Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Investigation Into The Potential For Acquired Cross Tolerances Of Amphetamines, Benjamin Weldon

CMC Senior Theses

In the United States, the treatment of ADHD through use of psychostimulants in adolescents is a growing reality that many people know today and many more will know in the coming years. Although the effectiveness of psychostimulants is a known asset, the benefits of these medications may not be a permanent solution, suggesting not only the presence of a tolerance build up, but as many stimulants are prescribed in a joint effort to combat ADHD, a possible cross tolerance between two prescribed medications. There are minimal studies published that have addressed the topic of cross stimulation tolerance buildup between prescription …

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …

Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales

Biomedical Engineering Undergraduate Honors Theses

Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …

Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith

Undergraduate Honors Thesis Projects

Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …

Molecular Analysis Of Mchm Toxicity In Zebrafish, Cassandra Pelton

Honors College Theses

In early 2014 Freedom Industries, located in Charleston, WV, leaked approximately 10,000 gallons of 4-methylcyclohexane methanol into the Elk River. This river serviced approximately 300,000 people as a source of municipal water. Its effects on the people and surrounding wildlife is largely unknown.

Chemicals in surface runoff have the potential to induce aquatic animal trait changes, such as altered movement and feeding, that can ultimately alter predator-prey dynamics in aquatic systems. However, chemicals with high potential to enter aquatic systems, like 4-methylcyclohexane methanol (MCHM) used to clean coal, were tested using only short-term, single-species studies prior to use. Data from …

Formulation Of Coffee Extract As Polymeric Nanoparticles And Studying Their Potential Biological Activities, Nouran Sharaf

Theses and Dissertations

Coffee extract was prepared and optimized (by solvent extraction) and subsequently entrapped into PLGA nanoparticles using single emulsion-solvent evaporation method (using Design Expert software). Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform-Infrared Spectroscopy and Folin Ciocalteau assay were used to characterize the NPs and to aid in selecting the optimum formulation conditions. The optimized NPs were in-vitro evaluated for their antimicrobial (by agar-well diffusion method), antioxidant (by DPPH assay) and anticancer (by MTT assay) activities. Finally, the release rate study was conducted for the NP sample showing the highly promising results.

The succeeded NP sample, in terms of the most …

Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM_2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Pence-Boyce STEM Student Scholarship

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus …

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B₃and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B₃are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD⁺decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD⁺levels. BHB is naturally produced by the body when individuals fast …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R₅K]W₅, [R₆K]W₅, [R₅K]W₆, [R₇K]W₅, [R₅K]W₇, [R₆K]W₆, and [R₇K]W₇ were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate, Barkha J. Yadav

Theses and Dissertations

Synthetic cathinones are stimulant drugs of abuse that act at monoamine transporters e.g. the dopamine transporter (DAT) as releasing agents or as reuptake inhibitors. More than >150 new synthetic cathinones have emerged on the clandestine market and have attracted considerable attention from the medical and law enforcement communities.

threo-Methylphenidate (tMP) is an FDA approved drug for the treatment of ADHD and narcolepsy, which also acts as a DAT reuptake inhibitor and is widely abused. tMP and synthetic cathinones share some structural similarities and extensive structure-activity relationship (SAR) studies on tMP have been conducted. However, much less is known about the …

Testing Cr(Ii)-Btc For Ammonia Adsorption Capabilities: A Research Proposal, Tyler Hemingway

Undergraduate Honors Theses

Excerpt from Purpose and Hypothesis

The purpose of this thesis is to determine the ability of a particular metal-organic framework (MOF), Cr(II)-BTC, to adsorb ammonia (NH₃) gas. This particular MOF was chosen for this study due to the Cr having open metal sites, which are generally suitable locations for ammonia adsorption as seen in other MOFs.^1,2,3 This study will be done by testing Cr(II)-BTC’s ability to adsorb as well as another MOFs ability to adsorb ammonia. From this data, the ability of Cr(II)-BTC to adsorb ammonia repeatedly and under dry or humid conditions will also be determined. …

The Shady Persecution Of Doping: Performance Enhancement Drugs And Meaning In Sport, Tyrin Antwan Stevenson

Senior Projects Fall 2018

This project deals with the debate around performance enhancement drugs, utilizing a philosophical approach to meaning in sport to shed light on the topic.

Healthy People Are Bad For Capitalism, Eri King

Theses and Dissertations

Healthy People are Bad For Capitalism is a four part installation that creates an alternative space for the chemicals, Red 40 and Monosodium Glutamate. Presented as a holistic center that offers healing services and remedies, Center for the Red 40 and MSG Healing explores the homeopathic doctrine of Like Cures Like (what make a human ill also cures them) through the relationship between Traditional Japanese Healing Practices, and Western Capitalism.

Healthy People are Bad For Capitalism presents Red 40 MSG Apothecary, Red 40 Zen MSG Healing Rock Garden, Theta Wave Eternal Flame Meditation and Red 40 MSG …

Microtransplantation Of Rat Brain Neurolemma Into Xenopus Laevis Oocytes To Study The Effect Of Environmental Toxicants On Endogenous Voltage-Sensitive Ion Channels, Edwin Murenzi

Masters Theses

Microtransplantation of mammalian neurolemma into Xenopus laevis oocytes has been used to study ion channels in terms of their structure and function in the central nervous system. Use of microtransplanted neurolemma is advantageous in that tissue can be obtained from various sources, ion channels and receptors are present in their native configuration and they can be used to evaluate numerous channelpathies caused by environmental toxicants. Here we show that Xenopus oocytes injected with fragments of rat brain neurolemma successfully express functional native ion channels that are assembled in their own plasma membrane. Using a high throughput two electrode voltage clamp …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

An Analysis Of Women’S Access To Acute Opioid Detoxification Services In Maine: Identifying The Barriers To Treatment, Karen E. Conley

Muskie School Capstones and Dissertations

The lack of treatment facilities and services for opioid use disorder in Maine, combined with an increased prevalence of addiction, creates a potential for health inequity between men and women that may be intensified by barriers in access to care. This capstone study utilized detoxification screening inquiry forms and data obtained from the Milestone Foundation’s acute opioid detoxification program to assess and categorize barriers to access by gender. A barriers model was developed based on existing literature and was to identify potential associations among and between the known barriers to accessing treatment. Barriers were described as internally or externally based, …

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 …

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …

Effects Of Different Brands Of Coffee On The Transcriptional Activity Of Drosophila Cyp6a8 Gene Promoter, Marie Ashley Scott

Chancellor’s Honors Program Projects

No abstract provided.

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Ten Weeks With Green Beans...And Then Some: Determination Of Bisphenol-A (Bpa) In Canned Goods From Arkansas Markets Using Fluorescence Spectrophotometry, Rachel Pruett

Honors Theses

Bisphenol A (BPA) is a chemical widely used in production of consumer goods. It has come under scrutiny recently after being labeled as an endocrine disruptor (ED), mostly causing adverse effects in infants and young children. It has been associated with diabetes, cardiovascular disease, and abnormal maturation. Because it is so commonly used in product development, humans are exposed to BPA through various means, such as ingestion or dermal absorption. It is a concern that the combined exposure could cause serious effects even in small doses.

In canned foods, the chemical is made into an epoxy resin to provide a …

Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee

Theses and Dissertations

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds

By Daniel E. Lee, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2015

Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry

Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …

Tuning Responsiveness Of Polypeptide Based Block Copolymers For Drug Delivery, Ashley J. Johnson

Dissertations

The goal of this dissertation was to tune the pH response and self-assembled morphologies of amphiphilic polypeptide block copolymers for use as drug delivery vehicles. Poly(L-lysine) and poly(L-glutamtic acid) are responsive, ionizable polypeptides that undergo secondary structure transitions, from α-helix to random coil, whereby the change in conformation of the peptide chain results in changes to the global morphology of a self-assembled system. The main focus of this work was to understand how changes in the polymer composition and the local environment can lead to control over the behavior of the overall system. First, the responsive behavior of poly(L-lysine) block …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …