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1. Full Text Pharmacological Optimization for Successful Traumatic Brain Injury Drug Development
by Poloyac, Samuel M and Bertz, Richard J and McDermott, Lee and Marathe, Punit
Journal of neurotrauma, ISSN 0897-7151, 02/2019
The purpose of this review is to highlight the pharmacologic barrier to drug development for traumatic brain injury (TBI) and to discuss best practice... 
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2. Full Text Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system
by Tortorici, Michael A and Kochanek, Patrick M and Poloyac, Samuel M
Critical Care Medicine, ISSN 0090-3493, 09/2007, Volume 35, Issue 9, pp. 2196 - 2204
OBJECTIVES:Therapeutic hypothermia has been shown to decrease neurologic damage in patients experiencing out-of-hospital cardiac arrest. In addition to being... 
Critical care | Drug metabolism | Pharmacokinetics | Cytochrome P450 | Hypothermia | critical care | CARDIOPULMONARY BYPASS | cytochrome P450 | HIGH-DOSE FENTANYL | MODERATE HYPOTHERMIA | CARDIAC-ARREST | TRAUMATIC BRAIN-INJURY | THERAPEUTIC HYPOTHERMIA | hypothermia | PLASMA FENTANYL CONCENTRATIONS | BILIARY-EXCRETION | drug metabolism | pharmacokinetics | MILD INTRAOPERATIVE HYPOTHERMIA | CORONARY-ARTERY SURGERY | CRITICAL CARE MEDICINE | Hypothermia, Induced - adverse effects | Pharmaceutical Preparations - metabolism | Chlorzoxazone - metabolism | Humans | Anesthetics - metabolism | Hypnotics and Sedatives - metabolism | Anticonvulsants - metabolism | Midazolam - metabolism | Cardiovascular Agents - metabolism | Neuromuscular Blocking Agents - metabolism | Cytochrome P-450 Enzyme System - physiology
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3. Full Text Altered drug metabolism in critically ill children: A significant source of adverse effects?
by Poloyac, SM
PEDIATRIC CRITICAL CARE MEDICINE, ISSN 1529-7535, 01/2012, Volume 13, Issue 1, pp. 118 - 119
HYPOTHERMIA | HOSPITALIZED-PATIENTS | critical illness | ENZYMES | pediatrics | pharmacokinetics | midazolam, cytochrome P450 | MIDAZOLAM | UNITS | INTENSIVE-CARE | CRITICAL CARE MEDICINE | Humans | Critical Illness | Female | Male | Midazolam - pharmacokinetics | Multiple Organ Failure - drug therapy | Inflammation - physiopathology
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4. Full Text Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release
by Suofu, Yalikun and Li, Wei and Jean-Alphonse, Frédéric G and Jia, Jiaoying and Khattar, Nicolas K and Li, Jiatong and Baranov, Sergei V and Leronni, Daniela and Mihalik, Amanda C and He, Yanqing and Cecon, Erika and Wehbi, Vanessa L and Kim, JinHo and Heath, Brianna E and Baranova, Oxana V and Wang, Xiaomin and Gable, Matthew J and Kretz, Eric S and Di Benedetto, Giulietta and Lezon, Timothy R and Ferrando, Lisa M and Larkin, Timothy M and Sullivan, Mara and Yablonska, Svitlana and Wang, Jingjing and Minnigh, M. Beth and Guillaumet, Gérald and Suzenet, Franck and Richardson, R. Mark and Poloyac, Samuel M and Stolz, Donna B and Jockers, Ralf and Witt-Enderby, Paula A and Carlisle, Diane L and Vilardaga, Jean-Pierre and Friedlander, Robert M
Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, 09/2017, Volume 114, Issue 38, pp. E7997 - E8006
G protein-coupled receptors ( GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that... 
G protein-coupled receptor | Neuroprotection | Melatonin | Mitochondria | Ischemia | MUTANT | ACTIVATION | mitochondria | MULTIDISCIPLINARY SCIENCES | IDENTIFICATION | EXPERIMENTAL-MODELS | DAMAGE | ischemia | INTERLEUKIN-1-BETA CONVERTING-ENZYME | INHIBITION | neuroprotection | MOUSE MODEL | melatonin | RECEPTORS | CEREBRAL-ISCHEMIA | Signal Transduction | Cytochromes c - metabolism | Brain Ischemia - genetics | Brain Ischemia - metabolism | Male | Cytochromes c - genetics | Mitochondria - metabolism | Brain Injuries - genetics | Brain Injuries - metabolism | Receptor, Melatonin, MT1 - genetics | Animals | Mitochondria - genetics | Melatonin - biosynthesis | Mice | Melatonin - genetics | Receptor, Melatonin, MT1 - metabolism | Physiological aspects | G proteins | Biological Sciences | PNAS Plus
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5. Full Text A mitochondrial pathway for biosynthesis of lipid mediators
by Tyurina, Yulia Y and Poloyac, Samuel M and Tyurin, Vladimir A and Kapralov, Alexander A and Jiang, Jianfei and Anthonymuthu, Tamil Selvan and Kapralova, Valentina I and Vikulina, Anna S and Jung, Mi-Yeon and Epperly, Michael W and Mohammadyani, Dariush and Klein-Seetharaman, Judith and Jackson, Travis C and Kochanek, Patrick M and Pitt, Bruce R and Greenberger, Joel S and Vladimirov, Yury A and Bayir R, Hülya and Kagan, Valerian E
Nature Chemistry, ISSN 1755-4330, 2014, Volume 6, Issue 6, pp. 542 - 552
The central role of mitochondria in metabolic pathways and in cell-death mechanisms requires sophisticated signalling systems. Essential in this signalling... 
CHEMICAL INHIBITION | PEROXIDASE-ACTIVITY | CARDIOLIPIN | TESTICULAR CYTOCHROME-C | INDUCED APOPTOSIS | BRAIN-INJURY | MASS-SPECTROMETRIC CHARACTERIZATION | OXIDATIVE LIPIDOMICS | LUNG INJURY | PHOSPHOLIPASE A | CHEMISTRY, MULTIDISCIPLINARY | Lysophospholipids - metabolism | Whole-Body Irradiation | Oxidants - pharmacology | Calcium - metabolism | Brain - metabolism | Group IV Phospholipases A2 - metabolism | Chromatography, Liquid | Female | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | Intestine, Small - injuries | Oxidation-Reduction | Cytochromes c - metabolism | Mice, Inbred C57BL | Hydrogen Peroxide - pharmacology | Rats | Brain - radiation effects | Cardiolipins - metabolism | Mitochondria - metabolism | Fatty Acids, Unsaturated - metabolism | Mitochondria - drug effects | Cardiolipins - chemistry | Brain - drug effects | Animals | Intestine, Small - drug effects | Mice | Intestine, Small - metabolism
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6. Full Text Membrane transporters in traumatic brain injury: Pathological, pharmacotherapeutic, and developmental implications
by Hagos, Fanuel T and Adams, Solomon M and Poloyac, Samuel M and Kochanek, Patrick M and Horvat, Christopher M and Clark, Robert S.B and Empey, Philip E
Experimental Neurology, ISSN 0014-4886, 07/2019, Volume 317, pp. 10 - 21
Membrane transporters regulate the trafficking of endogenous and exogenous molecules across biological barriers and within the neurovascular unit. In traumatic... 
ATP-binding cassette transporters | Traumatic brain injury | Neurovascular unit | Solute carriers | Blood-brain barrier | Multidrug resistance | Brain | Medical research | Drug resistance in microorganisms | Neurons | Medicine, Experimental | Amino acids | Single nucleotide polymorphisms | Glutamate | Injuries | Blood proteins
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7. Full Text The cytochrome p450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease
by Schuck, Robert N and Zha, Weibin and Edin, Matthew L and Gruzdev, Artiom and Vendrov, Kimberly C and Miller, Tricia M and Xu, Zhenghong and Lih, Fred B and DeGraff, Laura M and Tomer, Kenneth B and Jones, H. Michael and Makowski, Liza and Huang, Leaf and Poloyac, Samuel M and Zeldin, Darryl C and Lee, Craig R
PLoS ONE, ISSN 1932-6203, 10/2014, Volume 9, Issue 10, p. e110162
Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its... 
SOLUBLE EPOXIDE HYDROLASE | HYDRODYNAMICS-BASED TRANSFECTION | MULTIDISCIPLINARY SCIENCES | MOUSE | ATHEROGENIC DIET | NONALCOHOLIC STEATOHEPATITIS | EICOSANOID METABOLISM | MICE | ARACHIDONIC-ACID | LARGE GENE LISTS | ENDOTHELIAL EXPRESSION | Biomarkers - metabolism | Fatty Liver - genetics | Epoxide Hydrolases - deficiency | Inflammation - pathology | Arachidonic Acid - metabolism | Liver - pathology | Liver - enzymology | Fatty Liver - blood | Fatty Liver - pathology | Mice, Inbred C57BL | Gene Expression Regulation | Cytochrome P-450 Enzyme System - metabolism | Hydrodynamics | Male | Inflammation - blood | Metabolic Networks and Pathways - genetics | Animals | Diet | Eicosanoids - metabolism | Lipids - blood | Atherosclerosis | Fatty Liver - enzymology | Inflammation - genetics | Epoxide Hydrolases - metabolism | Unsaturated fatty acids | Inflammation | Fatty liver | Analysis | Cytochrome P-450 | Cytochrome | Health sciences | Liver | Inflammatory response | Cardiovascular disease | Biosynthesis | Arachidonic acid | Phosphatase | Epoxide hydrolase | Biological effects | Atherogenic diet | Rodents | Hepatology | Drug therapy | Pharmaceutical sciences | Public health | Cardiovascular system | Enzymes | Liver diseases | Cytochrome P450 | Environmental health | Metabolism | Gene expression | Cholesterol | Biological activity | Nutrition research | Acids | Pharmacy | Mice | Laboratory animals | Apoptosis
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8. Full Text Abstract P198: WNK-SPAK-NKCC1 Cascade Activation Contributes to Worsened Brain Damage in Mice With Hypertension Co-Morbidity after Ischemic Stroke
by Bhuiyan, Mohammad Iqbal H and Huang, Huachen and Zhang, Ting and Molyneaux, Bradley J and Poloyac, Samuel M and Zhang, Jinwei and Deng, Xianming and Sun, Dandan and Sun, Dandan
Hypertension, ISSN 0194-911X, 09/2018, Volume 72, Issue Suppl_1
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9. Full Text Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children
by Clark, Robert S. B and Empey, Philip E and Bayir, Hülya and Rosario, Bedda L and Poloyac, Samuel M and Kochanek, Patrick M and Nolin, Thomas D and Au, Alicia K and Horvat, Christopher M and Wisniewski, Stephen R and Bell, Michael J
PLoS ONE, ISSN 1932-6203, 07/2017, Volume 12, Issue 7, p. e0180280
There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to... 
Intracranial Pressure - drug effects | Adjuvants, Pharmaceutic - pharmacology | Humans | Probenecid - blood | Child, Preschool | Acetylcysteine - cerebrospinal fluid | Male | Brain Injuries, Traumatic - cerebrospinal fluid | Glasgow Coma Scale | Intubation, Gastrointestinal | Female | Brain Injuries, Traumatic - blood | Probenecid - pharmacokinetics | Child | Brain Injuries, Traumatic - drug therapy | Double-Blind Method | Drug Administration Schedule | Probenecid - pharmacology | Glasgow Outcome Scale | Antioxidants - pharmacology | Biomarkers - blood | Body Temperature | Acetylcysteine - blood | Acetylcysteine - pharmacokinetics | Acetylcysteine - pharmacology | Adolescent | Survival Analysis | Adjuvants, Pharmaceutic - pharmacokinetics | Antioxidants - pharmacokinetics | Brain Injuries, Traumatic - mortality | Probenecid - cerebrospinal fluid | Brain | Usage | Clinical trials | Acetylcysteine | Children | Research | Health aspects | Injuries | Probenecid | Testing | Coma | Pediatrics | Drug delivery systems | Traumatic brain injury | Physicians | Critical care | Intracranial pressure | Cerebrospinal fluid | Epidemiology | Antioxidants | Randomization | Head injuries | Temperature effects | Rodents | Blood pressure | Pharmaceutical sciences | Antimicrobial agents | Patients | Morbidity | Medicine | Side effects | Brain research | Hospitals | Pharmacy | Biomarkers | Informed consent | Ventricle
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10. Full Text ABCB1 genotype is associated with fentanyl requirements in critically ill children
by Horvat, Christopher M and Au, Alicia K and Conley, Yvette P and Kochanek, Patrick M and Li, Lingjue and Poloyac, Samuel M and Empey, Philip E and Clark, Robert S.B
Pediatric Research, ISSN 0031-3998, 07/2017, Volume 82, Issue 1, pp. 29 - 35
BACKGROUND: The gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has... 
PEDIATRIC INTENSIVE-CARE | PAIN | MANAGEMENT | TRAUMATIC BRAIN-INJURY | SEDATION | PEDIATRICS | P-GLYCOPROTEIN EXPRESSION | GENE POLYMORPHISMS | WITHDRAWAL | DEPENDENCE | ANALGESIA | Genotype & phenotype | Pediatrics | Drug delivery systems | Glycoproteins
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11. Full Text The effect of therapeutic hypothermia on drug metabolism and response: cellular mechanisms to organ function
by Zhou, Jiangquan and Poloyac, Samuel M
Expert Opinion on Drug Metabolism & Toxicology, ISSN 1742-5255, 07/2011, Volume 7, Issue 7, pp. 803 - 816
Introduction: Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia... 
drug response | critical care | pharmacokinetics | therapeutic hypothermia | drug metabolism | BIOCHEMISTRY & MOLECULAR BIOLOGY | MILD HYPOTHERMIA | PHARMACODYNAMICS | MODERATE HYPOTHERMIA | GENTAMICIN | ENCEPHALOPATHY | ANESTHESIA | IMPACT | BIOTRANSFORMATION | CARDIAC-ARREST | PHARMACOLOGY & PHARMACY | TOXICOLOGY | Dose-Response Relationship, Drug | Inactivation, Metabolic | Animals | Humans | Hypothermia, Induced | Body Temperature | Aryl Hydrocarbon Hydroxylases - metabolism
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12. Full Text Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy
by Browning, Megan and Shear, Deborah A and Bramlett, Helen M and Dixon, C. Edward and Mondello, Stefania and Schmid, Kara E and Poloyac, Samuel M and Dietrich, W. Dalton and Hayes, Ronald L and Wang, Kevin K. W and Povlishock, John T and Tortella, Frank C and Kochanek, Patrick M
Journal of Neurotrauma, ISSN 0897-7151, 03/2016, Volume 33, Issue 6, pp. 581 - 594
Levetiracetam (LEV) is an antiepileptic agent targeting novel pathways. Coupled with a favorable safety profile and increasing empirical clinical use, it was... 
Original Articles | controlled cortical impact | rat | post-traumatic seizures | Keppra | neuroprotection | therapy | penetrating ballistic-like brain injury | fluid percussion | biomarker | excitotoxicity | HYPOTHERMIA | PROTEIN | SEIZURE PROPHYLAXIS | POSTTRAUMATIC EPILEPSY | STATUS EPILEPTICUS | MODEL | NEUROSCIENCES | CLINICAL NEUROLOGY | INTRAVENOUS LEVETIRACETAM | DEFICITS | CRITICAL CARE MEDICINE | Recovery of Function - drug effects | Rats | Male | Biomarkers - blood | Brain Injuries, Traumatic | Rats, Sprague-Dawley | Ubiquitin Thiolesterase - blood | Glial Fibrillary Acidic Protein - blood | Animals | Piracetam - analogs & derivatives | Piracetam - pharmacology | Nootropic Agents - pharmacology | Disease Models, Animal | Brain | Care and treatment | Dosage and administration | Research | Biological markers | Injuries | Levetiracetam | Brain damage | Drug therapy | Clinical outcomes | Neurobiology
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13. Full Text Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy
by Kochanek, Patrick M and Bramlett, Helen M and Shear, Deborah A and Dixon, C. Edward and Mondello, Stefania and Dietrich, W. Dalton and Hayes, Ronald L and Wang, Kevin K.W and Poloyac, Samuel M and Empey, Philip E and Povlishock, John T and Mountney, Andrea and Browning, Megan and Deng-Bryant, Ying and Yan, Hong Q and Jackson, Travis C and Catania, Michael and Glushakova, Olena and Richieri, Steven P and Tortella, Frank C
Journal of Neurotrauma, ISSN 0897-7151, 03/2016, Volume 33, Issue 6, pp. 66 - 614
Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multicenter, pre-clinical drug and circulating biomarker screening... 
Original Articles | pre-clinical modeling | controlled cortical impact | micropig | rat | reproducibility | therapy | penetrating ballistic-like brain injury | traumatic brain injury | fluid percussion | biomarker | drug | MICROGLIAL ACTIVATION | PERFORMANCE | INJURY | NEUROSCIENCES | RAT MODEL | NEUROPROTECTION | CLINICAL NEUROLOGY | HEMORRHAGIC-SHOCK | AMANTADINE | MICE | DEFICITS | CRITICAL CARE MEDICINE | Neuroprotective Agents - therapeutic use | Drug Evaluation, Preclinical - methods | Neurology - trends | Animals | Brain Injuries, Traumatic - drug therapy | Drug Evaluation, Preclinical - trends | Rats | Male | Neurology - methods | Rats, Sprague-Dawley | Disease Models, Animal | Brain | Usage | Care and treatment | Clinical trials | Research | Biological markers | Injuries | Biomarkers | Brain damage | Drug therapy | Neurobiology
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14. Full Text Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism
by Theken, Katherine N and Deng, Yangmei and Alison Kannon, M and Miller, Tricia M and Poloyac, Samuel M and Lee, Craig R
Drug Metabolism and Disposition, ISSN 0090-9556, 01/2011, Volume 39, Issue 1, pp. 22 - 29
Cytochrome P450 (P450)-mediated metabolism of arachidonic acid regulates inflammation in hepatic and extrahepatic tissue. CYP2C/CYP2J-derived... 
RAT-LIVER | SOLUBLE EPOXIDE HYDROLASE | INHIBITION | CLONING | ENZYMES | GENE-EXPRESSION | PHARMACOLOGY & PHARMACY | ARACHIDONIC-ACID | MODEL | SUPPRESSION | MODULATION | Tumor Necrosis Factor-alpha - metabolism | Microsomes - metabolism | Microsomes, Liver - metabolism | Arachidonic Acid - blood | Cytochrome P-450 Enzyme System - metabolism | Male | Lipopolysaccharides - immunology | Microsomes - drug effects | Tandem Mass Spectrometry | Inflammation - metabolism | Kidney - metabolism | Time Factors | Lung - metabolism | RNA - metabolism | Kidney - drug effects | Mice, Inbred C57BL | Immunity, Innate | Animals | Eicosanoids - metabolism | Lung - drug effects | Cytochrome P-450 Enzyme System - biosynthesis | Cytochrome P-450 Enzyme System - genetics | Heart - drug effects | Mice | Tumor Necrosis Factor-alpha - biosynthesis
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