Medicine and Health Sciences Commons^™

Botulinum Toxin For Abductor Type Spasmodic Dysphonia: A Systematic Review, Keyona Sutton

Honors Theses

A systematic review was conducted to show that BTX (Botulinum Toxin) is the most effective treatment for Abductor Spasmodic Dysphonia (ABSD). There were a total of 117 records screened for inclusion in this review. After the initial screening, there were seven successive rounds of screening for eligibility. This process produced a total of three eligible records that met the following conditions: patients presented with spastic abduction, electromyography BTX type A injection into the posterior cricoarytenoid muscle, and measurement of results with acoustic dimensions. After surveying all eligible studies, it was concluded that BTX is an effective treatment for ABSD. Every …

A Study Of Dextran As A Macromolecular Crowding Agent, Katherine Morgan

Honors Theses

Deoxyribonucleic acid (DNA) is the hereditary material in all living organisms. According to the Watson and Crick model, DNA exists as two long strands coiled into a double helix. However, DNA has been found to have the potential to exist in secondary forms known as G-Quadruplexes and i-motifs. I-motifs (intercalated-motif or iM) are formed under acidic conditions when sets of cytosines pair with protonated cytosines and are looped around each other. The pKa value for iMs in dilute solutions is approximately 6.5, but iMs can potentially exist at a higher, physiological pH value under crowded conditions. Within the interior of …

Lc-Ms Identification Of Serum Proteins Adsorbed Onto Ionic Liquid-Coated Nanoparticles, Anh M. Hoang

Honors Theses

Nanocarriers are promising candidates for drug delivery due to their size and tunable surface characteristics. However, when they are intravenously injected, few particles make it to their designated location. This is because upon entering the bloodstream, the serum in the blood, which is rich with a diversity of proteins, adsorbs onto the particles’ surfaces forming a protein corona. Many of the attached proteins trigger the mobile immune system and are removed by macrophages, and many particles are then filtered out by the liver and kidneys. Ionic Liquids (ILs), which consist of asymmetric, bulky components that are liquid

Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer

Honors Theses

Lectins are a type of glycan-binding protein that noncovalently bind glycans. Carbohydrates are molecules consisting of sugar units joined together. Glycans are carbohydrates. Hence, glycans are also sugars. Lectins and lectin-glycan complexes have a range of biological roles and can be found in animals (including humans), plants, bacteria, viruses, and yeasts and fungi.¹ Many scientists focus on the computational study of these complexes due to their intricate roles in many living organisms. Computational study is important in furthering our knowledge of lectin-glycan complexes and other such protein complexes. However, computational study is not perfect. There are many challenges in …

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

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 …

The Effects Of Thc On Hiv Tat Protein-Mediated Neuroinflammation, Camille Martin

Honors Theses

Although antiretroviral therapies have allowed people living with human immunodeficiency virus (HIV) to achieve normal life expectancies, they cannot cure HIV nor the neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological disorders including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition. The mechanisms by which HIV promotes neurological impairment are not known, but may involve actions of its neurotoxic proteins. One such protein that has been well-characterized is the HIV trans-activator of transcription (Tat). Tat exerts neurotoxic effects via various means, one of which is to activate microglia, the macrophages of …

Effects Of Waterborne Benzo[A]Pyrene Embryonic Exposure On Development, Behavior, Reproduction, And Mitochondrial Bioenergetics In Zebrafish, Megha Patel

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen leading to adverse effects in the development of both humans and animals. BaP is also continuously present in the environment leading to regular exposure via inhalation or ingestion. Because organisms’ early life stages can be more susceptible to contaminant exposure, our focus was on BaP’s adverse impacts on survival, length, weight, behavior, bioenergetic state, and fecundity following developmental exposures. To study BaP’s impacts, zebrafish (Danio rerio) were used as a model organism. BaP is a ligand for the aryl hydrocarbon receptor (AHR in humans; Ahr in …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Investigation Into The Detection Of Drug Metabolites In Latent Fingerprints, Paige Oden

Honors Theses

Fingerprinting has proved a useful mode of identification for thousands of years. Following numerous technological advancements, it has become a technique for categorizing and keeping track of people over large geographical spaces for almost half of a century. Those living in the beginnings of fingerprinting used them as a form of signature as it was something completely unique to each individual that could not be replicated. Although they are no longer used as the primary form of signature, it certainly remains a biomarker of identity. Over the past century the practice has been heavily refined in order to identify people …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Ionic Liquid-Solvated Chitosan Nanoparticles As A Novel Method Of Treating Atopic Dermatitis, Leslie Bell

Honors Theses

Atopic dermatitis, or eczema, is an inflammatory skin disease resulting in dry, red, and itchy skin that affects almost 20% of the population of the Western world. This disease creates a physical, emotional, as well as financial burden on those affected, as well as their families. Current treatment options are only somewhat effective, and do not have a long duration of release and therefore efficiency. Furthermore, treatment plans involving corticosteroids need to be closely regulated to monitor side effects such as skin thinning. Other options include topical tacrolimus, emollients, and oral antihistamines, each with varied side effects. This project is …

Analysis Of Multigenerational Behavioral Effects Of Dietary Benzo[A]Pyrene Exposure In Adult Zebrafish, Mary Beth Gillespie

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon that is linked to negative reproductive and developmental effects in humans and animals. Because BaP is carcinogenic, and its continued presence in the environment allows it to be inhaled and ingested, better understanding of the effects of BaP is needed. To determine the behavioral effects of BaP exposure, zebrafish were used as a model. Wild-type zebrafish (5D) underwent two separate 21-day dietary exposures to 2.5 and 25 μg BaP/g fish to compare how BaP exposure affects locomotor activity. Following the dietary exposure, fish were mated to obtain and raise the F1 generation to …

Investigations Involving Mononuclear And Dinuclear Transition Metal Catalysts For Photochemical Carbon Dioxide Reduction, Ansu Edwards

Honors Theses

There is currently a global energy crisis, which is in desperate need of solutions. New energy sources are required that will not pollute as much as our longstanding reliance on nonrenewable fossil fuels as an energy source. This pollution involves large amounts of greenhouse gas emissions, predominantly carbon dioxide (CO₂), that contribute to environmental problems such as climate change. In this context, a fairly recent research direction to address this problem is the development of transition metal catalysts that can convert CO₂ into reduced carbon products that can serve as chemical fuels. This work focuses on the …

The Effect Of Chronic Alcohol Consumption On Exercise-Induced Muscle Damage In Young Men, Emma Hamilton, Grant Hilliard

Honors Theses

PURPOSE: To investigate the effects of chronic alcohol consumption on exercise-induced muscle damage of the knee extensors in young men. METHODS: Twenty-one males (age 21.9 ± 1.1 yr; weight 183.4 ± 27.6 lbs; height 174.0 ± 13.1 cm) performed 100 maximal eccentric contractions at 30°/sec of the knee extensors using their non-dominant leg. The isometric and isokinetic muscle strengths (60°/sec and 180°/sec) were measured pre-exercise and immediately, 24 h, 48 h, 72 h, 96 h, and 120 h post-exercise. Muscle soreness and plasma creatine kinase (CK) activity were measured pre-exercise and 24 h, 48 h, 72 h, 96 h, and …

The Effects Of Progesterone Induced Blocking Factor And 17-Hydroxyprogesterone Caproate On The Pathophysiology Of Preeclampsia, Kyleigh M. Comley

Honors Theses

Preeclampsia (PE) is responsible for about 20% of the 13 million preterm births each year worldwide, including 100,000 cases annually in the United States. Despite being a leading cause of maternal and perinatal morbidity, the mechanisms of pathogenesis are still largely unknown. PE is progesterone deficient state characterized by hypertension, chronic immune activation, endothelial dysfunction and severe forms can lead to seizures. Treatment of seizures includes the administration of magnesium sulfate (MgSO4) though not all PE patients are responsive, and it does not decrease PE-associated hypertension. To resolve these conditions, PE patients are delivered early thereby making PE the leading …

Synthesis Of Novel Long Chain Unsaturated Fatty Acid Analogs Of Capsaicin, Eli Bettiga

Honors Theses

A number of key studies have shown that the natural product capsaicin displays in vitro and in vivo antitumor effects against a variety of cancers, however, both the analgesic and cancer-related therapeutic potential of capsaicin have been limited by its unpleasant pungent side effects and modest potency. N-acyl vanillylamides (N-AVAMs) are a unique class of compounds that are simple side chain modified capsaicin derivatives. Limited structure-activity relationship (SAR) studies of N-AVAMs demonstrated that substitution of the capsaicin side-chain with longer unsaturated fatty acid groups results in non-pungent analogs with improved anti-invasive activity relative to capsaicin. In an effort to ultimately …

Development Of An Immunoblot To Detect Human Antibodies Against Sars-Cov-2 Virus Proteins, Shivum Desai

Honors Theses

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a virus that infects cells in the lungs, nasal passages, and intestines via the ACE2 receptors of the host, and leads to the coronavirus disease (COVID-19). Since the occurrence of the pandemic in December 2019, there have been 114 million cases worldwide in which 2.5 million lives have unfortunately been taken away.

Being diagnosed with a past infection stems questions among those that have tested positive through antibody testing. The problem here is that patients were notified that they have antibodies resulting from a SARS-CoV-2 infection, but in fact they may not …

The Histone Deacetylase Inhibitor Largazole: A Potential Chemotherapeutic Agent, Hannah Lynn Carson

Honors Theses

Histone deacetylase enzymes are known for their inherent activity as epigenetic modifiers. Although, they have become recognized for their role in cancer progression and other diseases. But also, histone deacetylases have other non-histone targets, for example, microtubules, which play important roles in cancer metastasis, apoptosis, and replication. With histone deacetylase inhibitors (HDACi), our research explored HDACi effects on breast cancer cell lines. The overall goal was to understand the potential of largazole, a class one histone deacetylase inhibitor on breast cancer cell lines. The research consisted of two parts: sulforhodamine B (SRB) viability assays under hypoxic and normoxic conditions. The …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

Synthesis Of Aromatic Fluorinated Ketones For Evaluation At The Gaba Receptor, Madeline Griffin

Honors Theses

GABA is a neurotransmitter that inhibits the excitation of neurons. Targeting this specific receptor has the potential to inhibit the central nervous system and possibly treat addiction, anxiety, or mood disorders. Previous research has shown that fluorinated ketones can have valuable applications in the medicinal chemistry of addiction. Some fluorinated ketones have shown activity at the GABA receptor. The main goal of this project was to synthesize aromatic fluorinated ketones for biological evaluation at the GABA_B receptor. Another goal was to compare both the monofluorinated and difluorinated analogues synthesized in order to quantify differences in activity from fluorination state. …

Synthesis And Characterization Of Pamam-Fatty Acid “Janus-Type” Dendritic Hybrids For Biomedical Applications, Abigail Grace Barker

Honors Theses

Janus dendrimers are amphiphilic macromolecules that have shown promising potential in the biomedical field. Due to their unique structure and properties, these branched block copolymers have the ability to self-assemble into bioinspired spherical nanoaggregates. Because they possess a hydrophobic and hydrophilic moiety, these aggregates show potential as drug delivery systems that can transport both hydrophobic and hydrophilic drugs. However, many of the proposed dendrimer systems suffer from certain weaknesses that hinder their practical usage as clinical treatment options. Some of these shortcomings include specificity, solubility, size, surface charge, and mechanical properties. To combat these problems, we synthesized and characterized a …

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 …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Detection And Characterization Of Delta-9-Tetrahydrocannabinol And Novel Synthetic Cannabinoid Metabolites Using Human Liver Microsomes, Seema Murugan

Honors Theses

Marijuana and synthetic cannabinoids are the most commonly used and trafficked illicit drug. ∆⁹-tetrahydrocannabinol (THC) is the primary active compound in marijuana. Synthetic cannabinoids were created as a method to study the effects of cannabinoids on the endocannabinoid system, which consists of endogenous cannabinoids, cannabinoid receptors, and the synthetic and degrading enzymes responsible for the synthesis and degradation of endocannabinoids. Cannabinoids activate the same receptors as endocannabinoids. Synthetic cannabinoids gained popularity as recreational drugs due to their ability to avoid detection. Synthetic cannabinoids have been found to have a greater binding affinity to the cannabinoid CB₁ receptor …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

A Raman Spectroscopic And Quantum Chemical Investigation Of Serotonin, It's Intramolecular Interactions, And The Solvent Effects Of Methanol, Ethanol, And Water, Mallory Loe

Honors Theses

Serotonin, or 5-hydroxytryptamine, is a neurotransmitter and metabolite vital to the normal function of the cardiovascular, gastrointestinal, and nervous systems. Although it might be colloquially known as the ‘happiness drug,’ malfunctions in serotoninergic pathways can result in mental health disorders, heart disease, irritable bowel syndrome, and even collateral death. Without a current method to directly measure, or even detect, serotonin in the human body, these diseases, along with many others, pose a threat of developing without proper warning. Raman spectroscopy presents a unique method to vibrationally characterize molecules based upon the inelastic scattering of light. Serotonin’s unique, amphipathic structure presents …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

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 …

Synthesis Of Pharmaceutical And Personal Care Products And Pesticide Metabolites Of Environmental Concern, Isaiah Edwards

Honors Theses

Human pollution of aquatic environments by introduction of pharmaceutical and personal care products (PPCPs) as well as agrichemicals presents a grave threat to the health of aquatic organisms. Many of these chemicals not only exhibit toxicity to the species of complex ecosystems at various levels but also undergo metabolic transformation into moieties that have different and sometimes more potent physiochemical profiles. PPCP and pesticides as well as their metabolites impact organisms via a number of different mechanisms, with the most serious arguably being endocrine disruption. Two emerging pollutants, gemfibrozil and bifenthrin, possess naturally occurring metabolites that were determined to warrant …