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Pharmacology, Toxicology and Environmental Health

Theses/Dissertations

2020

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Full-Text Articles in Life Sciences

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson Dec 2020

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …


Antiparasitic Peptide From The Ocean: Discovery, Synthesis And Structure-Activity Relationship Study, Kh Tanvir Ahmed Dec 2020

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 …


Pharmaceuticals And Personal Care Products In Pacific Northwest Coastal Ecosystems: Spatial Variation, Organism Effects, And Consumer Perspectives, Amy Lynne Ehrhart Dec 2020

Pharmaceuticals And Personal Care Products In Pacific Northwest Coastal Ecosystems: Spatial Variation, Organism Effects, And Consumer Perspectives, Amy Lynne Ehrhart

Dissertations and Theses

Anthropogenic pollution poses a threat to marine organisms and ecosystems worldwide. Common chemical pollutants that enter the marine environment include legacy contaminants, which are well known and heavily regulated or banned pollutants, and emerging contaminants, which are more recently recognized as pollutants and often lack regulatory limits for their use and discharge. Wastewater treatment plant (WWTP) effluent is a major source of various contaminants of concern, particularly pharmaceutical and personal care products (PPCPs) that are not fully removed during treatment. PPCPs exist at low concentrations in the environment and may have unknown and subtle effects on marine life. Data gaps …


Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr. Dec 2020

Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.

Theses & Dissertations

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities, stigma and pill fatigue are limitations. These have led to the development of long acting (LA) ART. These include, but are not limited to, implantable devices, new chemical entities, prodrug modifications and nanoformulations. To these ends, this thesis focues on the transformation of nucleoside reverse transcriptase inhibitors (NRTIs) into LA parenterals, While elusive, data from our laboratories demonstrated that modifications to the PROdrug and nucleoTide technology (ProTide) enables improvements in drug apparent half-life and tissue and cell …


Disadvantaged Vs. Non-Disadvantaged Drinking Water: San Joaquin County Groundwater Variable By Contaminant, Megan Brooks Dec 2020

Disadvantaged Vs. Non-Disadvantaged Drinking Water: San Joaquin County Groundwater Variable By Contaminant, Megan Brooks

Master's Projects and Capstones

This research explored drinking water wells that have detectable levels of arsenic and nitrate in disadvantaged vs. non-disadvantaged communities in San Joaquin County. The CalEnviroScreen 3.0 program and Groundwater Ambient Monitoring Program (GAMA) are used to measure disadvantaged communities and water quality data respectively. The CalEnviroScreen 3.0 scoring formula is used to calculate which census tracts are disadvantaged based on indices that measure pollution burden and population characteristics. The scoring is then combined with a census tract layer using Geographic Information Systems (GIS) technology. The disadvantaged community data are overlaid with GAMA groundwater well data to locate which communities are …


Investigating Dose-Dependent, Multi-Generational, And Strain-Specific Effects Of 17Α-Ethynylestradiol Exposure In Zebrafish (Danio Rerio), Decatur Mitochondria Foster Dec 2020

Investigating Dose-Dependent, Multi-Generational, And Strain-Specific Effects Of 17Α-Ethynylestradiol Exposure In Zebrafish (Danio Rerio), Decatur Mitochondria Foster

Dissertations and Theses

Endocrine disrupting chemicals (EDCs) pose a threat to biodiversity at the individual, population, and ecosystem level, as they can interfere with processes that are responsible for regulating metabolism, development, behavior, and reproduction in living organisms. 17α-ethynylestradiol (EE2) is a synthetic estrogen and EDC utilized in pharmaceutical and livestock industries, and contaminates waterways worldwide. This research explores the effects of dose-dependent and multi-generational exposure of EE2 in three strains of zebrafish. High dose (10-25 ng/L EE2) exposure led to complete reproductive failure, as well as significantly decreased survival and growth. A period in clean water (depuration) after exposure allowed for some …


Eelgrass (Zostera Marina) Population Decline In Morro Bay, Ca: A Meta-Analysis Of Herbicide Application In San Luis Obispo County And Morro Bay Watershed, Tyler King Sinnott Dec 2020

Eelgrass (Zostera Marina) Population Decline In Morro Bay, Ca: A Meta-Analysis Of Herbicide Application In San Luis Obispo County And Morro Bay Watershed, Tyler King Sinnott

Master's Theses

The endemic eelgrass (Zostera marina) community of Morro Bay Estuary, located on the central coast of California, has experienced an estimated decline of 95% in occupied area (reduction of 344 acres to 20 acres) from 2008 to 2017 for reasons that are not yet definitively clear. One possible driver of degradation that has yet to be investigated is the role of herbicides from agricultural fields in the watershed that feeds into the estuary. Thus, the primary research goal of this project was to better understand temporal and spatial trends of herbicide use within the context of San Luis …


The Effects Of Eating A High Fat Diet On Sensitivity Of Rats To Methamphetamine-Induced Conditioned Place Preference, Kayla Galindo Dec 2020

The Effects Of Eating A High Fat Diet On Sensitivity Of Rats To Methamphetamine-Induced Conditioned Place Preference, Kayla Galindo

Open Access Theses & Dissertations

Eating a high fat diet causes several negative health consequences, including dysfunction to dopamine systems. For example, eating a high fat diet enhances sensitivity of rats to methamphetamine-induced locomotor sensitization. However, it is not known if sensitivity to other (i.e., the rewarding) effects of methamphetamine are similarly enhanced in rats eating a high fat diet. Females are more sensitive than males to the behavioral effects of stimulants in general, and therefore might also be particularly vulnerable to the effects of diet on the rewarding effects of stimulant drugs. To test the hypoThesis that eating high fat chow enhances sensitivity of …


Regulation Of In Vitro And In Vivo Hepatic Stellate Cell Activation By The Ayrl Hydrocarbon Receptor, Shivakumar Rayavara Veerabhadraiah Dec 2020

Regulation Of In Vitro And In Vivo Hepatic Stellate Cell Activation By The Ayrl Hydrocarbon Receptor, Shivakumar Rayavara Veerabhadraiah

Boise State University Theses and Dissertations

Liver fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix material by activated hepatic stellate cells (HSCs). We recently reported that activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases HSC activation in vitro and in mouse models of experimental liver fibrosis. The goal of this project was to determine the mechanism by which AhR activation impacts HSC activation and the subsequent development of liver fibrosis. It is possible that HSCs are direct cellular targets for TCDD. Alternatively, TCDD could increase HSC activation indirectly by exacerbating hepatocyte damage …


Dendriplex - Cyclodextrin Conjugates For Gene Delivery To Retina, Durga Deepak Puro Nov 2020

Dendriplex - Cyclodextrin Conjugates For Gene Delivery To Retina, Durga Deepak Puro

USF Tampa Graduate Theses and Dissertations

Gene therapy holds promise for treating a wide range of diseases including cancer and several other polygenic and monogenic disorder arising in different organs. Due to its immune privilege nature, eye is an ideal organ for gene therapy,as various visual pathologies arise from gene defect and can lead to partial or complete vision loss. The last decade, several nanoparticles have been developed and tested for their transfection efficiency in vitro and in vivo. Among them, dendrimers with small size, good physicochemical properties and endosomal escape activity have shown high transfection efficiency in various cell lines. In an attempt to further …


Pharmacy: The Backbone Of Healthcare, Jordan Raye Myers Nov 2020

Pharmacy: The Backbone Of Healthcare, Jordan Raye Myers

Honors Theses

The field of pharmaceuticals is growing and changing everyday. Being a part of the creation of new medicines and new treatments is a dream. Throughout my life my favorite subject has always been science, specifically where the sciences of biology and chemistry intersect. Biology and chemistry have significant overlap in the field of pharmacy. I believe that the passion and love I have for combining these two sciences will reflect in my career as a pharmacist and open doors for me to positively impact the lives of patients and the pharmaceutical field. I chose to pursue a career in pharmacy …


Chemically Induced Phytoextraction Of Lead (Pb) Contaminated Soil By Switchgrass (Panicum Virgatum L.), Austin Gilly Nov 2020

Chemically Induced Phytoextraction Of Lead (Pb) Contaminated Soil By Switchgrass (Panicum Virgatum L.), Austin Gilly

Master of Science in Integrative Biology Theses

Soils contaminated with lead (Pb) from human activities including industrial byproducts create an environmental and human health risk. Phytoextraction through chemical acquisition of Pb in soils offer a potentially cost effective and ecologically driven approach to remediation. Switchgrass (Panicum virgatum L.) is known to have a tolerance for a wide range of heavy metals including Pb. Switchgrass is also able to grow in a wide range of climates. Soil chemistry manipulation, using chelates and plant growth promoters could provide an effective field method for phytoremediation using switchgrass. In this study chemically enhanced phytoextraction using the soil-fungicide Infuse (active ingredient …


Molecular Mechanisms Regulating The Platelet Thrombin Receptor Par4, Pierre E. Thibeault Nov 2020

Molecular Mechanisms Regulating The Platelet Thrombin Receptor Par4, Pierre E. Thibeault

Electronic Thesis and Dissertation Repository

Proteinase activated receptor 4 (PAR4) is a G-protein-coupled receptor with an important role in the platelet response to vascular injury. In platelets, PAR4 activation, by thrombin-cleavage of its N-terminus and unmasking of a tethered ligand, leads to G-protein- and beta-arrestin-mediated intracellular signalling pathways which result in platelet activation, shape change, and ultimately, platelet aggregation. As an important platelet thrombin receptor, PAR4 is an interesting target for the development of anti-platelet therapeutics. However, molecular determinants of PAR4 activation, signalling, and signal regulation remain poorly understood. In this thesis, mechanisms of PAR4 activation and signalling were studied through determination of the molecular …


A National Approach To Address The Impact Of Land-Based Pollution On Marine Environment In Liberia, Kansualism Berk Kansuah Nov 2020

A National Approach To Address The Impact Of Land-Based Pollution On Marine Environment In Liberia, Kansualism Berk Kansuah

World Maritime University Dissertations

No abstract provided.


Hepatobiliary Polycyclic Aromatic Hydrocarbons In Pelagic Fishes Of The Gulf Of Mexico, Madison R. Schwaab Oct 2020

Hepatobiliary Polycyclic Aromatic Hydrocarbons In Pelagic Fishes Of The Gulf Of Mexico, Madison R. Schwaab

USF Tampa Graduate Theses and Dissertations

Fisheries populations and their ecosystems are negatively impacted by both chronic and acute inputs of pollutants, including oil spills such as the Deepwater Horizon platform blowout in 2010 in the Gulf of Mexico (GoM). After Deepwater Horizon, toxicological studies of demersal fishes of the northern GoM were undertaken to characterize impacts and to establish baseline contaminant levels in the aftermath of the spill. In this study, I quantify polycyclic aromatic hydrocarbon (PAH) concentrations in eight pelagic fish species to demonstrate oil exposure differences between species, region and time. Analysis of biliary PAH metabolite equivalents using high performance liquid chromatography was …


Can Viruses Cause Lupus?, Stephen I. Reeder Oct 2020

Can Viruses Cause Lupus?, Stephen I. Reeder

Selected Honors Theses

Like so many autoimmune diseases, the exact cause of systemic lupus erythematosus (SLE) remains unknown. Evidence points to both genetics and environment playing roles in the onset of the disease, but neither acts independent of the other. Genetics are the easier of the two to study with recent advances in the field making it easier to isolate genes shared by individuals with the disease. However, genetic studies reveal that there is almost certainly an environmental component to the development of SLE. The underlying pathology and existing research on environmental contributors to the development of SLE suggest that viruses could potentially …


Identifying Seasonal And Daily Variations In Arg-Containing Bioaerosols Generated During The Wastewater Treatment Process, Mirza Isanovic Oct 2020

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 Effects Of Radical Containing Combustion Derived Particulate Matter In Adult Mouse Respiratory System, Jeffrey Harding Aug 2020

The Effects Of Radical Containing Combustion Derived Particulate Matter In Adult Mouse Respiratory System, Jeffrey Harding

LSU Doctoral Dissertations

Epidemiological data associates high levels of combustion-derived particulate matter (PM) with deleterious respiratory outcomes, but the mechanism underlying those outcomes remains elusive. It has been acknowledged by the World Health Organization that PM exposure contributes to more than 4.2 million all-cause mortalities worldwide each year. Current literature demonstrates that PM exacerbates respiratory diseases, impairs lung function, results in chronic respiratory illnesses, and is associated with increased mortality. The proposed mechanisms revolve around oxidative stress and inflammation promoting pulmonary physiological remodeling. Our data demonstrate that environmentally persistent free radicals (EPFRs) stabilized on the surface of PM are capable of inducing oxidative …


Next Generation Aryl Hydantoins As Antischistosomal Agents, Derek A. Leas Aug 2020

Next Generation Aryl Hydantoins As Antischistosomal Agents, Derek A. Leas

Theses & Dissertations

Schistosomiasis, also known as “snail fever,” is both an acute and chronic disease spread by trematode flukes from the tropical parasitic worm genus Schistosoma. The flukes are spread via diseased freshwater snails, which release the parasites into the water column where they find a new human host. According to the World Health Organization (WHO), 99 million people were treated for schistosomiasis in 2017. The primary treatment used to combat schistosomiasis is the drug praziquantel (PZQ), but due to high drug pressure and widespread administration, its effectiveness has eroded because of rising drug resistance. Furthermore, PZQ is active against adult but …


Triclosan Disrupts Immune Cell Function By Depressing Ca2+ Influx Via Acidification Of The Cytoplasm, Suraj Sangroula Aug 2020

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 …


Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri Aug 2020

Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri

Theses & Dissertations

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of a novel Pyrrolomycin (MP-1) in mouse plasma. MP-1 was extracted from plasma utilizing a structural analog (PL-3) as the internal standard (IS). Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 x 2.1 mm) protected with Acquity UPLC C18 guard column. Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction …


Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon Aug 2020

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 …


The Use Of Ultra-High Pressure Liquid Chromatography In High-Throughput Pharmaceutical Separations, Glenn Anthony Kresge Aug 2020

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 …


Determinants Of The Carbon Footprint Of German Swimmers 2020., Ann-Marie Muehlbauer Aug 2020

Determinants Of The Carbon Footprint Of German Swimmers 2020., Ann-Marie Muehlbauer

Master's Theses

The current climate situation is placing our planet and future generations at risk, which demonstrates the urgency to combat climate change and conduct research to support this effort. Calculating the carbon footprint of active sport participation represents an important opportunity to conduct additional research. This study examined the environmental attitudes and practices of swim club members in Germany. The study had three goals: First, to calculate the total and partial carbon footprint of German swimmers; second, to understand how sport organizations induce participants to engage in pro-environmental behavior; and third, to analyze various factors associated with carbon footprint, such as …


Prevalence Of Anticoagulant Rodenticides In Ferruginous Hawk Nestlings And Evaluation Of A Novel Method To Rapidly Assess Exposure, Ariana Joyce Dickson Aug 2020

Prevalence Of Anticoagulant Rodenticides In Ferruginous Hawk Nestlings And Evaluation Of A Novel Method To Rapidly Assess Exposure, Ariana Joyce Dickson

Boise State University Theses and Dissertations

Anticoagulant rodenticides (ARs) are compounds commonly used to control rodent pests by inhibiting an enzyme critical for synthesis of clotting factors in their blood. Secondary and tertiary poisoning of non-target species frequently occur, especially of predators that consume rodents, including many species of raptors. Although raptor exposure to ARs has been documented on at least three continents, patterns, pathways and the sub-lethal effects of exposure are not well studied. This has created a substantial need to monitor the effects of ARs in free-living populations. I evaluated the prevalence of secondary, non-target exposure to anticoagulant rodenticides experienced by a predatory raptor, …


The Assessment Of Co2 Exposures, Workload Demands, And Musculoskeletal Disorder Risk On Heart Rate For Select Craft Brewery Job Tasks, David L. Huizen Aug 2020

The Assessment Of Co2 Exposures, Workload Demands, And Musculoskeletal Disorder Risk On Heart Rate For Select Craft Brewery Job Tasks, David L. Huizen

Dissertations

Americans have embraced craft beer, and the ensuing demand has resulted in an ever-increasing number of craft breweries opening over the past 20 years. Craft brewers are generally small employers and, as such, lack the resources necessary to address the safety and health of their employees adequately. Brewers face many safety and health hazards in their work environment. These hazards include exposures to carbon dioxide (CO2), workload demand, and MSD risk. It is essential to evaluate these hazards in craft breweries as they handle carbon dioxide (CO2) differently than large breweries by having the CO2 …


Potential Toxicity Of Silver Nanoparticles To Microbial Communities And Macroinvertebrates, Joseph Kusi Aug 2020

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 …


Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss Aug 2020

Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss

Biomedical Sciences Theses & Dissertations

Bacteriophages (phages), viruses that infect bacteria, have many applications in medicine, agriculture, molecular biology, and other fields. As antibiotic resistance becomes an increasing problem, interest in phages has grown. The traditional techniques of phage discovery are successful for some phages, but others require modified procedures to achieve detectable host infection.

Mycobacterium is a diverse bacterial genus characterized by a unique cell wall containing mycolic acids, which aids in survival and pathogenesis. The aims of the present research were to isolate mycobacteriophages, use bioinformatics techniques to analyze mycobacterial prophages, and combine genetic analysis with multi-well plate host range studies to identify …


N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil Aug 2020

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 …


Opioids Disrupt Sleep And Wakefulness In C57bl/6j Mice, Clarence E. Locklear Aug 2020

Opioids Disrupt Sleep And Wakefulness In C57bl/6j Mice, Clarence E. Locklear

Masters Theses

Opioid use disorder (OUD) is a major public health burden. According to the National Institutes of Health (NIH), studies helping to understand the mechanisms of OUD will help improve prevention and treatment. Opioids long have been shown to disrupt sleep and sleep disruption enhances the likelihood of addiction relapse in humans. The NIH refers to the mouse as one of the most powerful animal systems to study because of the genetic homologies between human and mouse. Prior to the present research, no studies have quantified the effect of opioids on states of sleep and wakefulness in mice. The current study …