Pharmacology, Toxicology and Environmental Health Commons^™

The Effects That Liquid And Solid Cattle Manure Have On The Water Quality Of Drainage Ditches In Putnam County, Ohio, Janelle Horstman

Honors Projects

Lake Erie has experienced harmful algal blooms with increased frequency since the mid-1990s due to excess nutrients from Rivers, such as the Maumee River, and largely agricultural watersheds. Nonpoint source pollution from agriculture contributes to eutrophication, algal blooms, and the degradation of water quality. This creates stress on aquatic fauna, reduced aesthetic quality, odor, and limits of the water for usage of drinking, recreation, and industry. This research paper asks what the contributions of having access to manure application records, soil records, and information about antibiotics have on what is known about manure management and antibiotic resistance, which has been …

Isolation And Characterization Of Natural Alpha-Glucosidase Inhibitors From Antioxidant Rich Red Wine Grapes (Vitis Vinifera), Hoda Chaouki Kadouh

Wayne State University Dissertations

Background: Diabetes is currently a global public health problem affecting people at all ages. Dietary antioxidants have been associated with a reduced risk of type 2 diabetes. Grape pomace contains considerable amounts of polyphenols and it has been reported to exhibit an inhibitory activity against alpha- glucosidases. Alpha-glucosidases, in turn, play a major role in controlling starch digestion and therefore postprandial blood glucose, a target for diabetes management.

Objective: This study aims to investigate the anti-diabetes potential of a selection of six grape pomaces and prepare and purify active components in the active variety that specifically inhibit intestinal alpha-glucosidases. The …

Wastewater Influent And Effluent Concentrations Of 17 Beta-Estradiol: A Study Of The Influence Of A University Community And The Risk To Environmental Health, Kyle Heffron

Masters Theses

The concentration of 17β-estradiol (E2) was measured through stages of wastewater treatment at a central Illinois wastewater treatment plant (WWTP). E2 concentration was quantified using a competitive enzyme linked immunosorbent assay (ELISA). The concentration of E2 was compared with demographic effects of a university, physical parameters of the wastewater (dissolved oxygen, pH, and temperature) and daily influent and effluent flow rates. Effluent concentrations ranged from 0 to 25.3 ng L^-1 with an average discharge of 3.6 ng L^-1. E2 concentration was shown to increase at the start of each university semester, however, this trend was not observed …

The Effects Of 1, 3, & 7 Trisubstituted And 8-Cyclopentyl Alkylxanthines On Respiration In Newborn Rats, Nathan Creel Davidson

Masters Theses

Methylxanthines have been shown to be promising respiratory stimulants in newborns suffering from recurrent apnea. The respiratory stimulant effects of methylxanthines are most likely due to their antagonism of adenosine receptors. These drugs have been shown to stimulate respiration in newborn rats in doses in excess of 10 mg/kg body weight. Structure-activity studies have shown that methylxanthines not only differ in the antagonism of A₁ and A₂ adenosine receptors but also, as a consequence of their different chemical structures, differ in potency as respiratory stimulants. To assess this, two potent A₁ adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and …

Novel Compounds As Potential Alzheimer's Disease Therapeutics And Inhibitors Of The Nlrp3 Inflammasome, Jeremy E. Chojnacki

Theses and Dissertations

Alzheimer’s disease is a devastating neurodegenerative disorder and the leading cause of dementia. The disease manifests via several pathologies including neuroinflammation, oxidative stress, metal ion dyshomeostasis, and cell death. To address the multifaceted nature of this disorder, the design of several diverse compounds, targeting many pathological effects, was generated. First, a series of compounds based on curcumin and diosgenin were synthesized following the bivalent design strategy. Two compounds were discovered to have neuroprotective ability, anti-oxidative function, and anti-Aß oligomerization (AßO) properties. A second set of molecules was also designed, wherein a hybrid compound strategy was utilized. Three hybrids were to …

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 …

The Association Of Cold Weather And All-Cause And Cause-Specific Mortality In The Island Of Ireland Between 1984 And 2007, Ariana Zeka, Stephen Browne, Helen Mcavoy, Patrick Goodman

Articles

Background: This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods: A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and an extended cold period (October-March), using distributed lag models. Model stratification by age 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

by

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 …