Chemicals and Drugs Commons^™

Producing A Subunit Vaccine For Porcine Epidemic Diarrhea Virus, Zayn Khamis

Electronic Thesis and Dissertation Repository

Porcine epidemic diarrhea virus (PEDv) causes disease and mortality to piglets worldwide. Most vaccines used to combat the disease have been ineffective live attenuated virus vaccines. The goal of this project was to produce a plant-made subunit vaccine based off the membrane protein of the virus. This is the first time this protein has been produced in plants. An elastin-like polypeptide fusion membrane protein accumulated up to 0.8 mg/g of fresh leaf weight when transiently expressed in Nicotiana benthamiana. Virus-like particles were also produced for the first time for PEDv, and were able to form with just the membrane …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Effects Of Prenatal Exposure To Bisphenol A On Fetal Lung Development, Ayten Hijazi

Electronic Thesis and Dissertation Repository

Prenatal exposure to bisphenol A (BPA), one of the most prevalent endocrine disrupting chemicals, is associated with lung dysfunction and diseases in later life. However, it is unknown if this association has a fetal origin. In this thesis, a series of in vivo and in vitro experiments were conducted to determine the effects of prenatal exposure to BPA on fetal lung development, and define the underlying molecular mechanisms. Environmentally relevant doses of BPA were administered to pregnant mice via diet from embryonic day (E) 7.5 to 18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of …

Traveling With Stowaways: The Human Microbiome And Travel, Alisha N. Hughes

Global Honors Theses

The human microbiome is a research field that is fairly new and thus, not yet fully understood. However, past research has revealed that the human host and the microorganisms interact with each other. To comprehend how influential the connection between host and its stowaways is, the following text will first offer general information on the human microbiome, before moving on to a pilot case study proposal. With the use of similar case studies, this proposal aims to investigate how the human microbiome changes when the host travels and analyzes the changes and their affects on the individual’s health. The paper’s …

Investigating Metal Cations As Potential Inhibitors Of Iapp Aggregation: Kcl, Cacl2, And Cucl2, Megan Burke

Honors Thesis

IAPP is an amyloid protein that misfolds, causing toxic aggregation in the pancreas of Type II Diabetes patients. In this study, three metal cations (KCl, CaCl2, and CuCl2) are tested in Thioflavin T assays and atomic force microscopy (AFM) to see if they inhibit the aggregation of IAPP.

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Antibodies To Heterogenous Nuclear Ribonucleoprotein A1 Penetrate Neurons Leading To Multiple Downstream Effects Resulting In Neurodegeneration, Joshua Nathan Douglas

Theses and Dissertations (ETD)

Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system. MS is believed to occur in genetically susceptible individuals due to an unknown environmental stimulus. MS patients produce autoantibodies to heterogenous nuclear ribonuclearprotein A1 (hnRNP A1), an RNA binding protein (RBP) highly expressed in neurons. hnRNP A1 functions in pre-mRNA splicing, mRNA trafficking, and translation. Furthermore, the anti-hnRNP A1 antibodies are specific to a N-terminal region termed ‘M9’ which serves as a nuclear export sequence/nuclear localization sequence (NES/NLS) responsible for nuclear/cytoplasmic transport of the protein. In this manuscript we will provide data revealing that anti-hnRNP A1 …

Studies On The Prevalence And Control Of Parasitic Helminths In "Natural" Laying Hens, Brittany R. Weir

Animal Science Undergraduate Honors Theses

One societal trend that has been gaining much traction and popularity since the 21^st century began is “organic” and/or “natural” food products. In 1999, the global market accounted for $15.2 billion dollars worth of organic food and drink, compared to the market in 2014 where we consumed $80 billion dollars worth (Willer et. al, 2016). With “natural” production of food animals however, “natural” parasite transmission may be a consequence. To that end, this experiment examines the prevalence of helminths in 110 “natural” laying hens from three regional farms and the efficacies of fenbendazole, piperazine, and levamisole on what should …

Exploring The Mechanisms Of Action Of Antifungal Peptides Using Saccharomyces Cerevisiae., Michelle L. Mason

Biological Sciences Undergraduate Honors Theses

Candida albicans is a normal inhabitant of the skin and mucosal membranes of humans, however, in individuals with depressed immune systems or disrupted cutaneous flora, Candida can overgrow and cause serious infection. Candida infection is the fourth leading cause of nosocomial infection in the United States. These infections are often associated with longer hospital stays and higher mortality. Current drug therapies for this infection are largely ineffective due to the increased drug resistance of Candida species, and for some therapeutics, high levels of drug toxicity to humans. Histatin 5 is a naturally occurring salivary peptide that has strong antifungal properties. …

The Effects Of Smoking On The Calcification Of The Aortic Valve, Brittany Pendergraft

Biological Sciences Undergraduate Honors Theses

Calcific Aortic Valve Disease is responsible for approximately 28,000 deaths annually and the complete mechanism is not completely understood. The disease is known to be effected by an inflammatory response, osteogenic response and an oxidative stress response that leads to thickening and mineralization of the aortic valve. Originally, this disease was thought to be brought on by age and deterioration of the valve but these rapid stress responses when the valve is disrupted by biochemical and mechanical stress has led to its classification as an active disease. Smoking has been shown to have many of the same effects experienced by …

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …