Pharmacology, Toxicology and Environmental Health Commons^™

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Modulation Of Estrogen Metabolism And Prevention Of Pathologies, Bodhisattwa Mondal

Theses & Dissertations

Estrogens have been implicated in non-cancerous pathologies such as Fuchs Endothelial Corneal Dystrophy (FECD), and accumulating evidence suggests estrogen genotoxicity leads to initiation of multiple types of cancer among Caucasian populations. These studies were mono-racial, and restoration of estrogen metabolism imbalance using naturally occurring compounds were not definitive. Therefore, the role of estrogen metabolism in FECD, in cancer initiation among African American (AA) populations, its modulation by environmental toxicant arsenic trioxide (As₂O₃), and by antioxidants polydatin (PD) and resveratrol were explored.

In human breast epithelial non-transformed MCF10A cells, As₂O₃ – induced cytotoxicity was …

Herbicide Toxicity To Non-Target Aquatic Organisms Does Not Increase In Mixtures With Surfactants, Courtney L. Telfort

Honors College Theses

Agricultural herbicides enter aquatic environments after rain events where they affect microscopic aquatic plants (phytoplankton) and animals (zooplankton) that form the base of aquatic food webs. Atrazine, an herbicide with low solubility in water, is often mixed with surfactants such as alkyl polyglucoside (APG) to improve effectiveness. Although APG has low-toxicity, a potential drawback to increased atrazine solubility is greater adverse effects on aquatic organisms. I hypothesized that atrazine and APG decrease phytoplankton abundance more than atrazine alone. Specifically, I predicted phytoplankton abundance should 1) decrease with increasing concentrations of the mixture compared to the same atrazine concentrations individually, and …

Biotransformation Of Praziquantel By Cunninghamella Elegans, Umbelopsis Ramanniana, And Yarrowia Lipolytica Metabolism, Samuel Chivers

Theses & Dissertations

Schistosomiasis is a neglected tropical disease rampant in developing countries. Widespread chemotherapy is reliant on a single drug, praziquantel, which increases the risk of resistance and creates an urgent need for the development of new alternatives for treatment. Fungal biotransformation is a well-documented tool in the pharmaceutical synthesis of new drugs. This study examined the efficacy of four fungal strains, Cunninghamella elegans (ATCC 9245 and ATCC 8688a), Umbelopsis ramanniana, (ATCC 9628) and Yarrowia lipolytica (ATCC 20225), in the biotransformation of praziquantel. Colonies were cultured, dosed with praziquantel, incubated for 5, 10 or 15 days to metabolize, after which the …

An Analysis Of Citizen Science And Its Effect On Marine Plastic Pollution, Kathryn Munster

Renée Crown University Honors Thesis Projects - All

My Honors thesis is an analysis of pollution data to gain more insight about the growing problem of marine plastic pollution. I retrieved online datasets collected by the Clean Swell trash collection mobile application and then analyzed this data using the Python programming language. After my Python analysis, I used Tableau to create data visualizations. This paper analyzes the effect that citizen science has on plastic pollution. Syracuse University’s recycling and trash figures, provided by Syracuse Haulers, are also analyzed. The purpose of including Syracuse University’s data is to bring a local point of view to this project and possibly …

The Chelation Of Metal Ions By Vicibactin, A Siderophore Produced By Rhizobium Leguminosarum Atcc 14479, Joshua Stinnett

Undergraduate Honors Theses

Vicibactin is a small, high-affinity iron chelator produced by Rhizobium leguminosarum ATCC 14479. Previous work has shown that vicibactin is produced and secreted from the cell to sequester ferric iron from the environment during iron-deplete conditions. This ferric iron is then transported into the cell to be converted into ferrous iron. This study uses UV-Vis spectroscopy as well as ion trap-time of flight mass spectroscopy to determine that vicibactin does form a complex with copper(II) ions, however, at a much lower affinity than for iron(III). Stability tests have shown that the copper(II)-vicibactin complex is stable over time. The results of …

Design Of Cotton Fabric-Based Binary And Ternary Composite Materials Containing Nanostructured Zno, Tio2, And Plasmonic Nanoparticles: Photocatalytic Applications, Latanya Downer

Master of Science in Chemical Sciences Theses

Nanostructure metals and metal oxides can be used for surface functionalization and combined with different materials to increase functionality. Recently, surface functionality has been of interest due to its multi-component and its ability to generate new material properties. One of its main application is the creation of nanomaterials because of its novel physical properties which contribute towards stabilization, strength, and catalytic properties. Nanomaterials makes it possible to fabricate objects in the nanoscale size range which offers beneficial physical properties. The nanomaterial distinctiveness allows for the creation of materials with unique characteristics for different applications such as photocatalytic coatings. Semiconductor and …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …

Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud

Electronic Theses and Dissertations

Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …

Multimodality Somatostatin Analog For Fluorescence-Guided Surgery In Cancer, Servando Hernandez Vargas

Dissertations and Theses (Open Access)

Cancer surgery remains the primary curative treatment for most solid cancers and has major therapeutic implications for patients with neuroendocrine tumors (NETs). Anatomical and functional imaging technologies are widely used during the pre- and postoperative stages, but intraoperative disease recognition relies on direct visual inspection and the hands of surgeons. The limited number of clinical tools for real-time intraoperative visual feedback restricts the ability to remove the complete cancer source and is partially responsible for the high rate of disease recurrence in patients. Intraoperative imaging with fluorescent contrast agents has the potential to improve the ability of surgeons to detect …

Internal Design Of A Hydroponics Greenhouse For Tri Cycle Farms, Sarah Gould

Biological and Agricultural Engineering Undergraduate Honors Theses

Hydroponics is the agricultural technique of growing plants without soil, using other growing media and added nutrients in a solvent. It is an attractive agricultural method over conventional agriculture because it is more water efficient, is less labor intensive, yields higher quality crops in less time, and is easier to control. According to the Digital Journal, “hydroponics crop value is anticipated to grow to USD 27.29 Billion by 2022 at an estimated CAGR of 6.39% from 2015 to 2020” (Sawant, 2016). Alongside this growing market acceptance for hydroponics, there is also a local demand that requires only a small transportation …

Risk Assessment For Tce Contamination At The Plymouth Tube Sitegila River Indian Reservation, Az, Eric Canteenwala

Creative Activity and Research Day - CARD

Trichloroethylene or TCE is a volatile organic compound and Group A known human carcinogen that has been widely used in a variety of industrial and commercial applications and is one of the most common types of environmental contaminants found at industrial sites. A human health risk assessment was conducted using indoor air, soil vapor and groundwater monitoring well sample data to assess whether historic contamination posed a current risk to workers occupying a factory at the former Plymouth Tube Site in Chandler, Arizona. Sample data was analyzed using US EPA guidance and basic risk assessment calculations to quantify the cancerous …

Pbrm1 Regulates Stress Response In Epithelial Cells, Elizabeth G. Porter, Alisha Dhiman, Basudev Chowdhury, Benjamin C. Carter, Hang Lin, Jane C. Stewart, Majid Kazemian, Michael K. Wendt, Emily C. Dykhuizen

Department of Biochemistry Faculty Publications

Polybromo1 (PBRM1) is a chromatin remodeler subunit highly mutated in cancer, particularly clear cell renal carcinoma. PBRM1 is a member of the SWI/SNF subcomplex, PBAF (PBRM1-Brg1/Brm-associated factors), and is characterized by six tandem bromodomains. Here we establish a role for PBRM1 in epithelial cell maintenance through the expression of genes involved in cell adhesion, metabolism, stress response, and apoptosis. In support of a general role for PBRM1 in stress response and apoptosis, we observe that loss of PBRM1 results in an increase in reactive oxygen species generation and a decrease in cellular viability under stress conditions. We find that loss …

3 Cm Researchers Honored With Endowed Chairs, Children's Mercy Hospital

Our Story Continues

Susan Abdel-Rahman, PharmD received the Marion Merrell Dow/Missouri Chair in Pediatric Clinical Pharmacology. Shao Jiang, MD received the Frederick J. McCoy Endowed Chair in Plastic Surgery and Craniofacial Research. Cy Nadler, PhD received the Josh Barnds and Stella Carlson Endowed Professorship for Autism.

Uncertainties Treatment For Wastewater-Based Epidemiological Estimation Of The Consumption Of Illicit And Prescribed Neuropsychiatric Drugs In Two Urban Communities In Kentucky Using Ammonium Normalized Population And Monte Carlo Simulation, Rhinannon Huffines, Tara Croft, Manoj Pathak, Bikram Subedi

Scholars Week

The conventional estimation of the prevalence of substance use in a community based on self-reported surveys typically underestimates the actual consumption. Drug’s residues in raw wastewater collected from the centralized wastewater treatment plants were utilized – Wastewater-Based Epidemiology (WBE) – to determine the consumption rate of illicit and prescribed neuropsychiatric residues in two urban communities in eastern Kentucky and two rural communities in western Kentucky. The ammonical nitrogen content in raw wastewater samples was used to minimize the uncertainty associated with the population dynamicity. Uncertainties associated with the several WBE parameters to back-calculate the consumption rate of drugs such as …

A Retrospective Study Of The Opioid Epidemic And Fentanyl Related Overdose Fatality Cases In A Florida West Coast Medical Examiner District Population, Anne Terese Powell

USF Tampa Graduate Theses and Dissertations

Opioids are scheduled by the propensity for misuse and abuse with a high rate of dependency and risk of fatal overdose. Opioids can be divided into different classes, including, natural, synthetic, and semi-synthetic. Opiates are naturally occurring and come directly from the opium poppy plant; whereas the semi synthetics opioids are chemical modifications of the poppy plant. Synthetic opioids attach to the opioid receptor but contain no part of the poppy plant. The increased variety and frequency in opioid prescriptions contributed to an opioid epidemic in the United States which is still on going.

According to the CDC, the opioid …

A Site Characterization And Assessment Of The Bushy Park Reservoir, A Charleston-Area Drinking Water Source, And Its Surrounding Watersheds In Response To Community Concerns, Bradley Joseph Chandler

Theses and Dissertations

Access to clean, safe drinking water is considered a basic human right (WHO 2004). It is vital to maintain adequate monitoring of source waters as well as to investigate claims of degraded source waters. In June of 2017, inaccurate reporting led many community members in Mt. Pleasant, SC to believe that their drinking water might be tainted, leading to elevated cases of brain cancer in children. Though steps were taken to test and ensure the drinking water was safe, fear over the health of the city’s drinking water still persists. This is largely due to the involvement of famed water …

Relative Importance Of Ions And Particles In Silver Nanoparticle Uptake And Accumulation In Keystone Estuarine Organisms; Prorocentrum Minimum And Crassostrea Virginica, Shelby Victoria Butz

Theses and Dissertations

In marine systems, silver is regarded as being one of the most toxic and readily accumulated metals, and is known to be taken up and accumulate within marine invertebrates, fish, phytoplankton and seaweeds. Reported open ocean concentrations of silver range from 0.1 – 2 ng L-1 while silver concentrations in coastal waters are typically 5 to 10 times higher than open ocean values (0.1 - 50 ng L-1). The determination of silver in marine and coastal waters presents several challenges including low concentrations and matrix complexity of seawater, which creates interferences and other challenges for many instrumental techniques creating a …

Nutrient Limitation Of Phytoplankton In Lake Wateree, South Carolina: Implications For Future Water Quality Management, Kara M. Clyburn

Theses and Dissertations

Cultural eutrophication is a primary contributor to phytoplankton production in freshwater lakes from excess anthropogenic nutrient inputs, and resulting impacts on water quality, aquatic ecosystems, human and animal health are increasing worldwide. Understanding the factors that limit phytoplankton growth is an important strategy for identifying and managing nutrient sources and successfully controlling the over- enrichment of nitrogen (N) and/or phosphorus (P) in freshwater lakes. The Redfield molecular ratio of carbon (C), N and P maintains that the C:N:P molar ratio is 106:16:1 when nutrients are not limiting, and the ecosystem is balanced. A N:P molar ratio > 20:1 tends to be …

Agent-Based Modelling For Simulation-Based Design Of Sustainable Faecal Sludge Management Systems., Adrian Mallory, Martin Crapper, Rochelle H. Holm

Faculty and Staff Scholarship

Re-using faecal sludge (FS) to generate value has the potential to contribute towards solving the issue of long term sanitation solutions in growing urban areas across sub-Saharan Africa; however, hitherto, no design tools have been available that are capable of simulating a system involving economic factors, complex social issues and environmental circumstances. We hypothesized that Agent-Based Modelling (ABM), when deployed with appropriate rigour, can provide such a tool. Extensive field work was carried out in a Malawian city, investigating the adoption of Skyloo above-ground composting toilets by households, and the operation of the municipal FS site. 65 semi-structured interviews and …

Ecological Determinants Of Respiratory Health: Examining Associations Between Asthma Emergency Department Visits, Diesel Particulate Matter, And Public Parks And Open Space In Los Angeles, California, Jason A. Douglas, Reginald S. Archer, Serena E. Alexander

Agricultural and Environmental Sciences Faculty Research

Los Angeles County (LAC) low-income communities of color experience uneven asthma rates, evidenced by asthma emergency department visits (AEDV). This has partly been attributed to inequitable exposure to diesel particulate matter (DPM). Promisingly, public parks and open space (PPOS) contribute to DPM mitigation. However, low-income communities of color with limited access to PPOS may be deprived of associated public health benefits. Therefore, this novel study investigates the AEDV, DPM, PPOS nexus to address this public health dilemma and inform public policy in at-risk communities. Optimized Hotspot Analysis was used to examine geographic clustering of AEDVs, DPM, and PPOS at the …

Nanoparticle Synthesis For Glucose-Loaded Mesoporous Silica And Sucrose Hydrolysis Strategies For Bioanalyte Detection Applications Using A Personal Glucose Meter, Xiomar Emauel Bustos Perez

USF Tampa Graduate Theses and Dissertations

Point-of-care (POC) tests are a reliable, portable, easy to use, and more affordable alternative to regular laboratory diagnostic tests. They bypass the necessity of expensive equipment, human labor, and technical expertise. The personal glucose meter (PGM) is a POC device that measures glucose levels in blood. Lately, the PGM have been used as a tool to detect other bioanalytes in different applications. There are two analytes which POC detection would be beneficial for patients: creatinine and tacrolimus. Creatinine is used to calculate glomerular filtration rate, a measurement of kidneys function that can help to diagnose kidney failure, and other nephropathies. …

Environmental Insights From A Utah Pilot Study On Well-Being, Casey Trout

Research on Capitol Hill

This project focuses on the importance of the natural environment to the well-being of those surveyed during a 2018 pilot study. The pilot study marked the beginning of the Utah Well-being Project, a 5-year study to assess well-being across Utah communities.

The survey asked participants questions about their overall well-being and their well-being in relation to twelve commonly articulated “domains”, including those that are listed in Figures 1 and 2.

Effects Of Chronic Ethanol Exposure On Stress Coping Style And Genetic States Of Zebrafish (Danio Rerio), Alexander Goodman

UNO Student Research and Creative Activity Fair

Neurotransmitter systems are important in regulating the stress response. If a behavioral response is disproportional to a stressor it is characterized as anxiety-like behavior. Many anxiolytic compounds, such as ethanol, increase stressor engagement, but how these compounds interact with an organism on a neurogenetic level is less understood. In this study, I assessed the impact of chronic ethanol treatment on behavior and gene expression of GABA_Areceptors subunits on two strains of zebrafish. Each strain was selectively bred to display the proactive or reactive stress coping style where proactive individuals will actively engage a stressor more than reactive individuals. …

Request For Applications: Neuroscience Summer Research Education Program, University Of Mississippi. Brain Wellness Constellation

Brain Wellness

The Brain Wellness Undergraduate Summer Research Program is an initiative of the UM-UMMC Flagship Constellations. The program will provide stipends to undergraduate students for collaborative research experiences in neuroscience related to brain wellness. In this way it will serve to develop new pipelines for pre-graduate and pre-medical students interested in neuroscience to gain research experience and develop collaborative connections between neuroscience faculty at the Oxford and Jackson campuses.

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

Description Of An Innovative Pediatric Individualized Therapeutics Clinic: Working Toward Precision Drug Therapy., Tracy L. Sandritter, Jean C. Dinh, Jennifer A. Wagner, Jennifer Lowry

Manuscripts, Articles, Book Chapters and Other Papers

The GOLDILOKs® (Genomic and Ontogeny-Linked Dose Individualization and cLinical Optimization for KidS) Clinic aims to provide families and physicians with data to make more informed decisions with regard to pharmacological therapy by using innovative therapy and genomic technologies. The objectives are two-fold: (1) To describe the utility of the GOLDILOKs® Clinic to referring prescribers by evaluating the type of referrals made to the GOLDILOKs® Clinic and (2) to assess the most often utilized technologies (e.g., genotyping) completed to formulate therapy recommendations. Patient data from July 2010 to June 2016 was retrospectively reviewed following Institutional Review Board (IRB) approval. The GOLDILOKs® …

A Critical Evaluation Of Trpa1-Mediated Locomotor Behavior In Zebrafish As A Screening Tool For Novel Anti-Nociceptive Drug Discovery, Meejung Ko, Logan C. Ganzen, Emre Coskun, Arbaaz Mukadam, Yuk Fai Leung, Richard Van Rijn

Purdue University Libraries Open Access Publishing Fund

Current medications inadequately treat the symptoms of chronic pain experienced by over 50 million people in the United States, and may come with substantial adverse effects signifying the need to find novel treatments. One novel therapeutic target is the Transient Receptor Potential A1 channel (TRPA1), an ion channel that mediates nociception through calcium influx of sensory neurons. Drug discovery still relies heavily on animal models, including zebrafish, a species in which TRPA1 activation produces hyperlocomotion. Here, we investigated if this hyperlocomotion follows zebrafish TRPA1 pharmacology and evaluated the strengths and limitations of using TRPA1-mediated hyperlocomotion as potential preclinical screening tool …

Geographic And Socio-Economic Variation In Markers Of Indoor Air Pollution In Nepal: Evidence From Nationally-Representative Data, Saruna Ghimire, Shiva Raj Mishra, Abhishek Sharma, Adugna Siweya, Nipun Shrestha, Bipin Adhikar

School of Public Health Faculty Research

Background In low-income countries such as Nepal, indoor air pollution (IAP), generated by the indoor burning of biomass fuels, is the top-fourth risk factor driving overall morbidity and mortality. We present the first assessment of geographic and socio-economic determinants of the markers of IAP (specifically fuel types, cooking practices, and indoor smoking) in a nationally-representative sample of Nepalese households. Methods Household level data on 11,040 households, obtained from the 2016 Nepal Demographic and Health Survey, were analyzed. Binary logistic regression analyses were conducted to assess the use of fuel types, indoor cooking practices, indoor smoking and IAP with respect to …