Medicine and Health Sciences Commons^™

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Role Of Thymidine Phosphorylase In Type 2 Diabetes-Associated High-Risk Of Thrombosis, Adam Belcher

Theses, Dissertations and Capstones

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are the leading causes of death globally that disproportionally affects patients with type 2 diabetes mellitus (T2DM) at a 2-4-fold rate compared to non-diabetic patients. These CVDs result from a blood clot, also known as a thrombus, formed in arteries that can block blood flow resulting in tissue damage and death. Antiplatelet drugs, such as aspirin and clopidogrel, used to prevent thrombosis have been found to be less effective in diabetics and increase the risk of hemorrhagic events. The T2DM epidemic has made it imperative to find therapies that decrease …

Therapeutic Efficacy Of Antioxidants In Ameliorating Obesity Phenotype And Associated Comorbidities, Steven Tun, Caleb James Spainhower, Cameron Lee Cottrill, Hari Vishal Lakhani, Sneha S. Pillai, Anum Dilip, Hibba Chaudhry, Joseph I. Shapiro, Komal Sodhi

Pharmacology, Physiology and Toxicology

Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Biochemistry and Microbiology

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

The Role Of Vascular Endothelial Growth Factor At The Blood-Brain Barrier In Diabetes, Aileen J. Marcelo

Theses, Dissertations and Capstones

Diabetes is a risk factor for stroke and vascular dementia. Clinical studies using gadolinium-magnetic resonance imaging techniques have shown diabetic patients exhibit a permeability increase at the blood-brain barrier (BBB) (Starr et al, 2003). The BBB, a vascular interface at the level of brain microvascular vessels, functions to provide nutrients and oxygen from the peripheral circulation, mediates waste efflux from the brain, and protects the brain from toxins. These functions are due to the presence of tight junction proteins. Animal studies have shown increased BBB permeability is due to a decrease in these proteins (Hawkins et al, 2007). Based on …

Upregulation Of Heme Oxygenase-1 Combined With Increased Adiponectin Lowers Blood Pressure In Diabetic Spontaneously Hypertensive Rats Through A Reduction In Endothelial Cell Dysfunction, Apoptosis And Oxidative Stress, Jian Cao, George Drummond, Kazuyoshi Inoue, Komal Sodhi, Xiao Ying Li, Shinji Omura

Pharmaceutical Science and Research

This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl2) to upregulate HO-1. Treatment with SnCl2 not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the peripheral blood (p<0.005) and an improvement of femoral reactivity (response to acetylcholine). Thus induction of HO-1 accompanied with increased plasma adiponectin levels in diabetic hypertensive rats alters the phenotype through a reduction in oxidative stress, thereby permitting endothelial cells to maintain an anti-apoptotic environment and the restoration of endothelial responses thus preventing hypertension.

Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough

MIIR Faculty Research

Background

Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading.

Methods

Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …