Pharmacology, Toxicology and Environmental Health Commons^™

Imatinib Reverses Doxorubicin Resistance By Affecting Activation Of Stat3-Dependent Nf-Κb And Hsp27/P38/Akt Pathways And By Inhibiting Abcb1, Jonathan T. Sims, Sourik S. Ganguly, Holly Bennett, J. Woodrow Friend, Jessica Tepe, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Despite advances in cancer detection and prevention, a diagnosis of metastatic disease remains a death sentence due to the fact that many cancers are either resistant to chemotherapy (conventional or targeted) or develop resistance during treatment, and residual chemoresistant cells are highly metastatic. Metastatic cancer cells resist the effects of chemotherapeutic agents by upregulating drug transporters, which efflux the drugs, and by activating proliferation and survival signaling pathways. Previously, we found that c-Abl and Arg non-receptor tyrosine kinases are activated in breast cancer, melanoma, and glioblastoma cells, and promote cancer progression. In this report, we demonstrate that the c-Abl/Arg inhibitor, …

Atrazine And Nitrate In Public Drinking Water Supplies And Non-Hodgkin Lymphoma In Nebraska, Usa, Martha G. Rhoades, Jane L. Meza, Cheryl L. Beseler, Patrick J. Shea, Andy Kahle, Julie M. Vose, Kent M. Eskridge, Roy F. Spalding

School of Natural Resources: Faculty Publications

A secondary analysis of 1999–2002 Nebraska case-control data was conducted to assess the risk of non-Hodgkin lymphoma (NHL) associated with exposure to nitrate- and atrazine-contaminated drinking water. Water chemistry data were collected and weighted by well contribution and proximity of residence to water supply, followed by logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). We found no association between NHL risk and exposure to drinking water containing atrazine or nitrate alone. Risk associated with the interaction of nitrate and atrazine in drinking water was elevated (OR, 2.5; CI, 1.0–6.2). Risk of indolent B-cell lymphoma was higher …

Toxicological Effects Of Cerium Oxide Nanoparticle Aggregates On Caenorhabditis Elegans, Steven N. Rogers

Theses, Dissertations and Capstones

Assessing the toxicity and unique reactivity of nanoparticles in biological systems has become an relevant and quickly growing area of environmental toxicology research. The broad use of nanoparticles in industrial and commercial commodities results in exposure of these nano-compounds to the environment, the ecosystems, and humans. While previous data has suggested that cerium oxide (CeO₂) nanoparticles are relatively safe to cultured cells much less is known about the potential toxicity of these materials at the organismal level. In this study we employed transgenic Caenorhabditis elegans (C. elegans) strains to assess the toxicity of CeO₂ nanoparticles under “real-world” …

Nucleic Acid Oxidation In Human Health And Disease, Mu-Rong Chao, Pavel Rossner Jr., Siamak Haghdoost, Hueiwang Anna Jeng, Chiung-Wen Hu

Community & Environmental Health Faculty Publications

No abstract provided.

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Psychologists And Medications In The Era Of Interprofessional Care: Collaboration Is Less Problematic And Costly Than Prescribing, William N. Robiner, Tim R. Tumlin, Tanya Tompkins

Faculty Publications

Increasing emphasis on interprofessionalism and teamwork in healthcare renders psychologists’ collaborations critical and invites reexamination of psychologists’ roles related to medications. The Collaboration Level outlined by the APA’s Ad Hoc Task Force is more achievable and in synch with health reform than prescription privileges (RxP). RxP remains controversial due to training and safety concerns, lacking support from health professionals, psychologists, and consumers. Differences in educational preparation of psychologists relative to prescribing professionals are discussed. Enactment of only three of 170 RxP initiatives reveals RxP to be a costly, ineffectual agenda. Alternatives (e.g., integrated care, collaboration, telehealth) increase access without risks …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Chlomid, Niki Smith

Natural Sciences Student Research Presentations

This poster details the use of Clomid and provides a chemical analysis.

Exposure To Persistent Organic Pollutants And Metabolic Diseases, Zafar Zayirovich Aminov

Legacy Theses & Dissertations (2009 - 2024)

Background: The metabolic syndrome (MetS) is a group of diseases that tend to occur together, including diabetes, hypertension, central obesity, cardiovascular disease and hyperlipidemia. Exposure to persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) have been associated with increased risk of development of several of the components of the MetS.

Function And Regulation Of Intestinal P450 Enzymes : Insights From Conditional Cytochrome P450 Reductase Knockout Mouse Models, Yi Zhu

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of this thesis work was to investigate the function and regulation of intestinal P450 enzymes (P450s). The central hypotheses are that 1) small intestinal (SI) P450s play an important role in the first-pass clearance of oral drugs and in bioactivation of chemicals that cause intestinal toxicity, 2) endogenous regulatory compounds produced by intestinal P450s are important for protection against chemical-induced colon inflammation, and 3) there is a cross talk between the liver and the SI that helps to maintain the overall xenobiotic-metabolism capacity of the digestive tract.

Role Of P450 Enzymes In Tobacco Dependence And Lung Tumorigenesis, Lei Li

Legacy Theses & Dissertations (2009 - 2024)

The overall aim of this study is to better define the roles of P450 enzymes, particularly those in the CYP2A, 2B, and 2F gene subfamilies, in the metabolism and actions of tobacco-related chemicals. Tobacco smoke contains numerous compounds that are deleterious to health, including the primary addictive component nicotine and procarcinogenic compounds, such as naphthalene (NA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Our main hypotheses are i) that CYP2A and 2B enzymes are largely responsible for nicotine metabolism, and they can impact nicotine dependence; and ii) that CYP2A, 2B, and 2F enzymes play important and tissue-specific roles in NA and NNK bioactivation, leading …

Assessment Of Human Exposure To Perchlorate And Perfluoroalkyl Substances In The United States : Biomonitoring And Environmental Monitoring Approaches, Qian Wu

Legacy Theses & Dissertations (2009 - 2024)

Perchlorate is an oxidant in solid fuels and explosives and is produced in large quantities worldwide. Perchlorate is a ubiquitous environmental contaminant and is present in water, food, indoor environment and humans. Human exposure to perchlorate is a concern due to its ability to disrupt the thyroid gland functions.

The Effect Of Alpha-Cyclodextrin On Acute Blood Lipid And Glycemic Responses To A Fat Containg Meal, Evan Neil Fletcher

Wayne State University Theses

Obesity and hyperlipidemia have become major concerns in the United States over the past 30 years. Alpha-Cyclodextrin (á-CD), a naturally occurring soluble dietary fiber, has been shown to reduce dietary fat absorption and improve blood lipid levels in an animal model (mouse and rat) and in human studies. In the current double blind study, 34 healthy male and female participants were recruited to test if á-CD had any acute effect on blood lipid and glycemic responses to a fat containing meal. The participants received the á-CD on one occasion and a placebo the other to determine if there was any …

Does The Use Of Varenicline For Smoking-Cessation Therapy Create Or Increase Depression In Patients Without Existing Depressive Illness?, Brett R. Brown

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of varenicline for smoking-cessation therapy creates or increases depression in patients without existing depressive illness.

STUDY DESIGN: Review of two randomized controlled trials published in 2011 and one observational cohort study published in 2009, all English language.
DATA SOURCES: Two randomized, double-blind, controlled clinical trials comparing varenicline to placebo in smoking cessation, and one observational cohort study comparing varenicline use within subjects. All articles were found using PubMed and EBSCO.

OUTCOMES MEASURED: Changes in depression was evaluated using the MontgomeryÅsberg Depression Rating Scale …

The Antiinflammatory Action And Pharmacokinetics Of A Novel Glucosamine-Based Di-Peptide Aminosugar, Mohammad H. Gilzad-Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

Purpose. We have previously shown favorable in vitro gut permeability for three novel dipeptide esters of glucosamine (GlcN) likely facilitated by the peptide transporter 1 (PepT1). Herein, we report the development of a novel assay for the determination of bioavailability of the peptide ester of interest, the anti-inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as well as its pharmacokinetics under healthy and inflammatory conditions.

Methods. A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that were cannulated in their right jugular vein for …

Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami

Theses and Dissertations--Pharmacy

Obesity and drug abuse share common neural circuitries including the mesocoticolimbic and striatal dopamine reward system. In the current study, a rat model of diet-induced obesity (DIO) was used to determine striatal dopamine function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. For the outcome study, rats were randomly assigned a high-fat (HF) or a low-fat (LF) diet for 8 wk. Following the 8-wk HF-diet exposure, rats were segregated into obesity-prone and obesity-resistant groups based on maximum and minimum body weight gain, respectively, and neurobehavioral outcomes were evaluated. For the predictor study, neurobehavioral antecedents were evaluated prior to …

Methylphenidate And Atomoxetine Treatment During Adolescence In The Spontaneously Hypertensive Rat: Mechanisms Underlying High Cocaine Abuse Liability In Attention Deficit/Hyperactivity Disorder, Sucharita S. Somkuwar

Theses and Dissertations--Pharmacy

Effects of pharmacotherapies for Attention Deficit/Hyperactivity Disorder (ADHD) on cocaine abuse liability in ADHD are not understood. Spontaneously Hypertensive Rats (SHR), an ADHD model, exhibited greater cocaine self-administration than control Wistar-Kyoto and Wistar rats. Methylphenidate, but not atomoxetine during adolescence enhanced cocaine self-administration in adult SHRs compared to controls. The mesocortical dopaminergic system, including medial prefrontal (mPFC) and orbitofrontal (OFC) cortices, is important for ADHD and cocaine addiction. Dopamine and norepinephrine transporter (DAT and NET) are molecular targets for methylphenidate, atomoxetine and cocaine action.

In the current studies, SHR, Wistar-Kyoto and Wistar were administered methylphenidate (1.5 mg/kg/day, p.o.), atomoxetine (0.3 …

Fine Tuning A Well-Oiled Machine: Influence Of Nk1.1 And Nkg2d On Nkt Cell Development And Function, Sunil K. Joshi, Mark L. Lang

Bioelectrics Publications

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but …

Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer

Articles

No abstract provided.

Does Nicotine Replacement Therapy Reduce The Withdrawal Symptom Of Craving, Or Urge To Smoke, In Dependent Adult Smokers During Smoking Cessation?, Theresa Dijoseph

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not nicotine replacement therapy reduces the withdrawal symptom of craving, or urge to smoke, in dependent adult smokers during smoking cessation.

STUDY DESIGN: Systematic review of three English language and peer-reviewed randomized-controlled trials published in 2009, 2010, and 2011.

DATA SOURCES: One single-blinded randomized-controlled crossover trial, one double-blinded, placebo controlled, randomized-controlled crossover trial, and one single-blinded, placebo controlled, randomized-controlled crossover trial

OUTCOMES MEASURED: Withdrawal symptoms of craving, irritability, difficulty concentrating, and restlessness were measured on a 100mm visual analog scale (VAS). Adverse effects (AEs) of mouth and …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and biochemical activities of novel water-soluble β-lactam analogues of combretastatin A-4 are described. The first series of compounds investigated, β-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells. They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells. The second series of compounds, β-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of …

The Biology And Taxonomy Of Head And Body Lice— Implications For Louse-Borne Disease Prevention, Denise L. Bonilla, Lance A. Durden, Marina E. Eremeeva, Gregory A. Dasch

Environmental Health Sciences: Faculty Publications

Sucking lice (Phthiraptera: Anoplura) are obligate blood-feeding ectoparasites of placental mammals including humans. Worldwide, more than 550 species have been described and many are specific to a particular host species of mammal [1]. Three taxa uniquely parasitize humans: the head louse, body louse, and crab (pubic) louse. The body louse, in particular, has epidemiological importance because it is a vector of the causative agents of three important human diseases: epidemic typhus, trench fever, and louse-borne relapsing fever. Since the advent of antibiotics and more effective body louse control measures in the 1940s, these diseases have markedly diminished in incidence. However, …

Evaluation Of A Novel Rapid Diagnostic Test For Schistosoma Haematobium Based On The Detection Of Human Immunoglobulins Bound To Filtered Schistosoma Haematobium Eggs, Johnathan M. Sheele, Jimmy H. Kihara, Sarah Baddorf, Jonathan Byrne, Bhaskara Ravi

Mathematics & Statistics Faculty Publications

Objectives To determine whether the detection of human IgG bound to Schistosoma haematobium eggs from filtered urine could be used as a rapid diagnostic test (RDT-Sh).

Methods We filtered 160 urine samples from children in the Kwale District of Kenya to isolate S.haematobium eggs and used anti-human IgG antibody conjugated to horseradish peroxidase to bind to the human IgG attached to the eggs. We then added 3,35,5-tetramethylbenzidine base (TMB), which turns blue in the presence of horseradish peroxidase to detect the S.haematobium eggs. The RDT-Sh was compared in a blinded manner to urine microscopy.

Results The RDT-Sh was positive in …

Evaluation Of Occupational Risk Factors For Nurses And Cnas: Analysis Of Florida Workers' Compensation Claims Database, Sheila Mohammed

USF Tampa Graduate Theses and Dissertations

Musculoskeletal injuries lead to most claims even though needlestick injuries receive the most attention. In 2010, health expenditures in the United States neared $2.6 trillion. CNAs, orderlies, and attendants had the highest rates of musculoskeletal disorders of all occupations with an incidence of 249 per 10,000 compared to 34 per 10,000 for all workers. The financial burden of back injuries in the healthcare industry is estimated to add up to $20 billion annually. Data was extracted for cause of injury, nature of injury and body part injured. Extracted data was analyzed both descriptively and by logistic and linear regression using …

Asbestos Exposure In The Research Laboratory, Ediberto D. Garcia

USF Tampa Graduate Theses and Dissertations

Introduction: Asbestos has been employed in a myriad of industrial applications for more than a century. Of the 181 Mt of asbestos produced worldwide, over 31 Mt was consumed in the U.S. The production and consumption of this mineral eventually was found to cause asbestosis, lung cancer and mesothelioma. While the brunt of the human exposure to asbestos occurred in insulation work, many more workers in other jobs were expose to asbestos fibers. Very little is known about the potential exposure to asbestos in research labs.

Goal: In order to investigate potential research lab work exposures, we simulated lab work …

Asbestos Risk Assessment In Pakistan: Current Scenario And Way Forward, Adeel Ahmed Khan, Asaad Ahmed Nafees, Zafar Fatmi

Community Health Sciences

No abstract provided.

Dreissena Rostiformis Bugensis: Desiccation Of Adult Quagga Mussels Found In Lake Mead As A Preventive Measure Against Overland Dispersal In The Western United States, Matthew Kappel

UNLV Theses, Dissertations, Professional Papers, and Capstones

The expansion of civilization across all borders of the world has proven to affect major components of ecosystems. Since the introduction and establishment of the aquatic invasive species (AIS),Dreissena rostiformis bugensis, commonly known as the quagga mussel, into the United States there has been an extensive amount of time and money spent on controlling and preventing their expansion across the United States. The quagga mussel is of major concern because of its ability to disrupt the ecological communities in previously non-infested bodies of water, which may cause a loss in biodiversity and effect environmental health. The quagga mussel has spread …