologically-based pharmacokinetics ID MULTIDRUG-RESISTANCE PROTEIN; HUMAN P-GLYCOPROTEIN; SPRAGUE-DAWLEY RATS; SUBSTRATE-SPECIFICITY; MEMBRANE TRANSPORTERS; DRUG-BINDING; AMINO-ACIDS; MRP1 ABCC1; MONKEYS; ROUTE AB Significant interspecies differences exist between human and rodent with respect to absorption, distribution, and excretion of bisphenol A (BPA) and its primary metabolite, BPA-glucuronide (BPA-G). ATP-Binding Cassette (ABC) transporter enzymes play important roles in these physiological processes, and their enzyme localization (apical vs. basolateral) in the plasma membrane allows for different cellular efflux pathways. In this study, we utilized an ATPase assay to evaluate BPA and BPA-G as potential substrates for the human and rat ABC transporters: P-glycoprotein (MDR1), multidrug resistance associated proteins (MRPs), and breast cancer resistant protein (BCRP). Based on high ATPase activity, BPA is likely a substrate for rat mdr1b but not for human MDR1 or rat mdr1a. Results indicate that BPA is a potential substrate for rat mrp2 and human MRP2, BCRP, and MRP3. The metabolite BPA-G demonstrated the highest apparent substrate binding affinity for rat mrp2 and human MRP3 but appeared to be a nonsubstrate or potential inhibitor for human MRP2, MDR1, and BCRP and for rat mdr1a, mdr1b, and bcrp. Analysis of ABC transporter amino acid sequences revealed key differences in putative binding site composition that may explain substrate specificity. Collectively, these results suggest that in both rat and human, apical transporters efflux BPA into the bile and/or intestinal lumen. BPA-G would follow a similar pathway in rat; however, in human, due to the basolateral location of MRP3, BPA-G would likely enter systemic and portal blood supplies. These differences between human and rodent ABC transporters may have significant implications for interspecies extrapolation used in risk assessment. C1 [Mazur, Christopher S.; Marchitti, Satori A.; Kenneke, John F.] US EPA, Off Res & Dev, Natl Exposure Res Lab, Ecosyst Res Div, Athens, GA 30605 USA. [Dimova, Mira] Univ Georgia, Coll Agr & Environm Sci, Athens, GA 30605 USA. [Lumen, Annie; Fisher, Jeff] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mazur, CS (reprint author), US EPA, Off Res & Dev, Natl Exposure Res Lab, Ecosyst Res Div, 960 Coll Stn Rd, Athens, GA 30605 USA. EM mazur.chris@epa.gov NR 40 TC 20 Z9 20 U1 1 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2012 VL 128 IS 2 BP 317 EP 325 DI 10.1093/toxsci/kfs167 PG 9 WC Toxicology SC Toxicology GA 991JY UT WOS:000307698500002 PM 22552776 ER PT J AU Soon, GX Min, M Struble, KA Chan-Tack, KM Hammerstrom, T Qi, KR Zhou, S Bhore, R Murray, JS Birnkrant, DB AF Soon, Guoxing (Greg) Min, Min Struble, Kimberly A. Chan-Tack, Kirk M. Hammerstrom, Thomas Qi, Karen Zhou, Susan Bhore, Rafia Murray, Jeffrey S. Birnkrant, Debra B. TI Meta-Analysis of Gender Differences in Efficacy Outcomes for HIV-Positive Subjects in Randomized Controlled Clinical Trials of Antiretroviral Therapy (2000-2008) SO AIDS PATIENT CARE AND STDS LA English DT Article ID INFECTION; DESIGN; WOMEN AB Women are often underrepresented in randomized clinical trials (RCT) of HIV-1 drugs. As a result, determining whether women have different virologic outcomes compared to men is not always possible because the gender-related analyses usually lack statistical power. To address this important public health concern, the Food and Drug Administration's (FDA) Division of Antiviral Products (DAVP) created a database including 20,328 HIV-positive subjects from 40 RCTs in 18 New Drug Applications (NDAs) submitted to the FDA between 2000 and 2008. These RCTs were conducted for at least 48 weeks in duration and were used to support approval of new molecular entity, new formulation, or major label change. To delineate potential gender differences in antiretroviral treatment (ART), we evaluated the percentage of subjects with HIV RNA less than 50 copies per milliliter at 48 weeks. Analyses of the database represent the most systematic review of gender-related ART efficacy data to date. Overall, the meta-analyses did not demonstrate statistically or clinically significant gender differences in virologic outcome at week 48. However, the corresponding subgroup analyses appear to show several statistically significant gender differences favoring males. C1 [Soon, Guoxing (Greg)] US FDA, Off Biostat, Div Biometr 4, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Struble, Kimberly A.; Chan-Tack, Kirk M.; Murray, Jeffrey S.; Birnkrant, Debra B.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bhore, Rafia] Univ Texas SW Med Ctr Dallas, Div Biostat, Dallas, TX 75390 USA. RP Soon, GX (reprint author), US FDA, Off Biostat, Div Biometr 4, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 3636, Silver Spring, MD 20993 USA. EM Guoxing.Soon@fda.hhs.gov FU FDA Office of Women's Health FX This work was supported by the funding from the FDA Office of Women's Health. Preliminary data analyses were previously presented at the 16th Conference on Retroviruses and Opportunistic Infections, Montreal, Canada, February 8-11, 2009 (Poster 987b). We gratefully acknowledge the expert advice provided by Fraser Smith, Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. NR 52 TC 34 Z9 34 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD AUG PY 2012 VL 26 IS 8 BP 444 EP 453 DI 10.1089/apc.2011.0278 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 983KS UT WOS:000307118800002 PM 22734949 ER PT J AU Parshikov, IA Netrusov, AI Sutherland, JB AF Parshikov, Igor A. Netrusov, Alexander I. Sutherland, John B. TI Microbial transformation of azaarenes and potential uses in pharmaceutical synthesis SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE Azaarenes; Biotransformation; Drugs; Heterocyclic compounds; Pharmacology ID CONTAINING HETEROCYCLIC-COMPOUNDS; INDOLICUM DSM 3383; CUNNINGHAMELLA-ELEGANS; AROMATIC-COMPOUNDS; N-OXIDATION; MICROBIOLOGICAL TRANSFORMATION; MYCOBACTERIUM-TUBERCULOSIS; BACTERIAL-DEGRADATION; CARBOLINE DERIVATIVES; ANTIMALARIAL ACTIVITY AB Pyridine, quinoline, acridine, indole, carbazole, and other heterocyclic nitrogen-containing compounds (azaarenes) can be transformed by cultures of bacteria and fungi to produce a variety of new derivatives, many of which have biological activity. In many cases, the microbial biotransformation processes are regio- and stereoselective so that the transformation products may be useful for the synthesis of new candidate drugs. C1 [Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Parshikov, Igor A.] First Moscow State Med Univ IM Sechenov, Moscow, Russia. [Netrusov, Alexander I.] Moscow MV Lomonosov State Univ, Moscow, Russia. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov OI netrusov, alexander/0000-0002-2803-3037; Parshikov, Igor/0000-0003-1466-1128 NR 134 TC 9 Z9 9 U1 1 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD AUG PY 2012 VL 95 IS 4 BP 871 EP 889 DI 10.1007/s00253-012-4220-z PG 19 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 979VJ UT WOS:000306848600005 PM 22740048 ER PT J AU Li, X Bethune, LA Jia, Y Lovell, RA Proescholdt, TA Benz, SA Schell, TC Kaplan, G McChesney, DG AF Li, X. Bethune, L. A. Jia, Y. Lovell, R. A. Proescholdt, T. A. Benz, S. A. Schell, T. C. Kaplan, G. McChesney, D. G. TI Surveillance of Salmonella Prevalence in Animal Feeds and Characterization of the Salmonella Isolates by Serotyping and Antimicrobial Susceptibility SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; FOOD; PATHOGENS; TREATS; DOG AB This article presents the surveillance data from the Feed Contaminants Program (2002-2009) and Salmonella Assignment (2007-2009) of the U. S. Food and Drug Administration (FDA), which monitor the trend of Salmonella contamination in animal feeds. A total of 2,058 samples were collected from complete animal feeds, feed ingredients, pet foods, pet treats, and supplements for pets in 2002-2009. These samples were tested for the presence of Salmonella. Those that were positive for Salmonella underwent serotyping and testing for antimicrobial susceptibility. Of the 2,058 samples, 257 were positive for Salmonella (12.5%). The results indicate a significant overall Salmonella reduction (p <= 0.05) in animal feeds from 18.2% (187 samples tested) in 2002 to 8.0% (584 samples tested) in 2009. Among these samples, feed ingredients and pet foods/treats had the most significant reduction (p <= 0.05). Of the 45 Salmonella serotypes identified, Salmonella Senftenberg and Salmonella Montevideo were the top two common serotypes (8.9%). Of the 257 Salmonella isolates obtained, 54 isolates (21%) were resistant to at least one antimicrobial. The findings provide the animal feed industries with Salmonella prevalence information that can be used to address Salmonella contamination problems. Our findings can also be used to educate pet owners when handling pet foods and treats at home to prevent salmonellosis. C1 [Li, X.] US FDA, Ctr Vet Med, Off Surveillance & Compliance, Div Anim Feeds, Rockville, MD 20855 USA. [Bethune, L. A.] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA USA. [Jia, Y.] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Silver Spring, MD USA. RP Li, X (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, Div Anim Feeds, HFV 222,7519 Standish Pl, Rockville, MD 20855 USA. EM xin.li@fda.hhs.gov NR 25 TC 23 Z9 23 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD AUG PY 2012 VL 9 IS 8 BP 692 EP 698 DI 10.1089/fpd.2011.1083 PG 7 WC Food Science & Technology SC Food Science & Technology GA 988QU UT WOS:000307506400003 PM 22735034 ER PT J AU Jackson, EE Erten, ES Maddi, N Graham, TE Larkin, JW Blodgett, RJ Schlesser, JE Reddy, RM AF Jackson, Emily E. Erten, Edibe S. Maddi, Neeraj Graham, Thomas E. Larkin, John W. Blodgett, Robert J. Schlesser, Joseph E. Reddy, Ravinder M. TI Detection and Enumeration of Four Foodborne Pathogens in Raw Commingled Silo Milk in the United States SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BULK TANK MILK; ESCHERICHIA-COLI O157-H7; POLYMERASE-CHAIN-REACTION; SPORE-FORMING BACTERIA; FOOD-BORNE PATHOGEN; NEW-YORK-STATE; LISTERIA-MONOCYTOGENES; PSYCHROTROPHIC BACILLUS; RISK-ASSESSMENT; DAIRY FARMS AB A nationwide survey was conducted to obtain qualitative and quantitative data on bacterial contamination of raw commingled silo milk intended for pasteurization. The levels of total aerobic bacteria, total coliforms, Enterobacteriaceae, Escherichia coli, and Staphylococcus aureus were determined using the TEMPO system. The prevalence rates and levels of presumptive Bacillus cereus, E. coli O157:H7, Listeria monocytogenes, and Salmonella spp. were determined in 214 samples. B. cereus was detected in 8.91% of samples, at 3.0 to 93 CFU/ml. E. colt O157:H7 was detected in 3.79 to 9.05% of samples, at <0.0055 to 1.1 CFU/ml, depending on the assay utilized. Salmonella spp. were recovered from 21.96 to 57.94% of samples, at <0.0055 to 60 CFU/ml. L. monocytogenes was detected in 50.00% of samples, at <0.0055 to 30 CFU/ml. The average log-transformed counts of total viable bacteria were slightly lower in samples containing no pathogens. No correlation was observed between the levels of organisms detected with the TEMPO system and the presence or levels of any pathogen except E. coli O157:H7. A higher average log-transformed count of total viable bacteria was observed in samples positive for this organism. The high prevalence rates of target pathogens may be attributed to a variety of factors, including detection methods, sample size, and commingling of the milk in the silo. The effects of commingling likely contributed to the high prevalence rates and low levels of target pathogens because of the inclusion of milk from multiple bulk tanks. The high prevalence rates also may be the result of analysis of larger sample volumes using more sensitive detection methods. These quantitative data could be utilized to perform more accurate risk assessments and to better estimate the appropriate level of protection for dairy products and processing technologies. C1 [Jackson, Emily E.; Graham, Thomas E.; Larkin, John W.; Blodgett, Robert J.; Schlesser, Joseph E.; Reddy, Ravinder M.] US FDA, College Pk, MD 20740 USA. [Erten, Edibe S.; Maddi, Neeraj] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Erten, Edibe S.] Univ Illinois, Urbana, IL 61801 USA. [Maddi, Neeraj] Midwest Foods, Chicago, IL 60632 USA. RP Reddy, RM (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM ravinder.reddy@fda.hhs.gov FU Research Participation Program appointment at the Center for Food Safety and Applied Nutrition FX This project was supported in part by a Research Participation Program appointment at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education via an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The authors thank the National Conference on Interstate Milk Shipments for their support and assistance in obtaining raw milk samples. NR 72 TC 11 Z9 11 U1 2 U2 26 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2012 VL 75 IS 8 BP 1382 EP 1393 DI 10.4315/0362-028X.JFP-11-548 PG 12 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 987JM UT WOS:000307413100003 PM 22856561 ER PT J AU Sulaiman, IM Anderson, M Oi, DH Simpson, S Kerdahi, K AF Sulaiman, Irshad M. Anderson, Mickey Oi, David H. Simpson, Steven Kerdahi, Khalil TI Multilocus Genetic Characterization of Two Ant Vectors (Group II "Dirty 22" Species) Known To Contaminate Food and Food Products and Spread Foodborne Pathogens SO JOURNAL OF FOOD PROTECTION LA English DT Article ID REGULATORY ACTION CRITERIA; PHYLOGENETIC ANALYSIS; FLIES DIPTERA; EVOLUTIONARY RELATIONSHIPS; ELONGATION FACTOR-1-ALPHA; MOLECULAR PHYLOGENY; INSECT PHYLOGENY; SP APICOMPLEXA; FILTH; SEQUENCES AB The U.S. Food and Drug Administration utilizes the presence of filth and extraneous materials as one of the criteria for implementing regulatory actions and assessing adulteration of food products of public health importance. Twenty-two prevalent pest species (also known as the "Dirty 22" species) have been considered by this agency as possible vehicles for the spread of foodborne diseases, and the presence of these species is considered an indicator of unsanitary conditions in food processing and storage facilities. In a previous study, we further categorized the Dirty 22 species into four groups: group I includes four cockroach species, group II includes two ant species, group III includes 12 fly species, and group IV includes four rodent species. Here, we describe the development of three nested PCR primer sets and multilocus genetic characterization by amplifying the small subunit rRNA, elongation factor 1-alpha, and wingless (WNT-1) genes of group II Dirty 22 ant species Monomorium pharaonis and Solenopsis molesta. These novel group II Dirty 22 species-specific nested PCR primer sets can be used when the specimens cannot be identified using conventional microscopic methods. These newly developed assays will provide correct identification of group II Dirty 22 ant species, and the information can be used in the control of foodborne pathogens. C1 [Sulaiman, Irshad M.; Anderson, Mickey; Simpson, Steven; Kerdahi, Khalil] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Oi, David H.] USDA, Ctr Med Agr & Vet Entomol, Gainesville, FL 32608 USA. RP Sulaiman, IM (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. EM irshad.sulaiman@fda.hhs.gov FU Division of Field Sciences (DFS) of the FDA FX This study was supported in part by funding from the Division of Field Sciences (DFS) of the FDA. I. M. Sulaiman is the principal investigator of the DFS Challenge Initiative Program grant. The funders had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript. NR 49 TC 3 Z9 3 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2012 VL 75 IS 8 BP 1447 EP 1452 DI 10.4315/0362-028X.JFP-12-098 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 987JM UT WOS:000307413100010 PM 22856568 ER PT J AU Beukelman, T Xie, FL Chen, L Baddley, JW Delzell, E Grijalva, CG Lewis, JD Ouellet-Hellstrom, R Patkar, NM Saag, KG Winthrop, KL Curtis, JR AF Beukelman, Timothy Xie, Fenglong Chen, Lang Baddley, John W. Delzell, Elizabeth Grijalva, Carlos G. Lewis, James D. Ouellet-Hellstrom, Rita Patkar, Nivedita M. Saag, Kenneth G. Winthrop, Kevin L. Curtis, Jeffrey R. CA SABER Collaboration TI Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FACTOR-ALPHA THERAPY; RHEUMATOID-ARTHRITIS; SAFETY; ETANERCEPT; RISK; METHOTREXATE; EFFICACY; CHILDREN AB Objective To compare the incidence of hospitalized bacterial infections among children with and children without juvenile idiopathic arthritis (JIA) and to examine the effects of selected medications. Methods Using national Medicaid data from 2000 through 2005, we identified a cohort of children with JIA and a comparator cohort of children with attention deficit hyperactivity disorder (ADHD). Exposures to methotrexate (MTX), TNF inhibitors, and oral glucocorticoids (GCs) were determined using pharmacy claims. Patients hospitalized with bacterial infections were identified using coded discharge diagnoses. We calculated adjusted hazard ratios (HRadj) to compare infection incidence rates while adjusting for relevant covariates. Results We identified 8,479 JIA patients with 13,003 person-years of followup; 36% took MTX and 16% took TNF inhibitors. Compared with ADHD patients, JIA patients who were not currently taking MTX or TNF inhibitors had an increased rate of infection (HRadj 2.0 [95% confidence interval (95% CI) 1.5, 2.5]). Among JIA patients not receiving TNF inhibitor therapy, MTX users had a similar rate of infection as those not currently taking MTX (HRadj 1.2 [95% CI 0.9, 1.7]). TNF inhibitor use (irrespective of MTX) resulted in a similar rate of infection as use of MTX without a TNF inhibitor (HRadj 1.2 [95% CI 0.8, 1.8]). Use of high-dose GCs (=10 mg/day of prednisone or equivalent) increased the rate of infection as compared with no GC use, after adjustment for MTX and TNF inhibitor use (HRadj 3.1 [95% CI 2.0, 4.7]). Conclusion Children with JIA had an increased rate of infection compared to children with ADHD. Among children with JIA, the rate of infection was not increased with MTX or TNF inhibitor use, but was significantly increased with high-dose GC use. C1 [Beukelman, Timothy] Univ Alabama Birmingham, Div Pediat Rheumatol, Birmingham, AL 35233 USA. [Grijalva, Carlos G.] Vanderbilt Univ, Nashville, TN USA. [Lewis, James D.] Univ Penn, Philadelphia, PA 19104 USA. [Ouellet-Hellstrom, Rita] US FDA, Silver Spring, MD USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Beukelman, T (reprint author), Univ Alabama Birmingham, Div Pediat Rheumatol, 1600 7th Ave S,CPP 210, Birmingham, AL 35233 USA. EM tbeukelman@peds.uab.edu FU Agency for Healthcare Research and Quality (AHRQ); FDA, US Department of Health and Human Services [1U18-HS-017919-0]; NIH through the University of Alabama at Birmingham Center for Clinical and Translational Science [5KL2-RR-025776]; NIH [5P60-AR-56116, AR-053351]; AHRQ [R01-HS-018517]; Novartis; Pfizer; Abbott; Merck; Amgen; Millennium; Centocor; Eli Lilly; Savient; Ardea; Regeneron; URL; Genentech; Wyeth; Bristol-Myers Squibb; Crescendo; Roche/Genentech; UCB; Consortium of Rheumatology Researchers of North America FX Supported by the Agency for Healthcare Research and Quality (AHRQ) and the FDA, US Department of Health and Human Services (as part of grant 1U18-HS-017919-0, administered through the AHRQ CERTs Program). Dr. Beukelman's work was supported by the NIH (grant 5KL2-RR-025776 through the University of Alabama at Birmingham Center for Clinical and Translational Science). Dr. Grijalva's work was supported by the NIH (grant 5P60-AR-56116). Dr. Curtis' work was supported by the NIH (grant AR-053351) and the AHRQ (grant R01-HS-018517).; Dr. Beukelman has received consulting fees, speaking fees, and/or honoraria from Novartis (less than $10,000) and a research grant from Pfizer. Dr. Baddley has received consulting fees, speaking fees, and/or honoraria from Abbott and Merck (less than $10,000 each). A portion of Dr. Delzell's salary was funded by a contract from Amgen. Dr. Lewis has received consulting fees, speaking fees, and/or honoraria from Pfizer, Abbott, and Millennium (less than $10,000 each) and a research grant from Centocor. Dr. Saag has received consulting fees, speaking fees, and/or honoraria from Eli Lilly, Merck, Novartis, Savient, Ardea, Regeneron, URL, and Abbott (less than $10,000 each) and from Amgen (more than $10,000). Dr. Winthrop has received consulting fees, speaking fees, and/or honoraria from Amgen, Genentech, Abbott, and Wyeth (less than $10,000 each). Dr. Curtis has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Crescendo, and Pfizer (less than $10,000 each) and from Roche/Genentech, UCB, Centocor, the Consortium of Rheumatology Researchers of North America, and Amgen (more than $10,000 each). NR 26 TC 50 Z9 51 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 2012 VL 64 IS 8 BP 2773 EP 2780 DI 10.1002/art.34458 PG 8 WC Rheumatology SC Rheumatology GA 980PX UT WOS:000306906500038 PM 22569881 ER PT J AU Hung, GC Nagamine, K Li, B Lo, SC AF Hung, Guo-Chiuan Nagamine, Kenjiro Li, Bingjie Lo, Shyh-Ching TI Identification of DNA Signatures Suitable for Use in Development of Real-Time PCR Assays by Whole-Genome Sequence Approaches: Use of Streptococcus pyogenes in a Pilot Study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB A stepwise computational approach using three layers of publicly available software was found to effectively identify DNA signatures for Streptococcus pyogenes. PCR testing validated that 9 out of 15 signature-derived primer sets could detect as low as 5 fg of target DNA with high specificity. The selected signature-derived primer sets were successfully evaluated against all 23 clinical isolates. The approach is readily applicable for designing molecular assays for rapid detection and characterization of various pathogenic bacteria. C1 [Hung, Guo-Chiuan; Nagamine, Kenjiro; Li, Bingjie; Lo, Shyh-Ching] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. RP Lo, SC (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. EM shyhching.lo@fda.hhs.gov FU Research Participation Program at the Center for Biologics Evaluation and Research FX This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 6 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2012 VL 50 IS 8 BP 2770 EP 2773 DI 10.1128/JCM.01155-12 PG 4 WC Microbiology SC Microbiology GA 986WY UT WOS:000307378400036 PM 22593599 ER PT J AU Tamta, H Pawar, RS Wamer, WG Grundel, E Krynitsky, AJ Rader, JI AF Tamta, H. Pawar, R. S. Wamer, W. G. Grundel, E. Krynitsky, A. J. Rader, J., I TI Investigation of cytochrome P450-mediated toxicity of extracts of Polygonum multiflorum and Chelidonium majus SO PLANTA MEDICA LA English DT Meeting Abstract CT International Congress on Natural Products Research on Global Change, Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA, PSE and SIF CY JUL 28-AUG 01, 2012 CL New York, NY SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP) C1 [Tamta, H.; Pawar, R. S.; Wamer, W. G.; Grundel, E.; Krynitsky, A. J.; Rader, J., I] Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD AUG PY 2012 VL 78 IS 11 BP 1142 EP 1142 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 982KT UT WOS:000307042800497 ER PT J AU Pawar, RS Grundel, E Eason, M Krynitsky, AJ Rader, JI AF Pawar, R. S. Grundel, E. Eason, M. Krynitsky, A. J. Rader, J., I TI Determination of biogenic amines in Acacia rigidula and its dietary supplements SO PLANTA MEDICA LA English DT Meeting Abstract CT International Congress on Natural Products Research on Global Change, Natural Products and Human Health/8th Joint Meeting of AFERP, ASP, GA, PSE and SIF CY JUL 28-AUG 01, 2012 CL New York, NY SP Amer Soc Pharmacognosy (ASP), Soc Med Plant & Nat Prod Res (GA), Italian Soc Phytochem (SIF), Phytochem Soc Europe (PSE), French Speaking Soc Pharmacognosy (AFERP) C1 [Pawar, R. S.; Grundel, E.; Krynitsky, A. J.; Rader, J., I] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Eason, M.] Lady Bird Johnson Wildflower Ctr, Austin, TX 78739 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD AUG PY 2012 VL 78 IS 11 BP 1262 EP 1263 PG 2 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 982KT UT WOS:000307042801477 ER PT J AU Howard, HJ Jones, KM Rudenko, L AF Howard, H. J. Jones, K. M. Rudenko, L. TI Agency Perspectives on Food Safety for the Products of Animal Biotechnology SO REPRODUCTION IN DOMESTIC ANIMALS LA English DT Article AB Animal biotechnology represents one subset of tools among a larger set of technologies for potential use to meet increasing world demands for food. Assisted reproductive technologies (ART) such as artificial insemination and embryo transfer continue to make positive contributions in food animal production. The US Food and Drug Administration (FDA) performed a comprehensive risk assessment to identify potential food consumption or animal health risks associated with animal cloning, an emerging ART. At that time, FDA concluded that animal cloning posed no unique risks either to animal health or to food consumption, and food from animal clones and their sexually reproduced offspring required no additional federal regulation beyond that applicable to conventionally bred animals of the species examined. At this time, no new information has arisen that would necessitate a change in FDA's conclusions on food from animal clones or their sexually reproduced offspring. Use of recombinant DNA technologies to produce genetically engineered (GE) animals represents another emerging technology with potential to impact food animal production. In its regulation of GE animals, FDA follows a cumulative, risk-based approach to address scientific questions related to the GE animals. FDA evaluates data and information on the safety, effectiveness and stability of the GE event. FDA carries out its review at several levels (e. g. molecular biology, animal safety, food safety, environmental safety and claim validation). GE animal sponsors provide data to address risk questions for each level. This manuscript discusses FDA's role in evaluation of animal cloning and GE animals. C1 [Howard, H. J.; Jones, K. M.; Rudenko, L.] US FDA, Ctr Vet Med, Anim Biotechnol Interdisciplinary Grp, Rockville, MD 20855 USA. RP Howard, HJ (reprint author), US FDA, Ctr Vet Med, Anim Biotechnol Interdisciplinary Grp, 7500 Standish Pl, Rockville, MD 20855 USA. EM harlan.howard@fda.hhs.gov NR 24 TC 0 Z9 0 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0936-6768 J9 REPROD DOMEST ANIM JI Reprod. Domest. Anim. PD AUG PY 2012 VL 47 SU 4 SI SI BP 127 EP 133 DI 10.1111/j.1439-0531.2012.02066.x PG 7 WC Agriculture, Dairy & Animal Science; Reproductive Biology; Veterinary Sciences SC Agriculture; Reproductive Biology; Veterinary Sciences GA 980UG UT WOS:000306918700020 PM 22827361 ER PT J AU Cleeland, CS Allen, JD Roberts, SA Brell, JM Giralt, SA Khakoo, AY Kirch, RA Kwitkowski, VE Liao, ZX Skillings, J AF Cleeland, Charles S. Allen, Jeff D. Roberts, Samantha A. Brell, Joanna M. Giralt, Sergio A. Khakoo, Aarif Y. Kirch, Rebecca A. Kwitkowski, Virginia E. Liao, Zhongxing Skillings, Jamey TI Reducing the toxicity of cancer therapy: recognizing needs, taking action SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; AMERICAN SOCIETY; RADIATION-THERAPY; PROSTATE-CANCER; ADVERSE EVENTS; TARGETED THERAPIES; SAFETY ASSESSMENT; MYELOID-LEUKEMIA; BREAST-CANCER; LUNG-CANCER AB Our understanding of the biology of cancer and the application of this knowledge to cancer treatment has greatly outpaced what we know of the biology underlying the symptoms and toxic effects that therapies produce. These adverse effects of therapy cause substantial discomfort and distress to patients and their families, limit treatment tolerability and can persist indefinitely in post-treatment survivorship. Despite these concerns, little research effort is targeted at documenting the nature of these effects. Similarly, limited efforts are being made in the drug-development arena to identify or develop treatments that might prevent or reduce toxicities. A panel of clinicians and researchers as well as representatives from advocacy groups, federal agencies and the pharmaceutical industry was convened to identify gaps in cancer treatment toxicity research and to provide direction for future action. With an emphasis on coordinating multidisciplinary efforts, this panel has presented a strategy to increase funding for the field and develop a coherent research agenda. Cleeland, C. S. et al. Nat. Rev. Clin. Oncol. 9, 471-478 (2012); published online 3 July 2012; doi:10.1038/nrclinonc.2012.99 C1 [Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Liao, Zhongxing] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Allen, Jeff D.; Roberts, Samantha A.] Friends Canc Res, Arlington, VA 22202 USA. [Brell, Joanna M.] NCI, Community Oncol & Prevent Trials Res Grp, Rockville, MD 20892 USA. [Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Serv, New York, NY 10065 USA. [Khakoo, Aarif Y.] Amgen Inc, Metab Disorders, Res, San Francisco, CA 94080 USA. [Kirch, Rebecca A.] Amer Canc Soc Inc, Qual Life & Survivorship, Washington, DC 20004 USA. [Kwitkowski, Virginia E.] US FDA, Off Hematol Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Skillings, Jamey] Pfizer Inc, Pfizer Med Affairs, New York, NY 10017 USA. RP Cleeland, CS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA. EM ccleeland@mdanderson.org FU C. Stratton Hill Colloquium on Pain and Its Relief FX The authors thank Tim Ahles (American Association for Cancer Research Survivorship Task Force, New York, NY, USA), Ann O'Mara (National Cancer Institute [NCI], Bethesda, MD, USA), Jamie H. Von Roenn (ASCO, Chicago, IL, USA), Elaine B. Yu (Genentech, San Francisco, CA, USA) and Nora Janjan (National Center for Policy Analysis, Dallas, TX, USA) for their insightful comments during the drafting of this article. We also acknowledge Jeanie F. Woodruff for editorial assistance, and M. Catherine Rodgers for administrative assistance (both at The University of Texas MD Anderson Cancer Center, Houston, TX, USA). The authors wish to acknowledge the overall contribution of those who participated in and contributed to the March 2011 colloquium entitled Developing Strategies for Reducing Cancer Treatment-Related Toxicities and Symptoms in Houston, TX, USA: Lyndah K. Dreiling (Amgen, Thousand Oaks, CA, USA), Marilee Duffield (Alere Health, Marietta, GA, USA), Robert F. Gagel (The University of Texas MD Anderson Cancer Center, Houston, TX, USA), Mark Gorman (National Coalition for Cancer Survivorship, Silver Spring, MD, USA), Amy Guo (Novartis, East Hanover, NJ, USA), Carol A. Hahn (American Society for Therapeutic Radiation Oncology, Durham, NC, USA), Joan S. McClure (National Comprehensive Cancer Network, Fort Washington, PA, USA), Andrew Miller (Lance Armstrong Foundation, Austin, TX, USA), Scarlott K. Mueller (Oncology Nursing Society Foundation, Pittsburgh, PA, USA), Robert Z. Orlowski (The University of Texas MD Anderson Cancer Center, Houston, TX, USA), Lorna Patrick (NCI, Rockville, MD, USA), Ellen B. Smith (Texas Oncology, Austin, TX, USA), Mark Stephens (National Patient Advocate Foundation, Washington, DC, USA), Steve G. Waguespack (The University of Texas MD Anderson Cancer Center, Houston, TX, USA), Robert A. Warriner III (patient advocate and Diversified Clinical Services, Spring, TX, USA) and Armin D. Weinberg (Baylor College of Medicine, Houston, TX, USA). Funding support for the meeting was provided by the C. Stratton Hill Colloquium on Pain and Its Relief. The opinions expressed in this article are those of the panellists and do not constitute a policy position of the NIH, National Cancer Institute, US Department of Health and Human Services or the US government. NR 81 TC 31 Z9 32 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD AUG PY 2012 VL 9 IS 8 BP 471 EP 478 DI 10.1038/nrclinonc.2012.99 PG 8 WC Oncology SC Oncology GA 979WH UT WOS:000306852700007 PM 22751283 ER PT J AU Hu, L Bray, MD Geng, YS Kopecko, DJ AF Hu, Lan Bray, Mechelle D. Geng, Yansheng Kopecko, Dennis J. TI Campylobacter jejuni-Mediated Induction of CC and CXC Chemokines and Chemokine Receptors in Human Dendritic Cells SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; GUILLAIN-BARRE-SYNDROME; SIGNAL-TRANSDUCTION; CYTOKINE PRODUCTION; ENDOTHELIAL-CELLS; HUMAN MONOCYTES; INFECTION; TRANSCRIPTION; ACTIVATION AB Campylobacter jejuni is a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms of C. jejuni pathogenesis have not been characterized in detail, host inflammatory responses are thought to be major contributing factors to the resulting typical acute colitis. The intestinal mucosal chemokine response is particularly important in the initial stages of bacterium-induced gut inflammation. Chemokines attract blood phagocytes and lymphocytes to the site of infection and regulate immune cell maturation and the development of localized lymphoid tissues. The production of chemokines by dendritic cells (DCs) following Campylobacter infection has not yet been analyzed. In the current study, we infected human monocyte-derived DCs with C. jejuni to examine the production of key proinflammatory chemokines and chemokine receptors. The chemokines, including CC families (macrophage inflammatory protein 1 alpha [MIP-1 alpha], MIP-1 beta, RANTES) and CXC families (growth-related oncogene alpha [GRO-alpha], IP-10, and monokine induced by gamma interferon [MIG]), were upregulated in Campylobacter-infected DCs. Chemokine receptors CCR6 and CCR7, with roles in DC trafficking, were also induced in Campylobacter-infected DCs. Further, Campylobacter infection stimulated the phosphorylation of P38, P44/42, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein kinases (MAPKs) in DCs. NF-kappa B activation was specifically involved in chemokine induction in DCs infected with C. jejuni. Additionally, STAT3 was significantly increased in Campylobacter-infected DCs compared to that in uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophils, and T lymphocytes during human intestinal infection with Campylobacter. C1 [Hu, Lan; Bray, Mechelle D.; Geng, Yansheng; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM dennis.kopecko@fda.hhs.gov NR 41 TC 6 Z9 7 U1 5 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2012 VL 80 IS 8 BP 2929 EP 2939 DI 10.1128/IAI.00129-12 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977PQ UT WOS:000306677300034 PM 22689814 ER PT J AU Mocca, B Wang, W AF Mocca, Brian Wang, Wei TI Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRUNCATED DENITRIFICATION PATHWAY; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHIAL EPITHELIAL-CELLS; FLOW-CYTOMETRIC DETECTION; IGD-BINDING-PROTEIN; NF-KAPPA-B; MORAXELLA-CATARRHALIS; HEME OXYGENASE-1; PHOSPHATIDYLSERINE EXPRESSION; NASOPHARYNGEAL COLONIZATION AB In mammalian cells, nitric oxide (NO center dot) is an important signal molecule with concentration-dependent and often controversial functions of promoting cell survival and inducing cell death. An inducible nitric oxide synthase (iNOS) in various mammalian cells produces higher levels of NO center dot from L-arginine upon infections to eliminate pathogens. In this study, we reveal novel pathogenic roles of NO center dot generated by bacteria in bacterium-host cell cocultures using Moraxella catarrhalis, a respiratory tract disease-causing bacterium, as a biological producer of NO center dot. We recently demonstrated that M. catarrhalis cells that express the nitrite reductase (AniA protein) can produce NO center dot by reducing nitrite. Our study suggests that, in the presence of pathophysiological levels of nitrite, this opportunistic pathogen hijacks host cell signaling and modulates host gene expression through its ability to produce NO center dot from nitrite. Bacterium-generated NO center dot significantly increases the secretion of tumor necrosis factor alpha (TNF-alpha) and modulates the expression of apoptotic proteins, therefore triggering host cell programmed death partially through TNF-alpha signaling. Furthermore, our study reveals that bacterium-generated NO center dot stalls host cell division and directly results in the death of dividing cells by reducing the levels of an essential regulator of cell division. This study provides unique insight into why NO center dot may exert more severe cytotoxic effects on fast growing cells, providing an important molecular basis for NO center dot-mediated pathogenesis in infections and possible therapeutic applications of NO center dot-releasing molecules in tumorigenesis. This study strongly suggests that bacterium-generated NO center dot can play important pathogenic roles during infections. C1 [Mocca, Brian; Wang, Wei] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. RP Wang, W (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. EM wei02.wang@fda.hhs.gov FU FDA/CBER operation fund FX This study was supported by FDA/CBER operation fund to W. Wang. NR 68 TC 6 Z9 6 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2012 VL 194 IS 15 BP 4059 EP 4068 DI 10.1128/JB.00476-12 PG 10 WC Microbiology SC Microbiology GA 977CP UT WOS:000306634300030 PM 22636782 ER PT J AU Finlin, BS Varma, V Nolen, GT Dube, J Starnes, CP Rasouli, N Kern, PA Peterson, CA AF Finlin, Brian S. Varma, Vijayalakshmi Nolen, Greg T. Dube, John Starnes, Catherine P. Rasouli, Neda Kern, Philip A. Peterson, Charlotte A. TI DHA reduces the atrophy-associated Fn14 protein in differentiated myotubes during coculture with macrophages SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Docosahexaenoic acid; Palmitic acid; Muscle atrophy; Fn14; MuRF-1; MAFbx ID INDUCED INSULIN-RESISTANCE; POLYUNSATURATED FATTY-ACIDS; FOXO TRANSCRIPTION FACTORS; SKELETAL-MUSCLE ATROPHY; MICE; PALMITATE; CANCER; GROWTH; CELLS; PHOSPHORYLATION AB Macrophages are an important component of muscle where they are involved in complex processes such as repair, regeneration and hypertrophy. We recently reported that macrophage numbers increase in the muscle of obese patients, suggesting that muscle-resident macrophages could be involved in the development of muscle insulin resistance that is associated with obesity. Coculture of activated macrophages with human muscle cells impairs insulin signaling and induces atrophy signaling pathways in the human muscle cells; this is exacerbated by the addition of palmitic acid. In this study, we tested the hypothesis that docosahexaenoic acid (DHA), a polyunsaturated fatty acid that has anti-inflammatory properties, would have the opposite effect of palmitic acid on muscle-macrophage cocultures. Surprisingly, DNA did not stimulate insulin signaling in human muscle myotubes that were cocultured with fibroblasts or macrophages. However, DNA inhibited Fn14, the TNF-like weak inducer of apoptosis receptor that increases the expression of the muscle-specific ubiquitin ligase MuRF-1 (muscle ring-finger protein-1). DHA treatment also increased the apparent molecular mass of MuRF-1 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, suggesting that DNA causes MuRF-1 to be posttranslationally modified. In conclusion, these results suggest that DNA may have a beneficial effect on muscle mass in humans by inhibiting the induction of Fn14 by infiltrating macrophages. (C) 2012 Elsevier Inc. All rights reserved. C1 [Peterson, Charlotte A.] Univ Kentucky, Coll Hlth Sci, Lexington, KY 40536 USA. [Finlin, Brian S.; Kern, Philip A.] Univ Kentucky, Dept Med, Div Endocrinol, Lexington, KY 40536 USA. [Finlin, Brian S.; Kern, Philip A.] Univ Kentucky, Barnstable Brown Diabet & Obes Ctr, Lexington, KY 40536 USA. [Varma, Vijayalakshmi; Nolen, Greg T.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Dube, John] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Starnes, Catherine P.] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40536 USA. [Rasouli, Neda] Univ Colorado Denver, Div Endocrinol, Dept Internal Med, Aurora, CO 80045 USA. [Rasouli, Neda] Eastern Colorado Hlth Care Syst, Vet Adm, Denver, CO 80220 USA. RP Peterson, CA (reprint author), Univ Kentucky, Coll Hlth Sci, Lexington, KY 40536 USA. EM cpete4@uky.edu FU Veterans Administration [DK 80327, OK 71349, AG20941] FX This work was supported by the following grants: DK 80327 (P.A.K.), OK 71349 (C.A.P. and P.A.K.), AG20941 (C.A.P.) and a merit grant from the Veterans Administration (N.R). NR 43 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD AUG PY 2012 VL 23 IS 8 BP 885 EP 891 DI 10.1016/j.jnutbio.2011.04.013 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 980FX UT WOS:000306880100005 PM 21852085 ER PT J AU Beal, J Silverman, B Bellant, J Young, TE Klontz, K AF Beal, Jennifer Silverman, Benson Bellant, Jodeanne Young, Thomas E. Klontz, Karl TI Late Onset Necrotizing Enterocolitis in Infants following Use of a Xanthan Gum-Containing Thickening Agent SO JOURNAL OF PEDIATRICS LA English DT Article AB Adverse event reports submitted to the US Food and Drug Administration suggested a possible association between necrotizing enterocolitis and ingestion of a commercial feed thickener by premature infants. Review in 2011 of 22 cases with exposure revealed a distinct illness pattern. (J Pediatr 2012;161:354-6) C1 [Beal, Jennifer; Silverman, Benson; Klontz, Karl] US FDA, Ctr Food Safety & Appl Nutr, Riverdale, MD 20770 USA. [Bellant, Jodeanne] Providence St Vincent Med Ctr, NICU, Portland, OR USA. [Young, Thomas E.] Univ N Carolina, WakeMed Fac Phys Neonatol, Chapel Hill, NC USA. RP Beal, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Univ Stn,CPK2,RM3120,4300 River Rd, Riverdale, MD 20770 USA. EM Jennifer.Beal@fda.hhs.gov NR 10 TC 11 Z9 12 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2012 VL 161 IS 2 BP 354 EP 356 DI 10.1016/j.jpeds.2012.03.054 PG 3 WC Pediatrics SC Pediatrics GA 977VV UT WOS:000306693800037 PM 22575248 ER PT J AU Li, BG Chen, JQ AF Li, Baoguang Chen, Jin-Qiang TI Real-Time PCR Methodology for Selective Detection of Viable Escherichia coli O157:H7 Cells by Targeting Z3276 as a Genetic Marker SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; PROPIDIUM MONOAZIDE; MULTIPLEX PCR; STAPHYLOCOCCUS-AUREUS; QUANTITATIVE PCR; MESSENGER-RNA; DEAD CELLS; EAE GENES; O157-H7; O157H7 AB The goal of this study was to develop a sensitive, specific, and accurate method for the selective detection of viable Escherichia coli O157:H7 cells in foods. A unique open reading frame (ORF), Z3276, was identified as a specific genetic marker for the detection of E. coli O157:H7. We developed a real-time PCR assay with primers and probe targeting ORF Z3276 and confirmed that this assay was sensitive and specific for E. coli O157:H7 strains (n = 298). Using this assay, we can detect amounts of genomic DNA of E. coli O157:H7 as low as a few CFU equivalents. Moreover, we have developed a new propidium monoazide (PMA)-real-time PCR protocol that allows for the clear differentiation of viable from dead cells. In addition, the protocol was adapted to a 96-well plate format for easy and consistent handling of a large number of samples. Amplification of DNA from PMA-treated dead cells was almost completely inhibited, in contrast to the virtually unaffected amplification of DNA from PMA-treated viable cells. With beef spiked simultaneously with 8 x 10(7) dead cells/g and 80 CFU viable cells/g, we were able to selectively detect viable E. coli O157:H7 cells with an 8-h enrichment. In conclusion, this PMA real-time PCR assay offers a sensitive and specific means to selectively detect viable E. coli O157:H7 cells in spiked beef. It also has the potential for high-throughput selective detection of viable E. coli O157:H7 cells in other food matrices and, thus, will have an impact on the accurate microbiological and epidemiological monitoring of food safety and environmental sources. C1 [Li, Baoguang; Chen, Jin-Qiang] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Li, BG (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD USA. EM baoguang.li@fda.hhs.gov FU DHS FX We thank DHS for providing funding. NR 40 TC 16 Z9 17 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2012 VL 78 IS 15 BP 5297 EP 5304 DI 10.1128/AEM.00794-12 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 975ST UT WOS:000306532500032 PM 22635992 ER PT J AU Ponce-Rivas, E Munoz-Marquez, ME Khan, AA AF Ponce-Rivas, Elizabeth Munoz-Marquez, Maria-Enriqueta Khan, Ashraf A. TI Identification and Molecular Characterization of Class 1 Integrons in Multiresistant Escherichia coli Isolates from Poultry Litter SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; IMPORTED SEAFOOD; GENE CASSETTES; PREVALENCE AB This study describes the prevalence of arrays of class 1 integron cassettes and Qnr determinants (A, B, and S) in 19 fluoroquinolone-resistant Escherichia coli isolates from chicken litter. qnrS and qnrA were the predominant genes in these fluoroquinolone-resistant isolates, and an uncommon array of aacA4-catB3-dfrA1 gene cassettes from a class1 integron was found. Additionally, aadA1 and dfrA1 gene cassettes, encoding resistance to streptomycin and trimethoprim, constituted the most common genes identified and was located on megaplasmids as well on the chromosome. Antibiotic resistance, pulsed-field gel electrophoresis (PFGE), and plasmid data suggest a genetically diverse origin of poultry E. coli isolates. C1 [Munoz-Marquez, Maria-Enriqueta] Univ Autonoma Baja California, Fac Ciencias Quim & Ingn, Tijuana, Mexico. [Khan, Ashraf A.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM eponce@cicese.mx RI Khan, Ashraf/E-8133-2013; Ponce-Rivas, Elizabeth/K-3278-2016 OI Ponce-Rivas, Elizabeth/0000-0002-2842-7300 FU U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported in part by an appointment to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 20 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2012 VL 78 IS 15 BP 5444 EP 5447 DI 10.1128/AEM.00660-12 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 975ST UT WOS:000306532500052 PM 22635994 ER PT J AU Williams, JB Peterson, ED Brennan, JM Sedrakyan, A Tavris, D Alexander, JH Lopes, RD Dokholyan, RS Zhao, Y O'Brien, SM Michler, RE Thourani, VH Edwards, FH Duggirala, H Gross, T Marinac-Dabic, D Smith, PK AF Williams, Judson B. Peterson, Eric D. Brennan, J. Matthew Sedrakyan, Art Tavris, Dale Alexander, John H. Lopes, Renato D. Dokholyan, Rachel S. Zhao, Yue O'Brien, Sean M. Michler, Robert E. Thourani, Vinod H. Edwards, Fred H. Duggirala, Hesha Gross, Thomas Marinac-Dabic, Danica Smith, Peter K. TI Association Between Endoscopic vs Open Vein-Graft Harvesting and Mortality, Wound Complications, and Cardiovascular Events in Patients Undergoing CABG Surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROSPECTIVE RANDOMIZED-TRIAL; ARTERY-BYPASS-SURGERY; PROPORTIONAL HAZARDS MODEL; SAPHENOUS-VEIN; PROPENSITY-SCORE; SOCIETY; DISCRETE; MEDICARE; SURVIVAL; DATABASE AB Context The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question. Objective To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States. Design, Setting, and Patients An observational study of 235 394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008. Main Outcome Measures All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization. Results Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12 429 events] vs 13.4% [13 096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18 419 events] vs 19.7% [19 232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122 899 events] vs 3.6% [4047/112 495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001). Conclusion Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality. C1 [Williams, Judson B.; Smith, Peter K.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Williams, Judson B.; Peterson, Eric D.; Brennan, J. Matthew; Alexander, John H.; Lopes, Renato D.; Dokholyan, Rachel S.; Zhao, Yue; O'Brien, Sean M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Peterson, Eric D.; Brennan, J. Matthew; Alexander, John H.; Lopes, Renato D.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Sedrakyan, Art] Weill Cornell Med Coll, New York, NY USA. [Tavris, Dale; Duggirala, Hesha; Marinac-Dabic, Danica] US FDA, Silver Spring, MD USA. [Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiovasc & Thorac Surg, New York, NY USA. [Thourani, Vinod H.] Emory Univ, Sch Med, Joseph B Whitehead Dept Surg, Atlanta, GA 30322 USA. [Edwards, Fred H.] Univ Florida, Shands Hosp, Jacksonville, FL USA. RP Smith, PK (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 3442, Durham, NC 27710 USA. EM smith058@mc.duke.edu RI O'Brien, Sean/H-6268-2013 FU US Food and Drug Administration through Society of Thoracic Surgeons; National Institutes of Health [T32-HL069749]; National Heart, Lung, and Blood Institute [U01-HL088953]; Eli Lilly; Janssen Pharmaceuticals; Society of Thoracic Surgeons; AstraZeneca; Boehringer-Ingelheim; Daiichi Sankyo FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Peterson reported receiving grants from Eli Lilly, Janssen Pharmaceuticals, and Society of Thoracic Surgeons. Dr Alexander reported being a co-investigator for the Duke Core Clinical Center in the National Institutes of Health CT Surgery Network and being on the Veterans Affairs Cooperative Studies Program Protocol Review Committee. Dr Lopes reported being a consultant for and board membership of Boehringer-Ingelheim and Bristol-Myers Squibb, and receiving grants from AstraZeneca, Boehringer-Ingelheim, and Daiichi Sankyo. Dr Thourani reported receiving honoraria for lectures and being on the advisory board of Maquet Medical. Dr Smith reported receiving honoraria from Society of Thoracic Surgeons. No other authors reported any financial disclosures.; This study was funded by the US Food and Drug Administration through a contract with the Society of Thoracic Surgeons. Dr Williams is supported in part by training grant T32-HL069749 from the National Institutes of Health and is a Cardiothoracic Surgical Trials Network Scholar supported by grant U01-HL088953 from the National Heart, Lung, and Blood Institute, which also supports Drs Smith, Alexander, Thourani, and Michler as investigators of the Cardiothoracic Surgical Trials Network. NR 39 TC 31 Z9 37 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2012 VL 308 IS 5 BP 475 EP 484 DI 10.1001/jama.2012.8363 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 981DQ UT WOS:000306947400025 PM 22851114 ER PT J AU Fang, J Jadhav, PR AF Fang, Jing Jadhav, Pravin R. TI From in vitro EC50 to in vivo dose-response for antiretrovirals using an HIV disease model. Part I: A framework SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE HIV; EC50; IC50; Pharmacokinetics; Pharmacodynamics; Viral dynamics; Dose selection; Model based drug development ID HEALTHY-VOLUNTEERS; ANTIVIRAL ACTIVITY; INFECTED PATIENTS; PHARMACOKINETICS; MARAVIROC; THERAPY; TENOFOVIR; DRUG; ZIDOVUDINE; SAFETY AB Plasma drug concentrations and human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) data from short-term monotherapy trials in antiretroviral (ARV) na < ve/experienced HIV-infected patients for one drug (i.e., lead case, a representative drug for a given class) from four distinct classes of ARV drugs [non-nucleoside reverse transcriptase inhibitors (NNRTIs); nucleotide reverse transcriptase inhibitors (NtRTIs); co-receptor antagonists (CRAs); and integrase strand transfer inhibitors (INSTIs)] were obtained. For each drug (the lead case; for example, etravirine for NNRTIs), the pharmacokinetic (PK)-pharmacodynamic (PD) disease model was used to estimate the in vivo IC50 value based on the relationship between plasma drug concentrations and HIV-1 RNA decline. The disease model was a mechanistic viral dynamic model with the addition of a transduction delay for HIV-1 RNA decay. The model characterized the observed time-course of plasma drug concentrations and HIV-1 RNA in each lead case trial reasonably well. The estimated viral dynamic parameters were in good agreement with the literature values. The scaling factor (SF) was calculated as a ratio using the estimated in vivo IC50 value and protein binding corrected EC50 value for the lead case. For NNRTIs, the calculated SF was found to be 9.47 based on etravirine analysis. Using the same approach, the SF for CRAs (maraviroc), INSTIs (GSK1349572), and NtRTIs (tenofovir) were 4.35, 1.63, and 0.27. The SF is reflective of the uncertainty between in vitro measurement of drug potency and the specific model-based drug potency parameter (IC50). The use of SF and PK-PD disease models can be a valuable tool to predict dose-response of NMEs and support rational dose selection for monotherapy trials. C1 [Fang, Jing; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Fang, Jing] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. RP Jadhav, PR (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM pravinj@gmail.com NR 27 TC 4 Z9 5 U1 2 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD AUG PY 2012 VL 39 IS 4 BP 357 EP 368 DI 10.1007/s10928-012-9255-3 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 976HJ UT WOS:000306571300004 PM 22736302 ER PT J AU Fang, J Jadhav, PR AF Fang, Jing Jadhav, Pravin R. TI From in vitro EC50 to in vivo dose-response for antiretrovirals using an HIV disease model. Part II: Application to drug development SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE HIV; EC50; IC50; Pharmacokinetics; Pharmacodynamics; Comparator modeling; Rational dose selection; Model-based drug development ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITOR; ANTIVIRAL ACTIVITY; CCR5 ANTAGONIST; INFECTED ADULTS; TREATMENT-NAIVE; POTENT ACTIVITY; PHARMACOKINETICS; SAFETY; INTEGRASE AB The purpose of this research was to qualify a previously derived quantitative model-based framework that proposed an in vitro-in vivo linkage to predict the dose-response relationship of an antiretroviral (ARV) new molecular entity (NME) in a monotherapy trial. Human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) data from monotherapy trials in ARV na < ve/experienced HIV-infected subjects for eight drugs (i.e. application case, a representative drug for a given class used for external validation) across four distinct classes of ARV agents (co-receptor antagonists; non-nucleoside reverse transcriptase inhibitors; nucleotide reverse transcriptase inhibitors; and integrase strand transfer inhibitors) were obtained. Using the in vitro EC50 (protein binding corrected) and a class-specific scaling factor (SF), the in vivo IC50 was calculated for each drug. The integrated pharmacokinetic (PK)-pharmacodynamic (PD) disease model used the predicted in vivo IC50 to simulate the HIV-1 RNA-time profiles for dosing regimens that were studied in the monotherapy trials for each drug. The simulated HIV-1 RNA time profiles were then compared to the observed data. The simulated HIV-1 RNA-time profiles matched well with those observed in the monotherapy trials except for one drug in the INSTIs class. The derived SF represents a useful in vitro-in vivo linkage to predict the dose-response relationship for a NME using in vitro data. The mechanistic PK-PD disease model-based framework is useful to assist the dose selection for monotherapy trials and comparator modeling approaches. C1 [Fang, Jing; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Fang, Jing] SUNY Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. RP Jadhav, PR (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM pravinj@gmail.com NR 37 TC 2 Z9 3 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD AUG PY 2012 VL 39 IS 4 BP 369 EP 381 DI 10.1007/s10928-012-9257-1 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 976HJ UT WOS:000306571300005 PM 22773164 ER PT J AU Mondal, AK Das, SK Varma, V Nolen, GT McGehee, RE Elbein, SC Wei, JY Ranganathan, G AF Mondal, Ashis K. Das, Swapan K. Varma, Vijayalakshmi Nolen, Greg T. McGehee, Robert E. Elbein, Steven C. Wei, Jeanne Y. Ranganathan, Gouri TI Effect of Endoplasmic Reticulum Stress on Inflammation and Adiponectin Regulation in Human Adipocytes SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID NF-KAPPA-B; UNFOLDED PROTEIN RESPONSE; ADIPOSE-TISSUE; INSULIN-RESISTANCE; DOWN-REGULATION; OBESITY; EXPRESSION; CELLS; DYSREGULATION; PIOGLITAZONE AB The endoplasmic reticulum (ER) of adipocytes plays a major role in the assembly and secretion of adipokines. The levels of serum adiponectin, secreted by adipocytes, are decreased in insulin resistance, diabetes, and obesity. The role of ER stress in downregulating adiponectin levels has been demonstrated in mouse models of obesity. Studies examining human adipose tissue have indicated that there is an increase in the ER stress transcript HSPA5 with increased body mass index (BMI). However, it is not established whether ER stress results in changes in adiponectin levels or multimerization in human adipocytes. We examined whether the induction of ER stress using tunicamycin, thapsigargin, or palmitate alters the messenger RNA (mRNA) and protein expression of adiponectin and the mRNA expression of chaperones ERP44 and ERO1 in adult-derived human adipocyte stem (ADHAS) cells. ER stress was measured using key indicators of ER stress-HSPA5, ERN1, CHOP, and GADD34, as well as changes in eIF2 alpha phosphorylation. Because ER stress is suggested to be the proximal cause of inflammation in adipocytes, we further examined the change in inflammatory status by quantitating the change in I kappa beta-alpha protein following the induction of ER stress. Our studies indicate that: (1) ER stress markers were increased to a higher degree using tunicamycin or thapsigargin compared to palmitate; (2) ER stress significantly decreased adiponectin mRNA in response to tunicamycin and thapsigargin, but palmitate did not decrease adiponectin mRNA levels. In all three instances, the induction of ER stress was accompanied by a decrease in adiponectin protein as well as adiponectin multimerization. All three inducers of ER stress increased tumor necrosis factor-alpha (TNF-alpha) mRNA and decreased I kappa beta-alpha protein in adipocytes. The data suggest that ER stress modifies adiponectin secretion and induces inflammation in ADHAS cells. C1 [Wei, Jeanne Y.; Ranganathan, Gouri] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72227 USA. [Wei, Jeanne Y.; Ranganathan, Gouri] Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72227 USA. [McGehee, Robert E.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72227 USA. [Mondal, Ashis K.; Das, Swapan K.; Elbein, Steven C.] Wake Forest Sch Med, Winston Salem, NC USA. [Varma, Vijayalakshmi; Nolen, Greg T.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Ranganathan, G (reprint author), Univ Arkansas Med Sci, Dept Geriatr, 4301 W 7th St, Little Rock, AR 72227 USA. EM ranganathangouri@uams.edu FU Veterans Administration; National Institutes of Health (NIH) grants [UL1 RR029884, R01DK71346, R01DK71349]; Wake Forest School of Medicine development funds FX This study was supported by Merit Review Grants (G.R., S.C.E.) from the Veterans Administration, Wake Forest School of Medicine development funds (S.C.E., S.K.D.), and National Institutes of Health (NIH) grants UL1 RR029884, R01DK71346, and R01DK71349 (R.E.M.). This manuscript is dedicated to the memory of late Dr. Steven C. Elbein. NR 34 TC 14 Z9 18 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD AUG PY 2012 VL 10 IS 4 BP 297 EP 306 DI 10.1089/met.2012.0002 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 976OR UT WOS:000306594700010 PM 22545589 ER PT J AU Freed, M AF Freed, Melanie TI Effect of protocol parameters on contrast agent washout curve separability in breast dynamic contrast enhanced MRI: A simulation study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE breast DCE-MRI; optimization; protocol; ROC ID QUANTITATIVE-EVALUATION; TEMPORAL RESOLUTION; DIAGNOSTIC-ACCURACY; GENETIC RISK; CANCER; MAMMOGRAPHY; LESIONS; WOMEN; MULTICENTER; PHANTOM AB Variability in diagnostic performance of breast dynamic contrast-enhanced MRI has highlighted the need for improved standardization. While guidance exists on some aspects of the technique, currently, there is no standardized method for selecting repetition time and flip angle, which are important determinants of image contrast. This study develops a theoretical framework for quantitative optimization of temporal aspects of dynamic contrast-enhanced MRI based on area under the receiver operating curve. Optimizations in simulation demonstrate the potential for increases in area under the receiver operating characteristic curve by up to 0.20 and specificity at a sensitivity of 90% by up to 19%, depending on the protocol. These results suggest that careful selection of repetition time and flip angle can improve diagnostic performance and identify these quantities as potentially important parameters for future standardization. Magn Reson Med, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Freed, Melanie] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. RP Freed, M (reprint author), Pontificia Univ Catolica Chile, Fac Fis, Ave Vicuna Mackenna 4860, Santiago 7820436, Chile. EM freed@fis.puc.cl FU FDA's Office of Womens Health; Center for Devices and Radiological Health FX Grant sponsors: FDA's Office of Womens Health and an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration NR 34 TC 3 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2012 VL 68 IS 2 BP 516 EP 522 DI 10.1002/mrm.23234 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 972YZ UT WOS:000306318900022 PM 22144368 ER PT J AU Tonry, JH McNichol, BA Ramarao, N Chertow, DS Kim, KS Stibitz, S Schneewind, O Kashanchi, F Bailey, CL Popov, S Chung, MC AF Tonry, Jessica H. McNichol, Beth A. Ramarao, Nalini Chertow, Daniel S. Kim, Kwang Sik Stibitz, Scott Schneewind, Olaf Kashanchi, Fatah Bailey, Charles L. Popov, Serguei Chung, Myung-Chul TI Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells SO CELLULAR MICROBIOLOGY LA English DT Article ID MURINE MACROPHAGES; S-LAYER; SPORES; CAPSULE; GENE; THURINGIENSIS; VIRULENCE; PLASMID; CEREUS; ESCAPE AB To achieve widespread dissemination in the host, Bacillus anthracis cells regulate their attachment to host endothelium during infection. Previous studies identified BslA (Bacillus anthracisS-layer Protein A), a virulence factor of B. anthracis, as necessary and sufficient for adhesion of vegetative cells to human endothelial cells. While some factors have been identified, bacteria-specific contributions to BslA mediated adhesion remain unclear. Using the attenuated vaccine Sterne 7702 strain of B. anthracis, we tested the hypothesis that InhA (immune inhibitor A), a B. anthracis protease, regulates BslA levels affecting the bacteria's ability to bind to endothelium. To test this, a combination of inhA mutant and complementation analysis in adhesion and invasion assays, Western blot and InhA inhibitor assays were employed. Results show InhA downregulates BslA activity reducing B. anthracis adhesion and invasion in human brain endothelial cells. BslA protein levels in ?inhA bacteria were significantly higher than wild-type and complemented strains showing InhA levels and BslA expression are inversely related. BslA was sensitive to purified InhA degradation in a concentration- and time-dependent manner. Taken together these data support the role of InhA regulation of BslA-mediated vegetative cell adhesion and invasion. C1 [Tonry, Jessica H.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei; Chung, Myung-Chul] George Mason Univ, Dept Biosci, Manassas, VA 20110 USA. [Tonry, Jessica H.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei; Chung, Myung-Chul] George Mason Univ, Biomed Res Lab, Manassas, VA 20110 USA. [McNichol, Beth A.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Ramarao, Nalini] INRA Micalis UMR Microbienne & Environm 1319, F-78285 La Miniere, Guyancourt, France. [Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kim, Kwang Sik] Johns Hopkins Univ, Div Pediat Infect Dis, Sch Med, Baltimore, MD 21287 USA. [Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA. RP Chung, MC (reprint author), George Mason Univ, Dept Biosci, 10650 Pyramid Pl, Manassas, VA 20110 USA. EM mchung3@gmu.edu FU U.S. Department of Energy [DE-FC52-FC04NA25455] FX We thank members of our laboratory for critical comments and discussion. We thank David Derby, a George Mason University aspiring scientist summer internship student (ASSIP) for skilled technical assistance. This work was supported by the U.S. Department of Energy Grant DE-FC52-FC04NA25455. NR 30 TC 9 Z9 10 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD AUG PY 2012 VL 14 IS 8 BP 1219 EP 1230 DI 10.1111/j.1462-5822.2012.01791.x PG 12 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 974BO UT WOS:000306405000007 PM 22452315 ER PT J AU Yang, YC Tan, YM Blount, B Murray, C Egan, S Bolger, M Clewell, H AF Yang, Yuching Tan, Yu-Mei Blount, Benjamin Murray, Clarence Egan, Sara Bolger, Michael Clewell, Harvey TI Using a physiologically based pharmacokinetic model to link urinary biomarker concentrations to dietary exposure of perchlorate SO CHEMOSPHERE LA English DT Article DE Perchlorate; Biomarker; Physiologically based pharmacokinetic modeling; Dietary exposure ID THYROID-STIMULATING-HORMONE; UNITED-STATES; DRINKING-WATER; IODIDE UPTAKE; BREAST-MILK; INHIBITION; WOMEN; EXCRETION; KINETICS; RAT AB Exposure to perchlorate is widespread in the United States and many studies have attempted to character the perchlorate exposure by estimating the average daily intakes of perchlorate. These approaches provided population-based estimates, but did not provide individual-level exposure estimates. Until recently, exposure activity database such as CSFII, TDS and NHANES become available and provide opportunities to evaluate the individual-level exposure to chemical using exposure surveillance dataset. In this study, we use perchlorate as an example to investigate the usefulness of urinary biomarker data for predicting exposures at the individual level. Specifically, two analyses were conducted: (1) using data from a controlled human study to examine the ability of a physiologically based pharmacokinetic (PBPK) model to predict perchlorate concentrations in single-spot and cumulative urine samples; and (2) using biomarker data from a population-based study and a PBPK model to demonstrate the challenges in linking urinary biomarker concentrations to intake doses for individuals. Results showed that the modeling approach was able to characterize the distribution of biomarker concentrations at the population level, but predicting the exposure-biomarker relationship for individuals was much more difficult. The type of information needed to reduce the uncertainty in estimating intake doses, for individuals, based on biomarker measurements is discussed. Published by Elsevier Ltd. C1 [Tan, Yu-Mei] US EPA, Res Triangle Pk, NC 27711 USA. [Yang, Yuching; Clewell, Harvey] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Blount, Benjamin] Ctr Dis Control & Prevent, Atlanta, GA USA. [Murray, Clarence; Egan, Sara; Bolger, Michael] US FDA, College Pk, MD USA. RP Tan, YM (reprint author), US EPA, Res Triangle Pk, NC 27711 USA. EM yyang@thehamner.org; tan.cecilia@epa.gov; bkb3@cdc.gov; Clarence.murray@fda.hhs.gov; Katie.egan@fda.hhs.gov; Philip.bolger@cfsan.fda.gov; hclewell@thehamner.org NR 45 TC 3 Z9 3 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD AUG PY 2012 VL 88 IS 8 BP 1019 EP 1027 DI 10.1016/j.chemosphere.2012.03.074 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 970VQ UT WOS:000306160800017 PM 22520969 ER PT J AU Zhao, JQ Tang, SX Ragupathy, V Gaddam, D Wang, X Zhang, PH Nyambi, PN Hewlett, I AF Zhao, Jiangqin Tang, Shixing Ragupathy, Viswanath Gaddam, Durga Wang, Xue Zhang, Panhe Nyambi, Phillipe N. Hewlett, Indira TI CRF22_01A1 is Involved in the Emergence of New HIV-1 Recombinants in Cameroon SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; recombinant; genetic diversity; phylogenetic analysis; CRF22_01A1; CRF02_AG; Cameroon ID GROUP-O INFECTIONS; TYPE-1 GROUP-M; GENETIC DIVERSITY; RESISTANCE MUTATIONS; BLOOD-DONORS; SAUDI-ARABIA; SUBTYPE-A; IDENTIFICATION; FORM; LINEAGES AB Cameroon is a West African country where high genetic diversity of HIV-1 has been reported. The predominant CRF02_AG is involved in the emergence of more complex intersubtype recombinants. In this study, we sequenced the full-length genome of a novel unique recombinant form of HIV-1, 02CAMLT04 isolated in blood donors in urban Cameroon. Phylogenetic tree and bootscan analysis showed that 02CAMLT04 was complex and seemed to be a secondary recombinant derived from CRF02_AG and CRF22_01A1. The genomic composition of 02CAMLT04 strain showed that it is composed of 3 segments; 24% of the genome is classified as CRF02_AG, spanning most of the envelope gene. The remaining 76% of the genome is classified as CRF22_01A1. In addition, the sequence analysis of 13 full-length sequences from HIV-1-positive specimens received from Cameroon between 2002 and 2010 indicated that 5 specimens are pure CRF22_01A1 viruses, and 6 others have homology with CRF22_01A1 sequences in either gag, pol, or env region, whereas 6% of strains contain portions of CRF22_01A1. Further study demonstrated that CRF22_01A1 is a primary prevalence strain co-circulating in Cameroon and is involved in complex intersubtype recombination events with subtypes (D or F), subsubtypes (A1 or F2), and CRFs (CRF01_AE or CRF02_AG). Our studies show that novel recombinants between CRF22_01A1 and other clades and recombinant forms may be emerging in Cameroon that could contribute to the future global diversity of HIV-1 in this region and worldwide. C1 [Zhao, Jiangqin; Tang, Shixing; Ragupathy, Viswanath; Gaddam, Durga; Wang, Xue; Zhang, Panhe; Hewlett, Indira] US FDA, Mol Virol Lab, CBER, Bethesda, MD 20892 USA. [Nyambi, Phillipe N.] NYU, Sch Med, Dept Pathol, New York, NY USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, CBER, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM indira.hewlett@fda.hhs.gov FU National Heart, Lung, and Blood Institute; IAA-National Heart, Lung, and Blood Inter-Agency [BY1-HB-5026-01] FX Supported by The National Heart, Lung, and Blood Institute for funding part of this work through an IAA-National Heart, Lung, and Blood Inter-Agency Agreement BY1-HB-5026-01. NR 29 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2012 VL 60 IS 4 BP 344 EP 350 DI 10.1097/QAI.0b013e318258c7e3 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 971YF UT WOS:000306242300008 PM 22549382 ER PT J AU Cheng, GC Chen, DT Chen, JJ Soong, SJ Lamartiniere, C Barnes, S AF Cheng, Gary C. Chen, Dung-Tsa Chen, James J. Soong, Seng-jaw Lamartiniere, Coral Barnes, Stephen TI A chain reaction approach to modelling gene pathways SO TRANSLATIONAL CANCER RESEARCH LA English DT Article DE Chain reaction; gene expression change; estrogen synthesis pathway; nutrient diets AB Background: Of great interest in cancer prevention is how nutrient components affect gene pathways associated with the physiological events of puberty. Nutrient-gene interactions may cause changes in breast or prostate cells and, therefore, may result in cancer risk later in life. Analysis of gene pathways can lead to insights about nutrient-gene interactions and the development of more effective prevention approaches to reduce cancer risk. To date, researchers have relied heavily upon experimental assays (such as microarray analysis, etc.) to identify genes and their associated pathways that are affected by nutrient and diets. However, the vast number of genes and combinations of gene pathways, coupled with the expense of the experimental analyses, has delayed the progress of gene-pathway research. The development of an analytical approach based on available test data could greatly benefit the evaluation of gene pathways, and thus advance the study of nutrient-gene interactions in cancer prevention. In the present study, we have proposed a chain reaction model to simulate gene pathways, in which the gene expression changes through the pathway are represented by the species undergoing a set of chemical reactions. We have also developed a numerical tool to solve for the species changes due to the chain reactions over time. Through this approach we can examine the impact of nutrient-containing diets on the gene pathway; moreover, transformation of genes over time with a nutrient treatment can be observed numerically, which is very difficult to achieve experimentally. We apply this approach to microarray analysis data from an experiment which involved the effects of three polyphenols (nutrient treatments), epigallo-catechin-3-O-gallate (EGCG), genistein, and resveratrol, in a study of nutrient-gene interaction in the estrogen synthesis pathway during puberty. Results: In this preliminary study, the estrogen synthesis pathway was simulated by a chain reaction model. By applying it to microarray data, the chain reaction model computed a set of reaction rates to examine the effects of three polyphenols (EGCG, genistein, and resveratrol) on gene expression in this pathway during puberty. We first performed statistical analysis to test the time factor on the estrogen synthesis pathway. Global tests were used to evaluate an overall gene expression change during puberty for each experimental group. Then, a chain reaction model was employed to simulate the estrogen synthesis pathway. Specifically, the model computed the reaction rates in a set of ordinary differential equations to describe interactions between genes in the pathway (A reaction rate K of A to B represents gene A will induce gene B per unit at a rate of K; we give details in the "method" section). Since disparate changes of gene expression may cause numerical error problems in solving these differential equations, we used an implicit scheme to address this issue. We first applied the chain reaction model to obtain the reaction rates for the control group. A sensitivity study was conducted to evaluate how well the model fits to the control group data at Day 50. Results showed a small bias and mean square error. These observations indicated the model is robust to low random noises and has a good fit for the control group. Then the chain reaction model derived from the control group data was used to predict gene expression at Day 50 for the three polyphenol groups. If these nutrients affect the estrogen synthesis pathways during puberty, we expect discrepancy between observed and expected expressions. Results indicated some genes had large differences in the EGCG (e.g., Hsd3b and Sts) and the resveratrol (e.g., Hsd3b and Hrmt12) groups. Conclusions: In the present study, we have presented (I) experimental studies of the effect of nutrient diets on the gene expression changes in a selected estrogen synthesis pathway. This experiment is valuable because it allows us to examine how the nutrient-containing diets regulate gene expression in the estrogen synthesis pathway during puberty; (II) global tests to assess an overall association of this particular pathway with time factor by utilizing generalized linear models to analyze microarray data; and (III) a chain reaction model to simulate the pathway. This is a novel application because we are able to translate the gene pathway into the chemical reactions in which each reaction channel describes gene-gene relationship in the pathway. In the chain reaction model, the implicit scheme is employed to efficiently solve the differential equations. Data analysis results show the proposed model is capable of predicting gene expression changes and demonstrating the effect of nutrient-containing diets on gene expression changes in the pathway. One of the objectives of this study is to explore and develop a numerical approach for simulating the gene expression change so that it can be applied and calibrated when the data of more time slices are available, and thus can be used to interpolate the expression change at a desired time point without conducting expensive experiments for a large amount of time points. Hence, we are not claiming this is either essential or the most efficient way for simulating this problem, rather a mathematical/numerical approach that can model the expression change of a large set of genes of a complex pathway. In addition, we understand the limitation of this experiment and realize that it is still far from being a complete model of predicting nutrient-gene interactions. The reason is that in the present model, the reaction rates were estimated based on available data at two time points; hence, the gene expression change is dependent upon the reaction rates and a linear function of the gene expressions. More data sets containing gene expression at various time slices are needed in order to improve the present model so that a non-linear variation of gene expression changes at different time can be predicted. C1 [Cheng, Gary C.] Univ Alabama Birmingham, Dept Mech Engn, Birmingham, AL 35294 USA. [Chen, Dung-Tsa] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, 12902 Magnolia Dr, Tampa, FL 33612 USA. [Chen, James J.] Food & Drug Adm, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. [Soong, Seng-jaw] Univ Alabama Birmingham, Ctr Comprehens Canc, Biostat & Bioinformat Unit, Birmingham, AL 35294 USA. [Lamartiniere, Coral] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. [Barnes, Stephen] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. RP Chen, DT (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM dung-tsa.chen@moffitt.org FU National Cancer Institute [5P30 CA-13148, 1P50 CA89019, 1U54 CA100949] FX This work was supported by grants from the National Cancer Institute (5P30 CA-13148, 1P50 CA89019, and 1U54 CA100949). We thank Mrs. Connie Pitts for secretarial assistance. NR 28 TC 4 Z9 4 U1 0 U2 1 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD AUG PY 2012 VL 1 IS 2 BP 61 EP 73 DI 10.3978/j.issn.2218-676X.2012.05.06 PG 13 WC Oncology SC Oncology GA V42VZ UT WOS:000209642600002 PM 22943042 ER PT J AU Chancey, C Winkelman, V Foley, JB Silberstein, E Teixeira-Carvalho, A Taylor, DR Rios, M AF Chancey, C. Winkelman, V. Foley, J. B. Silberstein, E. Teixeira-Carvalho, A. Taylor, D. R. Rios, M. TI Distribution of hepatitis C virus in circulating blood components from blood donors SO VOX SANGUINIS LA English DT Article DE blood donors; detection; erythrocytes; hepatitis C virus; plasma ID WHOLE-BLOOD; HCV RNA; MONONUCLEAR-CELLS; NON-A; PLASMA; PLATELETS; VIREMIA; ASSAY; QUANTITATION; INFECTIONS AB Background and Objectives Current nucleic acid tests (NAT) for blood donor screening use plasma as the test sample and, consequently, cannot detect virions bound to blood cells of infected donors. Hepatitis C virus (HCV) RNA and infectious virions have been detected in association with the cellular components of blood of patients with active liver disease; however, studies comparing HCV viral loads in whole blood and plasma have generated contradictory results. The aim of this study was to investigate the distribution of HCV in different compartments of the peripheral blood from HCV-infected blood donors, which may differ from that observed in patients with HCV-associated liver disease. Materials and Methods Hepatitis C virus-positive donor specimens were identified by NAT and antibody testing. HCV RNA was extracted from samples of whole blood and their corresponding components (RBC and plasma). Viral RNA was quantified by real-time qRT-PCR. Results Hepatitis C virus was present in all blood components from infected donors from which RNA could be amplified. For the majority of samples, plasma (34/46) had the highest detectable concentration of HCV RNA, and RBC (37/46) had the lowest. Specimens with negative NAT and positive antibody assays also produced qRT-PCR negative results. Conclusion These results indicate that including the RBC fraction in the tested sample will not increase assay sensitivity. Although 10% of the specimens had a higher viral load in whole blood, there was no significant overall increase in sensitivity to justify changes in the specimen format. Thus, plasma specimens are well suited for blood donor screening for HCV. C1 [Chancey, C.; Foley, J. B.; Silberstein, E.; Teixeira-Carvalho, A.; Taylor, D. R.; Rios, M.] US FDA, DETTD, OBRR, CBER, Bethesda, MD 20014 USA. [Winkelman, V.] Creat Testing Solut, MDL Dept, Tempe, AZ USA. [Teixeira-Carvalho, A.] Fundacao Oswaldo Cruz, CPqRR, Belo Horizonte, MG, Brazil. RP Rios, M (reprint author), 8800 Rockville Pike,Bldg 29,Room 131,HFM 315, Bethesda, MD 20892 USA. EM maria.rios@fda.hhs.gov FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil; U.S. Food and Drug Administration; Food and Drug Administration, Center for Biologics Evaluation and Research FX The authors would like to acknowledge Pradip Akolkar for critical reading of this manuscript. A.T.C. thanks Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil, and U.S. Food and Drug Administration for fellowships.; This project was internally funded by the Food and Drug Administration, Center for Biologics Evaluation and Research. NR 26 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2012 VL 103 IS 2 BP 99 EP 106 DI 10.1111/j.1423-0410.2012.01598.x PG 8 WC Hematology SC Hematology GA 973MS UT WOS:000306364800002 PM 22404907 ER PT J AU Mahmood, I Goteti, K AF Mahmood, Iftekhar Goteti, Kosalaram TI Prediction of drug concentration-time data in humans from animals: a comparison of three methods SO XENOBIOTICA LA English DT Article DE Allometry; concentrations-time; single- and multi-compartment system; pharmacokinetics ID INTERSPECIES CORRELATION; RHESUS-MONKEYS; SCALE-UP; PHARMACOKINETICS; PLASMA; CIPROFLOXACIN; CLEARANCE; DOGS; RATS; ERYTHROMYCIN AB 1. The main objective of this work is to evaluate three methods to predict concentration-time data of drugs in humans in a multi-compartment system using animal pharmacokinetic parameters following intravenous administration. The prediction of concentration-time data in humans in a multi-compartment system was based on two proposed methods of Mordenti. The third method was based on the assumption that all drugs follow a single-compartment system. 2. Ten drugs from the literature were chosen that were described by two-compartment model in both human and animals. Two-compartment model parameters (CL, V-c, V-ss, V-beta, alpha, A, beta and B) of at least 3 animals were scaled to humans and then were used to predict plasma concentrations-time data in humans. Allometrically scaled pharmacokinetic parameters from animals were also used to predict human profile using one-compartment model as a comparison. 3. The results indicated that in a multi-compartment system, application of pharmacokinetic constants provided better prediction of concentration-time data in humans than the assumption that all drugs follow a single-compartment model. Both the proposed methods of Mordenti provided almost similar concentration-time profiles for most of the drugs. For some drugs, predicted alpha values were substantially higher than the observed values. This prediction error in alpha resulted in under-prediction of drug concentrations in distribution phase. In order to reduce the prediction error in alpha, Waijma's method for the prediction of alpha was modified which resulted in an improved prediction of concentration-time data in humans. Overall, Mordenti's proposed 2 methods and where necessary by modifying Waijma's method for the prediction of alpha can be used for reasonably accurate prediction of concentration-time data of drugs in humans. C1 [Mahmood, Iftekhar] US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Goteti, Kosalaram] MedImmune LLC, Clin Pharmacol, Gaithersburg, MD USA. [Goteti, Kosalaram] MedImmune LLC, DMPK, Gaithersburg, MD USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 29 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 EI 1366-5928 J9 XENOBIOTICA JI Xenobiotica PD AUG PY 2012 VL 42 IS 8 BP 756 EP 765 DI 10.3109/00498254.2012.660210 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 971HG UT WOS:000306193800006 PM 22360447 ER PT J AU Ji, P Chowdhury, BA Yim, S Sahajwalla, CG AF Ji, Ping Chowdhury, Badrul A. Yim, Sarah Sahajwalla, Chandrahas G. TI Dosing regimen determination for juvenile idiopathic arthritis: A review of studies during drug development SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE juvenile idiopathic arthritis; clinical pharmacology; pediatric; clinical trials; pharmacokinetics; population pharmacokinetics; clinical pharmacokinetics; simulations ID PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; METHOTREXATE; PHARMACOKINETICS; CHILDREN; NAPROXEN; THERAPY; SULFASALAZINE; ETANERCEPT AB Juvenile idiopathic arthritis (JIA) is the most common childhood arthritis. In the past 10-15 years, the medical treatment options of JIA have greatly evolved and expanded due to a better understanding of the disease and the application of biologic agents. Regulations pertinent to pediatric clinical research have also helped provide a legal basis for investigating the effects of drugs and biologics in pediatrics and facilitate the pediatric drug development. The evaluation of clinical pharmacology, efficacy, and safety has provided valuable labeling information for pediatric use, including comparing exposure between adult and pediatric patients, bridging different formulations and regimens, providing appropriate dose selection recommendation with the modeling and simulation approach, and assessing the risks and benefits. This review summarizes the drugs and biologics with JIA labeling implications and discusses the application of clinical pharmacology, safety, and efficacy assessment in determining pediatric dosing regimens. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:26212634, 2012 C1 [Ji, Ping; Sahajwalla, Chandrahas G.] US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, Silver Spring, MD USA. [Chowdhury, Badrul A.; Yim, Sarah] US FDA, Div Pulm Allergy & Rheumatol Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Sahajwalla, CG (reprint author), US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, Silver Spring, MD USA. EM Chandrahas.Sahajwalla@fda.hhs.gov NR 49 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2012 VL 101 IS 8 BP 2621 EP 2634 DI 10.1002/jps.23184 PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 965JO UT WOS:000305764100001 PM 22653876 ER PT J AU Berendt, RT Samy, R Carlin, AS Pendse, A Schwartz, P Khan, MA Faustino, PJ AF Berendt, Robert T. Samy, Raghu Carlin, Alan S. Pendse, Anil Schwartz, Paul Khan, Mansoor A. Faustino, Patrick J. TI Spontaneous carbonate formation in an amorphous, amine-rich, polymeric drug substance: Sevelamer HCl product quality SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE amorphous; polymeric drugs; solid-state stability; water sorption; desorption; solid-state NMR; relaxation time; FTIR; calorimetry (DSC); thermogravimetric analysis ID STATE NMR-SPECTROSCOPY; CROSSOVER DESIGN; HYDROCHLORIDE; HEMODIALYSIS; WATER AB Spectral differences among multiple manufacturers/lots of sevelamer HCl were observed by Fourier transform infrared spectroscopy, and further characterization was performed to identify the cause for these differences. The drug substance is a polymer that possesses a large molecular weight, is amorphous, and is practically insoluble in both water and organic solvents. Thus, solid-state characterization methods (spectroscopic and thermal) were required to identify and characterize differences among the samples to assess possible differences in product quality. 13C cross-polarizationmagic-angle-spinning nuclear magnetic resonance spectroscopy of sevelamer HCl substances demonstrated the presence of a carbonyl-containing species, which was attributed to a carbonate impurity among samples. Stability studies demonstrated that this carbonate impurity formed spontaneously upon exposure of the drug substance to atmospheric water vapor and carbon dioxide, even under ambient conditions. Mechanistically, this behavior likely arises from the large number of primary and secondary amine groups, the hygroscopicity of the HCl salt, and a high degree of molecular mobility due to the amorphous nature of the drug substance. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:26812685, 2012 C1 [Berendt, Robert T.; Samy, Raghu; Carlin, Alan S.; Khan, Mansoor A.; Faustino, Patrick J.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Pendse, Anil; Schwartz, Paul] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Rockville, MD 20855 USA. RP Faustino, PJ (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 12 TC 1 Z9 1 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2012 VL 101 IS 8 BP 2681 EP 2685 DI 10.1002/jps.23228 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 965JO UT WOS:000305764100007 PM 22700351 ER EF