Pharmacology, Toxicology and Environmental Health Commons^™

Epoxy Resin Monomers With Reduced Skin Sensitizing Potency, Niamh F. O'Boyle, Ida B. Niklasson, Ali R. Tehrani-Bagda, Tamara Delaine, Krister Holmberg, Kristina Luthman, Ann-Therese Karlberg

Articles

Epoxy resin monomers, including diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to cause widespread contact allergy. This research describes a number of alternative epoxy resin monomers, designed with the aim of reducing the skin sensitizing potency whilst maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, assessed for skin sensitizing potency using the in vivo murine local lymph node assay, and tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. All the novel epoxy resin monomers had decreased skin …

Site-Directed Mutagenesis Of Conserved Amino Acids Residues In N5-Carboxyaminoimidazole Ribonucleotide Mutase: Converting N5-Cair Mutase Into Aminoimidazole Ribonnucleotide Carboxylase & Developing A High-Throughput Screening Assay For The Discovery Of N5-Carboxyaminoimidazole Ribonucleotide Mutase, Zhiwen Shi

Wayne State University Theses

The de novo purine biosynthesis pathway plays a critical role in providing new purines to the cell. Previous studies have shown differences between the human and bacterial pathways which suggests that pathway may be a potential target for antibiotic drug discovery. Three critical enzymes are involved in the pathway divergence. In the bacterial pathway, N5-CAIR synthetase (PurK) first converts AIR to N5-CAIR, which is then transformed into CAIR catalyzed by the enzyme N5-CAIR mutase (Class I PurE). In the human pathway, AIR carboxylase (Class II PurE) catalyzes the direct conversion of AIR to CAIR. Class I and Class II PurEs …

Design Of Functional Dendrimer Nanocarriers And Their Formulations In Propellant-Based Inhalers For Pulmonary Drug Delivery, Lin Yang

Wayne State University Dissertations

This Dissertation focuses on addressing two of the major challenges in developing pressurized metered dose inhalers for pulmonary drug / gene delivery to and through the lungs. First challenge is to design biocompatible moieties for the steric stabilization of suspension formulations in HFO-based propellants. Using a combination of tools including ab initio calculation, molecular dynamics simulation and high pressure tensiometry, potential fluorocarbon-philic moieties were systematically screened. Surfactants with those chemistries as tail fragments were studied at the HFO|H2O interface for their ability to lower the interfacial tension at HFO|H2O interface. Selected surfactants were further optimized for surfactant balance by altering …

Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago

Open Access Dissertations

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 0.3% of the total U.S. population, and its prevalence increases with age. Two neuropathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain involved in initiating and sustaining movement, and the presence of cytosolic inclusions called Lewy bodies (LBs) in various brain regions. LBs are enriched with fibrillar forms of the presynaptic protein &agr;-synuclein (aSyn). Two autosomal recessive genes implicated in familial PD are PARK9, encoding the P-type ATPase ATP13A2, a lysosomal ATPase; and …

Species - Dependent Cardiac And Motor Responses To Cholinergic Stimulation In Daphnia Pulex And Daphnia Magna, Bryan James Hannan

Wayne State University Theses

The role of acetylcholine (ACh) in regulating the activity of the heart and `feeding current' driven by the beating thoracic appendages of Daphnia pulex and Daphnia magna was evaluated using acetylcholinesterase inhibitors (AChE-I) and muscarinic receptor agonists. Single animals, tethered to a stainless steel pin, were tested in a watertight aquatic chamber that allowed free movement of appendages and swimming antennae. Heart contraction rate and the rate of thoracic appendage beating were quantified optically by measuring fluctuating changes in light-intensity caused by movement. Physostigmine, neostigmine, oxotremorine, pilocarpine as well as nicotine were used to study ACh and AChE. Atropine was …

Military Contamination And Persistent Organochlorine Pesticide Exposure Among Alaska Natives, Samuel Byrne

Legacy Theses & Dissertations (2009 - 2024)

St. Lawrence Island Alaska is located in the Bering Sea, only 36 miles from Siberia. The island is home to approximately 1600 Siberian Yupik residents, who rely heavily on subsistence hunting and gathering. There are two formerly used defense (FUD) sites on the island, one of which has been the subject of an approximate $110 million cleanup effort. Environmental monitoring suggests localized soil and watershed contamination with PCBs, organochlorine pesticides and heavy metals. Previous research suggests the site may be a source of PCB exposure for local residents. The primary aim of the study was to determine whether subsistence activities …

Paternal Occupational Pesticide Exposure And Neural Tube Defects In The National Birth Defects Prevention Study, Stacy Marie Pettigrew

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT

Sleep Duration And Diabetes In An Adult Population Of Rural Upstate New York, Tarak Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Within the past five decades, there has been a rapid increase in the number of diabetic cases in the US. The number of diabetic cases increased from 1.5 million in 1959 to 25.8 million in 2011. Around the same time period, the average sleep duration per night decreased from 8 hours to 6.9 hours.

Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan

Legacy Theses & Dissertations (2009 - 2024)

Glucocorticoids (GCs) are potent regulatory factors for inflammation. The synthesis of GCs involves several cytochrome P450 enzymes, such as mitochondrial CYP11A1, CYP11B1, and microsomal CYP21. Previous studies have indicated that the GCs, including those released from adrenal glands, and those synthesized in extra-adrenal tissues, such as intestine, exert inhibitory effects on inflammatory bowel disease (IBD). In a previous study using an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, the results suggested that the intestinal P450s had a protective role in DSS-induced acute colitis. In this study, using a hypomorphic CPR mouse model (Cprlow), which presents a global …

Atrazine In Maternal Drinking Water Supply Below The Federal Maximum Contaminant Level And Risk Of Preterm Birth, Small For Gestational Age, Cryptorchidism And Hypospadias, Daniel Rice

Legacy Theses & Dissertations (2009 - 2024)

The prevalence of preterm birth, small for gestational age (SGA), and hypospadias has been increasing for several decades in the U.S resulting in significant morbidity and mortality and direct costs to society. Drinking water provides a mechanism for prolonged chronic exposure to environmental contaminants but is one of the least assessed environmental exposures in pregnancy and birth outcomes. To test the hypothesis that maternal exposure to atrazine through drinking water during pregnancy, or one or more trimesters of gestation, is associated with an increased risk of preterm birth, small for gestational age, cryptorchidism and hypospadias a retrospective cohort study was …

Improving The Microbial Source Tracking Toolbox : Evaluating The Use Of Selective Enrichments And Artificial Sweeteners In A Multi-Tiered Approach, Stacey A. Helming

Legacy Theses & Dissertations (2009 - 2024)

Microbial contamination of surface waters is a public health concern world-wide, with non-point source fecal input contributing to millions of cases of waterborne illness annually. Numerous techniques have been proposed to monitor for non-point source fecal contamination, but few studies have explored the correlation of multiple chemical and microbial fecal source tracking markers in ambient waters. Therefore, the purpose of these studies was to evaluate the use of multiple "ideal" markers of fecal contamination and improve upon any analytical techniques required to identify species-specific fecal contamination in surface waters. The use of selective enrichments to improve the sensitivity of end-point …

Symbiotic Associations Between Vibrio Cholerae And Copepods And Their Potential Public Health Impact, Gretchen Boria Pérez

Legacy Theses & Dissertations (2009 - 2024)

Vibrio cholerae O1 concentrate in copepods by attaching to their chitinous exoskeleton and gut, making these planktonic crustaceans participants in the spread of cholera in marine and estuarine environments. The role of the symbiosis in the spread of gastrointestinal disease caused by non-O1 serotypes has not been well-studied in fresh water systems. The goal of these studies was to determine whether symbiotic association of V. cholerae with copepods affects virulence of hemolysin/cytolysin toxin, suspected in V. cholerae non-O1 related morbidity. The reverse-transcription-polymerase chain reaction was used to evaluate the relative transcriptional response of hlyA, encoding hemolysin, by a non-O1 strain …

Perfluorinated Compounds, Thyroid Function, And Neuropsychological Status In Older Residents Of Upper Hudson River Communities, Srishti Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Perfluorinated compounds (PFCs) are widespread in the environment. Minimal data exist regarding the neurotoxicity and thyroid disruptive property of PFCs in aging populations and the possible mediating effects of thyroid hormones (THs). In this study, we assessed associations among PFCs, thyroid function, and neuropsychological status, and determined if the neurotoxic effects of PFCs are mediated by changes in THs in an aging population. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), thyroid stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), and total triiodothyronine (T3) in serum and performed neuropsychological tests in men and women aged 55-74 years and living …

Exposure Assessment And Risk Management Of Engineered Nanoparticles : Investigation In Semiconductor Wafer Processing, Michele Shepard

Legacy Theses & Dissertations (2009 - 2024)

Engineered nanomaterials (ENMs) are currently used in hundreds of commercial products and industrial processes, with more applications being investigated. Nanomaterials have unique properties that differ from bulk materials. While these properties may enable technological advancements, the potential risks of ENMs to people and the environment are not yet fully understood. Certain low solubility nanoparticles are more toxic than their bulk material, such that existing occupational exposure limits may not be sufficiently protective for workers. Risk assessments are currently challenging due to gaps in data on the numerous emerging materials and applications as well as method uncertainties and limitations.

Runner Identity And Sponsorship: Evaluating The Rock ‘N’ Roll Marathon, Nancy L. Lough, Jennifer Pharr, Jason O. Owen

Environmental & Global Health Faculty Research

The economic value of participation sport has been reported to eclipse spectator sport significantly. However, scholars have acknowledged the relative lack of research on this important segment of the sport market. The purpose of this study was to analyze the relationship between runner identity and race sponsor effectiveness. Surveys were sent to participants in the Las Vegas Rock ‘n’ Roll Marathon. The survey was constructed to measure runner identity, and sponsor effectiveness as interpreted through rates of recognition, recall and purchase intention. Runners were divided into three groups based on their runner identity score. Of the predictive variables, only runner …

Development And Evaluation Of Plga-S-S-Peg Micelles Coencapsulating Curcumin Difluorinated And Paclitaxel For Synergistic Therapeutic Efficacy, Lakshmi Deepika Cheemalakonda

Wayne State University Theses

ABSTRACT

DEVELOPMENT AND EVALUATION OF PLGA-S-S-PEG MICELLES COENCAPSULATING CURCUMIN DIFLUORINATED AND PACLITAXEL FOR SYNERGISTIC THERAPEUTIC EFFICACY

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LAKSHMI DEEPIKA CHEEMALAKONDA

August 2014

Advisor: Dr. Joshua Reineke Major: Pharmaceutical Sciences Degree: Master of Science

Solid tumors like pancreatic tumor has unique property of forming a dense desmoplastic layer around the tumor cells making it difficult for the drug to transport across this layer. Multi drug resistance is also one of the major limitation of chemotherapy. Therefore the aim of this project was to make PLGA-SS-PEG micelles encapsulating CDF and paclitaxel for synergistic cancer therapy. CDF was found to have 16-fold better …

Functional Studies Of 5-Carboxyaminoimidazole Ribonucleotide Synthetase And Mutase From Thermotoga Maritima, Mingyang Zhao

Wayne State University Theses

De novo purine biosynthesis is divergent depending upon the organism. In bacteria, yeasts and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxyaminoimidazole ribonucleotide (CAIR) by N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (Class I PurE). In animals, AIR is converted into CAIR by AIR carboxylase (Class II PurE). The distinction makes PurK and Class I PurE good targets in design of antimicrobial drugs. N5-CAIR is chemically unstable with t1/2 of about 0.9 minutes at pH 7.8 and 37 °C. If the production of N5-CAIR is not regulated relative to its conversion to CAIR, ATP utilization can rapidly become non-stoichiometric. …

Proteomic Discovery Of Protein Phosphatase 1 Catalytic Subunit Protein Interaction Partners In Human Skeletal Muscle, Zhao Yang

Wayne State University Theses

Protein Phosphatase 1 (PP1), a member of Serine/ Threonine Phosphatase family, targets its dephosphorylation activity on serine and threonine residues. As the catalytic subunit of PP1, PP1c can achieve its substrate specificity only by binding with PP1 regulatory subunits. Previous researches have shown that PP1c can involve in multiple functional regulation by associating with various interaction partners. Since serine/ threonine phosphorylation on the Insulin receptor substrate-1 (IRS1) may direct inactivation and degradation of IRS1, this phosphorylation activity is believed to be a source of Insulin Resistance. PP1 is hypothesized to dephosphorylate serine/ threonine site on IRS1, which may rescue the …

Comparative Study Of The Prevalence Of Psk41 In Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates Against Non- Heterogenous Vancomycin-Intermediate Staphylococcus Aureus Isolates And The Prevalence By Patient Severity, Poorva Mukund Divekar

Wayne State University Theses

COMPARATIVE STUDY OF THE PREVALENCE OF PSK41 IN HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AGAINST NON- HETEROGENOUS VANCOMYCIN-INTERMEDIATE STAPHYLOCOCCUS AUREUS ISOLATES AND THE PREVALENCE BY PATIENT SEVERITY

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POORVA DIVEKAR

December 2014

Advisor: Dr. Emily T. Martin

Major: Pharmaceutical Sciences

Degree: Master of Science

Earlier studies have reported that pSK41 plays an important role in the transfer of vancomycin resistance from Vancomycin-resistant Enterococci (VRE) to S. aureus. This transfer leads to the development of Vancomycin-resistant S. aureus (VRSA). Thirteen VRSA cases have been reported in the United States since 2002. To determine and compare the prevalence of pSK41 in hVISA isolates …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …