Pharmacology, Toxicology and Environmental Health Commons^™

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 …

Evaluation Of The Methanol Whole Root Extract Of Securidaca Longipedunculata For Antitrypanosomal Activity In Vitro And In Vivo, Eke Ifeanyi Gabriel, Ihedioha Thelma Ebere, Ezeh Ikenna Onyema, Ezeudu Terry Adaku, Eze Ukamaka Uchenna, Okoye Chidozie Nwabuisi, Anaga Aruh Otah

The Thai Journal of Pharmaceutical Sciences

Securidaca longipedunculata is a medicinal plant used in different parts of Africa for treatment of various ailments including sleeping sickness in Northern Nigeria. On this basis, the methanol root extract of S. longipedunculata was investigated for ant...

Islet Dysfunction In Diabetes, Syeda Khadija

Wayne State University Dissertations

Type 2 Diabetes [T2DM] is a chronic condition resulting from gradual failure of pancreatic beta cells to synthesize and secrete sufficient insulin to meet the metabolic demands and the inability of tissues [muscle, adipose and liver] to efficiently utilize the secreted insulin leading to an overall increase in blood glucose levels [hyperglycemia]. As indicated by recent estimates from the International Diabetes Federation, the prevalence of the disease in the year 2014 has risen to a record 387 million worldwide. The main objective of my project was to study the mechanisms involved in pancreatic beta cell dysfunction in diabetes, specifically in …

Characterization Of Contaminants On Firefighter"S Protective Equipment A Firefighter's Potential Exposure To Heavy Metals During A Structure Fire, Donald F. Gagas

Online Theses and Dissertations

This research measured heavy metals, specifically cadmium, chromium, copper, and lead, on the surface of the firefighters bunker gear. Despite the fact that many studies have been conducted regarding the presence of organics in smoke emissions from structure fires, very few studies have investigated the extent of heavy metal emissions found during a structure fire. Using a wipe test procedure samples were collected from firefighters following a structure fire and analyzed for metals. Three locations on the bunker gear were used, the knee, elbow, and chest areas. The results showed that varying amounts of cadmium, chromium, copper and lead adhere …

Developing Proteomic And Cytokine Biomarkers For Vulvodynia, Ashvin Iyer

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Vulvodynia is a chronic, heterogeneous, and multifactorial disease. This condition may affect up to 18 percent of the female population including Caucasians, African Americans, Africans and Hispanics particularly those sexually active at child bearing age. The etiology of this condition is complex and multifactorial and it is frequently accompanied by physical disabilities, psychological distress and sexual dysfunction. Clinically, vulvodynia can be generalized or localized and pain can be provoked or unprovoked. Patients may also describe vulvar paresthesias or dysesthesias that may last hours. The International Society for the Study of Vulvar Disease (ISSVD) recognizes vulvar pain related to a specific …

Expression Of Aquaporins In Mouse Choroid Plexus And Ependymal Cells, Pankaj Patyal

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The choroid plexuses (CPs) are highly vascularized epithelial structures lying in the brain ventricles, forming the blood-cerebrospinal fluid (CSF) barrier. CPs are composed of a monolayer of cuboidal epithelial cells, derived from ependymal cells (EPCs), joined by tight junctions, and surrounding a core of fenestrated capillaries. Choroid plexus epithelial cells (CPECs) secrete most of the CSF through poorly understood mechanisms that involve aquaporins (AQPs) and various solute transport proteins like the Na+-K+-2Cl- cotransporter 1 (NKCC1). It is thought that the concerted action of these membrane proteins directs the transepithelial movement of solutes and water across CPECs. Net water movement across …

Effect Of Progesterone, Terbutaline And Leptin On The Function Of Alveolar Type Ii Cells, Shamili Sammohi

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The "surfactant" produced by type II pneumonocytes is deficient in term and preterm infants born and diagnosed with Respiratory Distress Syndrome (RDS). Corticosteroids such as dexamethasone or betamethasone are clinically used as the primary line of treatment to stimulate the production of surfactant. The steroidal hormone, progesterone appears to play a role in the fetal lung development and also appears to increase the expression of inflammatory markers in both term and preterm infants. However, the impact of progesterone on surfactant production remains unknown. Like progesterone, the tocolytic drug terbutaline has also been implicated in phosphatidylcholine production in the pneumonocytes of …

Na+/K+ Pump And Cl--Coupled Na+ And K+ Co-Transporters In Mouse Embryonic Fibroblasts Lacking The Tuberous Sclerosis Complex Tsc1 And Tsc2 Genes., Jasser Ali S. Alzhrani

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The tuberous sclerosis complex 1 and 2 (TSC1 and TSC2) genes and their products hamartin and tuberin, respectively, are involved in several regulatory cellular mechanisms, including the mTOR pathway that is important for proliferation, cell migration, and protein synthesis. In addition, it has been suggested that this pathway plays a role in regulating Na+-K+-2Cl- and K+-Cl- cotransporters (NKCC and KCC, respectively) [41, 42, 43]. Therefore, the TSC1 and TSC2 genes are expected to play a significant role in regulating cell volume, and K+ and Cl- homeostasis. This study tests the hypothesis that the TSC1 and TSC2 genes, which control cell …

Role Of Angiotensin Ii Type 1a Receptors On Renal And Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In The Two-Kidney One-Clip (2k1c) Model Of Renovascular Hypertension, Laale F. Alawi

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Activation of the renin angiotensin system (RAS) and increased formation of angiotensin (Ang) II contribute to the progression of chronic kidney disease (CKD). Ang II, the major biologically active peptide of RAS, acts mainly as a vasoconstrictor through binding to the Ang II type 1 receptor (AT1R), which leads to increased blood pressure, fluid retention, and aldosterone secretion. The actions of Ang II are antagonized by its conversion to the vasodilator Ang (1-7), partly generated by the action of angiotensin converting enzyme 2 (ACE2) and/or neprilysin (NEP). The metalloprotease ADAM17 has a crucial role in the shedding of renal ACE2 …

Identification And Quantification Of The Collagen Type I, Iii And V In Rabbit Patellar Tendons, Mahesh Chandra Kodali

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Tendon injuries pose a great clinical challenge to orthopedic surgeons. Over 200,000 patients undergo tendon repair every year in the United States alone. The role of progression of a tendon injury is multifactorial as a lot of factors come into play during and after the injury at various phases of healing process. There is a still a vast requirement for thorough elucidation and understanding of the pathophysiology and the factors involved in the progression of tendon injury. Although the degenerative role of several MMPs and ADAMTs have been reported, yet there is very less information on the actual role and …

Interaction Between Na/ K-Atpase And Bcl-2 Proteins Bclxl And Bak, Tariq M. Alqahtani

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In silico analysis predicts interaction between the Na/ K-ATPase (NKA) and Bcl-2 protein canonical motifs BH3 and BH1. Such interaction is consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine (CHE), a BH3 mimetic, in human lens epithelial cells (HLEC). This report establishes proof of concept: co-immuno-precipitation and immuno-colocalization showed unequivocal and direct interaction between NKA and Bcl-2 proteins. Particularly, NKA-antibodies co-immunoprecipitated BclXl and BAK in three different epithelial cell lines, HLECs and A549 lung cancer cells, whereas anti-Bcl-2 antibodies failed to pull down NKA. The molecular mass of the BAK proteins pulled down by antibodies against NKA and BclXl …

Endothelial Cell Derived Mvs And Exosomes: Release And Functional Study, Langni Liu

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Extracellular vesicles are membrane derived vesicles exists in all organs. The two major functioning extracellular vesicles are exosomes (EXMs) and microvesicles (MVs). EXMs released from cell membranes via exocytosis with size between 30-150 nm in diameter and MVs directly budded from plasma membrane and size between 100-1000 nm. Ceramide is one of the most important factor in lipid mechanism for EXM release and also associated with MV release. Ceramide generated from breakdown of sphingomyelin by neutral sphingomyelinase (nSMase). In this study, we used an nSMase inhibitor (GW4869) and an analogue of ceramide (C6-ceramide) to modulate the release of MVs and …

Differential Effects Of The Ahr On Immunoglobulin Gene Expression In Human B Cells, Naga Lakshmi Kaulini Burra

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent and persistent environmental toxin known to inhibit immunoglobulin (Ig) gene expression in various animal models. TCDD is thought to modulate gene expression through the aryl hydrocarbon receptor (AhR) and thereby a subsequent alteration in gene expression. The AhR is a ligand-activated transcription factor that regulates xenobiotic-metabolizing enzymes. The mouse 3'Ig heavy chain regulatory region (3'IghRR) is a sensitive transcriptional target of TCDD that may mediate, in an AhR-dependent manner, the inhibitory effect of TCDD on Ig expression. Human B cells could also be a sensitive target of TCDD. The current study focuses on determining the …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Development Of Irreversible Substrate Competitive Probes For Pka Activity, Robert A. Coover

Theses and Dissertations

The current environment for drug discovery and disease treatment relies heavily on genomic analysis, structural biology and chemical biology techniques. With the enormous advances in genomic analysis and structural biology, the use of and desire for targeted therapies has increased. However, as more genomic data for cancer disease state pathology becomes available we must ask increasingly difficult questions and even produce new technologies, such as activity-based probes, to answer these questions.

In particular, targeted kinase inhibitors for the treatment of cancer has become a mainstay for drug development for both industry and academia, but it is evident that the genomic …

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Development Of Clinically Relevant In Vitro Performance Tests For Powder Inhalers, Xiangyin Wei

Theses and Dissertations

While realistic in vitro testing of dry powder inhalers (DPIs) can be used to establish in vitro–in vivo correlations (IVIVCs) and predict in vivo lung doses, the aerodynamic particle size distributions (APSDs) of those doses and their regional lung deposition remains unclear. Four studies were designed to improve testing centered on the behavior of Novolizer®. Different oropharyngeal geometries were assessed by testing different mouth-throat (MT) models across a realistic range of inhalation profiles (IPs) with Salbulin® Novolizer®. Small and large Virginia Commonwealth University (VCU) and Oropharyngeal Consortium (OPC) models produced similar ranges for total lung dose in vitro (TLD …

Integrated Nanoscale Imaging And Spatial Recognition Of Biomolecules On Surfaces, Congzhou Wang

Theses and Dissertations

Biomolecules on cell surfaces play critical roles in diverse biological and physiological processes. However, conventional bulk scale techniques are unable to clarify the density and distribution of specific biomolecules in situ on single, living cell surfaces at the micro or nanoscale. In this work, a single cell analysis technique based on Atomic Force Microscopy (AFM) is developed to spatially identify biomolecules and characterize nanomechanical properties on single cell surfaces. The unique advantage of these AFM-based techniques lies in the ability to operate in situ (in a non-destructive fashion) and in real time, under physiological conditions or controlled micro-environments.

First, AFM-based …

Bacterial Communication And Its Role As A Target For Nanoparticle-Based Antimicrobial Therapy, Kristen Publicover Miller

Theses and Dissertations

The goal of this dissertation is to establish the environmental and public health importance of alternative forms of antimicrobial therapy, specifically those that utilize nanotechnology to combat quorum sensing-controlled bacterial infections. Quorum sensing (i.e. chemical communication) is an inherent characteristic that is essential to bacterial pathogenesis and biofilm formation (where most infections occur). A thorough review of the literature has been conducted to establish an understanding of the state of nanotechnology research as it relates to combatting bacterial infections. This synthesis, provided in Chapter 1, demonstrates how the chemical and structural designs of nanoparticles can be manipulated to specifically target …

High-Content Screening In Zebrafish Embryos Identifies Abamectin As A Potent Neurotoxicant, Tara Diane Raftery

Theses and Dissertations

During development, the nervous system is a sensitive target for chemical exposure in both humans and animal models, and early life-stage exposures can lead to long-term effects on motor activity, sensory function, and cognition. Currently, there are minimal to no developmental neurotoxicity (DNT) data available for thousands of chemicals used in commerce, and it is impractical to screen these chemicals in rodent models using the existing DNT test guideline, as this test is costly, time- and animalintensive, and low-throughput. Therefore, there is a recognized need to use alternative non-mammalian models to support screening and prioritization of chemicals for DNT testing, …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Relationship Between Autophagy, Senescence, And Dna Damage In Radiation Sensitization By Parp Inhibition, Moureq Alotaibi

Theses and Dissertations

Radiotherapy continues to be a primary modality in the treatment of cancer. DNA damage induced by radiation can promote apoptosis as well as both autophagy and senescence, where autophagy and senescence can theoretically function to prolong tumor survival. A primary aim of this work was to investigate the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiation sensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population. In …

Synthetic Cannabinoids Versus Delta-9-Tetrahydrocannabinol: Abuse-Related Consequences Of Enhanced Efficacy At The Cannabinoid 1 Receptor, Travis Grim

Theses and Dissertations

In the past ten years, synthetic cannabinoids (SC) have emerged as drugs of abuse. Unlike D⁹-tetrahydrocannabinol (THC), many SCs are associated with serious health complications and death. One way in which THC and SCs differ lies with their enhanced potency and efficacy at the CB₁ receptor. No current methods exist to measure efficacy at the CB₁ receptor in vivo, and the abuse-related properties of SC cannabinoids are not well explored. Here, we utilized CB₁ wild type (WT), heterozygous (HET), and knockout (KO) mice. By employing CB₁ ligands which differ in efficacy we have …

Detecting Diesel Particulate Matter Using Real Time Monitoring Under The Influence Of An Exhaust Fan System, Yasir Helal Alghamdi

Masters Theses

"Diesel Particulate Matter (DPM) is a complex mixture of diesel exhaust gas that consists of carbon, ash, metallic abrasion particles, sulfates and silicates. The diesel soot particle includes a solid core made of elemental carbon, and organic carbon compound attached to the surface of the soot particle. The main source of DPM is diesel exhaust gas. The National Institute for Occupational Safety and Health (NIOSH) and the Environmental Protection Agency (EPA) have determined that DPM is the source of most of the emissions of carbon monoxide, carbon dioxide, oxide of nitrogen, and hydrocarbons in underground coal, metal and non metal …

Effect Of Vitamin E Supplementation On Inflammatory Markers And Nutrition Status In Thalassemia Intermedia Patients, Watcharee Prapawatwech, Bunchoo Pongtanakul, Kulwara Meksawan

The Thai Journal of Pharmaceutical Sciences

Inflammation is a complication found in thalassemic patients. It may be diminished by supplementation of vitamin E. The purpose of this study was to investigate the effects of 12-week vitamin E supplementation on inflammatory markers in patients with tha...

Approximation Of Fire-Return Intervals With Point Samples In The Southern Range Of The Coast Redwood Forest, California, Usa, Gregory Jones, Will Russell

Faculty Publications, Environmental Studies

A legacy of past fires is evident in the form of blackened basal hollows found throughout the southern range of the coast redwood (Sequoia sempervirens [D. Don] Endl.) forest.  A deeper look reveals cambial scars dating back centuries, telling a story of low- to moderate-intensity fires that burned periodically across California’s Central Coast bioregion.  While attempts have been made to reconstruct the fire history of this forest type, estimates of the fire-return interval vary widely, and the relationship of the fire-return interval to varying cultural influences is not fully understood.  We analyzed 373 fire scars from 70 cross-sections removed from …

Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini

Theses and Dissertations

DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol (Tg) at the first (Tg1) , second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3’ terminus was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate …

Expression And Pharmacological Modulation Of Pain-Depressed Behavior In Rats, Michael D. Leitl

Theses and Dissertations

Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This goal of this dissertation was to conduct preclinical research experiments designed to address a set of three inter-related aims that examine the expression, mechanisms and treatment of pain-related depression of Intracranial Self-Stimulation (ICSS) in rats. First, studies evaluated the hypothesis that acute acid-induced depression of ICSS was mediated by a kappa opioid receptor mediated decrease in mesolimbic dopamine release in the nucleus accumbens. Results support a role for depressed mesolimbic dopamine release in pain-related depression of ICSS; however, …

Structural Determinants Of Abuse-Related Neurochemical And Behavioral Effects Of Para-Substituted Methcathinone Analogs In Rats, Julie S. Bonano

Theses and Dissertations

Methcathinone (MCAT) is the β-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like “bath salts” in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse …

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix F. Gene Ontology Maps, Trevor Fish, Abby Benninghoff

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This archive includes 10 individual image files, each of which depicts a Gene Ontolgoy map for GO terms representing hypermethylated gene promoters unique for the indicated tissue(s) (listed first in file name) compared to other tissues (listed in parentheses in file name).