Pharmacology, Toxicology and Environmental Health Commons^™

The Role Of Human Dopamine Transporter Threonine 261 And Serine 262 In Amphetamine Regulation Of Transporter Function And Surface Expression, Sina Abdollahi

Theses and Dissertations

Amphetamine (AMPH) has been used clinically and recreationally around the world for years. A 2021 study reports a 67.5% rise in AMPH use from 2010-2017 across all fifty states. Study also shows that 30% of patients with AMPH-induced psychosis end up with primary psychosis over time. AMPH works by inhibiting monoamine (Norepinephrine (NE), Serotonin (5-HT), and Dopamine (DA) reuptake followed by triggering transporter mediated monoamine release and consequently increases monoamine concentrations in extracellular synaptic space. AMPH also works as a substrate for monoamine transporters, enters the neuron, and once its inside the neuron, it will prevent the storage of monoamines …

Assessing Stakeholder Needs And Preferences For Coastal Swimming Advisories In Charleston, South Carolina, Zachary Haynes Hart

Theses and Dissertations

The Beaches Environmental Assessment and Coastal Health (BEACH) Act was established in 2000 to reduce the risk of illness among recreational users of beaches in the United States. Specifically, the Act provides coastal states and territories with annual grants to conduct routine water quality monitoring at beaches and to notify the public when pathogen levels exceed safe thresholds. Many coastal states use beach signs, agency websites, and press releases to notify the public, but a 2011 evaluation of the public notification component of the BEACH Act found that few states are choosing methods based on target audience characteristics and interests. …

Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal

Theses and Dissertations

Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that …

Biochar Applications To The Remediation Of Lead And Polychlorinated Biphenyl Contaminated Water, Victory Itua Igberase

Theses and Dissertations

This study investigated the performance of biochar materials as adsorbents to remove Pb and polychlorinated biphenyl (PCB) in aqueous solutions. Batch adsorption and column experiment packed with biochar and geomaterials (pumice) in 1:1 volume ratio was evaluated to address the efficacy of biochar in removing Pb while only batch adsorption was employed for PCB removal with biochar materials. Overall, PT biochars performed the best (42–53 mg g−1) followed by BE biochars (10–32 mg g−1) and AB biochars (17–27 mg g−1) while high temperature biochars were favored in terms of maximum Pb adsorption capacity. Column Pb breakthrough showed similar results, with …

Uptake, Acuumulation, And Toixicity Of Silver Nanoparticles To Juvenile Bivalve Mollusc’S Hard Clam Mercenaria Mercenaria, Hanaa Radhi Jolan Al Hameed

Theses and Dissertations

Nanoscience and nanotechnology have gained attention in the last 20 - 30 years. Manufactured nanoparticles (NPs), which are defined as having at least one dimension between 1 and 100 nm, are the main products of nanotechnology. Nanoscale materials often have novel properties due to their size and this has made them so attractive for a range of processes and sectors. These attractive properties have enhanced their use in a wide range of consumer products and applications including electronic, biomedical, and pharmaceutical. The overall objective of this dissertation was: 1) to investigate the transformation of well-characterized AgNPs, at environmentally relevant concentrations …

Partitioning Of Volatile Organic Compounds Into The Multiple Environmental Compartments, Jeonghyeon Ahn

Theses and Dissertations

Volatile organic compounds (VOCs) dominate the class of pollutants that accumulate in the atmosphere and indoors. Partitioning coefficient is a measure of a compound’s ability to distribute between two phases. Assessing the partitioning of VOCs is essential to determine their transport, fate, behavior, and adverse environmental and health impacts across multiple environmental compartments. Studies on VOC partitioning have been limited because discriminating the small mass fraction of VOCs in aerosol particles is difficult to quantify. The partitioning of VOCs into soil, air, and aerosol particle phases was investigated under dynamic laboratory conditions. A bench-scale system that precisely controlled the relative …

The Interactive Effects Of Nontoxic Levels Of Microplastics - Textile Microfibers And Tire Wear Particles, On The Acute Toxicity Of Bifenthrin In The Estuarine Grass Shrimp, Palaemonetes Pugio, Xiaoxuan Fan

Theses and Dissertations

Contemporary pollution issues are primarily focused on Contaminants of Emerging Concern (CECs) which may include Brominated and Fluorinated flame retardants, Pharmaceuticals and Personal Care Products (PPCPs), Contemporary Use Pesticides (CUPs), nanomaterials and microplastics (Muraya et al., 2014). Tire wear particles and textile microfibers are examples of CECs which may gradually increase in the environment and may cause adverse effect on the health of some aquatic species (Marwood et al., 2011; Taylor et al., 2016). Microplastic particles are so small that they can be ingested by many marine species such as filter feeders and small particle feeders including mollusk and crustaceans, …

Health Communication Blindspot: A Case Study Of Harmful Algal Blooms In The South (Habits), Jaron Hoani King

Theses and Dissertations

A Harmful Algal Bloom (HAB) is a complex natural event that occurs when algae is in its growth stage and creates a harmful toxin as waste. HABs create both ecologic and public health challenges. The hypothesis of this thesis is that state and federal governments have different readability scores when compared side-by-side as measured by Simple Measures of Gobbledygook (SMOG). Because governments are the entity that most often claims responsibility for shared resources, this case study represents a snapshot of current governmental messaging about HABs in the South Atlantic states. These states have a long history of HAB events in …

Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan

Theses and Dissertations

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, …

Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot

Theses and Dissertations

Metabolic reprogramming is one of the important features of cancers, and there has been growing interest in targeting metabolic proteins to treat cancer. Glycogen is a polymer of glucose and serves as its storage unit in cells. Glycogen can provide energy to cells during the situations of high energy demand. A number of tumors are known to contain high levels of glycogen than their normal tissue counterparts. The liver plays an essential role in maintaining glucose homeostasis in the body via storing it into glycogen. The significance of glycogen metabolism in patients suffering from hepatocellular carcinoma (HCC) has not been …

Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang

Theses and Dissertations

ATP-binding cassette (ABC) transporters are responsible for the efflux of structurally distinct endo- and xenobiotics energized by ATP hydrolysis. MRP7/ABCC10 belongs to the 10th member of subfamily C and responsible for mediating MDR against a series of chemotherapeutic drugs such as taxanes, epothilones, Vinca alkaloids, anthracyclines and epipodophyllotoxins. Establishment of new in silico and in vitro models for MRP7 substrates/inhibitors prediction Considering the limited knowledge of MRP7, we established a homology model based on bovine MRP1 cryo-EM models. The final model was used for protein global motion analysis and docking analysis. Before docking, potential drug binding pockets were identified and …

Design, Synthesis And Pharmacological Evaluation Of Quinazolinamine Derivatives As Bcrp And P-Gp Inhibitors With Improved Metabolic Stability, Chao-Yun Cai

Theses and Dissertations

A series of twenty-two quinazolinamine derivatives showing potent inhibitory activities on BCRP and P-gp was synthesized. The reversal study showed that when combined with the potent dual BCRP and P-gp inhibitors 7-8, 29-31, and 34, the IC50 value of mitoxantrone was decreased from 6.50 µM to the range of 0.24 - 0.35 µM for BCRP, and IC50 value of colchicine was decreased from 7.34 μM to the range of 0.12 - 0.29 µM for P-gp. Cyclopropyl quinazolinamine 29 (VKCY-1), which was a dual BCRP and P-gp inhibitor, and azide quinazolinamine 40 (VKCY-2), which was a BCRP inhibitor, were selected for …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

The Cb1 Receptor Positive Allosteric Modulator, Zcz011, Attenuates Naloxone-Precipitated Withdrawal Signs In Oxycodone-Dependent Mice And Inhibits Small Intestinal Transit In Mice, Julien Dodu

Theses and Dissertations

The endogenous cannabinoid system tightly regulates a myriad of physiological and pathophysiological functions. Effects of cannabinoids in ameliorating opioid withdrawal signs has been known for decades. Naloxone precipitates several withdrawal signs (e.g., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid dependent rodents. ∆⁹-tetrahydrocannabinol (THC) has been shown to ameliorate opioid withdrawal in mice through the activation of cannabinoid type-1 (CB₁) receptors. Inhibition of the endocannabinoid degradative enzymes also attenuates these withdrawal signs (i.e., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid-dependent mice. Specifically, inhibition of fatty acid amide hydrolase (FAAH), …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Identifying Seasonal And Daily Variations In Arg-Containing Bioaerosols Generated During The Wastewater Treatment Process, Mirza Isanovic

Theses and Dissertations

Antibiotic resistance is a growing problem with the current global death count topping 700,000. In the United States alone there are 2.8 million antibiotic resistant bacterial (ARB) infections each year and approximately 35,000 deaths. If current trends continue the global ARB death count will reach 10 million surpassing current chronic disease deaths. Wastewater treatment plants play a vital role in protecting both the environment as well as local communities. The WWTP process allows for the removal of chemicals and contaminants from water that eventually makes its way back into the environment as well as into drinking water plants. Despite the …

The Use Of Ultra-High Pressure Liquid Chromatography In High-Throughput Pharmaceutical Separations, Glenn Anthony Kresge

Theses and Dissertations

The higher pressures and flow rates needed to increase throughput in ultra-high pressure liquid chromatography (UHPLC) can lead to thermal broadening due to viscous friction. The use of superficially porous particles and still-air thermal environments can help reduce this broadening, which is especially important in applications requiring high-throughput, isocratic separations, such as monograph methods for over-the-counter analgesics. In the first experiment discussed below, system suitability parameters (resolution and peak asymmetry) and temperature changes across the axial length of the column were monitored at conditions near column or system pressure limits. Results from this investigation indicated that shorter columns packed with …

Mechanistic Insight On Vibrio Gazogenes Mediated Intervention Of Aflatoxin Biosynthesis In Aspergillus Flavus, Rubaiya Jesmin

Theses and Dissertations

Aflatoxin is a liver carcinogen, mycotoxin, and a secondary metabolite that is produced by some plant pathogens within the genus Aspergillus when they infect crops such as corn, peanuts, and cotton. Given the significant adverse health and economic impacts of aflatoxin and a predicted rise of crop contamination with mycotoxins caused by a changing climate, there is a pressing need for exploring new aflatoxin mitigation methods. Previous studies in our laboratory have shown that metabolites from Vibrio gazogenes, an estuarine non-pathogenic bacterium, can inhibit aflatoxin synthesis. However, a direct interaction study between V. gazogenes and aflatoxin producing strains has …

Temporal Differences In The Emission And Atmospheric Dispersion Of Particulate Matter From Waste And Drinking Water Treatment Facilities, Abdulmalik Alsaif

Theses and Dissertations

Many countries encounter a growing shortage of water, and the reuse of treated or untreated wastewater is their main source. Wastewater Treatment Plants (WWTPs) are mainly designed to remove organic nutrients, large solids, and chemical substances. There are some possible issues regarding WWTPs that are close to residential areas around the world. One of the environmental effects from WWTP that might cause air pollution would be the emission of toxic chemical gases and microorganisms via aerosols that transport bacteria as well as viruses and fungal spores which can be harmful to human health. Therefore, particulate matters (PM) and metrological parameters …

Using A 3d In Vitro Ovarian Tissue Culture Model To Screen For The Female Reproductive Toxicity Of Pharmaceutical Compounds, Jingshan Xu

Theses and Dissertations

Ovarian toxicity (ovotoxicity) is one of the major side effects of pharmaceutical compounds for women at or before reproductive age. The current gold standard for screening of compounds for ovotoxicity largely relies on preclinical investigations using whole animals. However, in vivo models are time-consuming, costly, and harmful to animals. Here, we developed a three-tiered ovotoxicity screening approach starting from encapsulated in vitro follicle growth (eIVFG) and screened for the potential ovotoxicity of 8 preclinical compounds from AstraZeneca (AZ). Results from Tier 1 and 2 screenings using eIVFG showed that the first 7 tested AZ compounds, AZ-A, -B, -C, -D, -E, …

Understanding The Influence Of Changing Climate On Mycotoxin Contamination Of Food And Indoor Fungi-Mediated Respiratory Illness, Mayomi Helen Omebeyinje

Theses and Dissertations

Over the years, climate change has been a major core issue in public and environmental health. The World Health Organization (WHO) estimated that about 250,000 additional death per year would be attributed to climate change between 2030 and 2050 if this situation persists. Since our population depends on (but not limited to) the availability of clean water, good air quality, and exposure to environmental hazards/pathogens, the overall health impact caused by climate change is likely to be overwhelming in the nearest future. This dissertation explored the influence of climate change on fungi diseases and pathogenesis after severe weather conditions (hurricanes …

Computational Tools For Analyzing Correlations Between Microbial Biological Diversity And Ecosystems, Behzad Torkian

Theses and Dissertations

Metagenomics has developed into a reliable mechanism to analyze microbial diversity of microbial communities in the recent years. Through the use of next-generation sequencing, metagenomic studies can generate billions of short sequencing reads that are processed by computational tools. However, with the rapid adoption of metagenomics, a large amount of data has been produced. This high level of data production requires the development of computational tools and pipelines to manage data scalability and performance. In this thesis, we developed several tools that will aid in the exploration of the large amount of DNA sequence data, and we further developed a …

Microbiome Targeted Therapies In Gulf War Illness, Diana Agnes Kimono

Theses and Dissertations

Gulf war illness (GWI) is a chronic multisymptomatic disorder affecting about 30% of veterans of the 1990-1991 Persian Gulf war. Affected veterans complain of chronic symptoms which begun during or shortly after the war and persist 30 years later. This dissertation is a report of three studies which use a murine model to investigate the microbiome as a therapeutic target in GWI. Mice were exposed to pesticides and the prophylactic drug pyridostigmine bromide (PB) and studied these chemical’s impact on the microbiome in both an acute and persistence model of GWI.

The first study looks at the effect of altered …

The Use Of Polymer-Coated Magnetic Nanoparticles For Amelioration Oil Toxicity And Enhancement Microbial Remediation, Amjed Alabresm

Theses and Dissertations

Oil spills from different sources such as natural seeps, waste waters, runoffs and accidental oil spills can have serious effects on the environment while also resulting in potentially major economic damage. Due to the harmful effects of crude oil components on ecosystems, a rapid response to sequestrate oil is required to minimize any resulting environmental impact. Currently used oil removal methods, in addition to their advantages, also have severe limitations. New techniques have been developed including nanotechnology to address these limitations. A new type of nanoparticle (NP), composed of polyvinylpyrrolidone (PVP) coated iron oxide (magnetite), has been successfully used to …

Development, Validation, And Application Of A Novel Method To Separate And Quantify Silver Intracellular Uptake In Pseudomonas Aeruginosa, Mohammed A. Othman

Theses and Dissertations

Silver nanoparticles (AgNPs) have attracted tremendous attention as a potential broadspectrum antimicrobial agent to overcome multidrug resistant (MDR) infections. However, a comprehensive understanding to AgNPs bactericidal mechanism of action and the relative role of particulate versus ionic Ag in AgNPs antibacterial activity is lacking but essential for their optimization for potential medical applications. Therefore, a novel method to separate and quantify Ag internalization in P. aeruginosa was developed and validated through multimethod approach. The methods used were optical density at 600 nm (OD600), LIVE/DEAD staining, transmission electron microscopy (TEM), and sorbed Ag liberation assays. After optimizing the method, it was …

Bacterial Water Quality Monitoring As Citizen Science In Congaree National Park, South Carolina, Shea Mccarthy

Theses and Dissertations

Congaree National Park aims to preserve its natural and cultural resources while protecting these benefits for current and future enjoyment. Hydrologic features make up a large portion of the park and attract visitor recreation. There are several known sources of pollution that enter these waterways, mainly from upstream sources of waste discharge. The national park and its surrounding areas hold great ecological significance, however, there are many threats to the surface water quality in this area. Water quality degradation can impact the ecosystem, wildlife, and visitor experience. This project specifically considers exposure to fecal contamination in surface waters from upstream …

Retrospective Cohort Study Of Pure Tone Audiometry Threshold Shifts From Ototoxic Substance, Continuous Noise, And Impulse Noise Exposures At Tinker Air Force Base From 2005 To 2019, Marc J. Blair

Theses and Dissertations

This retrospective cohort epidemiology study sought to establish the comparative risks and potential indicators of hearing loss associated with combinations of ototoxic substances, impulse noise, and continuous noise exposure. Currently, there is not an existing model or methodology in the Department of Defense (DoD) that joins occupational exposure data and pure tone audiometric data. After developing an integrated database model for Tinker Air Force Base, the largest of three depot installations within Air Force Material Command, 2,372 individuals were grouped into eight combinations of exposure groups with a minimum three years exposure duration to hazards. The incidence rates and relative …