Pharmacology, Toxicology and Environmental Health Commons^™

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 …

Raman Micro-Spectroscopy For Rapid Screening Of Oral Squamous Cell Carcinoma, Luis Felipe Carvalho, Franck Bonnier, Kate O'Callaghan, Jeff O'Sullivan, Stephen Flint, Hugh Byrne, Fiona Lyng

Articles

Raman spectroscopy can provide a molecular-level fingerprint of the biochemical composition and structure of cells with excellent spatial resolution and could be useful to monitor changes in composition for dysplasia and early, non-invasive cancer diagnosis (carcinoma in situ), both ex-vivo and in vivo. In this study, we demonstrate this potential by collecting Raman spectra of nucleoli, nuclei and cytoplasm from oral epithelial cancer (SCC- 4) and dysplastic (pre-cancerous, DOK) cell lines and from normal oral epithelial primary cell cultures, in vitro, which were then analysed by principal component analysis (PCA) as a multivariate statistical method to discriminate the spectra. Results …

In Vivo Analysis Of A Salt Bridge At The External Gate Of The Drosophila Melanogaster Serotonin Transporter In Response To Amphetamines, Timothy J. Beenen

Open Access Theses

Monoamine neurotransmitter transporters are membrane proteins responsible for the clearing of biogenic amines from a synapse. These transporters are targets for many important pharmaceuticals including antidepressants, as well as psychostimulant drugs such as cocaine and amphetamines. Amphetamines are believed to elicit their psychostimulant activity primarily by inducing a reversal of the transport cycle and increasing neurotransmitter release into the synapse, though the mechanism of this activity is incompletely understood. Previous in vitro research has suggested functional significance of a conserved salt bridge in the serotonin transporter (SERT) in amphetamine-induced 5-HT efflux. This salt bridge is disrupted in the Drosophila melanogaster …

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal

Wayne State University Dissertations

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable. …

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome inhibitor-induced …

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 …

The Use Of Rna Interference To Mitigate Pulmonary Fibrosis In Response To Asbestos Exposure, Sarah Kinsey

Undergraduate Theses, Professional Papers, and Capstone Artifacts

The adverse health effects of exposure to asbestos are widely known and have been well documented. When a person is diagnosed with asbestosis, a chronic lung disease caused by inhaling asbestos fibers, few treatment options exist, none of which halt or reverse the progression of the disease. The rapidly growing field of gene therapy offers new avenues for potential treatments worthy of investigation. The detrimental effects of asbestos exposure are due to the physiological response of the lungs to asbestos fibers in the form of fibrosis, a result of excess extracellular collagen deposition. A protein called SPARC (Secreted Protein Acidic …

Characterization Of Metallic And Semimetallic Oxide Nanoparticles In Industrial Wastewater And Associated Toxicity, Gary Roth

Legacy Theses & Dissertations (2009 - 2024)

Engineered nanomaterials (ENMs) play an increasing role in manufacturing and consumer products. Currently, there is no standard approach to studying ENM toxicity, and a growing body of literature suggests that ENMs may have toxicity differing from similar compounds in bulk or dissolved form. I examined ENMs used in the semiconductor manufacturing process called chemical-mechanical planarization (CMP) for their properties, removal in the wastewater treatment system (WWT), in-vitro toxicity, and location post-inhalation in-vivo. It was found that ENMs in CMP slurries have morphology determined by their elemental composition, but assessment of size and concentration can differ substantially between accepted techniques. Particles …

Study Of Human Ovarian Follicular Fluid High Density Lipoprotein (Hdl) And Embryo Quality During In Vitro Fertilization (Ivf), Keewan Kim

Legacy Theses & Dissertations (2009 - 2024)

Follicular fluid (FF) is in direct contact with granulosa cells that surround a developing oocyte, and high density lipoprotein (HDL) is the sole lipoprotein found in FF. Therefore, we investigated 41 FF HDL particle components, including 26 HDL-cholesterol (HDL-C) subfractions measured for particle size, apolipoproteins, enzymes, and lipophilic micronutrients, in association with embryo quality on 180 women undergoing in vitro fertilization (IVF).

Role Of Caveolin-1 And Nrf2 In Nutritional Modulation Of Pcb Toxicity, Michael C. Petriello

Theses and Dissertations--Toxicology and Cancer Biology

Cardiovascular disease is the leading cause of mortality in Western societies and is linked to multiple modifiable risk factors including lifestyle choices. Emerging evidence implicates exposure to persistent environmental pollutants, such as polychlorinated biphenyls (PCBs), as a risk factor for the development or progression of cardiovascular disease. To reduce disease risks, it is critical to identify sensible means of biomedically reducing the toxicity of persistent organic pollutants and related environmental stressors.

First, we tested a hypothesis that endothelial cell inflammation and subsequent cardiovascular toxicity initiated by coplanar PCBs is modulated by the crosstalk between caveolae and Nuclear factor (erythroid-derived 2)-like …

Bacterial Communication And Its Role As A Target For Nanoparticle-Based Antimicrobial Therapy, Kristen Publicover Miller

Theses and Dissertations

The goal of this dissertation is to establish the environmental and public health importance of alternative forms of antimicrobial therapy, specifically those that utilize nanotechnology to combat quorum sensing-controlled bacterial infections. Quorum sensing (i.e. chemical communication) is an inherent characteristic that is essential to bacterial pathogenesis and biofilm formation (where most infections occur). A thorough review of the literature has been conducted to establish an understanding of the state of nanotechnology research as it relates to combatting bacterial infections. This synthesis, provided in Chapter 1, demonstrates how the chemical and structural designs of nanoparticles can be manipulated to specifically target …

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 …

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 …

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 …

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 …

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, …

Therapeutic Targeting Of Bmp2 In Nf1-Deficient Malignant Peripheral Nerve Sheath Tumors (Mpnsts), Sidra Ahsan

Wayne State University Dissertations

Neurofibromatosis type I (NF1)-deficient malignant peripheral nerve sheath tumor (MPNST) is an aggressive tumor for which the standard treatment is surgical removal with wide margins, often leaving behind cancer cells needing chemotherapy. RAS-GRD is the most widely studied functional target of NF1 implicated in tumorigenesis, however, therapeutic interventions targeting RAS activity have met with limited success. Using gene expression profiling, our lab identified BMP2-SMAD1/5/8 signaling pathway as a therapeutic target in MPNSTs, independent of the NRAS and MEK1/2 regulation. The overall goal of my research was to validate the significance of BMP2 in MPNSTs in novel cellular models, study the …

Full Issue: Volume 8, Number 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.