Pharmacology, Toxicology and Environmental Health Commons^™

Applied Drug Development And Combinatorial Strategies For Antimicrobial Treatment, Steven K. Lai Hing

Andrews Research Conference

Streptococcus mutans JH1140 is a strain of bacteria which produces a lantibiotic product, named mutacin 1140. Mutacin 1140 has been shown to be effective at inhibiting Gram-positive bacterial infections caused by Staphylococcus aureus and Streptococcus pneumoniae. Mutacin 1140 is a ribosomally synthesized peptide antibiotic that undergoes extensive posttranslational modifications (PTM). We have found that Mutacin 1140 and an aminoglycoside, Kanamycin, when combined together, act synergistically against Staphylococcus aureus. This was determined by performing serial kill curve dilution overlays on solid media, followed up with kill curve by microdilution plate, and most recently confirmed with kill curve CFU count plates …

Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero

Seton Hall University Dissertations and Theses (ETDs)

Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.

The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and thus the patients have to …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Ann N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Collected Faculty Scholarship

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisininbased combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nucleasebased gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90) or 50% parasite killing (50% lethal dose [LD50]). This mutation also reversed Dd2-mediated CQ …

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …

A Comparison Of Imputation Algorithms For Modeling Water Quality, Carter Alexander Allen

Senior Theses

This project addresses the need for predictive modeling tools to forecast expected concentrations of fecal bacteria in recreational waters in the Charleston, SC area. Data was provided by Charleston Waterkeeper, a water quality monitoring organization that has been measuring Enterococcus faecalis concentrations at 15 recreational sites since 2013. The data contain a non-negligible number of censored and missing observations, so three distinct imputation methods were developed and compared in terms of their effect on final predictive model characteristics. The best performing method relied on drawing samples from a truncated normal distribution to replace censored values, and using a partial model …

Toxic And Essential Trace Element Content Of Commonly Administered Pediatric Oral Medications, Robert A. Yokel, Sarah E. Seger, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications.

METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …

Beyond Capture: Development And Validation Of A Method To Assess Body Condition In Mule Deer (Odocoileus Hemionus) Using Camera Traps, Rachel A. Smiley 6820420

Honors Scholar Theses

Advances in technology and availability associated with camera traps have resulted in a rapid rise in their use to monitor wildlife distribution, abundance, and behavior. We focus on assessing body condition, a new application of camera traps. Body condition indices must relate to the percent body fat if they are to be useful. To acquire measurements of body fat, most body condition indices require capture or mortality of animals to estimate, which has limitations when applied to free-ranging animals. We developed a non-invasive, visual body condition index (VBCI) to assess body condition of mule deer that can be applied …

A Step Towards A "Greener" Dining Services: Procuring Locally For The Health Of Students And The Earth, Jessica Fischer

Senior Honors Projects

Supporting local food has been a goal of dining services for some time now. Buying local means you know exactly where your food is coming from. Typically the farmer has a direct relationship with the processors that puts pressure on them to abide by all laws and regulations. Secondly, the shorter time between the farm and your table, the less likely that nutrients will be lost during the time it takes to transport food across the country. Third, buying local food builds a sense of community. When you buy direct from a farmer, you’re engaging in a time-honored connection between …

Salmonella And Aeromonas Contamination In A 303(D) Listed Water Body Compared To Fecal Indicators & Water Quality Parameters, Elizabeth M. Morgan Ms.

Undergraduate Honors Theses

Since the passage of the Clean Water Act, concern about surface water quality has increased. Reducing exposure to pathogens and adverse impacts on human health because of contact with surface waters has become the focus of many regulatory agencies. Fecal pollution is often a cause of surface water impairment. Fecal indicators, such as fecal coliforms and Escherichia coli, are used as surrogates to evaluate the presence or absence of fecal pollution. However, a growing body of research has shown that these species lack key characteristics necessary to be adequate indicators. As such, explorations into the efficacy of indicator species …

Evaluation Of Perfluorohexane Sulfonate (Pfhxs) Exposure To Risk Of Liver Disease Caused By High Fat Fructose Diet, Dwight C. Anderson

Senior Honors Projects

Perfluorohexane sulfonate (PFHxS) has been used in products as surfactants[AS1] . These products include fluoropolymers and as protective and water-resistant coatings to different materials such as carpets, paper, and textiles. Also, evidence of PFHxS exposure has been reported in firefighters who use certain film forming foams. Current investigations have shown widespread exposure to PFHxS in the environment, specifically in drinking water. There has also been evidence of PFHxS accumulation in humans, with a half-life lasting several years.

PFHxS is one of several perfluoronated alkyl substances (PFAS). Other PFASs are considered to be hepatotoxic in rodents and potentially in humans. Studies …

Mercury Concentrations In Snowy Plovers And Sediments Of Their Breeding Environments In The Southern Great Plains, Laura Duffie

Electronic Theses and Dissertations

Western snowy plovers (Charadrius nivosus) are philopatric shorebirds sporadically distributed during the breeding season at saline lake and alkali flat breeding environments of the Southern Great Plains (SGP) of Oklahoma, New Mexico, and Texas. The major conservation threat to interior snowy plovers breeding on the SGP derives from anthropogenic modification of breeding environments. The SGP is one of the most intensively cultivated regions in the world, and excessive groundwater mining and resulting deterioration of artesian spring flows reduces site quantity and quality critical for regional successful nesting. Most saline lakes now primarily receive freshwater inputs via irregular precipitation …

Tgf-Beta Triggers Rapid Fibrillogenesis Via A Novel T Beta Rii-Dependent Fibronectin-Trafficking Mechanism, Archana Varadaraj, Laura M. Jenkins, Priyanka Singh, Anindya Chanda, John Snider, N.Y. Lee, Ayelet R. Amsalem-Zafran, Marcelo Ehrlich, Yoav I. Henis, Karthikeyan Mythreye

Faculty Publications

Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β–induced cell migration. Whereas TGF-β signaling is dispensable for rapid fibrillogenesis, stable …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC₉₀) or 50% parasite killing (50% lethal dose [LD₅₀]). This mutation …

Increasing Marine Debris Awareness Through Public Education And Analyzing Fish For Microplastic And Pollutant Contamination, Stephanie R. Dubois

Theses and Dissertations

Marine debris is any persistent solid material that is manmade and then disposed of into the world’s oceans. Outreach and education was used in combination with biological research using an indicator fish species to raise awareness about the impacts of marine debris and encourage change in behavior to reduce marine debris. Pre and post surveys were administered during marine debris education tours for K-12 students at the Coastal Studies Lab on South Padre Island, Texas to determine change in knowledge and behavior regarding marine debris. Pinfish were collected from Laguna Madre and stomachs and livers removed for microplastics content and …

Determining The Effects Of Social Media Monitoring To Identify Potential Foodborne Illness In Southern Nevada, Lauren Diprete

UNLV Theses, Dissertations, Professional Papers, and Capstones

Foodborne illness, commonly referred to as food poisoning, affects an estimated 1 in 6 Americans every year, despite the fact that it is entirely preventable. Many cases of foodborne illness go unreported; however, better reporting leads to faster health department response and containment. Social media monitoring, using software to identify trends in social media posts, is a novel new tool that has been tested in a variety of public health fields with promising preliminary results. The Southern Nevada Health District (SNHD) has employed social media monitoring software to identify potential foodborne illness within Southern Nevada. The purpose of this study …

Evaluation Of A Fluorescence Method For Quantifying Bioaerosol Concentrations On Air Quality Filter Samples, Rachel Kolberg

UNLV Theses, Dissertations, Professional Papers, and Capstones

Airborne particulate matter (PM) in outdoor environments contains many components that cause adverse human health effects. The size of the particulates determine in what manner the particles would bypass the body’s defense mechanisms to enter the respiratory system and is directly related to their health impacts. Currently the United States Environmental Protection Agency is enforcing the National Ambient Air Quality Standards (NAAQS) to regulate the annual and 24-hour average concentrations of PM2.5 and PM10 in the air. PM2.5 are fine particles with aerodynamic diameter <2.5μm, small enough to reach the deepest parts of the bronchi and lungs. PM10 include PM2.5 and larger particles with aerodynamic diameter of 2.5-10μm. Both PM2.5 and PM10 contain multiple components from multiple sources. Bioaerosols are an important component of PM, but there is limited knowledge about how bioaerosols contribute to PM2.5 and PM10 concentrations. There is also a lack of research about the incidence and prevalence of disease caused by bioaerosols and about the limits of exposure to bioaerosol particulates. The main barrier to assess bioaerosol concentrations and health-related effects is the absence of quick and inexpensive methodology for quantifying bioaerosols. This study explored the feasibility of using fluorescence microscopy to quickly quantify bioaerosols in PM2.5 and PM10 collected on polycarbonate filters. Bioaerosols were stained with a DNA marker directly on a filter, followed by fixation, microscopic imaging, and automatic counting. The method was first validated using reference samples prepared by depositing different known concentrations of E. coli onto blank polycarbonate filters. The results indicated a linear response over two orders of magnitude (R2 = 0.9) and an accuracy within ±25%. E. coli were also deposited onto selected ambient PM10 and PM2.5 filter samples to determine if pre-loaded particles would interfere with bioaerosol imaging and counting. It was found that despite an increase in uncertainty (variability), the calibration slope remained within ±10% of unity for both PM2.5 and PM10 samples. Bioaerosol concentrations in ambient samples, as quantified by this method, were on average 14% higher for PM10 than for PM2.5 acquired concurrently in a desert environment of Las Vegas, Nevada. The application of this method to other types of compliance filters, such as Teflon filters and tapes of a Beta Attenuation Monitor (BAM) were also explored in this study. By means of a high-yield approach this method is expected to facilitate bioaerosol research, support exposure and health assessments, and help refine NAAQS for PM2.5 and PM10.

A Rural And Urban Study Of The Food Environment In Select Nevada Geographies, Joseph Nickelson

UNLV Theses, Dissertations, Professional Papers, and Capstones

National and county level examination of urban and rural food environments has taken place, but primary validation of venue existence and in-venue data are lacking. The literature show disparities in access to healthy foods through low density of large grocers/supermarkets, low variety and quality of produce and higher prices for a healthy diet in rural versus urban geographies. Rural areas are of unique concern due to poor health indicators such as higher obesity rates, higher diabetes rates, lower incomes and lower educations than urban residents. The goal of this study was to explore differences in the community and consumer level …

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …