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Full-Text Articles in Medicine and Health Sciences
Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin
Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin
Electronic Theses and Dissertations
Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …
Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp
Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp
Electronic Theses and Dissertations
Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …
Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel
Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel
Electronic Theses and Dissertations
Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects …
Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass
Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass
Electronic Theses and Dissertations
Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …
Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel
Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel
Electronic Theses and Dissertations
Background: Streptozotocin (STZ) induced diabetes leads to various complications including cardiomyopathy. Recent data suggests transplanted bone marrow stem cells improve cardiac function in diabetic cardiomyopathy. However, whether modified ES, iPS cells, or factors released from these cells can inhibit apoptosis and fibrosis remains completely unknown. The present study was designed to determine the effects of transplanted ES cells overexpressing pancreatic transcription factor 1 a (Ptf1a), a propancreatic endodermal transcription factor, iPS cells, or their respective conditioned media (CM) on diabetic cardiomyopathy. Methods: Experimental diabetes was induced in male Sprague Dawley rats (8-10 weeks old) by intraperitoneal STZ injections (65 mg/kg …