Medicine and Health Sciences Commons^™

Pathophysiologic Mechanisms Of Immune-Mediated Drug Hypersensitivity Reactions To Sulfonamides, Elham A. Sultan

Electronic Thesis and Dissertation Repository

As sulfonamide hypersensitivity reactions are serious clinical problem, it is necessary to determine which patients tolerate therapy and which patients are at risk. Although the exact pathogenesis of these reactions remains unclear, the imbalance in the production and detoxification of reactive sulfamethoxazole (SMX) metabolites appears to be important in the propagation of these reactions. It is known that these reactive metabolites can cause lymphocytes toxicity and produce reactive oxygen species (ROS) which can damage proteins, lipids, and DNA. The hypothesis of this research is that there are differences in cytotoxicity and expression of oxidative stress to reactive SMX metabolites in …

Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn

Electronic Thesis and Dissertation Repository

The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD⁺, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD⁺ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD⁺ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD⁺ levels, establishing PARP in NAD⁺ consumption in this …

Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan

Electronic Thesis and Dissertation Repository

Abstract to be provided

Protective Effect Of Modified Human Fibroblast Growth Factor On Diabetic Nephropathy, Ana M. Pena Diaz

Electronic Thesis and Dissertation Repository

Oxidative stress is a key mechanism causing Diabetic Nephropathy (DN). Acidic fibroblast growth factor (aFGF) is known to confer protection from oxidative stress. However, it also has significant angiogenic activity. Hence, we have generated a mutated human acidic FGF (maFGF), with intact antioxidant properties but devoid of angiogenic activities. Recent evidence shows that maFGF treatment prevented diabetic cardiomyopathy and further in vitro studies suggest that this prevention is mediated by suppression of cardiac oxidative stress, hypertrophy and fibrosis. We hypothesized that maFGF treatment has a protective effect in DN.

We show that maFGF treatment did not affect body weight and …