Medicine and Health Sciences Commons^™

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Preclinical Development Of Novel Chemotherapeutic Agent Ac1lpszg: Formulation Optimization, In Vitro Characterization, And In Vivo Pharmacokinetics, Ritu Gupta

Dissertations (2016-Present)

Preclinical development of novel chemotherapeutic agent AC1LPSZG, a mammalian target of rapamycin (mTOR) inhibitor, involved development of sensitive reverse-phase ultra-performance liquid chromatography (UPLC) and LC-MS/MS methods for quantification of AC1LPSZG in in vitro study samples and rat plasma, respectively. Pharmacokinetic studies were done in SD rats after intravenous injection of cosolvent formulations. The resulting pharmacokinetic parameters were analyzed using non-compartmental analysis (NCA) and two-compartmental modeling. Poly (D, L-lactic-co-glycolic acid) (PLGA) is most used biodegradable synthetic polymer for nano drug delivery due to its non-toxic and biodegradable nature, and tunable release properties. PLGA nanoparticles (NPs) were prepared by ‘nanoprecipitation’ technique using …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Identification And Quantitation Of Unspecified Impurities Discovered In Novel Oral Irinotecan By Lc-Ms/Ms And Uhplc, Laura B. Miller

Forensic Science Master's Projects

Irinotecan is a cancer medication approved for medical use in the United States in 1996. It is currently administered via intravenous injection. However, intravenous dosing has disadvantages such as requirement of administration by a trained professional in a medical facility, possible severe adverse effects, pain at the injection site, and possible hemolysis if injected too rapidly. Previously oral administration was not feasible because the p-glycoprotein (p-GP) on the cell membrane of stomach cells acts as a defense mechanism against harmful substances by pumping the irinotecan back into the intestinal lumen for excretion. With the discovery of the p-GP inhibitor encequidar …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Investigation Of The Association Of Exposures To Fire-Related Hazards With Pulmonary Function Of Firefighters, David G. Goldfarb

Dissertations and Theses

Background. Firefighters are habitually exposed to hazardous toxicants which place them at an elevated risk for numerous adverse health outcomes. An example of this is the associations observed in other works between inhalation of combustion byproducts from urban structural fires and both acute and chronic pulmonary dysfunction. To-date, the characterization of firefighters’ exposures to dangerous chemicals in smoke from non-wildfire incidents, both directly through personal monitoring and indirectly from work-related records is scarce. Prior works investigating the association between routine firefighting and pulmonary function have relied on crude metrics such as years of service and numbers of responses to …

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Elisa Validation Method For The Detection Of Ketamine In Hair, Daria A. Centonza

Student Theses

An ELISA method was developed and validated to detect ketamine in human hair samples. Ketamine is an anesthetic drug that causes memory loss, dissociative sensations, and hallucinations. Due to these adverse effects, ketamine is a common drug used in drug facilitated sexual assaults (DFSAs). It is very important to be able to detect the substances used in DFSAs over a longer period of time due to the delayed reporting of these crimes. Victims, often out of fear and from the sedative/memory loss effects of the drugs, tend to report these crimes when it is too late to use urine and …

A Detailed Parameter Study Into The Dermal Absorption Of Chemical Warfare Agents And The Effects Of Pharmacokinetics, Koko Lear

Theses

Chemical warfare agents (CWAs) are substances of varying toxicity profiles. These chemicals exhibit complex dynamics and pose a serious health risk when released into the environment. A mathematical model based on Fick’s second law of diffusion was developed to comprehend how these compounds were absorbed into the skin. The analysis applied to both small and large doses and, successfully, predicted experimental results. This work also includes the effects of CWA physicochemical properties on evaporation and dermal absorption through the stratum corneum. A sensitivity analysis was conducted to assess the impacts of small variations in the initial dose, environmental conditions, and …

A Circular Economy Approach To Improve E-Waste Recycling In California: Economic Potential And Policy Options, Kripa Shah

Master's Projects and Capstones

The higher consumption rates of electronic devices along with their short life cycles and few repair options poses a huge challenge for E-waste industries to manage them effectively. E-waste comprises of hazardous materials and toxic constituents that can affect the environment and public health through improper disposal. However, they also contain few valuable materials that, if recovered, can reduce the dependence on virgin raw materials. Circular economy has the potential to utilize these valuable materials and gain environment and socio-economic benefits. The research explains how the adoption of a circular economy approach can help improve the E-waste recycling in California …

Clarifying Drug Reaction Terminology: Insights From Deaf College Students Allergic To Penicillin, Andrew Makarewicz

Undergraduate University Honors Capstones

Penicillin is considered to be the most frequently reported drug allergy, with roughly 10% of the U.S. population reporting an allergy (Lee, 2020; Sakoulas et al., 2019). However, current research suggests that more than 90% of people who report a penicillin allergy are actually not truly allergic (Blumenthal et al., 2015; Pongdee & Li, 2018). Confusion about side effects and allergic responses is a common way for penicillin allergies to be falsely reported (Stone et al., 2020). The Deaf community may experience this confusion at a higher rate due to health literacy barriers that likely hinder their learning and understanding …

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 …

Polymeric Nanocarriers For Delivery Of Small Molecules Inhibiting Tubulin Polymerization For The Treatment Of Pancreatic Cancer And Lung Metastatic Melanoma, Rajan Sharma Bhattarai

Theses & Dissertations

The aim of this thesis is to develop delivery systems for the novel small molecules which inhibit tubulin polymerization. One of the small molecules was modified to lipid conjugate to increase the lipophilicity of the molecules which in turn drastically improved the drug loading in amphiphilic polymeric system. The second molecule was conjugated to the amphiphilic polymeric backbone with pH sensitive Schiff’s linker for the tumor site specific delivery in lung metastatic melanoma model.

Chapter 1 discusses the tumor microenvironment for the solid tumor especially focusing on Pancreatic Ductal Adenocarcinoma (PDAC). Further the drug delivery system currently researched for addressing …

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …

Blue Zones: Unlocking Key Themes In The Centenarian's Life, Grace Beer, Grace O. Beer

Honors College Theses

Longevity has been sought after in certain areas of the world, and there are specific regions where this has been achieved. There is an American average life expectancy of 72 years old, but individuals in “Blue Zones” here in America and other areas of the world are expected to and have proven to live well beyond 100. The areas of Okinawa, Sardinia, Nicoya, Ikaria, and Loma Linda are classified as Blue Zones, and there could be more of an understanding of how these people live the way they do to have such healthy physical outcomes. To deeply understand the strategy …

Atrazine Levels In Rural Nebraska Counties And Parkinson's Disease, Muhammad Zahid

Capstone Experience

Parkinson's disease (PD) is a multifactorial disorder, connecting both genetic susceptibility and environmental risk factors. Several epidemiological and experimental studies support the evidence that pesticides exposure is positively associated with enhancing neurodegenerative diseases. The high amount of atrazine used in Nebraska and increased PD cases led us to evaluate the association between the long-lived water-soluble pesticide atrazine and PD in Nebraska counties. A person's exposure to atrazine may come from inhalation, dermal absorption, and ingestion. Three types of atrazine data covering 1992 to 2017 were used for this study: applied atrazine, atrazine in surface water, and atrazine in groundwater. In …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Environmental Factors And Human Health Interactions : Ultrafine Particles, Temperature Variability, And Proximity To Power Stations, Ian Ryan

Legacy Theses & Dissertations (2009 - 2024)

Background: Air pollution leads to more than four million premature deaths worldwide and nearly 200,000 in the US each year. While there is extensive research relating PM2.5 to hospital visits for various health outcomes, there is relatively little research on ultrafine particles (UFPs), a particularly small and dangerous air pollutant. Another important exposure is temperature due to its association with dehydration, heat stress, and cardiovascular-related hospital admissions. However, relatively little research has been conducted on diurnal temperature range (DTR), or the range of temperature within a single day, which is an important indicator of climate change. Importantly, the interaction between …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan

Electronic Theses and Dissertations

Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Blood Lead Levels In Minority Children: A Case Of Environmental Racism, Erick Rivera

Sociology & Criminal Justice Theses & Dissertations

Racial minorities in the United States have suffered from being disadvantaged. Among these disadvantages is environmental racism. This includes minority communities being ‘sacrifice zones’ for toxic waste and being exposed to lead poisoning. The purpose of this study is to examine differences in blood levels between white children and children of color. This research will follow a bivariate model for the first research question, “Do youth of color (under the age of 18) have higher BLLs than white children?” The bivariate model will look at the relationship between ethno-racial group and BLLs. Specifically, an analysis of variance (ANOVA) will be …

Barriers To Public Health In Latino American Indigenous Communities, Wilzave Quiles Guzman

Honors Program Theses and Research Projects

This paper focuses on barriers to public health in Latino American Indigenous communities. Indigenous people throughout the world are at a public health disadvantage due to a lack of clearly defined practices within the decision-making processes to plan, evaluate, and control finances from governmental and non-governmental entities in charge of managing health services. I argue that political, social, and institutional changes are still needed to achieve health equity in Indigenous communities and that these changes should go beyond implementing a universal health care program. I must recognize improvements made by many Latino American countries like Brazil, which prepared a plan …

Diversity Of Bacteriophage In Burkholderia Species, Abigail Price

Honors Projects

Bacteriophages are viruses that infect and replicate within bacteria and offer the potential of a therapeutic alternative to chronic infections that do not respond to antibiotic-based therapies. B. vietnamiensis is one of a number of Burkholderia species involved with chronic drug resistant infections in the lungs of individuals with compromised respiratory systems, as found in those with chronic obstructive pulmonary disease and, most especially, are of particular significance in patients with cystic fibrosis. The diversity of the Burkholderia species is explored by using online databases and looking at bacteriophage or phage-encoding viruses found in B. vietnamiensis. The open reading frames …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

Superfund And Society Benumbed: An In-Depth Look At Environmental Justice In South Carolina, Sydney A. Hampton

Senior Theses

This thesis investigates the relationship between superfund sites in minority communities and their public health through the lens of social vulnerability. Various demographic parameters were used to assess the risk associated with minority communities and exposure to hazardous waste. After investigating the history of the Environmental Justice movement, three superfund sites of interest in South Carolina, and demographic and public health data; each community was analyzed to determine association between exposure to hazardous waste and minority status. Each examined community exhibited characteristics contributing to heightened social vulnerability, potentially causing increased susceptibility to negative health outcomes from exposure to hazardous waste.

Oxybenzone And The Mammary Gland: Impact Of An Environmental Pollutant On Health, Disease & Ethical Decision-Making, Klara Matouskova

Doctoral Dissertations

The environmental pollutant and common sunscreen compound oxybenzone is a benzophenone type UV light chemical filter used in industrial and consumer goods. This chemical widely contaminates human tissues, non-human species, and environmental matrices. In this dissertation, oxybenzone is investigated for its effects on the mouse mammary gland in the offspring following perinatal exposure; after perinatal and prepubertal exposures as a dual environmental insult during two sensitive times of development; and in adults after exposure during pregnancy & lactation as an environmental factor potentially increasing the tissue susceptibility to mammary tumors. Chapter 1 introduces the mammary gland. Chapter 2 reviews UV …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …