A5004628392- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Free Radicals and Antioxidants
- Drug-Induced Hepatotoxicity and Protection
- Pharmacological Effects and Toxicity Studies
- Coenzyme Q10 studies and effects
- Biochemical and Molecular Research
- Phytochemicals and Antioxidant Activities
- Eicosanoids and Hypertension Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- Statistical Methods in Clinical Trials
- Liver Disease Diagnosis and Treatment
- Vitamin C and Antioxidants Research
- Virus-based gene therapy research
- Liquid Crystal Research Advancements
- Antioxidant Activity and Oxidative Stress
- Advanced battery technologies research
- Cytomegalovirus and herpesvirus research
- 3D Printing in Biomedical Research
- Protein purification and stability
- Anesthesia and Neurotoxicity Research
- Metabolism and Genetic Disorders
- Advanced Glycation End Products research
- Muscle Physiology and Disorders
Boehringer Ingelheim (United States)
2013-2024
Colorado State University
2013-2018
Repligen (United States)
2013-2018
Centre Hospitalier de l’Université de Montréal
2008-2018
University of Kentucky
2014
Université de Montréal
2011
Beckman Coulter Foundation
2007
Hôpital Saint-Luc
2006-2007
University of Toronto
1999-2006
McGill University
2005
Article Cancer Chemoprevention and Apoptosis Mechanisms Induced by Dietary Polyphenolics was published on December 1, 2000 in the journal Drug Metabolism Personalized Therapy (volume 17, issue 1-4).
Generating accurate in vitro intrinsic clearance data is an important aspect of predicting vivo human clearance. Primary hepatocytes suspension are routinely used to predict clearance; however, incubation times have typically been limited 4–6 hours, which not long enough accurately evaluate the metabolic stability slowly metabolized compounds. HepatoPac a micropatterened hepatocyte-fibroblast coculture system that can be for continuous incubations up 7 days. This study evaluated ability (CL)...
Catalytic concentrations of apigenin (a flavone containing a phenol B ring) and naringin or naringenin (flavanones caused extensive GSH oxidation at physiological pH in the presence peroxidase. Only catalytic H2O2 were required, indicating redox cycling mechanism that generated was involved. Extensive oxygen uptake ensued, extent which proportional to GSSG markedly increased by superoxide dismutase. These results suggest prooxidant phenoxyl radicals formed these flavonoids co-oxidized form...
An increased appreciation of the importance transporter and enzyme interplay in drug clearance a desire to delineate these mechanisms necessitates utilization models that contain full complement enzymes transporters at physiologically relevant activities. Additionally, development drugs with longer half-lives requires vitro systems extended incubation times allow characterization metabolic pathways for low-clearance drugs. A recently developed coculture hepatocyte model, HepatoPac, has been...
The commonest mitochondrial diseases are probably those impairing the function of complex I respiratory electron transport chain. Such impairment may contribute to various neurodegenerative disorders e.g. Parkinson's disease. In following, using hepatocytes as a model cell, we have shown for first time that cytotoxicity caused by inhibition rotenone but not III antimycin can be prevented coenzyme Q (CoQ1) or menadione. Furthermore, inhibitor was associated with collapse membrane potential...
Research Articles| May 06 2008 An (X;11) translocation in a girl with Duchenne muscular dystrophy: Repository identification No. GM1695 Subject Area: Genetics R.M. Greenstein; Greenstein aDepartments of Pediatrics and Physiology, University Connecticut Health Center, Farmington, Conn., Search for other works by this author on: This Site PubMed Google Scholar M.P. Reardon; Reardon T.S. Chan; Chan cDepartment Microbiology, Texas Medical Branch, Galveston, Tex. (present address) A.B. Middleton;...
In May 2022, there is an International Regulatory and Pharmaceutical Industry (Innovation Quality [IQ] Microphysiological Systems [MPS] Affiliate) Workshop on the standardization of complex in vitro models (CIVMs) drug development. This manuscript summarizes discussions conclusions this joint workshop organized executed by IQ MPS Affiliate United States Food Drug Administration (FDA). A key objective to facilitate around opportunities and/or needs for chart potential pathways increase model...
The ability to reduce the peroxidase (myeloglobin/H2O2)-generated ABTS•+ [2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) radical cation] has been used rank antioxidant activity of various agents including dietary flavonoids and chalcones. Surprisingly, we found that in presence catalytic concentrations phenol B-ring containing flavonoids, apigenin, naringenin chalcone phloretin, formation was initially increased. enhanced attributed peroxidase/H2O2 mediated generation polyphenolic...
The antiferroelectric smectic-${\mathit{C}}^{\mathrm{*}}$ (Sm-${\mathit{C}}^{\mathrm{*}}$) phases of two closely related chiral compounds have been studied with high-resolution calorimetric techniques. Both methylheptyloxycarbonylphenyl octyloxybiphenyl carboxylate (MHPOBC) and its octylcarbonylbiphenyl analog (MHPOCBC) exhibit Sm-${\mathit{C}}_{\mathrm{\ensuremath{\alpha}}}^{\mathrm{*}}$ Sm-${\mathit{C}}_{\mathit{A}}^{\mathrm{*}}$ phases....
Deoxyadenosine, a cytotoxic purine nucleoside, is excreted in large amounts by patients with severe combined immunodeficiency disease associated deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). To identify the source excretion macrophages was studied using mouse peritoneal as an experimental model system. Normally, excrete quantity uric acid into culture medium. However, presence deoxycoformycin, potent inhibitor deaminase, these also deoxyadenosine. Furthermore,...
A synthetic peptide corresponding to the N-terminal amino acid sequence of human gamma-interferon (HuIFN gamma), based on cDNA sequence, was used produce antibodies in rabbits that were reactive with native HuIFN gamma. Antibodies from all immunized neutralized antiviral activity Significant neutralization other and mouse IFN not observed. The had Cys-Tyr-Cys-Gln-Asp-Pro-Tyr-Val-Lys-Glu-Ala-Glu-Asn-Leu-Lys-Lys-Tyr-Phe-Asn-Ala ,and coupled keyhole limpet hemocyanin by disulfide linkage use...
The liver is a highly vascularized organ receiving dual input of oxygenated blood from the hepatic artery and portal vein. impact decreased flow on glucose metabolism how hepatocytes could adapt to this restrictive environment are still unclear. Using left vein ligation (LPVL) rat model, we found that cellular injury was delayed after onset ischemia. We hypothesized metabolic adaptation by maintain energy homeostasis account for lag phase. Liver characterized 13C- 1H-NMR spectroscopy...
Previous work demonstrated that human liver microsomes (HLM) can spontaneously bind to silica-coated magnetizable beads (HLM-beads) and these HLM-beads retain UGT activity. However, the contributions of individual isoforms is not directly assessable in this system except through use model inhibitors. Thus, a preparation wherein rUGT bound same form rUGT-beads would provide novel for measuring contribution direct manner. To end, enzyme activities kinetic parameter estimates various were...
Cytochrome P450 (P450) protein-protein interactions resulting in modulation of enzyme activities have been well documented using recombinant isoforms. This interaction has less clearly demonstrated a more physiologic vitro system such as human hepatocytes. As an expansion earlier work (Subramanian et al., 2010), which CYP2C9 activity decreased with increasing levels CYP3A4, the current study modulated CYP3A4 content hepatocytes to determine impact on CYP2C9. Modulation situ was enabled by...
The introduction includes a literature review of DNA reactive species and adduct formation that results from aromatic amine N-oxidation catalyzed by hepatic cytochrome P450 vs. nonhepatic peroxidases. Experimental evidence is then described for novel oxidative stress mechanism involving prooxidant N-cation radical both oxidases, which proposed as contributing induced cytotoxicity carcinogenesis. Aromatic radicals formed peroxidases were found to cooxidize GSH or NADH form oxygen species....