Pharmacology, Toxicology and Environmental Health Commons^™

An Analysis Of Water Quality At Orange County, California Beaches, Naomi Meurice

Pomona Senior Theses

Beaches in Southern California are highly recreated by residents and visitors, making beaches socially and economically important. Public health departments in coastal communities are in charge of measuring water quality and ensuring it is safe for users. Research in the past has indicated that beach water quality gets worse after storms, with bacteria levels jumping on the day of a storm and staying high for up to five days. Studies have shown these spikes in bacteria to be associated with storm runoff, with beaches closer to runoff discharge locations experiencing more impact. However, prior research has not considered the period …

Winter Dynamics Of Storm Water Management Ponds And Winter Tolerance In Three Aquatic Plant Species, Patrick Strzalkowski

Theses and Dissertations (Comprehensive)

The vast majority of the research into the performance of stormwater management ponds (SWMPs) has been performed in warm regions or during the warmer seasons in temperate regions. It is presumed that SWMPs are inactive in the winter as any potential stormwater is trapped in snow and ice. The main goal of this thesis was to test this presumption and to study the dynamics and performance of three SWMPs during the winter. Remote water level loggers were installed into the three SWMPs and daily grab samples from the influents and effluents were taken and analyzed for total phosphorus (TP), chloride, …

The Role Of Platelet-Activating Factor And Microvesicle Particles In Intoxicated Thermal Burn Injury-Induced Multiple Organ Failure, Rushabh Pawan Lohade

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Intoxicated thermal burn injury (ITBI) is more severe than thermal burn injury (TBI) alone and causes significant morbidity and mortality. Evidence from mouse models that replicate the human condition of multiple organ dysfunction has been informative. ITBI results in enhanced bacterial translocation from the gut, increased levels of proinflammatory mediators, and immune cell infiltration in various organs, resulting in inflammation in multiple organs with subsequent dysfunction. In addition, ITBI induces delayed systemic immunosuppression. To understand the mechanism(s) underlying ITBI-induced inflammation and damage in multiple organs, we investigate the role of Platelet-activating factor (PAF) and subcellular microvesicle particles (MVPs) in this …

The Path To U.S. National Registration Of A Toxic Bait For The Control Of The Small Indian Mongoose, Carmen C. Antaky, Steven C. Hess, Emily W. Ruell, Israel L. Leinbach, Shane R. Siers, Robert T. Sugihara

Human–Wildlife Interactions

The small Indian mongoose (Urva auropunctata [syn. Herpestes auropunctatus]; mongoose) is a highly invasive species in its introduced range that negatively impacts ecosystems. Mongooses depredate native species, serve as a vector of disease posing a risk to human health, and cause sanitation issues in food processing facilities and public areas. Introduced for biocontrol in the late 1800s in Hawaiʻi and the Caribbean, mongooses currently have well-established populations across multiple islands in both island archipelagos and have invaded numerous other locations throughout the world. The concern of accidental introduction to mongoose-free islands, the difficulty in species detection, and the …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Regulation Of Cathepsin L Expression And Activity By Cell Confluence And The Circadian Clock, Prashant Gaikwad

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Cathepsin L is a lysosomal cysteine protease that is encoded by the CTSL gene in humans. Previous results have shown that CTSL expression and activity towards the DNA repair protein XPA are elevated in lysates of confluent/quiescent HaCaT keratinocytes. Because other nuclear proteins, including 53BP1 and histone H3, have also been reported to be CTSL substrates under conditions of cell differentiation, senescence, or quiescence, CTSL expression and activity (cleavage) of multiple nuclear proteins was examined in lysates from HaCaT cells and other cell lines at various days after plating and cell confluency. Our study found that adding CTSL inhibitors to …

Characterization Of Atr Kinase Function In Quiescent Human Keratinocytes When Exposed To Solar Simulating Uv Radiation, Hrishikesh Tryambak Kadam

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Cell cycle control, DNA repair, and cell survival have all been linked to the ataxia-telangiectasia and Rad3-related (ATR) kinase, a vital part of the DNA damage response system. In this work, we looked at the role of ATR kinase in human keratinocytes that were dormant and exposed to solar simulating light (SSL). Our findings demonstrated that SSL activates the ATR kinase, phosphorylating downstream substrates such as KAP1, Chk2, and H2AX. In addition, we noticed that quiescent keratinocytes exposed to SSL experienced a decrease in viability when ATR kinase activity was inhibited. Our research indicates that in quiescent keratinocytes exposed to …

Validation Of A Cell Line Model For Studying Xpd Protein Function In Nucleotide Excision Repair, Naga Swathi Sree Kavuri

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The various environmental factors like toxic chemicals, chemotherapeutic agents and UV radiation impact human health by altering physiological functions of the normal living cells. One of the main consequences of exposure to these factors is DNA damage. Although, living system have inherent DNA repair mechanisms such as Nucleotide Excision Repair (NER), which removes DNA lesions from the genome in the form of small, approximately 30-nt-long DNA oligonucleotides. The accumulation of unrepaired DNA adducts as a result of this NER deficiency causes a variety of syndromes, including Xeroderma Pigmentosum (XP), Cockayne Syndrome, Neurological syndrome, and carcinoma of skin. To understand more …

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …

To Determine The Role Of The Platelet Activating Factor - Receptor In Folfirinox Therapy-Mediated Microvesicles Particle Generation, Krishna Awasthi

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Given that Pancreatic cancer continues to be one of the primary causes of cancer-related death and that existing treatment options have a poor success rate, it is important to investigate the role of potential factor(s) involved in pancreatic cancer growth or diminishing the effectiveness of chemotherapeutic agents. An alternative regimen for pancreatic cancer treatment called FOLFIRINOX has shown to increase the survival rate and improve Eastern Cooperative Oncology Group (ECOG) performance status score among the pancreatic cancer patients. However, FOLFIRINOX therapy is associated with several side effects. Through mechanisms involving the secretion of microvesicle particles (MVP), studies, including ours have …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Beyond Mitosis, Plk1-Mediated Phosphorylation Re-Wires Cancer Metabolism And Promotes Cancer Progression, Qiongsi Zhang

Theses and Dissertations--Toxicology and Cancer Biology

Polo-like kinase 1 (PLK1) is a well- characterized regulator of cell division and is known to be highly expressed in certain types of tumors. It has been demonstrated the multifaceted roles of PLK1 in regulation of transcription, translation, epigenetics, DNA damage and cellular metabolism et al. Despite these findings, the precise mechanisms by which PLK1 regulates these processes beyond mitosis remain unclear. PLK1-mediated phosphorylation and misregulation of its substrates has been linked to tumorigenesis, cancer progression, drug resistance and worse prognosis. In this study, we investigated the non-canonical functions of PLK1 in cancer metabolism and drug resistance. We found that …

Selective Gsk3b Overexpression In Medial Prefrontal Cortex Camkiia Cells Produces Sex-Specific Changes In Ethanol Self-Administration, Anxiety-Like Behavior, And Working Memory, Sam Gottlieb, Zachary Tatom, Michael F. Miles

Graduate Research Posters

Background: Glycogen synthase kinase 3 beta (Gsk3b) is central in a gene network regulated by ethanol in mouse medial prefrontal cortex (mPFC). GSK3B abundance/activity modulations regulate ethanol consumption, suggesting GSK3B could be a target in treating alcohol use disorder. However, the critical cell type in this ethanol response is not yet known, nor have sex differences in GSK3B modulations been fully investigated. Here we report results of GSK3B overexpression selectively in CamKIIa⁺ mPFC cells on multiple behaviors.

Methods: Mice underwent stereotaxic injections to overexpress GSK3B in mPFC CamKIIa⁺ cells or control virus (n=4-6/sex/virus). We assayed working …

Chemical, Microbial And Safety Profiling Of A Standardized Withania Somnifera (Ashwagandha) Extract And Withaferin A, A Potent Novel Phytotherapeutic Of The Millennium, Pawan Kumar, Samudra P. Banik, Apurva Goe, Sanjoy Chakraborty, Manashi Bagchi, Debasis Bagchi

Publications and Research

Background:Withania somnifera (L.) Dunal, popularly known as Ashwagandha, is an ethnomedicinal plant with multiple pharmacotherapeutic applications. The diverse medicinal properties of the plant are largely due to the presence of withanolides, a group of C28 ergostane based steroidal lactones, with several sites of unsaturation and oxygenation. Withaferin A, a major with anolide present in Ashwagandha plant accounts for its emerging new roles to treat cancer, arthritis, inflammatory responses, immunomodulatory properties, and neuronal disorders. The root and leaf extracts are specifically important constituent materials for the development of phytotherapeutics, mostly intended for oral consumption. Several studies have been carried out …

Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry Quantitation Of O-Cresol In Hydrolyzed Human Urine To Assess Toluene Exposure, Eric Langlois, Sébastien Gagné

Études primaires

Rationale

Toluene is a volatile organic compound used in domestic and industrial applications. The main routes of workplace exposure to toluene are inhalation and dermal contact. As toluene exposure can cause severe nervous system damage, its quantification is crucial to prevent occupational illness. Toluene is metabolized mainly as hippuric acid, S-benzylmercapturic acid and epoxides. These are rapidly converted to o-/p-cresol, which is then excreted in the urine as conjugated glucuronides and sulfates. o-Cresol and its conjugates can be chemically hydrolyzed to form free o-cresol, which can then serve as a urinary biomarker of toluene exposure. Current …

Effects Of Combined Ethanol And Nicotine Administration On Delay Discounting In Male And Female Sprague-Dawley Rats, Rebecca Lillian Chalme

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ethanol (EtOH) and nicotine (NIC) are among the most commonly used and co-used drugs in the world. Co-use occurs in people who use one or both drugs chronically, but also in people who only consume one or both drugs acutely, often in a “bingeing and chipping” pattern. Given that each drug on its own has previously been shown to affect impulsive choice in delay-discounting procedures, with some indication that drug effects could vary by sex, the purpose of the present experiments was to investigate effects of combined EtOH and NIC at a range of dose combinations on delay discounting in …

Gut-Lung Axis Of The Microbiome Alterations After Ultrafine Particles And Ozone Inhalation, Md Habibul Hasan Mazumder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Air pollution poses a significant threat to public health. It is a mixture of particulate matter, gaseous substances, and other secondary substances. Despite epidemiological research indicating the interactive effects of various components of air pollution, existing studies and regulatory limits often focus on single-exposure scenarios. The emerging understanding of the microbiome’s role in regulating immune response, metabolism, and pathophysiology of various diseases points towards interactions between environmental exposures and microbial dysbiosis. In this dissertation, mice were exposed to relevant deposited doses of carbon black (CB) and ozone (O3), and lung inflammation as well as the lung-gut axis of the microbiome …

Wastewater Pandemic Preparedness: Toward An End-To-End Pathogen Monitoring Program, Justin R Clark, Austen Terwilliger, Vasanthi Avadhanula, Michael Tisza, Juwan Cormier, Sara Javornik-Cregeen, Matthew Clayton Ross, Kristi Louise Hoffman, Catherine Troisi, Blake Hanson, Joseph Petrosino, John Balliew, Pedro A Piedra, Janelle Rios, Jennifer Deegan, Cici Bauer, Fuqing Wu, Kristina D Mena, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Student Publications

Molecular analysis of public wastewater has great potential as a harbinger for community health and health threats. Long-used to monitor the presence of enteric viruses, in particular polio, recent successes of wastewater as a reliable lead indicator for trends in SARS-CoV-2 levels and hospital admissions has generated optimism and emerging evidence that similar science can be applied to other pathogens of pandemic potential (PPPs), especially respiratory viruses and their variants of concern (VOC). However, there are substantial challenges associated with implementation of this ideal, namely that multiple and distinct fields of inquiry must be bridged and coordinated. These include engineering, …

Comparing The Microbiomes Of Dental Plaques In 19th Century Ancestral Remains, Ananya Udyaver

Undergraduate Research Posters

During the construction of VCU’s Hermes A. Kontos Medical Sciences Building in April 1994, nineteenth century ancestral remains were found in an abandoned well on the Medical College of Virginia (MCV) campus. This well, now known as the East Marshall Street Well (EMSW), is thought to have been used as a disposal location for cadaver dissection for surgical and other medical waste in the past. VCU is now seeking to use DNA sequencing technology to match and assemble bones from each individual for a proper burial, uncover the cultural and historical context in which these people lived, and bring a …