Pharmacology Commons^™

The Effects Of Alcohol On Crash Avoidance Reaction Time In A Driving Simulator Task In Humans, Aishwarya Vasudevan

Wayne State University Theses

AIM 1: Alcohol-impaired driving continues to be a significant cause of car crash injuries and deaths. The blood alcohol concentration (BAC) cut-off level for drunk driving is 0.08% in Michigan, and is estimated that lowering this cut-off to 0.05%would save 500–800 lives every year in the US alone. We used a portable virtual reality (VR)-based driving simulator to demonstrate the effects of alcohol at BAC concentrations 0.02-0.08%, grouped into 0.01% increments, on driving performance, specifically Crash Avoidance Reaction Time (CART), i.e., the time (in msec) required to initiate a steering avoidance response. We found that BAC concentrations as low as …

High-Throughput Screening Of Fda-Approved Drugs For Protecting Retinal Pigment Epithelial Cells Against Er Stress Induced Cell Death: Implications For Age-Related Macular Degeneration, Shaima Ali Jawarneh

Wayne State University Theses

Purpose: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population, characterized by the degeneration of the retinal pigment epithelium (RPE). The link between endoplasmic reticulum (ER) stress and AMD is well established, however FDA-approved medications for the treatment of AMD caused by unregulated ER stress are limited and have potential side effects. The purpose of this study was to conduct a comprehensive screening of the FDA-approved drug library in order to identify potential candidates that could be repurposed in order to protect against the degeneration and death of RPE cells due to ER stress.

Methods: …

The Effects Of Gestational Exposure To Buprenorphine Or Morphine On Offspring Development, Abigail Myers

Wayne State University Theses

The opioid crisis in the United States has grown to epidemic proportions with opioid dependence among pregnant women quadrupling from 1999-2014. Opioid-dependent pregnant women are commonly given opioid maintenance therapies (e.g., buprenorphine), but the developmental and neurological effects of these drugs on offspring development are poorly understood. Our study uses a translational rodent model to characterize the developmental consequences of gestational morphine (“MS”; mimicking opioid use disorder) or buprenorphine (“BUP”; mimicking opioid maintenance therapy) exposure on exposed offspring. Female rats started BUP (1.0 mg/kg) or MS (3-6.0 mg/kg) exposure 7 days before pregnancy to represent an established user and either …

Patholigical And Prognostic Role Of Mdig In Pancreatic Cancer, Srinivas Ashok Kumar

Wayne State University Theses

Pancreatic cancer is a highly aggressive malignant disease having very limited therapeutic options that ultimately results in its poor prognosis. It is still elusive on the etiology and tumorigenic mechanisms of pancreatic cancer. In the present report, we provide evidence showing involvement of the mineral dust-induced gene (mdig) in the pathogenesis and prognosis of the pancreatic cancer. Using immunohistochemistry approach on human pancreatic cancer tissue microarray, we found differential expression of mdig in pancreatic adenocarcinoma and normal pancreas. Based on the staining intensities of mdig in these tissue samples, we found that 12% of the cancer tissues were strongly positive …

Metformin, Glucotoxicity And Islet Dysfunction, Sartaj S. Baidwan

Wayne State University Theses

METFROMIN, GLUCOTOXICITY AND ISLET DYSFUNCTION

by

SARTAJ BAIDWAN

MAY 2017

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Master of Science

Glucotoxicity is the leading cause for β-cell dysfunction [e.g., defective glucose-stimulated insulin secretion] in Type 2 Diabetes [T2DM]. Recent studies from our lab have shown sustained Rac1 activation leading to the activation of downstream signaling steps including stress kinase [p53, p38MAPK] activation and mitochondrial dysregulation [caspase-3 activation] in pancreatic islet beta-cells exposed to glucotoxic [HG] conditions [20 mM; 24 hrs]. Metformin [MF] is an oral anti-diabetic drug that is being widely prescribed to T2DM. MF works by suppressing hepatic …

Endocrine-Disrupting Properties Of Pharmaceuticals And Personal Care Products (Ppcps): An Evaluation Using Aquatic Model Organisms, Manahil Monshi

Wayne State University Theses

Thousands of chemicals have introduced into the environment as a result of human activity since the industrial revolution, and the U.S. Government Accountability Office has estimated that as many as 1,500 new chemical entities are synthesized each year ("Key Issues: Toxic Chemicals - High Risk Issue," 2017). Many of these chemicals are now found in surface water and ground water and can have detrimental effects on environmental health and on human health. This anthropogenic contamination has resulted in the labeling of the diverse array of chemicals found in water, which are not routinely monitored or regulated, as contaminants of emerging …

Novel Protein Phosphatase 2a Complexes In Skeletal Muscle From Obese Insulin Resistant Human Participants, Divyasri Damacharla

Wayne State University Theses

Type 2 Diabetes is a metabolic disorder associated with insulin resistance and consequent high blood glucose levels. Maximum glucose disposal takes place in skeletal muscle and studying skeletal muscle insulin resistance is crucial. Protein Phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases belonging to PhosphoProteinPhosphatase (PPP) family. It constitutes about 80% of all serine/threonine phosphatases. It is regulated by numerous regulatory subunits as well as other substrate molecules and post translational modifications. This alters their localization, activity and also its target molecules. Many evidences show the effect of insulin on PP2Ac and its abnormal regulation in conditions of …

The Role Of E3 Ligase Parkin In Trafficking Of Monoamine Storage Vesicles In Rat Model Of Methamphetamine Neurotoxicity, Heli Dineshchandra Chauhan

Wayne State University Theses

Methamphetamine (METH), a psychostimulant, is a widely used drug of abuse. METH is toxic to dopaminergic (DAergic) and serotonergic (5-HT) nerve terminals in the striatum when administered at high doses. METH releases Dopamine (DA) from vesicular monoamine transporter 2 (VMAT2) containing synaptic vesicles and induces oxidative stress by auto-oxidation of DA. The VMAT2 plays a neurprotective role by sequestering cytoplasmic DA into vesicles for storage and protection from auto-oxidation. It has previously been shown that METH toxicity is associated with impaired VMAT2 trafficking and oxidative damage to the E3 ligase parkin. CDCrel1, a protein found to inhibit exocytosis, is regulated …

Effect Of Metformin On Global Phosphorylation Profiles Of Primary Skeletal Muscle Cells Derived From Overweight/Obese Insulin Resistant Human Participants, Nishit Shah

Wayne State University Theses

Metformin is a drug from the biguanide class and it has been in use for the treatment of type 2 diabetes for a long time, and it can improve insulin sensitivity in skeletal muscle. However, the mechanism for metformin’s action is unclear. Phosphatases and kinases, and their subunits are the proteins required for dephosphorylation and phosphorylation of proteins in cells during various signaling pathways. Phosphorylation studies of proteins from primary cell culture derived from skeletal muscle tissue from obese/overweight insulin resistant participants will help to understand the regulation of phosphorylation in phosphatases and kinases by metformin.

In the current research, …

The Effect Of Alpha-Cyclodextrin On Acute Blood Lipid And Glycemic Responses To A Fat Containg Meal, Evan Neil Fletcher

Wayne State University Theses

Obesity and hyperlipidemia have become major concerns in the United States over the past 30 years. Alpha-Cyclodextrin (á-CD), a naturally occurring soluble dietary fiber, has been shown to reduce dietary fat absorption and improve blood lipid levels in an animal model (mouse and rat) and in human studies. In the current double blind study, 34 healthy male and female participants were recruited to test if á-CD had any acute effect on blood lipid and glycemic responses to a fat containing meal. The participants received the á-CD on one occasion and a placebo the other to determine if there was any …