Pharmacology, Toxicology and Environmental Health Commons^™

Cardiovascular Effects Evoked By Airway Nociceptive Reflexes In Healthy And Cardiovascular Diseased Rats, Justin Shane Hooper

USF Tampa Graduate Theses and Dissertations

Acute inhalation of airborne pollutants alters cardiovascular function and has been shown to have its greatest affects on individuals with pre-existing cardiovascular disease. Evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the cardiovascular responses evoked by inhalation of AITC (TRPA1 agonist) and capsaicin (TRPV1 agonist) in healthy Sprague Dawley (SD) and Wistar Kyoto (WKY) rats, and cardiovascular diseased Spontaneously Hypertensive (SH) rats. Inhalation of the agonists by healthy SD and WKY rats caused significant bradycardia, atrio-ventricular (AV) block and prolonged PR-Intervals. Inhalation of …

Evaluation Of Pulmonary Function Among Workers Engaged In The Manufacture Of Hydraulic Fracking Ceramic Proppant, Humairat H. Rahman

USF Tampa Graduate Theses and Dissertations

Workers involved in hydraulic fracking processes are exposed to various types of chemicals and dusts in their workplaces, such as proppants, which hold open the fissures created in the fracking process. Recently, ceramic proppants have been developed that may be less hazardous to workers than traditional proppants. Pulmonary function testing of workers producing ceramic proppant was used to assess the potential inhalation hazards of ceramic proppant. Male workers (n = 100) from a producer of ceramic proppant were evaluated with pulmonary function test data collected and evaluated using The American Thoracic Society (ATS) acceptability criteria. A comparison group was selected …

Human Health Risk Characterization Of Petroleum Coke Calcining Facility Emissions, Davinderjit Singh

USF Tampa Graduate Theses and Dissertations

Calcined coke is a high quality carbon material produced by calcining green petroleum coke. Calcining is the process of heating green petroleum coke in a kiln to remove excess moisture, extract all remaining hydrocarbons, and modify the crystalline structure of the coke into a denser, electrically conductive product. The final product, calcined coke, is primarily used to make carbon anodes for the aluminum industry and recarburizing agent for industries such as the steel industry. If not appropriately controlled, the calcining process could lead to excess production of particulate emissions from either handling or storing of raw coke, or from the …

Assessment Of Acrolein-Induced Toxicity Using In-Vitro Modeling To Evaluate The Role Of Parp Inhibitors In Reducing Cytotoxicity, Kristina Marie Harand

USF Tampa Graduate Theses and Dissertations

Acrolein is an electrophilic α, β-unsaturated aldehyde. Additionally, acrolein is a metabolite of the antineoplastic alkylating agent cyclophosphamide and is implicated in off-target effects, including to bladder hemorrhagic cystitis and cyclophosphamide-induced cardiotoxicity, both of which have led to serious secondary iatrogenic injury during and following chemotherapy. At low concentrations acrolein inhibits cell proliferation without inducing apoptosis, while at high concentrations may result in secondary apoptosis promotion. This investigation assessed the role of the enzyme poly (ADP-ribose) polymerase (PARP) in acrolein induced toxicity using the established toxicological H9c2 (2-1) cardiomyoblast in vitro model. H9c2 (2-1) cells were plated in 24-well plates …

Assessment Of The Role Of Poly (Adp-Ribose) Polymerase In Drug-Induced Cardiomyopathy, Alexis I. Brinkerhoff

USF Tampa Graduate Theses and Dissertations

Drug-induced cardiotoxicity has resulted in a thorough evaluation of patient doses, treatments, and rehabilitation. One of the most commonly prescribed chemotherapeutic agents is cyclophosphamide. The active metabolite, acrolein, is one of the most potent inducers of cardiomyopathy. In this study, research was conducted on the H9c2 (2-1) cardiomyocyte cell line derived from the embryonic myocardium of rattus norvegicus to assess its competency for evaluation of the change in poly (ADP-ribose) polymerase (PARP) activity. The application of this model to study the effects of acrolein on PARP activation was chosen as an ideal determinant of cell damage produced by nitrogen mustards. …

Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries

USF Tampa Graduate Theses and Dissertations

The chemicals produced by biological systems, whether proteins, peptides, or terpenes, will always provide an intriguing topic for researchers. Invisibly controlling every aspect of nature, these molecules are responsible for life, evolution, and death. Specifically, here is described the secondary metabolites produced by Antarctic marine organisms as well as others, and how they are used to defend or attract other animals while potentially providing health benefits to mankind. This is done through collection, extraction, and separation of individual specimens. The respective mixtures of compounds after isolation are then analyzed via spectroscopic methods such as nuclear magnetic resonance spectroscopy, mass spectrometry, …

Use Of Spirometry For Medical Clearance And Surveillance In Occupations Requiring Respirator Use, Ushang Prakshbhai Desai

USF Tampa Graduate Theses and Dissertations

Medical certification of workers for respirator use is an important activity of occupational medicine health professionals. Spirometry is a diagnostic tool to evaluate respiratory distress/insufficiency that may affect respirator use. In this study, we analyzed the pulmonary function data of 337 workers from different occupations which required medical evaluation to wear a respirator. The American Thoracic Society and National Fire Protection Association criteria were used to evaluate employees. Of 337 workers who were cleared for respiratory use on the basis of medical questionnaires for respirator compliance, 14 (4.15%) failed to pass respirator compliance on the basis of NFPA criteria and …

Elucidation Of The Role Of Poly(Adp-Ribose) Polymerase In Drug-Induced Toxicity, Kambria Haire

USF Tampa Graduate Theses and Dissertations

Drug toxicity may cause liver injury, resulting in damage to cells and tissues. This damage can lead to cytotoxic events that may result in an activation of poly (ADP-ribose) polymerase (PARP). A study was conducted to determine if cocaine and acetaminophen toxicity lead to DNA damage and to the activation of the repair protein, PARP in the liver using the hepatotoxicants: cocaine and acetaminophen (APAP).

A dose-response analysis for cocaine concluded that a dose as low as 20 mg/kg resulted in elevated ALT levels. A higher dose of 60 mg/kg was tested for analyses but resulted in severe hemorrhaging. The …

Effects Of Nicotine On A Translational Model Of Working Memory, David Alderson Macqueen

USF Tampa Graduate Theses and Dissertations

Cognitive research with human non-smokers has demonstrated that nicotine generally enhances performance on tasks of attention but, working memory does not appear to be affected. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-human animals. To address this disparity, the present study investigated the effects of nicotine (2mg, 4mg nicotine gum, and placebo) on the performance of 30 non-smokers (15 male) completing a working memory task developed for rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rodents and the present study sought to determine whether the effect …

An Assessment Of Retractions As A Measure Of Scientific Misconduct And Impact On Public Health Risks, Alison J. Abritis

USF Tampa Graduate Theses and Dissertations

Research misconduct has been generally considered a limited issue, occurring in a small percentage of research studies. Studies of the number of article retractions use retraction percentages to perpetuate the idea that research misconduct is not a common event, and use information in the retraction notice to quantify types of research misconduct and types or research error. However, retractions appear to be the wrong variable with which to assess misconduct rates and characteristics. Using final misconduct findings in hard science research from the Office of Research Integrity (ORI) for investigations closed from 1993 through 2013, the number of publications and …

Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky

USF Tampa Graduate Theses and Dissertations

Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …

Statistical Analysis, Modeling, And Algorithms For Pharmaceutical And Cancer Systems, Bong-Jin Choi

USF Tampa Graduate Theses and Dissertations

The aim of the present study is to develop a statistical algorithm and model associ- ated with breast and lung cancer patients. In this study, we developed several statistical softwares, R packages, and models using our new statistical approach.

In the present study, we used the five parameters logistic model for determining the optimal doses of a pharmaceutical drugs, including dynamic initial points, an automatic process for outlier detection and an algorithm that develops a graphic user interface(GUI) program. The developed statistical procedure assists medical scientists by reducing their time in determining the optimal dose of new drugs, and can …

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 …

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 …

The Perception Of Emergency Department Physicians Regarding Economic And Regulatory Factors Impacting Management Of Drug Seeking Patients, Sharon Susanne Kelley

USF Tampa Graduate Theses and Dissertations

Abstract

Physicians in the emergency department (ED) are facing a number of unique challenges in the currently changing healthcare and economic climates. Dramatic increases in ED patient volumes have been noted nationwide with visits related to prescription opioid abuse and misuse alone having increased by 111% between 2004 and 2008.

Ironically, several challenges ED physicians are facing arise from regulatory and economic initiatives which were originally designed for the protection of patients. Regulatory requirements to address pain as the fifth vital sign, along with entities utilizing patient satisfaction based reimbursement, have inadvertently created an environment conducive to exploitation by the …

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 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 …

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 …

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 Urinary Pesticide Biomarkers Among A Sample Of The Population In The United States, Alex Lance Lebeau

USF Tampa Graduate Theses and Dissertations

Pesticide use in the United States continues to attract negative public attention. In recent years, this attention has focused on the effects that chronic, low-level pesticides may have, especially on children and various sub-populations. Over the past decade, studies have attempted to correlate negative health effects with detections of pesticide biomarkers in biological media. The current research investigates biomarker of exposure levels in a sample of the United States population. Data from the 2001-2002 NHANES dataset (n=11,039) was evaluated. The detection frequency of urinary biomarkers of exposure and the geometric mean from the NHANES pesticide dataset (n=3,152) were determined. Of …

Modulating The Pharmacokinetics Of Bioflavonoids, Adam John Smith

USF Tampa Graduate Theses and Dissertations

One of the largest obstacles in drug development is to overcome solubility and bioavailability problems. Preformulation strategies such as nanoparticle formation are often employed but sometimes create new issues and are limited in their effectiveness and applications. Since the majority of drugs are marketed and sold as solid forms, drug delivery systems are not always desirable. This is where solid-state chemistry becomes important. Traditional solid-state chemistry approaches are often successful but are sometimes too restrictive and cannot be applied to certain compounds. Cocrystals have emerged as an alternative solid-state technique that can be applied to a broad range of compounds. …

Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons

USF Tampa Graduate Theses and Dissertations

In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …

Use And Development Of Computational Tools In Drug Discovery: From Small Molecules To Cyclic Peptides, Daniel Navarrete Santiago

USF Tampa Graduate Theses and Dissertations

The scope of this work focuses on computationally modeling compounds with protein structures. While the impetus of drug discovery is the innovation of new therapeutic molecules, it also involves distinguishing molecules that would not be an effective drug. This can be achieved by inventing new tools or by refining old tools. Virtual screening (VS, also called docking), the computational modeling of a molecule in a receptor structure, is a staple in predicting a molecule's affinity for an intended target. In our Virtual Target Screening system (also called inverse-docking), VS is used to find high-affinity targets, which can potentially explain absorption, …

Maternal Immune Dysregulation In The Pathogenesis Of Neurodevelopmental Disorders: Interleukin-6 As A Central Mechanism And Therapeutic Target Of Flavonoids, Ellisa Carla Parker-Athill

USF Tampa Graduate Theses and Dissertations

Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has …

Store-Operated Calcium Channels In The Function Of Intracardiac Neurons, Timetria Bonds

USF Tampa Graduate Theses and Dissertations

Proper autonomic regulation of mammalian cardiac function is dependent upon very complex and precise communication among the intracardiac ganglia and individual neurons within the ganglia. An array of neuromodulators is found within the ganglia that direct neuronal activity by modulating the movement of calcium. The current study determines that opioidergic agonists, which have been found to contribute to severe cardiac disease states and intracellular calcium mobilization, are also responsible for changes in the function of the intracardiac neuron via their effects on store-operated calcium channels (SOCs).

Previous studies suggest that phosphorylation plays a role in SOC regulation. Using Fura-2 calcium …

Secreted Factors From Human Umbilical Cord Blood Cells Protect Oligodendrocytes From Ischemic Insult, Derrick Rowe

USF Tampa Graduate Theses and Dissertations

Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble …