Pharmacology, Toxicology and Environmental Health Commons^™

Exploring Policy Options To Combat Illegal Micro-Apartments In Hong Kong, Yung Yau, Daniel Chi Wing Ho

Faculty of Design & Environment (THEi)

Illegal building can take multiple forms, including squatter settlements and illegal building extensions. Among the various forms of illegal building, illegal microapartments (IMAs), which take the form of unauthorised subdivided housing units, have recently aroused wide public concern in Hong Kong. On account of their unlawful nature, IMAs pose serious threats to the safety of local communities by undermining structural stability and fire safety in buildings. They may also adversely affect natural lighting and ventilation for building occupants. Fatal fires in buildings with IMAs in recent years have demonstrated the painful consequence of ignoring this issue in the city. Nonetheless, …

Usage Of Extracellular Microvesicles As Novel And Promising Therapeutic Tool In Wound Healing, Sami Gamaleddin F. Alsabri

Browse all Theses and Dissertations

Introduction Extracellular Microvesicles (EMVs) can carry genetic messages and biologically active proteins throughout tissues and the body. Because of their transport capabilities, EMVs play an important role both diseased and healthy conditions. For example, EMVs play an important regenerative role in many damaged tissues. In the current studies, we examine the role of EMVs in epithelial wound healing. The potential use of EMVs as drug delivery vehicles has gained considerable scientific interest because they can be delivered in circulation, can be targeted to specific areas/cells, and can pass natural barriers. In the current work, we investigate the potential of EMVs …

Steroids: A Growing Dilemma In Athletics, Seara Ontiveros

Nebraska College Preparatory Academy: Senior Capstone Projects

A comprehensive and straight forward description of what exactly steroids are and what they do to the body is described by Gary Wadler, a health major at the New York University School of Medicine, he comments: “When the receptor sites in their bodies, which don’t have much testosterone in them, suddenly are presented with a lot of testosterone, they get activated…The unbalance of hormones increases the red blood cell formations... They’ll get more muscular, more defined. They’ll lose some fat, and increase their lean body mass, [they’ll] get stronger”. Although anabolic steroids and other hormones are consumed by many athletes …

Transfer Of Antibiotics From Wastewater Or Animal Manure To Soil Andedible Crops., Livia Min Pan, L.M. Chu

Faculty of Design & Environment (THEi)

Antibiotics are added to agricultural fields worldwide through wastewater irrigation or manure application, resulting in antibiotic contamination and elevated environmental risks to terrestrial environments and humans. Most studies focused on antibiotic detection in different matrices or were conducted in a hydroponic environment. Little is known about the transfer of antibiotics from antibiotic-contaminated irrigation wastewater and animal manure to agricultural soil and edible crops. In this study, we evaluated the transfer of five different antibiotics (tetracycline, sulfamethazine, norfloxacin, erythromycin, and chloramphenicol) to different crops under two levels of antibiotic-contaminated wastewater irrigation and animal manure fertilization. The final distribution of tetracycline (TC), …

Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata

Pharmacology and Physiology Faculty Publications

Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity …

Evaluation Of Childhood Exposure To Lead In Community Water Systems In Maine, Nicholas Flavin

Muskie School Capstones and Dissertations

The concentration of lead in Maine’s public drinking water was evaluated from 4,700 first-draw water samples collected from 358 Maine Community Water systems. Samples collected from 2012-2015 were obtained by request from the Maine Center for Disease Control and Prevention’s (MeCDC)’s Drinking Water Program.

Exposure and physiological uptake of lead can be mathematically modelled or predicted based on the amount of lead in “background” sources of contaminated media such as soil, dust, water, air or dietary items; the better the characterization of lead in these media, the better the exposure predictions. To assess childhood lead exposure, EPA recommends using the …

Amitraz And Its Metabolite Modulate Honey Bee Cardiac Function And Tolerance To Viral Infection, Scott T. O'Neal, Carlyle C. Brewster, Jeffrey R. Bloomquist, Troy D. Anderson

Department of Entomology: Faculty Publications

The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat. The goal of this study was to …

Examining The Regulation Of Kv7 K+ Channels In Airway Smooth Muscle Cells And Their Potential As Novel Therapeutic Targets For The Treatment Of Asthma, Jennifer Haick

Dissertations

Asthma is a disease characterized by nonspecific and exaggerated airway narrowing, termed airway hyperresponsiveness (AHR), which involves the excessive contraction of airway smooth muscle. Despite the fact that airway smooth muscle is widely studied and understood to play a role in AHR, little is known about the specifics of that role. Our laboratory recently found that Kv7 potassium (K+) channels are expressed in airway smooth muscle cells (ASMCs). Kv7 channels are voltage sensitive K+ channels whose outward flux of K+ ions promotes a negative resting membrane voltage in excitable cells, thereby opposing electrical excitability. Inhibition of K+ channels is known …

Characterization Of The Effect Of Aeration On A Commercially Available Fibrin Sealant For Use In Wound Therapy, Adam Robert Marek

Dissertations

Wound care affects millions of people worldwide each year, and the need for an effective wound therapy still exists. The aim of this study was to characterize a novel, aerated biopolymer, fibrin foam, which is generated through a patented mixing process using a commercially-available fibrin sealant. This research developed a distinct preparation of fibrin foam that creates a porous environment with improved wound healing properties. With this fibrin foam, characterization assessments were performed, including evaluation of mixing parameters, biocompatibility, and biomechanical strengths.

Fibrin foam is created by performing six passes through a mixing device, which generates a foam matrix with …

Molecularly Imprinted Polymers Synthesized As Adsorbents For Ergot Alkaloids: Characterization And In Vitro And Ex Vivo Assessment Of Effects On Ergot Alkaloid Bioavailability, Manoj B. Kudupoje

Theses and Dissertations--Animal and Food Sciences

Alkaloid toxicities negatively impact livestock health and production and are of serious economic concern to animal industries. To date, few strategies have been developed to evaluate alkaloid levels in feed or to counteract alkaloid toxicities. The present research evaluated the applicability of imprinting technology to synthesize polymers that have potential to interact with ergot alkaloids and therefore reduce their bioavailability in the GIT. The studies also evaluated applicability of synthesized polymers for use in the ruminal environment using an in vitro ruminal fermentation model, and for the ability to ameliorate vasoconstriction using ex vivo myographic evaluations.

In the first experiment, …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …

Deubiquitinases In Ubiquitin Homeostasis And Disease, Gorica Ristic

Wayne State University Dissertations

Protein quality control (PQC) is indispensable for normal cellular functions, ensuring proteins are properly folded and removing those proteins that are functioning aberrantly. Perturbations in PQC can lead to various malignancies, neurodegeneration and neurological diseases. The Ubiquitin-Proteasome Pathway (UPP) is one important pathway in PQC, it relies on ubiquitination-dependent post-translational modification to selectively degrade misfolded or short-lived protein. Ubiquitination is reversed by the action of proteases known as deubiquitinating enzymes (DUBs). By hydrolyzing ubiquitin linkages, DUBs are responsible for cleaving and activating newly produced ubiquitin molecules, editing poly-Ub chains, removing ubiquitin from a substrate protein and recycling mono-Ub. Here, I …

Protein Phosphatase 2a Function And Regulation In Insulin Resistant Human Skeletal Muscle Cells, Shukurat Sulaiman

Wayne State University Theses

Protein Phosphatase 2A (PP2A), a major serine/threonine phosphatase involved in insulin signaling pathway, plays a critical role in the development of insulin resistance and type 2 diabetes (T2D), which is characterized with hyperinsulinemic hyperglycemic condition. Moreover, majority of the glucose disposal takes place in the skeletal muscle which is also the main tissue responsible for insulin resistance. The catalytic subunit of PP2A (PP2Ac) can interact with multiple regulatory subunits and other regulatory proteins as well as substrates. These interactions are important for maintain normal PP2A function and subsequent cell signaling. We hypothesized that hyperinsulinemic hyperglycemic condition and insulin stimulation would …

Aluminum And Phthalates In Calcium Gluconate: Contribution From Glass And Plastic Packaging, Robert A. Yokel, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged~ 4000 [mu]g/L, compared to < 200 [mu]g/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity.

Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic …

Salvianolic Acid B For Pulmonary Delivery Towards Reversal Of Emphysema, Sneha Dhapare

Theses and Dissertations

A new pathobiologic hypothesis has recently emerged that the alveolar structural destruction and loss in emphysema are caused by the deficiency of vascular endothelial growth factor (VEGF). Therefore, this project hypothesized that such pathobiologic VEGF deficiency of emphysematous lungs can be recovered with a natural caffeic acid tetramer, salvianolic acid B (SalB), through activation of signal transducer and activator of transcription 3 (STAT3), so that emphysema can be reversed as a result of inhibition of induced cell death, stimulation of cell proliferation and migration, and promotion of stem cell recruitment to the lungs.

SalB was first shown to be potently …

Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk

Legacy Theses & Dissertations (2009 - 2024)

Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …

Biomarkers And Metabolic Mechanisms Of Tobacco Smoke-Induced Lung Disease, Matthew Alan Hartog

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of the research conducted in this dissertation is to determine the role of cytochrome (CYP) P450-mediated xenobiotic bioactivation in the development of tobacco smoke-induced lung toxicity. The central hypothesis of this work is that CYP-mediated bioactivation of specific tobacco smoke constituents is an important contributor to the generation of tobacco smoke-induced lung inflammation and injury. The specific aims are 1) to demonstrate that CYP-mediated metabolism contributes to the onset of lung inflammation following tobacco smoke inhalation; 2) to demonstrate that specific tobacco smoke constituents undergo CYP-mediated bioactivation in vivo; 3) to demonstrate that CYP-mediated bioactivation of tobacco …

Wheezing & Food Allergies In Infants Delivered Via Cesarean Section : The Upstate Kids Study, Temilayo Elizabeth Adeyeye

Legacy Theses & Dissertations (2009 - 2024)

This dissertation sought to assess the effect of cesarean delivery (CD) on the risk of developing wheezing or food allergies in early childhood; and whether breastfeeding mediates the association between CD and the outcomes. We also aimed to highlight the differences in immunoglobulin concentrations by mode of delivery (MOD) in newborn dried blood spots (DBS), and the subsequent development of wheezing and food allergies in infants during the first three years of life. Data from the Upstate KIDS cohort was analyzed. Modified Poisson regression was used to compare the risks for wheezing and food allergies by MOD. We used a …

Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal

Legacy Theses & Dissertations (2009 - 2024)

The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …

Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho

Legacy Theses & Dissertations (2009 - 2024)

Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …

Sources, Pathways, And Distribution Of Bisphenol A Diglycidyl Ether (Badge) And Its Derivatives In The Environment, Jingchuan Xue

Legacy Theses & Dissertations (2009 - 2024)

BADGE (bisphenol A diglycidyl ether) based epoxy resins have been used in a variety of applications since the 1940s. However, limited studies are available about the occurrence of BADGE and its derivatives (BADGEs) in the environment. The aims of this thesis were to determine the concentrations of BADGE and its derivatives in dental sealants and textile products from the U.S. to characterize the sources of these substances. Furthermore, concentrations of BADGEs in samples from various stages of waste water treatment plants (WWTPs) in the U.S. were also determined to investigate the environmental pathway and fate of these substances. BADGEs were …

Short Term Effects On Symptoms Of Atopic Dermatitis In Children By Weather And Polution, Paolo Kinsella

Natural Sciences Student Research Presentations

This slide presentation for the Natural Sciences Poster Session at Parkland College summarizes a Korean study (Kim et al) on the effects of weather and air pollution on the severity and persistence of atopic dermatitis, a prevalent condition in Korea.

Prenatal Methylmercury Exposure Through Rice Consumption In Rural China, Chuan Hong

Theses and Dissertations

Background: Methylmercury is one of the most toxic forms of mercury, which severely afflicts the developing fetus. Methylmercury exposure occurs not only through fish consumption but also through rice consumption. However, rice does not contain the same beneficial micronutrients that fish/shellfish has. Therefore, prenatal methylmercury exposure through maternal rice consumption may potentially increase adverse health effects on the developing fetus.

Objectives: The purpose of this dissertation was to investigate the magnitude of prenatal methylmercury exposure through rice consumption and the relationship between maternal mercury biomarkers and birth outcomes.

Methods: A total of 398 pregnant women were recruited at parturition in …

Biochemical, Structural, And Drug Design Studies Of Norovirus And Zika Virus Proteases, Ben Kuiper

Wayne State University Dissertations

Noroviruses, which are the leading cause of acute gastroenteritis, cause an estimated 677 million infections and 213,000 deaths each year worldwide. Noroviruses are classified into seven genogroups (GI-GVII); GI, GII, and GIV have been shown to be infectious in humans. However, GII noroviruses cause the majority of outbreaks (89%). No pharmacologic treatment or vaccine currently exists to treat or prevent norovirus infections.

Recently, the development of a norovirus replicon system, a murine model of norovirus infection, and the development of a biochemical protease assay have allowed for the design and development of norovirus inhibitors. However, the replicon and biochemical assay …

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 …

An Evaluation Of Endocrine Disrupting Effects Of Emerging Contaminants Using Daphnia Pulex And Danio Rerio, Lakshmi Neha Reddy Alla

Wayne State University Theses

The limit of the availability of water is based on two factors, scarcity and quality. Conserving and protecting our water resources one of the most critical issues facing humanity as we struggle to deal with contaminated lakes and rivers and climate change. The main aim of this study is to examine toxicity of known water contaminants on aquatic model organisms and be able to develop methodology that will enable the characterization of endocrine disrupting potential of water samples with unknown contaminants. Both the category of water contaminants known as pharmaceuticals, personal care products that are known as PPCPs and other …

Redox Responsive Cerium Oxide Nanoparticles And Cd44 Targeted Nanomicelles For Selective Cancer Therapy, Zhaoxian Wang

Wayne State University Theses

Redox-responsive cerium oxide nanoparticles (CNPs) can play a versatile role in cancer therapy due to their ability to induce oxidative stress under proper pH conditions. Hyaluronic acid micelles with a high affinity to CD44 receptor which achieved more cytotoxicity towards cancer cells. The polymer-coated CNPs and HA-SMA-TPGS-CDF nanomicelles were developed for cancer therapy. The results showed that the toxicity of CNPs in tumor cells was mediated by the pro-oxidant property of CNPs under relative low pH conditions (pH~6.5) of the tumor microenvironment whereas CNPs play a (cytoprotective) anti-oxidant role, scavenging reactive oxygen species and reducing oxidative stress under normal pH …

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 …

The Role Of Line-1 Transposable Element In Methamphetamine Neurotoxicity In The Neurogenic Zones, Dongyue Yu

Wayne State University Theses

Methamphetamine (METH) is a widely abused psychostimulant, which can cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes were identified after binge METH exposure, including histone modification, DNA methylation, and changes in miRNA levels. We have shown that binge METH increases expression and activity of Long INterspersed Element (LINE-1), a transposable element, in doublecortin-positive neurons within rat neurogenic zones [1]. The goal of the present study was to identify which type(s) of cells show increases in LINE-1 following binge METH exposure, and determine whether binge METH-induced increases in LINE-1 are associated with cell death. To achieve this goal, male …