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 …

Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson

All ETDs from UAB

Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …

Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer

All ETDs from UAB

The increasing prevalence of metabolic syndrome, diabetes, atherosclerosis, and many other diseases only recently associated with aberrant metabolism, have led to a de-mand for clinical assays to determine a patient’s mitochondrial health. With the rapidly growing interest in personalized medicine, such an assay would ideally be able to capture the metabolic changes associated with oxidative stress, inflammation, and therapy of a patient in a swift and non-invasive manner. Short of tissue biopsies, this burgeoning field of Translational Bioenergetics has had minimal success in obtaining sufficient human cells and the means to assess them both accurately and swiftly. The purpose of …

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

All ETDs from UAB

The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …