Pharmacology Commons^™

The Effect Of Waterpipe/Hookah On Platelet Function And The Impact Of Inhibition Of Gβγ Subunits On Hemostasis And Thrombogenesis, Ahmed Alarabi

Open Access Theses & Dissertations

Abstract (Hookah)

Cardiovascular diseases (CVD’s) is a major public health problem. Among CVD’s risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of CVD’s mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipe/hookah has been rising, mainly due to the perception that they are “less harmful” than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. We employed a waterpipe whole-body exposure protocol that mimics real‐life human …

Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz

Master's Theses

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …