Pharmacology, Toxicology and Environmental Health Commons^™

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 …

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 …

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 …

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 …

Pharmacometabolomics Profiling Of Preterm Infants Validates Patterns Of Metabolism Associated With Response To Dexamethasone Treatment For Bronchopulmonary Dysplasia, Bradley C. Stockard

Research Days

Background: Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response.

Objectives/Goal: Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort.

Methods/Design: 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed …

The Racial Divide: A Follow Up Study On Racial Disparity Amongst Covid-19 Survivors In An Urban Community, Christopher Millet, Emily Racoosin, Spandana Narvaneni, George Horani, Sherif Roman, Alisa Farokhian, Arslan Chaudhry, Sohail Chaudhry, Yezin Shamoon, Humberto Jimenez, Patrick Michael, Jin Suh

Journal of Community Hospital Internal Medicine Perspectives

Background Studies have shown that COVID-19 has had a disproportionate effect on minority groups in both the clinical and social settings in America. We conducted a follow up study on patients previously diagnosed with COVID-19 one year ago in an urban community in New Jersey. The purpose of the study was to evaluate the socioeconomic impact of COVID-19 as well as assess for receptiveness towards COVID-19 vaccination amongst various ethnic groups.

Methods This was a prospective cohort study consisting of patients who had recovered from COVID-19 one year prior. The patients included in the study had a confirmed COVID-19 diagnosis …

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

University Scholar Projects

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. My thesis focuses on identifying inhibitors capable of disrupting the Rev7/Rev3 TLS PPI. This study …

Towards The Determination Of Estrone And 17Β-Estradiol In Dairy Cattle Waste Using Solid Phase And Stir Bar Sorptive Extractions With Liquid Chromatography-Mass Spectrometry And Gas Chromatography-Mass Spectrometry, Pallavi Ragi

Masters Theses & Specialist Projects

Steroidal hormones are naturally produced as a part of many physiological processes and are excreted in the urine and feces of animals and humans. Farm animals in concentrated animal feeding operations (CAFOs) are routinely implanted with synthetic and natural hormones to enhance growth and production, contributing significantly to environmental steroid hormone contamination. Every year around 49 tons of estrogens are generated by livestock waste in the United States alone. Due to rainfall and runoff, these steroid hormones reach the environment when animal waste is applied as manure. Studies show that estrogens and other steroidal hormones present in the surface waters …

Generation Of A More Immunogenic Fh Vlp Platform To Support Covid-19 Vaccine Development, Jewel E. Voyer, Xinyuan Chen Phd.

Senior Honors Projects

The SARS-CoV-2 based pandemic has seen almost a million deaths in just the United States according to the CDC. This number is due to the increase of variants of COVID-19, therefore calling a demand in vaccine production. Vaccine adjuvants and carriers have been studied to increase the immunogenicity and safety of a variety of immunizations. Flagellin fused Hepatitis B core (FH) virus like particles (VLP) has been studied to have beneficial effects of TLR5, IL6 levels, and lack of body temperature rise in murine study. The FH platform also provides an improvement from its predecessors FljB alone which is a …

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 …

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

Capstone Experience: Master of Public Health

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 …

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 …

Megacity : A Reservoir Of Toxic Environmental Contaminants And Health Disease Burden, Omosehin Daniel Moyebi

Legacy Theses & Dissertations (2009 - 2024)

Ambient air pollution is a global environmental problem of concern with more than 95% of the world population living in areas with unhealthy air. World Health Organization (WHO) in 2019 stated that air pollution is a principal environmental risk to human health with about 7 million premature air pollution-related deaths annually. Several epidemiological studies have linked morbidity due to cardiovascular diseases (CVDs) to ambient air pollution exposure, especially in North America and Europe. However, the effect of air pollution in Karachi, Pakistan is understudied, which is the case for many urban centers in the developing countries. Karachi is a megacity …

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

Honors Scholar Theses

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. Our current work in this area is focusing on inhibitors capable of disrupting the Rev7/Rev3 …

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt

Electronic Theses and Dissertations

Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …

Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams

Electronic Theses and Dissertations

Hexavalent Chromium [Cr(VI)] is a known human lung carcinogen and general health hazard. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the major theory in its carcinogenic mechanism. Homologous recombination (HR) repair is a DNA repair pathway that prevents CIN by repairing DNA double-strand breaks. RAD51, a key mediator protein of HR repair, along with the RAD51 paralogs (RAD51B, C, D, XRCC2, and 3) are required for HR repair. During HR, RAD51 loads and forms a helical nucleoprotein filament structure to promote DNA strand exchange and stimulate pairing activity of DNA. Cr(VI) exposures have been shown …

Monarch Butterflies: Rearing Methodologies And The Impact Of Fungicide And Insecticide Exposures, Matthew Greiner

Department of Entomology: Dissertations, Theses, and Student Research

The North American migratory monarch butterfly, Danaus plexippus L., populations has experienced a ca. 90% decline over the past two decades. The decline is attributed to climate change, loss and degradation of overwintering habitat, and the loss of milkweed plants in the midwestern United States. The remaining milkweed stands often occur close to agricultural fields, and efforts to establish additional milkweed on the landscape focus on agricultural systems. However, milkweed plants near agricultural fields are likely exposed to pesticides that could adversely impact monarch caterpillars. Effective management of milkweed habitat supporting monarch caterpillars requires knowledge about the toxicological impacts of …

Unveiling The Opioid Crisis: The Impact Of Opioids On Body Systems And Alternative Treatment Options To Reduce The Nationwide Opioid Epidemic, Krishna S. Patel, Elizabeth A. Manheim Ph.D.

Kean Quest

No abstract provided.

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 …