Pharmacology, Toxicology and Environmental Health Commons^™

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …

Manufacturer Perspectives On Content Transparency And Material Health In The Us Building Products Industry, Alexandra A. Muller

Open Access Theses

Flawed U.S. federal regulation of chemicals has resulted in a materials market that undervalues human and environmental health in favor of the more traditional attributes of price, performance and aesthetics. In the building products industry, global, dynamic supply chains and proprietary information concerns further complicate the task of assessing the material health of products.

Voluntary material health programs in the green building industry are intended to incentivize the manufacture and selection of safer products by getting companies to gather and assess ingredient, hazard and risk information from their supply chain. Building product manufacturers considered early adopters of the main material …

The Interactive Effects Of Pesticide Exposure And Infectious Disease On Amphibian Hosts, Katherine M. Pochini

Open Access Theses

Natural systems are home to a multitude of natural and anthropogenic stressors, which draw an array of effects on ecological communities. While these effects have been investigated individually, it is important, given the routine co-occurrence of these stressors, to understand their interactive effects. Pesticide exposure and infectious disease are two common, co-occurring stressors that each have documented detrimental effects on species and, as evidence suggests, may have interactive effects. Moreover, existing research suggests that these interactive effects are highly context dependent, eliciting different results based on species, disease agent, toxin, and environment. Given the variability with which species may experience …

Assessment Of Concentrations Of Trace And Toxic Heavy Metals In Soil And Vegetables Grown In The Vicinity Of Manyoni Uranium Depositin Tanzania, F.A. Kapile, In Makundi

Tanzania Journal of Science

This study reports on determination of concentrations of trace and toxic heavy metals in soil and vegetables grown near of Manyoni uranium deposit. Soil and vegetable samples were collected from five sites namely Mitoo Mbuga, farming area, Miyomboni, Tambukareli and near water pump. The concentrations of heavy metals in soil and edible vegetables samples were analyzed using Energy Dispersive X-ray Fluorescence Spectrometry (EDXRF).All vegetable samples were found to have higher concentrations (in μg/g) of trace elements such as Ni (67.3) in pea leaves, Cu (14.9) in pumpkin leaves, Fe (478.6), (200.5) and (337.1) in pea, pumpkin and spinach leaves respectively, …

A Caenorhabditis Elegans Model To Detect Developmental Teratogens With Adverse Reproductive And Metabolic Effects, Alexis Ann Killeen

USF Tampa Graduate Theses and Dissertations

Obesity is a current epidemic in the United States. Greater than one third of adults and nearly one fifth of children are classified as obese (Ogden, 2014). Increased awareness of this problem has triggered interest into the potentially causal agents in our environment. These agents, termed obesogens, are a type of teratogen hypothesized to work during embryonic development by programming offspring to store excess fat. A type of teratogen, obesogens are also typically reprotoxic, affecting germline development and embryonic viability. These noxious teratogens span a variety of different chemical classes including estrogen mimics, metals and metalloids, biocides, and even voluntary …

From Milpas To The Market: A Study On The Use Of Metal Silos For Safer And Better Storage Of Guatemalan Maize, José Rodrigo Mendoza

Department of Food Science and Technology: Dissertations, Theses, and Student Research

This project aimed to implement the use of metal silos to improve quality and safety of maize consumed by inhabitants of the highlands of Guatemala. This manuscript includes a literature review of the maize production chain in Guatemala, a survey about agricultural practices used in the region of study, as well as a characterization of the analyzed maize regarding its mycoflora, nutritional composition, and insect infestation. To better understand the current situation regarding agricultural practices and maize consumption, a survey was carried out. Sample consisted of 280 families representing 14 rural communities distributed in the townships of Todos Santos and …

Omics As Therapeutic Platform: Environmental Factors To Parkinson's Disease, Hong-Duck Kim, Shana Warner, Kamini Singh, Jae-Hyeon Cho, Diane E. Heck

NYMC Faculty Publications

No abstract provided.

Exploration Of Chemical And Biological Management Strategies For Diaphorina Citri The Primary Vector Of Candidatus Liberibacter Asiaticus, Gretta Marie Sharp

Biology Theses

Diaphorina citri (Hemipteran: Psyllidae), the Asian citrus psyllid, is a phloem-feeding, invasive species endemic to southern Asia that was first identified in the United States in Florida in 1998. Since introduction, D. citri has spread across the major citrus growing regions of the United States. This is of great concern to the citrus industry because D. citri is the primary vector of Candidatus Liberibacter asiaticus the causal agent of Haunglongbing (HLB). Haunglongbing is the most economically devastating disease of citrus causing an estimated 8.92 billion dollars lost in revenue and 4.62 billion dollars lost in gross domestic product between 2006-2007 …

4,4’-Dichlorodiphenyltrichloroethane (Ddt) And 4,4’-Dichlorodiphenyldichloroethylene (Dde) Promote Adipogenesis In 3tl1 Adipocyte Cell Culture, J Kim, Q Sun, Y Yue, Kyong-Sup Yoon, K -Y Whang, J M. Clark, Y Park

SIUE Faculty Research, Scholarship, and Creative Activity

4,4’-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4’- dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 preadipocytes. Treatment …

Modification Of The In Vitro Uptake Mechanism And Anti-Oxidant Levels In Hacat Cells And Resultant Changes To Toxicity And Oxidative Stress Of G4 And G6 Poly (Amido Amine) Dendrimer Nanoparticles., Marcus Maher, Hugh Byrne

Articles

The mechanism of cellular uptake by endocytosis and subsequent oxidative stress has been identified as the paradigm for the toxic response of cationically surface charged nanoparticles. In an attempt to circumvent the process, the effect of increased cellular membrane permeability on the uptake mechanisms of poly (amidoamine) dendrimers generation 4 (G4) and 6 (G6) in vitro was investigated. Immortalised, non-cancerous human keratinocyte (HaCaT) cells were treated with DL-Buthionine-(S,R)-sulfoximine (BSO). Active uptake of the particles was monitored using fluorescence microscopy to identify and quantify endosomal activity and resultant oxidative stress, manifest as increased levels of reactive oxygen species, monitored using the …

Consequences Of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Tcdd) On Hepatic Stellate Cell Activation And Extracellular Matrix Remodeling During Chronic Liver Injury, Cheri Lou Lamb

Boise State University Theses and Dissertations

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Exposure to TCDD elicits a spectrum of toxic effects, many involving aberrant cell proliferation, activation, and differentiation. The liver is a target organ for TCDD toxicity, and increasing evidence indicates that AhR signaling regulates genes that coordinate deposition and remodeling of the extracellular matrix (ECM) in the liver. Hepatic stellate cells (HSCs) are central to ECM remodeling in the liver. We recently reported that TCDD treatment increases the activation of human HSCs in vitro. The goal of this study was to …

Investigating The Effects Of 17Α-Ethynylestradiol On Mitochondrial Genome Stability, Alicia M. Chivers

Dissertations and Theses

Environmental toxicants are ubiquitous throughout the environment as a result of human activity. Among these toxicants, environmental estrogens are a category of particular concern due to their environmental prevalence and potency in altering reproductive traits. While many studies have addressed the detrimental effects of environmental estrogens on both aquatic and terrestrial organisms, few have analyzed the potential for these compounds to alter mitochondrial function. Mitochondria are the primary energy-generating system for all eukaryotic life, supporting all aspects of development, metabolism, and growth. Each cell within the body contains many mitochondria which in turn contain multiple copies of their own DNA …

Investigations Of The Effects Of Different Ventilation Structures On Physiologically Based Pharmacokinetic Modeling (Pbpk) Simulations, Karen A. Yokley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Effect Of Bisphenol-A On Neurodevelopment In Drosophila Melanogaster Larvae, Alexandra M. Streifel

All College Thesis Program, 2016-2019

This paper examines the effects of the chemical preservative bisphenol-A on the developing nervous systems of Drosophila melanogaster, or fruit fly, larvae. This study examines the effects of bisphenol-A using both behavioral as well as morphological paradigms. It was determined that bisphenol-A significantly increased the amount of time larvae spent in seeking behavior, the number of peristaltic contractions, and the distance traveled in a linear fashion. In the morphological analysis, indications of increased dendritic area in experimental larvae existed, but there was not enough data to determine significance. For future research, it is recommended that more data be gathered to …

