Pharmacology, Toxicology and Environmental Health Commons^™

Antiparasitic Peptide From The Ocean: Discovery, Synthesis And Structure-Activity Relationship Study, Kh Tanvir Ahmed

Electronic Theses and Dissertations

Millions of people die every year because of infectious diseases, and malaria is among the top five of the deadliest infectious disease. In 2018, malaria took more than four hundred thousand lives, and more than half of them are children under five years of age. Most malaria-affected parts of the world are also the home of the most underprivileged people. Seemingly, antimalarial drug discovery never achieved the attraction that it requires. Like malaria, another infectious disease that is not extensively explored by drug discovery campaigns is American trypanosomiasis or Chagas disease. More than a hundred years have passed since discovering …

Triclosan Disrupts Immune Cell Function By Depressing Ca2+ Influx Via Acidification Of The Cytoplasm, Suraj Sangroula

Electronic Theses and Dissertations

Triclosan (TCS) is an antimicrobial agent that was effectively banned by the FDA from hand soaps in 2016, hospital soaps in 2017, and hand sanitizers in 2019; however, TCS can still be found in a few products. At consumer-relevant, non-cytotoxic doses, TCS inhibits the functions of both mitochondria and mast cells, a ubiquitous cell type. Via the store-operated Ca²⁺ entry mechanism utilized by many immune cells, mast cells undergo antigen-stimulated Ca²⁺ influx into the cytosol, for proper function. Previous work showed that TCS inhibits Ca²⁺ dynamics in mast cells, and here we show that TCS also inhibits …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …

Potential Toxicity Of Silver Nanoparticles To Microbial Communities And Macroinvertebrates, Joseph Kusi

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) are the most common nanomaterials incorporated in commercial products due to their antimicrobial activity. Recently, AgNPs were detected in surface waters suggesting the potential for bioavailability in the aquatic receptor organisms. This dissertation research attempts to understand the potential toxicity of AgNPs on water quality indicators, focusing on the microbial community and amphipods. This study evaluated whether: (1) the antimicrobial properties of AgNPs pose potential risks to microbial communities in pathogen impaired streams; (2) AgNPs can cause a shift in functional diversity and metabolic fingerprinting of microbial communities; (3) survival and growth of Hyalella azteca (amphipods) could …

Development Of A Pharmaceutical Tablet Authentication System Using Spectroscopic Techniques In Combination With Multivariate Chemometric Methods, Md Nayeem Hossain

Electronic Theses and Dissertations

The spread of falsified drugs is increasing worldwide. Currently, 10%-30% of drugs in the world are falsified. Unfortunately, the supply chain system of developing countries (from manufacturers to customers) is not well monitored and suffers the highest rates of fraudulent activities. Also, the rise of product procurement from the internet increases the chance of American consumers' exposure to poor quality drugs. To combat this horrendous activity, surveillance of pharmaceutical materials is required in the supply chain system. Spectroscopic techniques (e.g., Near-Infrared and Raman spectroscopies) can be a potential solution to authenticate samples in different locations; they are non-destructive, safe, rapid, …

Does Circularizing Source-Separated Food Waste Present A Risk To Our Food?, Astha Thakali

Electronic Theses and Dissertations

About a third of the food produced annually is wasted. Food waste recycling can be a way to close the loop and attain a more sustainable food system, however, the system must be carefully monitored and managed to avoid the introduction and build-up of contaminants. To study the potential presence of contaminants in food waste, source-separated food waste was collected and screened for five classes of contaminants (physical contaminants, heavy metals, halogenated organic contaminants, pathogens, and antibiotic resistance genes) from two separate regulatory environments (voluntary vs mandated food separation). The regulatory environment did not affect the level of contamination, except …

The Cardiovascular Effects Of Tobacco Product-Derived Aldehydes: Contribution Of Transient Receptor Potential Ankyrin-1., Lexiao Jin

Electronic Theses and Dissertations

Cardiovascular diseases (CVD) are the leading cause of death in most countries and are significant health and financial burden worldwide. Smoking contributes to more than 480,000 premature deaths annually -- accounting for one of every five deaths in the United States each year. Numerous studies have shown that smoking increases the risk of factors including endothelial dysfunction, thrombosis, and atherosclerosis, which may lead to an incidence of myocardial infarction, coronary artery disease, and stroke. Electronic cigarettes (e-cigarettes) are a new kind of tobacco product, and some studies show that e-cigarettes also could induce CVD since both e-cigarettes and conventional tobacco …

Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle

Electronic Theses and Dissertations

BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …

Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson

Electronic Theses and Dissertations

Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …

Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

The Role Of Slc7a11 In Controlling Extracellular And Intracellular Redox Environments Of Lung Fibroblasts - Potential Targets For Intervention In Aging And Idiopathic Pulmonary Fibrosis., Yuxuan Zheng

Electronic Theses and Dissertations

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (E_h) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular E_h(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system X_c^-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 …

Human Genetics, Psychotropic Drugs, And Acts Of Violence, Selma Jolanda Eikelenboom-Schieveld

Electronic Theses and Dissertations

From the start of the use of psychoactive prescription medications in the 1950s, physicians reported paradoxical adverse reactions, ranging from newly developing depressions to an increase in existing mood disorders, and extremely violent and bizarre acts of suicide and homicide. In this research, it is hypothesized that the pharmacological properties of the prescribed drugs or the interaction between the drugs and the enzymes that are primarily responsible for their metabolism (cytochrome P450s) could cause these reactions. Given that acts of violence could be medication-induced, the role of the rate of drug metabolism is discussed. Genetic testing of certain CYP450s could …

Surfacant Contamination Alters Freshwater Phytoplankton Community Composition, William H. Hodge

Electronic Theses and Dissertations

Pollution from cleaning and personal care products enter freshwater systems and have the potential to alter phytoplankton abundance and diversity. Alkyl polyglucoside (APG), a widely used foaming agent in detergents, decreases phytoplankton abundance, but whether sensitivity to APG is affected by taxonomic identity and/or the presence of competitors is unclear. Establishing taxon-specific responses to APG is important, because taxa differ in nutritional quality and palatability for zooplankton grazers.

Chapter one describes comparisons between how individual phytoplankton communities respond to the same range of APG concentrations to test hypotheses that: 1) chemical concentration determines how individual taxa respond to APG; 2) …