Pharmacology, Toxicology and Environmental Health Commons^™

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 …

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 …

Contaminants Of Emerging Concern: Effects Of Known Neuroactive Agents, Antibiotics, And Chemically Uncharacterized Photodegredates On Behavior And Physiology Of Daphnia Pulex, Vibhuti Matta

Wayne State University Theses

Emerging contaminants such as pharmaceuticals and personal care products (PPCPs), herbicides, pesticides, plasticizers, fire retardants, polycyclic aromatic hydrocarbons (PAHs), and other organic waste are increasingly being detected in surface water and ground water. These contaminants can enter into the environment through wastewater treatment plant effluent and agriculture runoff. Many of these emerging contaminants tend to be biologically active at very low concentrations, typically occur in water as part of complex mixtures, and may impact biota at concentrations not detected using traditional toxicity tests (e.g. LC 50 tests).

This study focuses on utilizing novel Daphnid optical bioassays to examine the toxicity …

Protein Ubiquitination In Primary Human Skeletal Muscle Cells Under Hyperinsulinemic Hyperglycemic Conditions, Majed Abdullah Alharbi

Wayne State University Theses

Ubiquitin proteasome system is a relatively newly discovered pathway for protein degradation. Many studies have successfully pointed out the critical functions that UPS plays in regulating many physiological processes. On the other hand, recent studies suggested that abnormal UPS activities might be involved in the pathophysiology of several disorders including type 2 diabetes. However, the specific changes in UPS during the development of insulin resistance and consequently T2D are still unclear.

UPS is composed of two major steps, a reversible ubiquitin conjugation to the targeted substrate followed by proteasomal degradation of the ubiquitinated proteins. In this study, we examined the …

A Retrospective Cohort Study Of High Prevalence Of St131 Among Extended Spectrum Β-Lactamase Producing E. Coli Among Inpatients In The Metropolitan Detroit Area, Pansy Awasthy

Wayne State University Theses

ABSTRACT

HIGH PREVALENCE OF ST131 AMONG EXTENDED SPECTRUM Β-LACTAMASE PRODUCING E. COLI AMONG INPATIENTS IN THE METROPOLITAN DETROIT AREA

by

PANSY AWSTHY

2015

Advisor: Dr. Emily T. Martin

Major: Pharmaceutical Sciences

Degree: Master of Science

Objectives: E.coli ST131 multi-locus sequence type (MLST) has been associated with extended spectrum β-lactamase (ESBL) production, conferring antimicrobial resistance, with increased virulence and with healthcare-associated infection. The high prevalence of multidrug antimicrobial resistance in ESBL-producing ST131 E.coli infections creates unique challenges in the studying patient outcomes and analysis are required to study ST131 E.coli amongst a large population of ESBL-producers. Our objective was to determine …

Combination Of Photodynamic Therapy With Fenretinide And C6-Pyridinium Ceramide Enhances Killing Of Scc17b Human Head And Neck Squamous Cell Carcinoma Cells Via The De Novo Sphingolipid Biosynthesis And Mitochondrial Apoptosis, Nithin Bhargava Boppana

Wayne State University Theses

The ceramide generated via the de novo sphingolipid biosynthesis has been shown to regulate apoptosis and cell death. The de novo sphingolipid biosynthesis includes ceramide synthase (CERS)-dependent acylation of dihydrosphingosine, giving rise to dihydroceramide, which is then converted to ceramide by a desaturase-dependent reaction. The mitochondrial pathway of apoptosis, characterized by induction of Bax associated with mitochondria and cytochrome c release/redistribution. Bcl2, an anti-apoptotic protein blocks apoptosis by inhibiting Bax. Elucidating the role of de novo sphingolipid biosynthesis and mitochondrial apoptosis in PDT, PDT+4HPR and PDT+LCL29 could help in improving the effectiveness on these anti-cancer treatments. The objective of this …

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, …

Exploring Novel Daptomycin Combinations With Β-Lactam Against Susceptible & Non-Susceptible Enterococcus Species, Animesh Raut

Wayne State University Theses

EXPLORING DAPTOMYCIN COMBINATION WITH β-LACTAM SYNERGY AGAINST SUSCEPTIBLE AND NON-SUSCEPTIBLE ENTEROCOCCI SPECIES

by

ANIMESH RAUT

August 2015

Advisor: Dr. Michael J. Rybak

Major: Pharmaceutical sciences

Degree: Master of Science

Objective: Enterococcus faecalis and Enterococcus faecium are generally resistant to daptomycin and β-lactam antibiotics. However, documented in vitro data suggests synergy between several β-lactam antibiotics and daptomycin against resistant organisms. Primary goal of the study was to check various combinations of β-lactam antibiotics with daptomycin (DAP) and assess the potential of synergy and conclude which could be the superior combination. Study also evaluated potential of β-lactam antibiotics to enhance activity of …