Pharmacology, Toxicology and Environmental Health Commons^™

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.

Development And Assessment Of Analytical Methods For Monitoring Current And Historical Exposures To Manganese : Blood, Urine, And Teeth, Meredith Lyn Praamsma

Legacy Theses & Dissertations (2009 - 2024)

Manganese, as an essential trace element, is a cofactor in numerous enzymes that aid in bone growth, cholesterol synthesis, and carbohydrate metabolism. Manganese can become toxic with overexposure, potentially leading to neurodegenerative effects and the disease manganism. Manganese concentrations in blood and urine have been widely used in monitoring current exposure and now there is interest in using manganese concentrations in teeth for monitoring historical exposure, especially in utero and in early childhood.

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.

Impact Of Black Carbon On Global Climate : A Half-Century Of Arctic Black Carbon -- Trends And Sources, Anthony Michael Dejulio

Legacy Theses & Dissertations (2009 - 2024)

Abstract

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 …

Oligospermines For Non-Viral Sirna Delivery, Maha Elsayed

Wayne State University Theses

In this thesis, delivery systems for siRNA delivery are introduced with special attention to non-viral vectors. Many successful vectors used in vivo were reviewed. Our work focused on the effect of different architectures of oligospermine polmers on their suitability for siRNA delivery in lung cancer cells. Different archituctures showed different polyplex structures and variable transfection efficiencies. Moreover, we presented a review on nanoimprint lithography techniques with an outlook on possible biological applications in the field of gene and drug delivery.

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 …

Estimation Of Aerosolized Antibiotic Resistant Bacteria Concentrations From Wastewater Treatment Facilities Using Spatially-Based Dispersion Modeling, Renee Nichole Dickman

Theses and Dissertations

Pathogenic bacteria can develop resistance to antibiotics to which they were previously sensitive, resulting in increased morbidity and mortality worldwide [1]. The increase in drug resistance in bacteria is an emerging public health concern. The activated sludge tanks of wastewater treatment plants are known sources of antibiotic resistant bacteria. These resistant bacteria can become aerosolized and disperse downwind. Using previously sampled aerosol concentrations and meteorological data, a Gaussian dispersion model was developed to estimate the concentration downwind from a selected wastewater treatment facility. The emission rate was calculated to be 7,941 CFU/m²/sec ± 2,149 CFU/m²/sec. This value was used in …

Olanzapine Sensitization And Clozapine Tolerance: From Adolescence To Adulthood In The Conditioned Avoidance Response Model, Jing Qiao, Hong Li, Ming Li

Department of Psychology: Faculty Publications

Disruption of conditioned avoidance response (CAR) in rodents is one trademark feature of many antipsychotic drugs. In adult rats, repeated olanzapine (OLZ) treatment causes an enhanced disruption of avoidance response (sensitization), whereas repeated clozapine (CLZ) treatment causes a decreased disruption (tolerance). The present study addressed (1) whether OLZ sensitization and CLZ tolerance can be induced in adolescent rats, and (2) the extent to which OLZ sensitization and CLZ tolerance induced in adolescence persists into adulthood. Male adolescent Sprague–Dawley rats (approximate postnatal days (BP) 43–47) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10 or 20 …

Does Ecosystem Disturbance Alter The Capacity Of Dissolved Organic Matter To Mitigate The Impact Of Copper To Hyalella Azteca?, Kelly Livingstone

Theses and Dissertations (Comprehensive)

The potential for aquatic ecosystem recovery as a result of dissolved organic matter (DOM) protecting against metal toxicity has become a significant area of research in environmental toxicology. It is a well-characterized relationship that DOM binds free metal ions in a concentration-dependant manner, making them unavailable for toxic action and a reduction in toxicity is seen. Less understood is source variability and how the upland terrestrial environment influences the protective quality of DOM. The aim of this study was to examine the influence of land disturbance (logging, fire, smelter emissions) on DOM quality by comparing the protective capacity of different …

Exploring The Sulfide Tolerance Of Ectosymbiotic Niphargus Amphipods From The Frasassi Caves, Central Italy, Jan Bauermeister, Karoline Assig, Sharmishtha Dattagupta

International Journal of Speleology

Two species of the crustacean amphipod genus Niphargus inhabit the sulfidic groundwaters of the Frasassi caves in central Italy, and both harbor filamentous, sulfide-oxidizing Thiothrix ectosymbionts. As sulfide is toxic to most aerobic organisms, it appeared possible that the ectosymbionts could help their Niphargus hosts with detoxification processes. In this study, mortality due to sulfide was compared between Niphargus individuals with ectosymbionts and individuals whose ectosymbionts had been killed by antibiotic treatment. Both Frasassi-dwelling Niphargus species revealed exceptionally high tolerances to sulfide compared to other amphipod species studied so far. Niphargus individuals without viable ectosymbionts tolerated sulfide levels exceeding those …

Cure From The Cave: Volcanic Cave Actinomycetes And Their Potential In Drug Discovery, Naowarat (Ann) Cheeptham Dr., Tara Sadoway, Devon Rule, Kent Watson, Paul Moote, Laiel C. Soliman, Nicholas Azad, Kingsley Donkor, Derrick Horne

International Journal of Speleology

Volcanic caves have been little studied for their potential as sources of novel microbial species and bioactive compounds with new scaffolds. We present the first study of volcanic cave microbiology from Canada and suggest that this habitat has great potential for the isolation of novel bioactive substances. Sample locations were plot ted on a contour map that was compiled in ArcView 3.2. Over 400 bacterial isolates were obtained from the Helmcken Falls cave in Wells Gray Provincial Park, British Columbia. From our preliminary screen, of 400 isolates tested, 1% showed activity against extended spectrum ß-lactamase E. coli, 1.75% against Escherichia …

Study Of Charge-Dependent Transport And Toxicity Of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos And Single Nanoparticle Plasmonic Spectroscopy, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs^+ζ), negatively (Ag-CALNNS NPs^−2ζ), and more negatively charged NPs (Ag-CALNNE NPs^−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as …

Predicting Barriers To Primary Care For Patients With Disabilities: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr, Michelle Chino

Environmental & Global Health Faculty Research

Background. People with disabilities continue to be identified as a group who experience disparate health/health care. They are less likely to engage in some health care services. Structural barriers are often identified as one of the reasons for the underutilization of some health care services by people with disabilities. However, to date no study has been conducted to understand why structural barriers persist twenty years after the Americans with Disabilities Act (ADA) became law.

Objectives. We examined the relationship between primary care practice administrators’ knowledge of the ADA and the number of accessibility barriers that patients with mobility disabilities might …

Molecular Mechanisms By Which C-Abl And Arg Mediate Melanoma Invasion And Metastasis, Sourik S. Ganguly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Metastasis is one of the main causes of death in cancer patients. Metastatic melanoma is a death sentence, as chemotherapeutic agents have a 5% success rate or do not extend survival beyond 10 months. The lack of effective chemotherapeutic agents for treating metastatic melanoma indicates a dire need to identify new drug targets and develop new therapies. Our lab has previously shown that the kinase activity of Abelson family of non-receptor tyrosine kinases (c-Abl and Arg) is elevated in invasive breast cancer cell lines as compared to non-invasive cell lines. Previous studies from our lab have shown that Abl …

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 …

Regulation Of 7-Dehydrocholesterol Reductase By Vitamin D3, Ling Zou

Theses and Dissertations--Pharmacy

7-Dehydrocholesterol (7-DHC) is the substrate of 7-dehydrocholesterol reductase (DHCR7) in the cholesterol synthesis pathway. Keratinocytes in human skin possess the enzymes necessary for cholesterol synthesis but are also responsible for vitamin D₃ synthesis from 7-DHC by exposure to UVB irradiation. It has been well established that DHCR7 is regulated by the SREBP pathway in the regulation of cholesterol synthesis, but little is known about the regulation of DHCR7 by the vitamin D pathway. In this study, the regulation of DHCR7 activity by vitamin D was explored. Treatment of adult human epidermal keratinocyte (HEKa) cells with vitamin D₃ resulted …

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 …

Environmental, Human And Socioeconomic Characteristics Of Pedestrian Injury And Death In Las Vegas, Nv, Jennifer Renee Pharr, Courtney Coughenour, Timothy J. Bungum

Environmental & Global Health Faculty Research

Background: Pedestrian crashes are a deterrent to physical activity, especially walking. The purpose of this study was to analyze pedestrian crash characteristics in Clark County, NV and to determine if there was a significant relationship between pedestrian crashes and socio-economic variables.

Methods: Police reported pedestrian crash data collected between January 2009 and December 2011 were analyzed. Frequencies and rates for pedestrian crashes, injuries and deaths were calculated for environmental and human characteristics. Chi square tests were utilized to determine if there were significant differences in environmental and human characteristics for pedestrian injuries and deaths. Zero-inflated negative binomial (ZINB) regression analysis …

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.

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 …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

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 …

The Assessment Of An In-Vitro Model For Evaluating The Role Of Parp In Ethanol-Mediated Hepatotoxicity, Jayme Coyle

USF Tampa Graduate Theses and Dissertations

This investigation assesses the role of poly(ADP-ribose) polymerase in ethanol-mediated hepatotoxicity using the untransfected HepG2 hepatocellular carcinoma line, an established, well-characterized toxicological model. HepG2 cells were treated with ethanol at concentrations between 100 mM and 800 mM, and assessed for markers of cytotoxicity. PARP-1 activity in total cell protein lysates was quantified as a proxy of apoptotic induction at six hours. Our results demonstrated a 1.43-fold AST activity increase in culture medium isolates of cells exposed to 800 mM without significant effect on cellular viability. PARP-1 activity varied greatly and results for enzyme activity remained inconclusive. The results suggest a …

Cd44 Containing Complexes As A Therapeutic Target In Multiple Myeloma, Anthony Gebhard

USF Tampa Graduate Theses and Dissertations

Our laboratory recently reported that treatment with the d-amino acid containing peptide HYD1 induces necrotic cell death in multiple myeloma (MM) cell lines. Due to the intriguing biological activity and promising in vivo activity of HYD1, we pursued strategies for increasing the therapeutic efficacy of the parent linear peptide. These efforts led to the development of a cyclized peptidomimetic, MTI-101, with increased in vitro activity and robust in vivo activity as a single agent using two myeloma models that consider the bone marrow microenvironment. MTI-101 treatment resulted in mechanistically similar hallmarks of HYD1 induced cell death, namely the generation of …

Development Of A Novel Method For Deriving Thresholds Of Toxicological Concern (Ttcs) For Vaccine Constituents, Jennifer Jessica White

USF Tampa Graduate Theses and Dissertations

Abstract

Safety assessment relating to the presence of impurities, residual materials and contaminants in vaccines is a focus area of research at the United States Food and Drug Administration (FDA). Sponsors who submit Investigational New Drug (IND) applications for new vaccine products must report the results of safety assessments to the Division of Vaccines and Related Products Applications (DVRPA). Scientifically defining thresholds of toxicological concern (TTCs) as they apply to vaccine constituents will provide a useful aid to the sponsors and public regarding safety assessments of compounds for which there is little or no toxicity data. TTCs are mathematically modeled …

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 …