Medicine and Health Sciences Commons^™

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 …

Using Poincaré And Coefficient Analyses To Assess Changes In Variability In Respiration As A Function Of Leptin Status, Sex, And Buprenorphine In Mice, Wateen Hussein Alami

Chancellor’s Honors Program Projects

No abstract provided.

Behavioral Sensitization Following Concurrent Exposure To 4-Methylmethcathinone (4-Mmc) And 3,4-Methylenedioxymethamphetamine (Mdma) In Male Sprague-Dawley Rats, Trent Bullock

Honors Theses

Recreational use of a new class of stimulant drugs known as synthetic cathinones is a recent public health concern. Although the Drug Enforcement Administration placed several of the most common of these substances permanently on schedule 1, their use is still prevalent as they remain low cost, accessible, and potent. Concomitant use of cathinone derivatives with other psychostimulant drugs is commonly reported by recreational users. Despite the prevalence of synthetic cathinone abuse, there is currently a paucity of scientific research regarding the behavioral and neurochemical effects of these drugs in mixtures with other drugs of abuse. The behavioral sensitization paradigm …

The Effects Of Aging And Estrogen Treatment During Aging On The Rat Epididymis, Kathryn Davis

Honors Theses

Previous studies from our lab have demonstrated that a normal estrogen environment in the testis contributes to maintaining spermatogenesis in adult rats and that estrogen treatment can attenuate the age-associated decline in sperm production. The purpose of this study was to determine if the estrogen environment of the epididymis is altered with age and what effects estrogen treatment may have on the epididymis during aging. The study compared untreated rats at 15 months of age to 18 month old rats that were treated with either vehicle, or estradiol- valerate, once every third day from 15 to 18 months. Mean concentrations …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Investigating The Efficacy And Anti-Resistance Activity Of Fexinidazole In Conjunction With Eflornithine Against Trypanosoma Brucei For Treatment Of Human African Trypanosomiasis, Mercy Toma

Selected Honors Theses

Human African Trypanosomiasis (HAT) is one of 17 neglected tropical disease prioritized by the World Health Organization (WHO). Neglected tropical diseases are diseases which affect poor or developing countries and which do not get as much as attention as the ‘big three’: malaria, tuberculosis and HIV/AIDS. HAT specifically affects coutries in Sub-Saharan Africa and is caused by a parasitic protozoa, Trypanosoma brucei. There are two stages of HAT: the early haemolymphatic and late meningo-encephalitic stages. There are also two subtypes of the disease caused by either T. b. gambiense or T.b rhodesiense forms of the parasite. There are four drugs …

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, …

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, …

An In Vivo Study Of The Effects Of Perinatal Caffeine Exposure On Synaptic Efficacy In The Hippocampus Of Freely Moving Adult Rats, Jee Eun Park

Senior Theses and Projects

The synapse from the perforant path to the dentate gyrus has been widely used successfully to demonstrate long-term potentiation, a cellular model underlying learning and memory. Caffeine is one of the most widely consumed psychoactive stimulants in the world. Caffeine consumption increases in alertness, improvements in motor skills, and neurological functions, and these effects have promoted its use throughout history. Although the many short term cognitive benefits of caffeine intake are well understood, the long term effects of caffeine exposure have been widely disputed. Despite this, it is estimated that over 80% of women continue to consume caffeine throughout pregnancy. …

Analysis Of Mammalian Carboxypeptidase O Expression Patterns, Christian Bardan

Honors Theses

Carboxypeptidase 0 (CPO) is a protease that cuts acidic amino acids from the carboxy termini of substrate proteins. This study aims to describe the expression patterns of CPO in small mammals. We have sampled tissue from four different species: thirteen-lined ground squirrel, eastern chipmunk, eastern mole, and northern short-tailed shrew. Samples were analyzed via Western blot using two CPO antibodies. Immunoreactive bands likely to be CPO, with molecular weights approximately 42 kDa, were seen predominantly in kidney, liver, and intestinal tissue samples. This suggests CPO could play a specific physiological function in these organs.

The Effects Of Omega-3 Fatty Acids On Intracellular Inositol Levels In Saccharomyces Cerevisiae, Jee Yeon (Joanne) Lee

Honors Theses

Bipolar disorder is a severe and chronic debilitating mental disorder characterized by extreme mood swings between mania and depression. The current medications for bipolar disorder, lithium and valproate, have been associated with numerous negative side effects. Although the therapeutic mechanism by which lithium and valproate (VPA) exert their effect is unknown, a leading hypothesis implicates inositol depletion as a mechanism of action. On the other hand, omega-3-fatty acids have been shown to relieve symptoms of bipolar disorder. In this study, we compare the effects of VPA to the effects of decosahexaenoic acid (DHA) on Saccharomyces cerevisiae growth and intracellular inositol …

Acid-Base Equilibria In Organic-Solvent/Water Mixtures And Their Relevance To Gas/Particle Partitioning In The Atmosphere And In Tobacco Smoke, Julia Lynn Degagne

Dissertations and Theses

Acid-base equilibria in organic particulate matter (PM) are poorly understood, but have important implications for air quality and public health. First, acid-base reactions in organic particulate matter affect the gas/particle partitioning of organic compounds in the atmosphere, and these processes are not currently represented in atmospheric and climate change models. Second, the acid-base balance of tobacco smoke affects the amount of nicotine absorbed by the smoker, and a greater understanding of this balance would help to relate cigarette smoke composition to the addictive properties of cigarettes. This work presents data related to both air quality and tobacco smoke modeling.

The …

Pharmaceutical Contaminants As Stressors On Rocky Intertidal And Estuarine Organisms: A Case Study Of Fluoxetine, Joseph Richard Peters

Dissertations and Theses

Contaminants such as pharmaceuticals are of increasing concern due to their ubiquitous use and persistence in surface waters worldwide. Limited attention has been paid to the effects of pharmaceuticals on marine life, despite widespread detection of these contaminants in the marine environment. Of the existing studies, the majority assess the negative effects of pharmaceuticals over an exposure period of 30 days or less and focus on cellular and subcellular biomarkers. Longer studies are required to determine if chronic contaminant exposure poses risks to marine life at environmentally relevant concentrations. Also scarce in the literature is examination of whole organism effects …

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 …

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 …

Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi

Theses and Dissertations--Pharmacy

The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies.

One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting …

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. …

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 …

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 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 …

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 …

Antibiotic Efficacy And Interaction In Escherichia Coli During Varying Nutrient Conditions, Kristina K. Millar

Scripps Senior Theses

Due to the recent rise in antibiotic resistant pathogens, and the difficulties surrounding the quest for new antibiotics, many researchers have started revisiting antibiotic interactions in hopes of finding new treatment options. The primary outcome of this project was to examine the efficacy of concomitant antibiotic use under varying nutrient conditions, to identify variations in antibiotic interactions. Antibiotic interactions were studied, utilizing E. coli as a model bacterial system, grown in four different media types. E. coli cultures were treated with streptomycin, tobramycin, erythromycin, and amikacin individually and in a pairwise fashion at varying doses. We found that at least …

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 …

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 …

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 …

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 …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …

Methcathinone Analogue Activity At The Human Serotonin Transporter, William Drake Varn

Theses and Dissertations

In the last few years, there has been continued concern about synthetic drug abuse in both the United States and worldwide. Small adjustments in drug compound structure often allow synthetic drug makers to manufacture a legal product that can produce the same highs as illegal counterparts. Unfortunately, this is happening faster than the government can outlaw the drug compounds, and a wide variety of synthetics are now appearing on the street. This study evaluated the effects on the human serotonin transporter of six different 4-para substituted methcathinone compounds. Using a Xenopus oocyte model, the efficacy of each MCAT analogue …

Understanding Dna Condensation By Low Generation (G0/G1) And Zwitterionic G4 Pamam Dendrimers, Min An

Theses and Dissertations--Chemistry

Cationic polymers have shown potential as gene delivery vectors due to their ability to condense DNA and protect it from cellular and restriction nucleases. Dendrimers are hyperbranched macromolecules with precisely defined molecular weights and highly symmetric branches stemming from a central core. The nanosize, tunable surface chemistries and ease of surface functionalization has made dendrimers an attractive alternative to conventional linear polymers for DNA delivery applications. The commercially available, cationic dendrimer poly(amidoamine) or PAMAM is the most widely studied dendrimer for use as a gene delivery vector. The aim of this dissertation is to provide an increased understanding of the …

Novel Spoxazomicins Derived From Streptomyces Sp. Rm-14−6 Attenuate Ethanol Induced Cytotoxicity In Vitro, Meredith A. Saunders

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol use disorder. Ultimately, chronic alcohol use may result in neurological deficits, with up to 85% of alcoholics exhibiting signs of cognitive decline. However, biochemical and behavioral factors contributing to this decline have remained elusive. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about mechanisms underlying these deficits and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for alcohol use disorders in a rodent organotypic hippocampal slice culture mode. Experiment 1 sought …