Pharmacology, Toxicology and Environmental Health Commons^™

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 …

Possible Mechanisms That Protect The Fetus From Maternal Rejection, Adina Ziemba-Goldfarb

The Science Journal of the Lander College of Arts and Sciences

There is no other foreign tissue transplant that has such a strongly parasitic relationship with its human host as the fetus. Although the fetus contains paternal genes, is completely tolerized by its maternal host in almost all pregnancies. This presents an immunological paradox and has generated a lot of attention from leading researchers in the reproductive and immunology fields. This paper reviews the leading explanations for this paradox; that it is attributed to a detailed mechanism of the maternal and fetal immune system in which tryptophan suppresses T-cells from attacking specific paternal cells, while maintaining a strong immune response against …

Full Issue: Volume 11, Number 1

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.