Chemicals and Drugs Commons^™

From Cough To Crip: The Development Of Codeine From A Purely Medical Substance Into A Popular Recreational Drug, Rhett C. Vaughn

Senior Theses

The research that was conducted aimed to elicit the influence that pop culture has on recreational drug consumption. Specifically, the usage of the drug codeine has become very popular in social media among many influencers. The research focuses on the prevalence of this drug across several media platforms, alongside the growing rate of consumption globally. Research was conducted primarily through combining various databases at various organizations and this study aims to compile the data into one coherent paper regarding codeine in pop culture. While, it cannot be solely attributed to one specific outlet or influence, this study found that alongside …

Combination Treatment With Cdk4/6 And Cdk8/19 Inhibitors In Er-Positive Breast Cancer, Samantha Tolentino Safa

Senior Theses

Cyclin-dependent kinases (CDK) 4 and 6 are the main drivers of proliferation in estrogen receptor (ER)-positive breast cancer cells. CDK4/6 inhibitors, such as the FDA-approved cytostatic drug, Palbociclib, induce G1 arrest and prevent cell cycle progression. Prolonged treatment with CDK4/6 inhibitors can lead to drug resistance in the clinic as well as in the lab. The mechanisms behind this resistance are varied, with preliminary evidence suggesting that it may be influenced by the senescence-associated secretory phenotype (SASP), CDK6 hyperactivation, or degradation of the retinoblastoma protein (Rb). In contrast to the cell cycle mediating CDK4/6, CDK8 and 19 are involved in …

Plk1 Pbd Selective Inhibition As A Potential Cancer Therapy, Lauren E. Wilder

Senior Theses

Polo-Like Kinase 1 (PLK1) is a protein that has been found to be overexpressed in a variety of cancers including prostate and colorectal cancers, and it is often an indicator of poor patient prognosis. It has functions in initiating, maintaining, and completing mitosis, so it has an important role in controlling the proliferation of cells. PLK1 contains a highly conserved catalytic kinase domain and a less-conserved Polo Box Domain (PBD). Inhibiting the phospho-ligand binding of the PBD is a potential cancer therapy because it would prevent the cell from properly completing the cell cycle, thus inducing apoptosis. In Dr. McInnes’ …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol, Cody Cody Mchale

Theses and Dissertations

Mast cells are classically recognized as the effector cells of Immunoglobulin E (IgE)-mediated hypersensitivity reactions (i.e. allergic reactions). Mast cells also play an important role in the innate immune response to parasitic helminth infection. Allergic disease including allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis, is a major health concern in the United States with greater than 60 million Americans suffering from allergy and asthma. In addition, mast cells have more recently been implicated in non-allergic disease including various human cancers, which will affect approximately 39.6% of U.S. men and women. Therefore, understanding the immunological and molecular mechanisms that regulate mast …

Exploring Alternative Therapeutic Interventions For The Treatment Of Leigh Syndrome, Stephanie Martin

Theses and Dissertations

Leigh syndrome is the most common mitochondrial disease, affecting 1:40,000 live births. It manifests with symptoms including ataxia, cognitive impairment, motor difficulties, and stroke. Leigh syndrome is a genetic condition caused by mutations in either the nuclear DNA or mitochondrial DNA that affects the assembly of the electron transport chains. Death typically occurs around 2-3 years of age, due to respiratory failure, as the body cannot produce sufficient ATP for survival. The genetic basis of Leigh syndrome means that there is no cure, and current treatments of the symptoms have proven ineffective. This thesis proposes two different therapeutic approaches for …

Operation Of The Leica Sp8 Multiphoton Confocal System Using Single Or Multiple Fluorochromes, Amy E. Rowley

Theses and Dissertations

The goal of this thesis is to systematically examine each decision made in obtaining images on the Leica SP8 Multiphoton Confocal Microscope and discuss the basic operating parameters in order to generate publication quality images. The capabilities of the LAS X software are discussed along with an in depth discussion of each icon in order, beginning with the Configuration icon, moving then to Acquire, and a brief overview of the possible imaging processing functions within the Process icon. At the conclusion of this thesis, the reader should feel comfortable with the operation of a confocal system and understand the tradeoffs …

The Role Of Cyclin-Dependent Kinase 8 In Vascular Disease, Desiree Leach

Theses and Dissertations

In response to injury, mature vascular smooth muscle cells (SMCs) undergo dedifferentiation, also known as phenotype modulation or switch. This process is characterized by a downregulation or loss of expression of contractile genes and concomitant with an increase in cell proliferation, migration, and extracellular matrix production, thereby leading to vascular lesion formation. However, the underlying molecular mechanism is not fully understood. The objective of my study was to determine whether cyclin-dependent kinase 8 (CDK8), a transcription-regulating kinase, plays a mediator role in vascular SMC dedifferentiation and lesion formation. Our results from immunochemical staining and Western blot revealed that CDK8 expression …

Individual Differences In Markers Of Cholinergic Signaling Correlating To Fear And Extinction Learning, Grace C. Jones

Theses and Dissertations

Posttraumatic stress disorder (PTSD) results when individuals are exposed to a life threatening event, assault, serious injury, or other traumatic incident. Individuals with PTSD are impaired in their ability to extinguish fear memories, resulting in intrusive symptoms that impair their ability to live otherwise healthy lives. It remains unclear why some individuals exposed to traumatic events develop PTSD while others do not. Acetylcholine has been shown to play a critical role in fear learning, but its role in fear extinction is not well understood. This study utilized a rat model of fear learning and extinction to determine if individual differences …

Muscarinic Acetylcholine Receptor M1’S Impact On Fear Extinction Learning, Joshua R. Mcelroy

Theses and Dissertations

Post-Traumatic Stress Disorder (PTSD) is a mental health disorder that can occur following a traumatic event like combat, assault, or disaster. Individuals with PTSD are unable to extinguish fear memories which can become chronic and disabling. However, it remains unclear why some individuals exposed to a traumatic event develop PTSD while others are resilient. Acetylcholine plays a critical role in fear learning, but its role in fear extinction is less well understood. In this investigation, we used a rat model of fear extinction to determine if individual differences in extinction learning are correlated with markers of cholinergic signaling. Cholinergic markers …

Synergism Of Quercetin And Sodium Butyrate For Controlling Growth Of Glioblastoma, Matthew Alan Taylor

Theses and Dissertations

Glioblastoma multiforme (GBM), or simply glioblastoma, is the most common and aggressive primary brain tumor, with a prevalence of approximately 20,000 new cases per year in the United States and a 3-year survival rate of just 2%. Quercetin (QCT) is a dietary flavonoid that can be found in common foods such as red kidney beans, cilantro, and onions. Despite little evidence showing any benefits through dietary intake of QCT, various studies show its promising anti-cancer results in vitro. In glioblastoma, QCT is able to cause significant amounts of apoptosis through a variety of mechanisms. These include activation of caspase-9 and …

Succination Impairs Protein Folding And Promotes Chop Stability In The Adipocyte During Diabetes, Allison Manuel

Theses and Dissertations

Type 2 diabetes mellitus has been diagnosed in ~21 million people in the United States and is closely correlated with obesity, prompting the need for a detailed understanding of adipocyte metabolism in the development of diabetes. The intake of excess nutrients surpasses the energy requirements of the cell and leads to increased mitochondrial stress in the adipocyte. We have shown that this is associated with increased levels of the mitochondrial metabolite fumarate. Fumarate can react with cysteine thiol groups to form the chemical modification S-(2-succino)cysteine (2SC), also termed protein succination. Succination is significantly increased in the adipose tissue of type …

Functional Role Of The Homeobox Transcription Factor Six1 In Neoplastic Transformation Of Human Keratinocytes, Maria Hosseinipour

Theses and Dissertations

The homeobox transcription factor SIX1 contributes to both tumor development and progression. Numerous studies have determined that the inappropriate expression of embryonic genes, in particular transcription factors, contributes to carcinogenesis. SIX1 is essential for the development of numerous organs including the auditory and olfactory system as well as the kidney, by promoting proliferation, survival and migration of progenitor cells during embryogenesis. SIX1 has also been shown to increase cancer cell proliferation, survival and invasion. The aberrant expression of SIX1 occurs in numerous adult and pediatric cancers. We have previously determined that our in-vitro model system for HPV16-mediated tumorigenesis shares many …

Garlic Inhibits Inflammation During Dengue Infection, Alex R. Hall

Theses and Dissertations

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. There has been a recent global trend of increased epidemic activity, and DENV infection is considered a serious emerging health problem worldwide. A relatively unexplored approach to develop new treatments for dengue virus infection and the prevention of severe disease development is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during the host response to dengue virus infection. Several studies have proposed that it is the oxidative stress response induced by dengue virus infection that is responsible …

The Role Of Inflammation In Atherosclerosis, Fatma Saaoud

Theses and Dissertations

Atherosclerosis is both a chronic inflammatory disease and lipid deposition disorder characterized by accumulation of lipids, fibrous tissue, and inflammatory cells in the arterial wall. Thus, investigating the role of inflammation and the immune system in the progression of atherosclerosis may help in the development of novel therapeutics for atherosclerotic disease. Current atherosclerosis therapy is aimed at lipid targets and focused primarily on reducing plasma cholesterol levels. Clinical and experimental data support the critical role of inflammation in atherosclerosis and suggest that reducing inflammation even without affecting lipid levels may reduce the event rate of cardiovascular disease. Yet, no pure …

Differences In Resting-State Functional Connectivity Of Chronic Migraine, With And Without Medication Overuse Headache, And The Effectiveness Of Sphenopalatine Ganglion Block As A Treatment For Repairing Dysfunctional Connectivity., Kaitlin Krebs

Theses and Dissertations

Chronic Migraine (CM) is a debilitating neurological condition that occurs when the migraine frequency progresses to a chronic state of more than 15 headache days per month. The overuse of analgesic medication (MOH) is one of the most prominent risk factor of this chronification and little is known about why it is a cause. The repetitive inhibition of the Sphenopalatine Ganglion is one promising treatment that is used to treat chronic migraine. The purpose of this study is to determine if a specific pattern of disruption is present for chronic migraine, both with and without medication overuse headache, and if …

Regulation Of Chronic And Acute Inflammatory Disease By Microrna And Microbiota, Pegah Mehrpouya-Bahrami

Theses and Dissertations

Inflammation is implicated in cancer development, degenerative diseases, allergies as well as artherosecelorsis. Dysregulated immune responses lead to chronic inflammation and tissue damage. Finding the ways to terminate inflammatory responses when no longer needed, demands further investigation. Herein, we investigated the modulation of acute and chronic inflammatory disease models by inducing antiinflammatory state. Acute inflammatory model was induced with SEB, an enterotoxin produced by a ubiquitous Gram-positive coccus, Staphylococcus aureus (S. aureus), which exerts profound toxic effects on the immune system, which leads to the cytokine storm and adverse immune response. SEB is the main cause of nosocomial infections, acute …

Morphogenic Effects Of Dopamine In Cultured Rat Hippocampal Astrocytes, Ashley L. Galloway

Theses and Dissertations

Dopamine is critical for processing of reward and addictive behaviors brought about by drugs of abuse. Scientific investigation of drugs of abuse and their effects on CNS function has traditionally been directed at understanding the role of neurons. However, astrocytes, which constitute approximately half of all human brain cells, play a dynamic role in many essential nervous system functions, including neurotransmission, ion homeostasis, and immune defense. Dopamine effects on astrocytes have been historically understudied, yet research indicates that astrocytes express dopamine receptors and are sensitive to dopaminergic activity. Importantly, astrocytes, comprise a morphologically heterogeneous population of cells, and a distinction …

The Identification Of The Direct And Indirect Pathways Through Which Leptin Facilitates Synaptic Plasticity In The Hippocampus, Catherine Van Doorn

Theses and Dissertations

Leptin, a peptide synthesized by adipocytes in the periphery, has been shown to play significant roles in feeding and energy expenditure mediated by the hypothalamus. Growing evidence supports the role of leptin in influencing synaptic plasticity in the hippocampus in that leptin dose-dependently enhances LTP, alters morphology and neurogenesis, facilitates spatial learning and memory, as well as memory retention. Models of leptin deficiency and resistance have further supported the importance of leptin in synaptic plasticity by exhibiting deficits in electrophysiological, morphological and behavioral tests that are improved after leptin restoration. The effects of leptin when applied directly into the hippocampus …

Deciphering The Interacting Regions And Functions Of The Rad51d-Nono Protein Complex During Dna Damage Response, Latarsha Porcher

Theses and Dissertations

Genomic instability is one of the major components represented in the “Hallmarks of Cancer.” DNA interstrand crosslinks and double-stranded breaks are two of the most severe causes of genomic instability. Homologous recombination (HR) plays a major role in resolving both types of DNA lesions, requiring a homologous template and the RAD51 paralog complex of proteins. One member of this complex is the RAD51D ovarian cancer susceptibility gene product. To better elucidate RAD51D modifications and functions, several protein interaction screens were performed, and one of the novel proteins identified was NONO (a.k.a. p54nrb). Decreased expression of either RAD51D or NONO conferred …

The Role Of Epidermal Stem/Progenitor-Like Cells In Hpv-Mediated Pre-Neoplastic Transformation, Yvon L. Woappi

Theses and Dissertations

The role of epidermal basal stem cells in dysplasia is a matter of great interest in the human papillomavirus (HPV)-driven cancers. To assess the relationship between “stemness” and HPV-mediated transformation, we made use of 3-D suspension culture and fluorescence activated cell sorting (FACS) to purify stem/progenitor-like cells from primary normal human keratinocyte (NHKc) cultures. We found that NHKc cells derived from multicellular keratinocyte spheroids were enriched for a basal subpopulation of epidermal stem-like cells, that could be maintained for prolonged time in culture and used to conduct transfection experiments with full-length HPV16 DNA. Thus, by using these stem cell enrichment …

Characterization Of Stard4 And Stard6 Proteins In Human Ovarian Tissue And Human Granulosa Cells And Cloning Of Human Stard4 Transcripts, Aisha Shaaban

Theses and Dissertations

Progesterone is essential hormone for pregnancy, which is produced by the human corpus luteum in early pregnancy until the placenta assumes this function. Transport of the cholesterol from the outer to the inner mitochondrial membrane is the rate limiting step for the de novo synthesis of pregnenolone (the precursor to progesterone), a process mediated by STARD1. STARD1 contains a C-terminal lipid binding domain which binds cholesterol and an N-terminal domain targeting STARD1 to the mitochondrial membrane. Unlike STARD1, STARD4 and STARD6 proteins lack a mitochondrial targeting sequence; however, they can bind cholesterol and increase steroidogenesis in model systems. In this …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

The Anti-Angiogenic Effects Of Sparstolonin B, Henry Rhodes Bateman

Theses and Dissertations

Sparstolonin B (SsnB) is a novel bioreactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. SsnB has demonstrated anti-inflammatory properties, inhibiting Toll-like receptor mediated inflammation in isolated macrophages and in mice. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including atherosclerosis, diabetic retinopathy, and tumor growth. The goal of the project was to investigate the anti-angiogenic effects of SsnB.

The first part of the project utilized in vitro functional assays to study how SsnB affected endothelial cells. SsnB inhibited endothelial cell tube …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Mass Spectrometry And Tandem Mass Spectrometry Characterization Of Protein Patterns, Protein Markers And Whole Proteomes For Pathogenic Bacteria, Jennifer Intelicato-Young

Theses and Dissertations

There have been many recent reviews published on MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight) MS (mass spectrometry) for identification of bacteria particularly with relevance to clinical microbiology. MALDI-TOF MS is now a mature technique for bacterial identification with great promise. The purpose of this review is to put into perspective MALDI-TOF MS and other widely used mass spectrometry methods for characterization of proteins. MALDI-TOF MS is used for rapid determination of a mass pattern of proteins for bacterial characterization; these proteins

are generally not identified. Alternatively, after gel separation, MALDI TOF-TOF MSMS (tandem mass spectrometry) or on-line LC-ESI MS-MS …

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

Resveratrol Attenuates The Development Of Trans-Aortic Constriction (Tac) Induced Heart Failure In Mice, Prakash Kumar Gupta

Theses and Dissertations

Heart failure (HF) still remains the leading cause of morbidity and mortality and imposes severe global affliction and enormous cost on the healthcare system. Although current pharmacological therapies have shown to slow down the progression of HF, but seems to have reached their limits in improving overall patient prognosis. Thus, an immediate call for novel alternate therapies are needed which act independently as well as in conjunction with current treatment modality. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload (PO) in mice. In the first series of studies, Male C57BL6 mice (26-28 g) …

High Fat Diet Induced Obesity In A Mouse Model For Colorectal Cancer, Kennerly Clinton Patrick

Theses and Dissertations

Obesity is widely correlated with the incidence of colorectal cancer (CRC). The exact mechanisms that link obesity to CRC risk have not yet been fully established, and only a limited number of animal models are available to study pathways involved in obesity-related colon carcinogenesis. The objective of this study was to determine the influence of HFD-induced obesity on AOM/DSS-mediated colorectal tumorigenesis, tumor proliferation, and symptom severity. Male C57BL/6 mice were fed a novel high fat diet, designed to mimic the standard American diet (12 % saturated fat & 28 % unsaturated fat), at 4 weeks of age until 16 weeks …