Pharmacology, Toxicology and Environmental Health Commons^™

The Effect Of Cannabinoids And Terpenes On The Activation Of Hmc3 Microglial Cells, Mohamed Marzouk

Honors Theses

Life expectancies of people living with HIV have significantly lengthened due to the availability of antiretroviral therapies. Despite their ability to increase survival, these treatments do not “cure” HIV, nor do the stop the onset of neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological impairments including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition that reduce quality of life for people living with HIV. Mechanistically, the neurological impairments may involve actions of neurotoxic proteins directly produced by the virus. One of these proteins that has been well-characterized is the HIV trans …

Early Life Δ9-Tetrahydrocannabinol Exposure Of F0 Zebrafish Causes Hyperactivity In F1 Offspring, Jenna Cripe

Honors Theses

As cannabis increases in its accessibility, potency, and acceptance across the United States, investigation into the multigenerational effects of Δ9-tetrahydrocannabinol (THC) exposure during key stages of development is critical. The aim of this study was to evaluate whether there would be behavioral impacts in the F1 offspring following a dose-response of THC exposure (0.08, 0.4, or 1 µM) during development in the F0 generation. Zebrafish (Danio rerio) were utilized in this study. Behaviors (locomotive activity and anxiety-like behavior) in the F1 generation were evaluated at 120 hours post-fertilization (hpf) with the larval photometer response (LPR) assay, and at 3, 11, …

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow

Honors Theses

Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …

Black Carbon And Meteorological Parameters At Two Locations In Northern Mississippi, Ashton Swader

Honors Theses

Black Carbon, which is a component of fine particulate matter, is a known pollutant that has been linked to the development of several diseases including cardiovascular disease. This pollutant can be measured by taking samples of air within a certain region and analyzing them using a transmissometer. It is known that black carbon concentrations tend to be higher in urban areas when compared to rural areas within a region. Black carbon concentrations can also vary depending on certain meteorological parameters such as temperature and humidity. There were no current studies that analyze the air quality in northern Mississippi due to …

Determination Of Metals And Microplastics In Sediment From Oyster Reefs In The Mississippi Sound, Shelby Goza

Honors Theses

This research centers on the determination of metals (Cd, Pb, V, Cr, Mn, Fe, Co, Ni, Cu) and microplastics (MPs) in marine sediment from oyster reefs in the Mississippi Sound Estuary. Oysters (Crassostrea virginica) are a vital part of the Gulf Coast economy, but their population has dramatically declined in recent years due to multiple stressors, including oil spills and fluctuations in salinity from flooding. Increasingly frequent flooding events also introduce high loads of MPs and sediments containing heavy metals from the Mississippi River. These pollutants can have deleterious effects on oyster biology; however, they have not been adequately …

Composition And Oxidative Potential Of Fine Particulate Matter From Pascagoula, Ms, Madison Smith

Honors Theses

Air pollution is one of the top-ranking risk factors for death and disability around the world, accounting for nearly 4.9 million deaths worldwide (State of Global Air, 2019). Specifically, fine particulate matter (PM_2.5) has been linked to many adverse effects on human health, yet there is very little known about what characteristics exactly cause these adverse health effects and how they cause them. Samples for this study were collected from Pascagoula, MS, a small town located on the Mississippi Gulf Coast that is home to many industrial yards, from September 2013 to December 2013. Black carbon (BC) analysis …

Responses To Fine Particulate Matter (Pm2.5) Exposures In Two Wild-Type Zebrafish Strains, Connor Necaise

Honors Theses

Atmospheric fine particulate matter (PM_2.5) exposure poses great health risks across the globe, causing both acute and chronic illnesses in humans. Therefore, a more complete understanding of the mechanisms in which PM_2.5 induces these adverse health effects is urgently needed. Oxidative stress due to PAHs and other common components of PM_2.5 is a proposed mechanism for its adverse health effects. However, little is known about the actual mechanisms of PM_2.5 damage in humans. This study aimed to distinguish behavioral differences in two lines of zebrafish (AB & 5D) as a result of developmental exposure to …

Lc-Ms/Ms Method Development And Analysis Of Tricyclic Antidepressants In Human Plasma, Shahbaz Gul

Honors Theses

Depression has become one of the most prominent problems in society, disrupting both personal and social lives. Tricyclic antidepressants (TCAs) were first developed in the 1950’s and became some of the leading anti-depressant medications on the market later that decade. Today, newer anti-depressants have risen to the forefront, being safer and having a lower side-effect probability. Nonetheless, TCAs continue to be prescribed for severe depression, especially in cases where the newer anti-depressants have failed. However, TCAs are still highly potent, the toxicity associated with these compounds cannot be ignored. They have considerable cardiovascular and neurological toxicity, and in the event …

Narrative Storytelling In Conjunction With Environmental Journalism, Abbey Edmonson

Honors Theses

This thesis explores the effectiveness of long-form narrative storytelling in relation to environmental journalism. It particularly focuses on effectively communicating the seriousness of climate change on a local level through narrative storytelling. The bulk of the information was gathered through multiple interviews with people experiencing the effects of climate change on the Mississippi Gulf Coast. By using interviews with local people interspersed with scientific data, I hope to be able to show the average reader that climate change is real and it can dangerously affect people on a local level, even in rural states like Mississippi.

Through my research, I …

Examining Public Water Systems Servicing Schools And Childcare Facilities To Inform Policy: A Study Of Lead Exposure In The Mississippi Delta, William Farmer

Honors Theses

Abstract

This study was initiated with the intent of identifying elementary schools and childcare facilities in the Mississippi Delta with children ages 6 and under that may have public water systems (PWSs) with lead exceedances of 5 ppb. We also aimed to identify the existence, and further the availability, of information regarding which public schools and childcare facilities were serviced by which public water systems. Based on the results of this study, considerations related to Mississippi’s ability to comply with the 2020 Revisions of the Lead and Copper Rule requiring testing in all public schools were determined. Seven principal counties …

Oxidative Potential And Composition Of Fine Particulate Matter At Two Locations In Mississippi, Victoria Claire Stevens

Honors Theses

Air pollution exposure has negative health effects on individuals across the globe. Negative impacts on human health have been documented in studies following both short-term and long-term exposure to air pollution, and these adverse effects have been seen even at the lowest levels of exposure. Fine particulate matter (PM_2.5) has specifically been linked to these negative health effects. These effects come from many sources, but one large contribution to the negative health effects comes from oxidative stress. In this study, samples were collected from Hernando, MS and Gulfport, MS in September 2013 and November 2013. Black carbon (BC) …

Characterizing Pm2.5 Air Samples Of Northeast Mississippi, Harley Nabors

Honors Theses

Ambient air pollution has been associated with adverse health effects throughout the entire world. Although epidemiologists study air pollution extensively, rural areas are often the least understood. In 2020, the Mississippi Department of Environmental Quality used less than 10 air sampling locations across the state leaving a large gap in air quality knowledge. In this study, fine particulate matter (PM2.5) air samples were collected from three different rural Mississippi cities–Ackerman, Eupora, and Houston, in the summer of 2020. Following collection onto filters, elemental black carbon analysis and an oxidative potential assay were both used to characterize the samples of interest. …

Surface-Eroding Drug Delivery Films For Sequential And/Or Intermittent Release Of Psychoactive Drugs, Jason Price

Honors Theses

ABSTRACT JASON BLAKE PRICE: Surface-Eroding Drug Delivery Films for Sequential and/or

Intermittent Release of Psychoactive Drugs For patients with psychiatric diseases, adherence to medication schedules, medication

errors, and abuse are common issues. Promising new forms of therapy for these patients, such as micro-dosed lysergic acid diethylamide (LSD), where patients receive 10-20% of a full dose every third day, present further drug delivery challenges. Sequential or intermittent release of drugs from an implanted device could ensure long-term drug compliance, automate drug dosing during the life of the implant, and eliminate potential for abuse and medication errors. To this end, we generated …

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Study Of Pharmaceutical Tablets Using Raman Mapping, Kyle Joseph Pauly

Honors Theses

Covalent bonds are the strongest type of bonds holding molecules together. Based on the pattern of bonding of the molecule, the atoms associated with the bond will vibrate at a specific frequency. Utilizing vibrational spectroscopy, such as Raman spectroscopy, these unique vibrational frequencies can be used to detect the presence of analytes over a selected area. Furthermore, the intensities of the vibrational modes can be tracked to comparatively quantify the concentration of analytes at various locations. This is a method of great importance due to its ability to compare pharmaceutical tablets synthesized with different techniques. Here, the presence and concentration …

Impacts Of Embryonic Exposure To Cannabidiol Or ∆9-Tetrahydrocannabinol On Zebrafish (Danio Rerio) Frailty In F0 And F1 Generations, Anika Faruque

Honors Theses

Exposure to cannabinoids during critical development periods has increased with epileptic children being commonly prescribed CBD for seizures and pregnant women taking it recreationally. Many studies have been done on the possible benefits and drawbacks of cannabinoid exposure on the human brain, but not much is known about how it can affect the developing brain long-term. To see the potential adverse effects of cannabinoid exposure during critical stages of development and discover potential developmental origins of disease in consuming cannabinoids during embryogenesis, zebrafish embryos (6-96 hours post fertilization) were exposed to varying concentrations of CBD (0.02, 0.1, 0.5 µM), THC …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

The Independent And Combined Effects Of Hypoxia And Tributyltin On The Eastern Oyster, Crassostrea Virginica, Ann Fairly Barnett

Electronic Theses and Dissertations

Oysters are vital to the health of estuarine ecosystems and provide critical ecosystem services, such as water quality improvement, nursery habitat for commercially important fisheries, and shoreline stabilization. Despite their ecological and economic importance, oyster reefs are exposed to many stressors, and oyster populations in Mississippi have declined dramatically in recent years. The present study focuses on the effects of hypoxia and tributyltin (TBT) on the Eastern oyster, Crassostrea virginica. Hypoxic events are increasingly comin coastal ecosystems worldwide, and TBT is a legacy toxicant once used as an antifoulant. The effects of these stressors were assessed on adult oysters deployed …

Continuous Production Of Raloxifene Hydrochloride Loaded Nanostructured Lipid Carriers Using Hot-Melt Extrusion Technology, Derick Muhindo

Electronic Theses and Dissertations

The aim of this study was to utilize a continuous process for the production of Raloxifene Hydrochloride (RX-HCl) loaded NLC formulations for extended drug release using hot-melt extrusion technology coupled with probe sonication, and also to evaluate the in vitro characteristics of the prepared NLCs by particle size, PDI, zeta potential, entrapment efficiency, drug loading, and in vitro drug release profile. Preparation of the NLCs using HME technology involved two main steps, first formation of a pre-emulsion after extrusion and then size reduction of the pre-emulsion using probe sonication to obtain the NLCs. Process parameters for the extrusion process like …

Pharmacokinetic Study Of Novel Anthraquinone Analogues, Yuhan Guo

Electronic Theses and Dissertations

Small molecules functioning as negative regulators of MDM2 have been considered as promising anti-cancer agents. A series of novel anthraquinone (AQ) analogues upregulate p53, a well-known tumor suppressor, by inactivating its antagonist protein MDM2. The novel AQ compounds synthesized through the modifications on the rhein scaffold were reported to have successfully arrested tumor growth. To have a better understanding of their underlying metabolism in vivo, pharmacokinetic (PK) studies were performed for the AQ compounds. A selective, accurate and reproducible assay methodology for PK study was set up for each AQ compound. The stabilities of AQ compounds were then evaluated …

Developing Zebrafish As An In Vivo Model To Screen Compounds For Anti-Cancer Activity In Human Breast Cancer, Trisha Dhawan

Electronic Theses and Dissertations

Breast Cancer (BC) is the most frequently diagnosed cancer; 1:8 women are at risk of developing BC in her lifetime. Cancer metastasis causes the majority of deaths in BC patients. Moreover, side effects of traditional chemotherapeutic drugs (TCD) impair the quality of life of these patients. Discovery and development of safe and effective new therapies is imperative for the treatment of BC and targeting metastasis. The goal herein is to further expand the applicability of in vivo xenotransplantation of human BC cells in transgenic zebrafish to screen potential chemotherapeutics for toxicity and efficacy. For xenotransplantation, MCF-7, BT-474, and MDA-MB-231 BC …

A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha

Electronic Theses and Dissertations

An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Safety Assessment And Chemical Fingerprint Analysis Of Medicinal Plants Commonly Consumed As Herbal Teas; Rooibos (Aspalathus Linearis) And Moringa (Moringa Oleifera), Omer I. Fantoukh

Electronic Theses and Dissertations

The first chapter discusses the significance of natural products, safety challenges, and quality issues concisely. Specifically, the impact of herb-drug interaction on consumers and the quest for chemical markers for chemical fingerprinting development are provided. Rooibos tea (Aspalathus linearis) is a popular South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of CYP450 isozymes. In chapter two, the phytochemical investigation of A. linearis resulted in the isolation and characterization of 14 phenolic compounds. Safety assessment of the phytochemicals through interaction with CYP, PXR, and P gp was conducted. The …

G-Quadruplexes As Molecular Targets For Transcriptional Control, Rhianna Kyelle Morgan

Electronic Theses and Dissertations

DNA G-quadruplexes (G4s) have gained interest in modern drug discovery efforts. The majority of G4 research, including the mass of this research, heavily focuses on cancer therapeutic development, as G4s are more pronounced in oncogenic promoters compared to the rest of the genome, our efforts extend towards neuroprotection as well. In particular, this work covers G4s in the promoters of MYC, VEGF, kRAS, and Bcl-2. MYC and VEGF harbor the two most well described promoter G4s to date, and their stabilization cultivates transcriptional silencing. Downregulation of MYC reduces cell growth and alters cell energetics; it is promising for a variety …

Effects Of Nanosilver And Silver Nitrate Exposure On Fathead Minnows (Pimephales Promelas) And Zebrafish (Danio Rerio), Adam D. Hawkins

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) due to their unique antimicrobial properties are among the most widely utilized nanoparticle. Because of the nature of the products that utilize AgNPs, environmental release of AgNPs is inevitable. At greatest risk is the aquatic ecosystem due to known toxicity of the Ag + ion to aquatic organisms. Our goal was to use two fish models, fathead minnows (Pimephales promelas; FHMs) and zebrafish ( Danio rerio; ZFs), to study the effects of AgNPs on gill histopathology, Na+/K+-ATPase immunoreactivity, mucus production, bioaccumulation, particle uptake characterization, gill gene expression, and lethality in varying water parameters in comparison to the …

The Efficacy Of Prostaglandin Synthase Inhibition On Attenuating Pressure Overload Induced Cardiac Remodeling, Krishna T. Nagalla

Electronic Theses and Dissertations

Chronic hypertension has long been known to cause left ventricular remodeling. Although previous studies pointed towards inflammation as the pathological driver of cardiac remodeling, the exact mechanistic pathway associated with pressure overload-induced cardiac remodeling remains to be elucidated. In order to address this issue, we designed this study to determine pathways associated with pressure overload induced cardiac remodeling and identify therapeutic targets to attenuate this maladaptive cardiac remodeling. Rats with surgically constricted abdominal aorta were used as an animal model for pressure overload and associated Left ventricular (LV) structure and functional changes were measured by pressure-volume admittance catheterization. Human cardiac …