The Emergence Of Systematic Review In Toxicology, Martin L. Stephens, Kellyn Betts, Nancy Beck, Vincent Cogliano, Kay Dickersin, George Gray, +8 Additional Authors

Environmental and Occupational Health Faculty Publications

The Evidence-based Toxicology Collaboration hosted a workshop on “The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology,” on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts …

Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo

Forensic Science Theses

Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …

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 …

Fipronil Promotes Adipogenesis Via Ampkα-Mediated Pathway In 3t3-L1 Adipocytes, Quancai Sun, Jeremy Yang, Kyong-Sup Yoon, John M. Clark, Yeonhwa Park

SIUE Faculty Research, Scholarship, and Creative Activity

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10 mM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The …

Examining Mechanism Of Toxicity Of Copper Oxide Nanoparticles To Saccharomyces Cerevisiae And Caenorhabditis Elegans, Michael Joseph Mashock

Dissertations (1934 -)

Copper oxide nanoparticles (CuO NPs) are an up and coming technology increasingly being used in industrial and consumer applications and thus may pose risk to humans and the environment. In the present study, the toxic effects of CuO NPs were studied with two model organisms Saccharomyces cerevisiae and Caenorhabditis elegans. The role of released Cu ions during dissolution of CuO NPs in growth media were studied with freshly suspended, aged NPs, and the released Cu2+ fraction. Exposures to the different Cu treatments showed significant inhibition of S. cerevisiae cellular metabolic activity. Inhibition from the NPs was inversely proportional to size …

Anticonvulsant And Procognitive Properties Of Novel Histamine H3 Receptor Antagonists In Male Adult Rats, Ali Kassem Saad

Theses

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R …

Expansion Of The Knockdown Resistance Frequency Map For Human Head Lice (Phthiraptera: Pediculidae) In The United States Using Quantitative Sequencing, K J. Gellatly, S Krim, D J. Palenchar, K Shepherd, Kyong-Sup Yoon, C J. Rhodes, S H. Lee, J M. Clark

SIUE Faculty Research, Scholarship, and Creative Activity

Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of the kdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of the kdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across …

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. …

Comparison Of Protein Phosphatase Inhibition Assay With Lc-Ms/Ms For Diagnosis Of Microcystin Toxicosis In Veterinary Cases, Caroline E. Moore, Jeanette Juan, Yanping Lin, Cynthia L. Gaskill, Birgit Puschner

Veterinary Diagnostic Laboratory Faculty Publications

Microcystins are acute hepatotoxins of increasing global concern in drinking and recreational waters and are a major health risk to humans and animals. Produced by cyanobacteria, microcystins inhibit serine/threonine protein phosphatase 1 (PP1). A cost-effective PP1 assay using p-nitrophenyl phosphate was developed to quickly assess water and rumen content samples. Significant inhibition was determined via a linear model, which compared increasing volumes of sample to the log-transformed ratio of the exposed rate over the control rate of PP1 activity. To test the usefulness of this model in diagnostic case investigations, samples from two veterinary cases were tested. In August …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …

3,5-Dichloroaniline: Biotransformation And Mechanistic Aspects Of Nephrotoxicity In Vitro, Christopher Robert Racine

Theses, Dissertations and Capstones

Chlorinated anilines have been used as important chemical intermediates in the production of a wide variety of pharmaceutical, industrial, and agricultural products. Exposure to chloroanilines can arise in both occupational and environmental settings and can lead to toxicity to multiple organs, including the kidney. Previous studies have established that of the mono- and dichlorinated anilines, 3,5-dichloroaniline (3,5-DCA) possesses the most nephrotoxic potential both in vitro and in vivo. However, little is known concerning the role of renal metabolism in nephrotoxicity. The studies presented in the following dissertation are the first to explore the toxicity, metabolism, and bioactivation of 3,5-DCA in …

An Analysis Of Virtual Place Learning/Navigation In Children And Young Adults Prenatally Exposed To Alcohol, Neil Christopher Dodge

Wayne State University Dissertations

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze …