Pharmacology, Toxicology and Environmental Health Commons^™

A California Without Rodenticides: Challenges For Commensal Rodent Management In The Future, Niamh Quinn, Sylvia Kenmuir, Laura Krueger

Human–Wildlife Interactions

Rodenticides are an essential tool in the integrated pest management of infestations of commensal rodents (Rattus norvegicus, R. rattus, and Mus musculus). With the introduction of Assembly Bill 1788, the California Ecosystems Protection Act of 2019, California is potentially facing a future with new restrictions on the use of anticoagulant rodenticides to manage commensal rodents in urban areas. Assembly Bill 1788 has been proposed specifically to protect predators from anticoagulant rodenticide poisoning and seeks to restrict the application of second-generation anticoagulant rodenticides (SGARs) for use in many urban and non-urban areas of California, USA. Exclusion and cultural …

Prevention Of Crystalline Silica-Induced Inflammation By The Anti-Malarial Hydroxychloroquine, Rachel Dawn Burmeister

Graduate Student Theses, Dissertations, & Professional Papers

Exposure to inhaled crystalline silica (cSiO2) is common in occupations where there is cutting, milling, or grinding of cSiO2 containing material. The Occupational Safety and Health Administration estimates that over 2 million workers may be exposed to inhaled cSiO2 in the United States. Inhalation of cSiO2 causes acute and chronic inflammation and may lead pulmonary diseases such as silicosis, as well as an increased risk of developing autoimmune diseases.Unfortunately, treatment of cSiO2-induced lung diseases is limited and primarily focused on supportive care.

Inflammation caused by cSiO2 begins when, cSiO2 particles are phagocytized by alveolar macrophages. Interaction between the particle and …

Chemical Characterization Of Pseudognaphalium Obtusifolium By Gas Chromatography - Mass Spectrometry (Gc-Ms) To Assess Potential Therapeutic Phytochemicals And Toxicological Concerns Using Simulated Use Conditions, Regina Ballentine

Theses and Dissertations

Chemical Characterization of Pseudognaphalium obtusifolium by Gas Chromatography – Mass Spectrometry (GC-MS) to Assess Potential Therapeutic Phytochemicals and Toxicological Concerns Using Simulated Use Conditions

By Regina Ballentine

Virginia Commonwealth University, 2019

Director: Sarah C. Rutan, Professor, Department of Chemistry

Currently, there is an increasing demand for natural therapies and herbal products to treat various ailments. It is generally believed that natural therapies have fewer side-effects than traditional western medicine; however, they are often used in different strengths and formulations without consistency of the levels of target compounds or knowledge about toxicity. Due to this growing trend, a comprehensive chemical evaluation …

Continuous Production Of Raloxifene Hydrochloride Loaded Nanostructured Lipid Carriers Using Hot-Melt Extrusion Technology, Derick Muhindo

Electronic Theses and Dissertations

The aim of this study was to utilize a continuous process for the production of Raloxifene Hydrochloride (RX-HCl) loaded NLC formulations for extended drug release using hot-melt extrusion technology coupled with probe sonication, and also to evaluate the in vitro characteristics of the prepared NLCs by particle size, PDI, zeta potential, entrapment efficiency, drug loading, and in vitro drug release profile. Preparation of the NLCs using HME technology involved two main steps, first formation of a pre-emulsion after extrusion and then size reduction of the pre-emulsion using probe sonication to obtain the NLCs. Process parameters for the extrusion process like …

Developing Zebrafish As An In Vivo Model To Screen Compounds For Anti-Cancer Activity In Human Breast Cancer, Trisha Dhawan

Electronic Theses and Dissertations

Breast Cancer (BC) is the most frequently diagnosed cancer; 1:8 women are at risk of developing BC in her lifetime. Cancer metastasis causes the majority of deaths in BC patients. Moreover, side effects of traditional chemotherapeutic drugs (TCD) impair the quality of life of these patients. Discovery and development of safe and effective new therapies is imperative for the treatment of BC and targeting metastasis. The goal herein is to further expand the applicability of in vivo xenotransplantation of human BC cells in transgenic zebrafish to screen potential chemotherapeutics for toxicity and efficacy. For xenotransplantation, MCF-7, BT-474, and MDA-MB-231 BC …

Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler

Dissertations

Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …

Environmental Influences On Rates Of Osteo- And Rheumatoid Arthritis, Azad Abdulrahman Mohammed

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Climate Change And Salmonella, New York State, Kevin Taylor Welch

Legacy Theses & Dissertations (2009 - 2024)

A study of climate change and Salmonella was conducted, serving as the evidence-based results for action to mitigate adverse Salmonella outcomes for the population of New York State (NYS), and to facilitate dissemination of findings in regard to validated approaches for broader use to mitigate climate change and adverse communicable disease outcomes in a variety of other settings. This study bolsters understanding of dynamic exposures and outcomes for improved and targeted public health approaches to localized climate change and communicable disease outcomes. The approach was developed and refined through continuously validated and calibrated methodology for the enhancement of disease control …

Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi

Legacy Theses & Dissertations (2009 - 2024)

Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA nucleosides can be important regulators of translation and play integral roles in the response to stress. Dynamic changes in tRNA modification status can regulate the translation of stress response proteins whose transcripts have distinct codon biases. The epitranscriptomic writer Alkylation repair homolog 8 (ALKBH8) plays a crucial part in the translation of codon biased transcripts, as it regulates stop codon recoding, which is a specialized form of translation used to generate selenoproteins. ALKBH8 modifies the wobble uridine of selenocysteine tRNA (tRNASec) to promote the decoding of an internal UGA codon …

Accumulation And Spatial Distribution Of Lead And Other Trace Elements In Keratinized Tissues : Investigations Based On Analytical Atomic Spectrometry, Mina W. Tehrani

Legacy Theses & Dissertations (2009 - 2024)

Human biomonitoring for toxic metals such as lead (Pb) provides information about absorbed dose from all exposure routes, and is critical for identifying exposed individuals and assessing health risks. Blood Pb and bone Pb are the primary validated biomarkers for assessing short-term and historical Pb exposures, respectively, while non-traditional matrices, including keratinized tissues, can provide complementary exposure information. Hard keratinized tissues – including hair, nails, hooves, and horns – grow incrementally, potentially preserving chemical exposure histories over a span of days to years. Analytical limitations and poor interlaboratory reproducibility, however, have led to debate around the use of human nails …

Current And Future Environmental And Human Health Impacts Associated With Biofuel/Biofuel Feedstock Production, Eun Kyung Lee

Legacy Theses & Dissertations (2009 - 2024)

Background: The demand for biobased products, such as food, fuel, and chemicals, has been continuously increasing. Meanwhile, agricultural production, serving as the primary stage of biobased products, is one of the largest contributors to greenhouse gas (GHG) emissions and nutrient releases. Although assessing spatially and temporally explicit environmental releases and impacts are required to inform a sustainable trajectory for agricultural production, such analyses are largely lacking due to data unavailability and feasibility of data analysis. Moreover, our current understanding of health impacts associated with biofuel production are lacking due to the limited assessment of health impacts resulted from biofuels’ entire …

The Independent And Combined Effects Of Hypoxia And Tributyltin On The Eastern Oyster, Crassostrea Virginica, Ann Fairly Barnett

Electronic Theses and Dissertations

Oysters are vital to the health of estuarine ecosystems and provide critical ecosystem services, such as water quality improvement, nursery habitat for commercially important fisheries, and shoreline stabilization. Despite their ecological and economic importance, oyster reefs are exposed to many stressors, and oyster populations in Mississippi have declined dramatically in recent years. The present study focuses on the effects of hypoxia and tributyltin (TBT) on the Eastern oyster, Crassostrea virginica. Hypoxic events are increasingly comin coastal ecosystems worldwide, and TBT is a legacy toxicant once used as an antifoulant. The effects of these stressors were assessed on adult oysters deployed …

Exploration Of Sonic Hedgehog Gene Expression In Fathead Minnows (Pimephales Promelas), Brooke Renee Greiner

Undergraduate Honors Theses

Pollutants, as a result of wastewater treatments, have been shown to have negative impacts on aquatic ecosystems. To better understand the possible consequences caused by effluents on ecosystems, it is important to examine ecotoxicology data. One of the most commonly used species for water quality testing is the fathead minnow, Pimephales promelas. Ecotoxicology can then be taken one step further to understand the effects of pollutants on a molecular level. Previous research had identified effluents as causes for abnormal minnow fin morphology. In order to collect additional data on development, tanks with fathead minnows were placed at the Charleston …

Do Humans Possess The Capability To Regenerate?, Chasha Wuensch

The Science Journal of the Lander College of Arts and Sciences

Urodele amphibians, including newts and salamanders, are amongst the most commonly studied research models for regeneration. The ability to regenerate, however, is not limited to amphibians, and the regenerative process has been observed in mammals as well. This paper discusses methods by which amphibians and mammals regenerate to lend insights into human regenerative mechanisms and regenerative potential. A focus is placed on the urodele and murine digit tip models, both of which share critical regenerative stages including wound healing, histolysis, and blastema formation. Formation of the blastema proved to be a crucial process necessary for regeneration, and is responsible for …

Car T-Cell Therapy For Acute Lymphoblastic Leukemia, Esther Langner

The Science Journal of the Lander College of Arts and Sciences

Despite all the available therapies, Acute Lymphoblastic Leukemia (ALL) remains extremely difficult to eradicate. Current available therapies, which include chemotherapy, radiation, and stem cell transplants, tend to be more successful in treating children than adults. While adults are more likely than children to relapse after treatment, the most common cause of treatment failure in children is also relapse. Improved outcomes for all ALL patients may depend upon new immunotherapies, specifically CAR T-cell therapy. CAR T-cell therapy extracts a patient’s own T-cells and modifies them with a CD19 antigen. This modification allows the new T-cells to recognize and kill cancer cells …

Full Issue: Volume 12, Number 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Capsacin And Analgesia, Mimi Kornwasser

The Science Journal of the Lander College of Arts and Sciences

Capsaicin is the active compound responsible for the pungency of hot chilli. Research has discovered its ability to desensitize peripheral nociceptive fibers which is useful in treating chronic pain disorders, specifically neuropathic pain syndromes. Capsaicin treatment comes in a variety of mediums including patches and creams and has been clinically proven to bring relief to patients with disorders such as post herpetic neuralgia, chronic regional pain syndrome and HIV related neuralgia. Exciting new forms of treatment are also in development and promise breakthroughs in the near future in this relatively young field of capsaicin-based analgesia.

Dentistry: Are Stem Cells The Future?, Tova Zemel

The Science Journal of the Lander College of Arts and Sciences

Stem cell research is currently advancing in every area of medicine. New information about regenerating stem cells is being uncovered on a daily basis. An area of stem cells that has not been focused on until recently is the use of dental stem cells. The objective of this paper is to elucidate the most current research about dental stem cells. Much of what is discussed in this paper has not been implemented yet, and is still in clinical trials. Dental stem cells are important because they could be an alternative way of treating caries, performing root canals, and other traumas …

Degeneration Of Rods And Cones In Retinitis Pigmentosa, Rachel Stern

The Science Journal of the Lander College of Arts and Sciences

Retinitis Pigmentosa, most commonly characterized by night blindness and loss of peripheral vision, is a rare genetically inherited group of diseases affecting the retina of the eye. It is estimated that 1 in 4000 people in the USA are affected by some form of the disease. Retinitis Pigmentosa (RP), is caused by a mutation or change in one or more of 55 genes. There are many causes to this disease as RP presents with many different symptoms and biological effects on the eye. These are then grouped together because they share a common result, deterioration of vision. Presently, there is …

The Effects Of Rf-Emf On The Child Brain, Aaron Skaist

The Science Journal of the Lander College of Arts and Sciences

It has long been debated whether or not cell phones have a deleterious effect on the brain. Recent studies indicate that the electro-magnetic field emitted by cell phones called RF-EMF is linked to cancer. Guidelines created to limit the exposure have not been changed since 1981 and do not consider children. The mechanism thought to cause cancer is reactive oxygen species (ROS), which cause the creation of micronuclei. RF-EMF poses a greater threat to children than adults. This is due to the major anatomical differences between the head of a child and an adult. The skull of a child is …

Should Subclinical Hypothyroidism Be Treated?, Rachel Kaufman

The Science Journal of the Lander College of Arts and Sciences

Subclinical Hypothyroidism, SCH, has been detected with increasing frequency in recent years and has brought about major controversies regarding management and treatment [Meier et al., 2001]. The condition is characterized as having a high concentration of thyroid stimulating hormone, yet normal thyroid hormone levels and is often asymptomatic. Scientific articles retrieved from various databases helped determine some of the long term risk factors associated with SCH, including progression to overt hypothyroidism, fatty liver disease, cardiovascular disease, neuropsychiatric complications and reproductive malfunctions. Studies determining the clinical and metabolic effects of L-thyroxine hormone replacement therapy on symptoms and potential risks of SCH …

Energy Drinks: Cardiovascular Effects And The Specific Components Responsible, Malka B. Gelbfish

The Science Journal of the Lander College of Arts and Sciences

Energy drink usage as a stimulant is on the rise among adolescents and young adults. While these drinks have positive energizing effects, they pose significant health concerns. This paper examines the adverse cardiovascular effects of energy drinks and the components that could possibly be responsible. Analysis was conducted by reviewing and comparing many studies available in this area of research. Studies of energy drinks in general and energy drinks versus drinks containing caffeine alone were analyzed. Additionally, this review investigated studies of the specific ingredients in energy drinks such as caffeine, taurine, guarana, and sugar. This review found that energy …

The Role Of Diet In Inflammatory Bowel Diseases, Aviva Smilow

The Science Journal of the Lander College of Arts and Sciences

Inflammatory Bowel Disease encompasses two diseases, Crohn’s Disease and Ulcerative Colitis. During the last 70 years the evolving of diet in the industrialized countries has led to the utilization of foods that have been processed rather than those in their more natural original state. This increase in the processing of foods has been correlated with the more recent occurrence of metabolic diseases such as Inflammatory Bowel Disease. Patients suffering from this problem exhibit lesser amounts of anti-inflammatory bacteria such as Roseburia and Faecalibacterium and increased amounts of pro-inflammatory bacteria Escheria and Fusobacterium. Since diet directly alters the composition of the …

Ultrafine Black Carbon: A Cumulative Assessment On The Physiology Of Lung - Derived Cells, M Esther Salinas

Open Access Theses & Dissertations

Combustion-derived nanomaterials are noxious ultrafine (<100 nm) aerosolized by-products generated by human activity. They pose threats to pulmonary health due to their small size, allowing them to penetrate deep into the alveolar regions causing detrimental responses downstream. Indeed, an examination between nanocarbon particle exposure and poor pulmonary health via cellular behavior was needed. I hypothesized that low-dose and long-term administrations of carbonaceous nanoparticles contribute to respiratory conditions by irritating lung-derived cells. Responses to ultrafine black carbon (UBC), a key component of airborne pollutants, by human lung A549 and murine lung LA4 epithelial cells, human peripheral-blood monocytes THP1, and murine macrophages RAW264.7 were investigated. These lines were chosen because epithelial cells and mononuclear cells (monocytes and macrophages) are the first to come in contact with inhaled particulate matter (PM) and contribute to stress and inflammation of pulmonary tissues. The cells were first plated on day zero and fed fresh UBC suspended in culture media on days one, four, and seven. The exposure regimen included three different low-level concentrations of UBC. On day ten, all cells were prepared for subsequent assays. Effects on cellular viability revealed that UBC was modestly cytotoxic while ATPase and esterase activity (termed enzyme vitality for the purpose of this study) were significantly diminished in a dose-dependent manner. Additionally, beta-galactosidase proportionally increased with UBC concentration compared to untreated cells, indicating that cellular senescence was promoted across all cell types. Multiple markers of oxidative stress were subsequently measured, showing non-uniform trends and displaying moderate accumulation of oxidative damage, contingent upon cell line and UBC treatment. However, a significant induction of inner mitochondrial membrane depolarization of human UBC-treated cells was observed; an aberrant cell-cycle progression was found across all cells. The implemented regimen of UBC exposure elicited an imbalance of free (reduced) glutathione, altered mitochondrial potential, and abnormal cell-cycle activity. This method demonstrated that modifications across both species induced changes to cellular fitness overall. The data supported that compounding nanosized black carbon exposure could negatively affect overall pulmonary cell health by distinctively modifying intracellular activity. Additionally, we further surmised that sustained exposure to nanocarbon could impair innate immunity. Therefore, reactive oxygen species (ROS), reactive nitrogen species (RNS), and cytokine levels upon continuous administrations to 3.0 μg/mL UBC after brief challenges to microbial proxies were assessed; on day 9, the cells were succumbed to three different microbial insults (LPS, Poly I:C, and Zymosan). On day 10, measurements demonstrated a moderate accumulation of oxidative stress, conditional to each cell type. Thus, UBC plus microbe approach triggered pro-oxidant levels and cytokine production across different cell types and diminished phagocytic response by murine macrophages. Based on the results, ultrafine-PM exposure may impair inflammatory function in response to pathogenic infections. In summation, our findings indicated that additive nanosized UBC in combination with microbe-like challenges may compromise cellular behavior, suggesting potential ways by which inhalation of ultrafine-PM may contribute to or exacerbate poor pulmonary health.

Efficacy And Tolerability Of Atomoxetine Use For Patients With Autism Spectrum Disorders And Attention-Deficit/Hyperactivity Disorder (Adhd) Symptoms: A Systematic Review And Meta-Analysis, Angie El-Said

Honors Undergraduate Theses

Introduction: Patients with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) show more symptoms of ADHD. Since there are more adverse events caused by psychostimulants compared to non-psychostimulants, the use of a non-psychostimulant such as atomoxetine might prove more beneficial for younger patients and/or those with comorbid ADHD. Objective: The aim of this thesis is to determine the efficacy and tolerability of atomoxetine in ASD patients presenting with ADHD, by examining (a) differences in ADHD symptoms for participants receiving atomoxetine versus those receiving placebos, and (b) risk differences in adverse events between these participants. Methods: An electronic search of both …

Medication Adherence For Foster Children From The Perspective Of Foster Care Providers, Odette Boyd

Walden Dissertations and Doctoral Studies

In 2015, over 427,000 children were in foster care and the largest population were in California's system. Of those children, more than 9,400 were prescribed psychotropic medications. Increases of psychotropic medication use have led to investigations and findings of medication oversights in foster care. Medication oversights included medication nonadherence, which was linked to an increase of problematic behaviors in foster children. The purpose of this phenomenological study was to explore the issues of medication adherence for foster care providers who care for foster children of mild to chronic health concerns who were prescribed medications and experienced multiple placements. By utilizing …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction, Ahmed Hamish Neamah Al-Darraji

Theses and Dissertations--Pharmacology and Nutritional Sciences

Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, …