A5075379718- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Gene expression and cancer classification
- Drug-Induced Hepatotoxicity and Protection
- Drug Transport and Resistance Mechanisms
- Molecular Biology Techniques and Applications
- Carcinogens and Genotoxicity Assessment
- Bone health and treatments
- Inflammatory mediators and NSAID effects
- Wound Healing and Treatments
- Skin and Cellular Biology Research
- Dermatologic Treatments and Research
- Bioinformatics and Genomic Networks
- Virus-based gene therapy research
- Fibroblast Growth Factor Research
- Statistical Methods in Clinical Trials
- Genetics, Bioinformatics, and Biomedical Research
- Hormonal Regulation and Hypertension
- Receptor Mechanisms and Signaling
- Animal testing and alternatives
- Cancer-related molecular mechanisms research
- Metabolomics and Mass Spectrometry Studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- MicroRNA in disease regulation
- Liver physiology and pathology
AbbVie (United States)
2015-2025
Ghent University Hospital
2019
Lake County
2015
Abbott Fund
2004-2012
American Society for Investigative Pathology
2012
Abbott (United States)
2005-2010
Abbott (United Kingdom)
2008-2010
Michigan State University
2005-2006
The Ohio State University
1998-2004
Pfizer (United States)
2004
Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2) aldosterone infusion (0.75 microg/h), 3) microg/h) plus the selective blocker eplerenone (100 mg. kg(-1). day(-1)). Aldosterone induced severe hypertension at [systolic blood pressure (SBP), 210 +/- 3 mmHg vs. 131 2 mmHg, P < 0.001], which partially attenuated by (SBP, 180 7 mmHg; 0.001 alone...
Gene expression profiling is a useful tool to predict and interrogate mechanisms of toxicity. RNA-Seq technology has emerged as an attractive alternative traditional microarray platforms for conducting transcriptional profiling. The objective this work was compare both transcriptomic determine whether offered significant advantages over microarrays toxicogenomic studies. RNA samples from the livers rats treated 5 days with five hepatotoxicants (α-naphthylisothiocyanate/ANIT, carbon...
Abstract The terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL) technique has been extensively used for the detection and quantification of apoptosis in histological tissue sections. However, interpretation specificity this assay have controversial. With accumulating knowledge molecular mechanisms cell death discovery caspases as key mediators apoptosis, more direct earlier measurements sections emerged. This study, using antibodies that specifically...
Aldosterone classically promotes unidirectional transepithelial sodium transport, thereby regulating blood volume and pressure. Recently, both clinical experimental studies have suggested additional, direct roles for aldosterone in the cardiovascular system. To evaluate activation of cardiomyocyte mineralocorticoid receptors, transgenic mice overexpressing 11β-hydroxysteroid dehydrogenase type 2 cardiomyocytes were generated using mouse α-myosin heavy chain promoter. This enzyme converts...
Most small molecule drugs interact with unintended, often unknown, biological targets and these off-target interactions may lead to both preclinical clinical toxic events. Undesired are not detected using current drug discovery assays, such as experimental poly-pharmacological screens. Thus, improvement in the early identification of represents an opportunity reduce safety-related attrition rates during development. In order better identify potential that could be linked predictable safety...
Idiosyncratic adverse drug reactions (IADRs) represent an important human health problem, yet animal models for preclinical prediction of these are lacking. Recent evidence in animals suggests that some IADRs arise from interaction with inflammatory episode renders the liver sensitive to injury. Diclofenac (DCLF) is one those drugs which clinical use limited by idiosyncratic We tested hypothesis modest inflammation triggered rats a small dose lipopolysaccharide (LPS) nonhepatotoxic DCLF...
Idiosyncratic drug toxicity refers to toxic reactions occurring in a small subset of patients and usually cannot be predicted during preclinical or early phases clinical trials. One hypothesis for the pathogenesis hepatic idiosyncratic is that, certain individuals, underlying inflammation results sensitization liver, such that injury occurs from an agent typically would not cause hepatotoxicity at therapeutic dose. We explored this possibility by cotreating rats with nonhepatotoxic doses...
The pace of technological innovation in the pharmaceutical industry, like many other sectors, is accelerating rapidly. This not only reshaping how Research and Development (R&D) conducted (e.g., introduction novel models, endpoints, instrumentation) but also influencing types therapeutic modalities being developed. In addition, societal regulatory expectations have evolved to emphasize approaches that align with 4Rs principles (Replacement, Reduction, Refinement, Responsibility)...
Abstract Following an observation of myocardial toxicity in rats with experimental TYK2 inhibitor (ABBV-712), investigative studies were performed to identify the mechanism. Telemetry-instrumented administered ABBV-712 or without atenolol investigate effects co-dosing on hemodynamic parameters and cardiac pathology. In vitro included cytotoxicity assessment human induced pluripotent stem cell-derived cardiomyocytes relaxation isolated rat aorta. Off-target pharmacology was evaluated by...
The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well epithelial cancers, and has an established role angiogenesis tissue repair.Because of these physiological effects the widespread use selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition would affect incisional skin wound healing.Using a cutaneous full-thickness, sutured, model hairless SKH-1 mice, evaluated healing process by comparing nonselective COX diclofenac, with SC-791....
Primary human hepatocytes (PHH) are a main instrument in drug metabolism research and the prediction of drug-induced phase I/II enzyme induction humans. The HepG2 liver-derived cell line is commonly used as surrogate for hepatocytes, but its use absorption, distribution, metabolism, excretion toxicity studies can be limited because lowered basal levels metabolizing enzymes. Despite widespread cells, comparison their transcriptomes with those PHH has not been well characterized. In this...
Currently, the only way to identify nongenotoxic hepatocarcinogens is through long-term repeat dose studies such as 2 year rodent carcinogenicity assay. Such assays are both time consuming and expensive require large amounts of active pharmaceutical or chemical ingredients. Thus, results assay not known until very late in discovery development process for new entities. Although many cases rodents considered be irrelevant humans, a positive finding may increase number demonstrate lack...
Drug-drug interactions involving induction of cytochrome P450 enzymes (P450s) can lead to loss drug efficacy. Certain drugs, particularly those used treat mycobacterial and human immunodeficiency virus (HIV) infections, are especially prone induce P450s. During studies examine drug-interaction potential compounds in cultured hepatocytes, exposure with...