Medical Pharmacology Commons^™

Vbp15, A Glucocorticoid Analogue, Is Effective At Reducing Allergic Lung Inflammation In Mice, Jesse M. Damsker, Blythe C. Dillingham, Mary C. Rose, Molly A. Balsley, Christopher R. Heier, Alan M. Watson, Erik J. Stemmy, Roslyn A. Jurjus, Tony Huynh, Kathleen Tatem, Kitipong Uaesoontrachoon, Dana M. Berry, Angela S. Benton, Robert J. Freishtat, Eric P. Hoffman, John M. Mccall, Heather Gordish-Dressman, Stephanie L. Constant, Erica K.M. Reeves, Kanneboyina Nagaraju

Pharmacology and Physiology Faculty Publications

No abstract provided.

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

University of Western Ontario - Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and ...

Induction Of Neurotrophic And Differentiation Genes In Neural Stem Cells By Valproic Acid, Walaa Saeed Almutawaa

Open Access Dissertations and Theses

Valproic acid (2-propylpentanoicacid) has long been in use as an anticonvulsant and mood-stabilizer. Recently, VPA has been shown to inhibit the activity of histone deacetylases (HDACs), resulting in chromatin remodelling and changes in gene expression. Although the molecular mechanism for VPA action in the central nervous is not well understood, many signalling pathways have been suggested as targets for this HDAC inhibitor. For instance, VPA was found to induce differentiation in adult hippocampal neural progenitor cells via the β-catenin-Ras-ERK pathway. Also, VPA up regulated Bcl-2, a neurotrophic/neuroprotective protein, with association of extracellular signal-regulated kinase (ERK-1) and phosphatidylinositol 3- kinase ...

Drugs, Devices, And Desires: A Problem-Based Learning Course In The History Of Medicine, Sarah Levitt, Anne Mckeage, P. K. Rangachari

Interdisciplinary Journal of Problem-based Learning

Problem-based learning (PBL) is well suited for courses in the history of medicine, where multiple perspectives exist and information has to be gleaned from different sources. A student, an archivist, and a teacher offer three perspectives about a senior level course where students explored the antecedents and consequences of medical technology. Two active learning strategies were used: (a) PBL to explore the historical basis of procedures used to diagnose, prevent and treat a single disease, tuberculosis, and (b) a concurrent inquiry-based component that permitted individual exploration of other medical technologies and demonstration of learning through diverse options (book reviews, conversations ...

Does Folic Acid Supplementation Prevent Nicotine-Induced Beta Cell Dysfunction, Catherine J. Nicholson

Open Access Dissertations and Theses

Previous studies suggest that nicotine impairs pancreatic function, which may explain the increased risk of T2DM in smokers. We have previously shown that nicotine exposure results in decreased beta cell function, an effect which appears to be mediated via increased beta cell oxidative stress. The goal of this study is to determine whether folic acid, an antioxidant, can prevent nicotine-induced beta cell dysfunction in the beta cell.

INS 1E cells, a rat pancreatic beta cell line, were treated with nicotine or vehicle ± 10µM folic acid for 48 hours. Nicotine treatment decreased both basal and glucose stimulated insulin secretion, but had ...

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions ...

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Molecular and Biomedical Pharmacology Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing ...

Mk-0448, A Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics And Pharmacodynamic Electrophysiology In Experimental Animal Models And In Humans., Behzad B. Pavri, Howard E Greenberg, Walter K. Kraft, Nicole Lazarus, Joseph J Lynch, Joseph J Salata, Mark T Bilodeau, Christopher P Regan, Gary Stump, Li Fan, Anish Mehta, John A Wagner, David E Gutstein, Daniel Bloomfield

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0 ...

Pharmacologic Management Of The Opioid Neonatal Abstinence Syndrome., Walter K. Kraft, John N Van Den Anker

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Opioid use in pregnant women has increased over the last decade. Following birth, infants with in utero exposure demonstrate signs and symptoms of withdrawal known as the neonatal abstinence syndrome (NAS). Infants express a spectrum of disease, with most requiring the administration of pharmacologic therapy to ensure proper growth and development. Treatment often involves prolonged hospitalization. There is a general lack of high-quality clinical trial data to guide optimal therapy, and significant heterogeneity in treatment approaches. Emerging trends in the treatment of infants with NAS include the use of sublingual buprenorphine, transition to outpatient therapy, and pharmacogenetic risk stratification.

Nevirapine Hepatotoxicity: Case Report And Discussion, Matt Baichi

The Medicine Forum

Nevirapine (viramune) is a nonnucleoside reverse transcriptase inhibitor commonly used in combination with other antiretroviral medicines in the treatment of HIV/AIDS. The safety profile of nevirapine, as determined by review of prospective clinical trials, reports rash with an incidence of 16% as the most common side effect. Clinical hepatitis is reported to occur with an incidence of 1%. A review of the literature shows many case reports of nevirapine-induced hepatotoxicity in patients receiving both treatment and prophylaxis for HIV. The purpose of this case report is to stress the importance of early recognition and withdrawal of the offending drug.

Gastrointestinal-Sparing Effects Of Novel Nsaids In Rats With Compromised Mucosal Defence, Rory W. Blackler

Open Access Dissertations and Theses

Nonsteroidal anti-inflammatory drugs are among the most commonly used prescription and over-the-counter medications, but they often produce significant gastrointestinal ulceration and bleeding, particularly in elderly patients and patients with certain co-morbidities. Novel anti-inflammatory drugs are seldom tested in animal models that mimic the high-risk human users, leading to an underestimate of the true toxicity of these drugs. In the present study we examined the effects of two novel NSAIDs and two commonly used NSAIDs in models in which mucosal defence was expected to be impaired. Naproxen, celecoxib, ATB-346 (a hydrogen sulfide- and naproxen-releasing compound) and NCX 429 (a nitric oxide- ...

Mini-Review: Decorin, A Guardian From The Matrix, Thomas Neill, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Decorin, an archetypal member of the small leucine-rich proteoglycan gene family, has a broad binding repertoire that encompasses matrix structural components, such as collagens, and growth factors, particularly those that belong to the transforming growth factor-β ligand superfamily. Within the tumor microenvironment, stromal decorin has an inherent proclivity to directly bind and down-regulate several receptor tyrosine kinases, which are often overexpressed in cancer cells. The decorin interactome commands a powerful antitumorigenic signal by potently repressing and attenuating tumor cell proliferation, survival, migration, and angiogenesis. This collection of interacting molecules also regulates key downstream signaling processes indirectly via the sequestration of ...

Effect Of Concomitant Medications Affecting Gastric Ph And Motility On Posaconazole Tablet Pharmacokinetics, Walter K. Kraft, P. Chang, Mlps Van Iersel, H. Waskin, G. Krishna, W. Kersemaekers

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Poster presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (52^nd ICAAC) held in San Francisco 9/9-9/12

Background: Posaconazole (POS) oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new POS tablet formulation has demonstrated improved bioavailability over oral suspension in healthy adults in the fasting state. This study evaluated the effect of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and motility (metoclopramide) on the pharmacokinetics of POS tablet.

Methods: This was a prospective, open-label, 5-way crossover study in 20 healthy volunteers. In each treatment period, a single ...