Pharmacology, Toxicology and Environmental Health Commons^™

Detection And Observed Correlations Of Statin And Beta-Blocking Pharmaceuticals In West Virginia Surface Waters And Ichthyofauna, Joseph W. Kingsbury

Graduate Theses, Dissertations, and Problem Reports

Within this thesis the source, presence, and the estimated ecotoxicological effects of cardiovascular medicines, specifically statins and beta-blockers are described within the Buckhannon, Tygart Valley, and West Fork Rivers of West Virginia. Included within this thesis is a general introduction providing key background information and relevant research related to the source, presence, and known toxicity of statins and beta-blockers. Following the general introduction there are 3 distinct chapters. Chapter 1 focuses on the estimated demographic based source loadings and the surface water concentration characteristics of statins and beta-blockers within the three rivers. Chapter 2 investigates the effects of statins and …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

The Exposome, Metabolic Dysfunction And Silicosis: A Pulmonary And Pathophysiology Study, Janet A. Thompson

Graduate Theses, Dissertations, and Problem Reports

The exposome encompasses the concept that an individual’s health is a combination of genetic, environmental, and occupational exposures. A worker’s exposomal profile could potentially influence their susceptibility to hazardous occupational exposures. Over 35% of adults in the United States have metabolic dysfunction (MetDys), yet interactions between MetDys and hazardous occupational exposures are generally unknown. MetDys is associated with HFWD-consumption and obesity and induces a chronic low grade systemic inflammation and alters serum adipokine profiles. Silicosis, a progressive inflammatory lung disease, results from occupational inhalation exposure to respirable crystalline silica particles. This research tests the hypothesis “Inflammation resulting from HFWD-induced …

Aging, A Pathological Factor In Neurological Injury, Aruvi Vijikumar

Graduate Theses, Dissertations, and Problem Reports

One of the main reasons for CNS drugs to fail in clinical development is not considering age as a risk factor while studying chronic age-related neurological/neurodegenerative diseases in preclinical studies. We first set out to gain a comprehensive understanding of the impact of age on various aspects (anatomical, immunological, and biochemical) in rodents that play a key role in determining the onset, progression, and evolution of disease severity. With advancing age, the vascular structure and function are compromised which is hypothesized to accelerate cognitive decline. The initial step toward developing novel therapeutics is to characterize the age-related vascular modifications. Utilizing …

Maternal Engineered Nanomaterial Inhalation Exposure: Cardiac Molecular Reprogramming In Progeny Through Epigenetic And Epitranscriptomic Mechanisms, Amina Kunovac

Graduate Theses, Dissertations, and Problem Reports

Introduction: Nano-titanium dioxide (TiO₂), a prominently utilized engineered nanomaterial (ENM), is being employed for its physiochemical properties in several fields including the food industry, manufacturing, and biomedicine. As the prevalence of this ENM, and other particulate matter grows, so does the concern for antagonistic consequences on long-term heart function in vulnerable populations, which until now have not been investigated. Due to the reliance of the heart on the ATP generating capacity of mitochondria for contraction, understanding the role of mitochondrial bioenergetics and structure is pivotal in understanding the repercussions of particulate matter exposure during gestation. As the mass …

In Vitro And In Vivo Toxicological Evaluation Of Emissions From The Fused Filament Fabrication Three-Dimensional Printing, Mariana T. Farcas

Graduate Theses, Dissertations, and Problem Reports

Fused filament fabrication (FFF), a three-dimensional (3-D) printing process, is an emerging technology that has recently gained wide popularity among both consumers and manufacturers. As filament is heated to above its glass transition temperature in a 3-D printer, a portion may undergo thermal decompostion, which releases ultrafine particles (UFP) and volatile organic compounds (VOCs) with potential adverse respiratory health effects are released into the air. This study's central hypotheses is that emissions generated during 3-D printing are toxic and exposure to these emissions induces pulmonary and systemic adverse health effects. Considering that currently, limited understanding is available on the health …

Determining The Effects Of Imidacloprid On Non-Target Soil Organisms In Hemlock Stands, Braley Burke

Graduate Theses, Dissertations, and Problem Reports

The hemlock woolly adelgid (HWA), Adelges tsugae Annand (Hemiptera: Adelgidae), is an invasive insect that is causing mortality of eastern hemlock trees, Tsuga canadensis, and Carolina hemlock trees, Tsuga caroliniana, across the eastern United States. To protect these ecologically important tree species, a neonicotinoid insecticide, imidacloprid, is commonly used. Imidacloprid is an effective treatment and can remain effective against HWA for four to six years but long-term (≥ one year after application) non-target effects of imidacloprid on forest ecosystems are not well-studied. This study examined terrestrial non-target effects of imidacloprid in hemlock stands with different treatment histories to …

Exploring Early Signaling Associated With Complex Stressors, Julia A. Penatzer

Graduate Theses, Dissertations, and Problem Reports

Humans are constantly exposed to a vast number of stressors in our everyday lives from social interactions to physical activity to chemical exposures, to name a few. These stressors have significant impacts on an individual, from the cellular to whole organismal level. The body contains an intricate communication system that elicits a number of both biological and physiological responses as it attempts to maintain homeostasis. Observing these responses to stressors, can offer insight into a number of outcomes, which can be beneficial (increasing life longevity) or detrimental (leading to a disease state). By measuring specific biological adaptations at particular time …

Valorization Of Xylan In Agroforestry Waste Streams, Harrison Appiah

Graduate Theses, Dissertations, and Problem Reports

Valorization of Xylan in Agroforestry Waste Streams.

Harrison Appiah

Microwave-assisted deep eutectic solvent and gamma-valerolactone metallic chloride catalyzed conversion of xylan to furfural were investigated using a 2x3 factorial experimental design at two levels of percent microwave power, reaction time, and catalyst concentration. The levels of each factor studied were (20%, 60% microwave power, 2, 4 minutes, and 10, 20mg) respectively. The effect of three metallic chloride catalysts (LiCl, FeCl3.6H20, CuCl2) on the conversion of xylan to furfural was also investigated. The gamma-valerolactone-ferric chloride sent system exhibited the highest mean yield of furfural (56.50%). The next highest furfural yield of …

Quantitation Of Fentanyl And Metabolites From Blow Fly Tissue And Development Effects Of Fentanyl On Lucilia Sericata, Joseph Allen Cox

Graduate Theses, Dissertations, and Problem Reports

Death investigations often involve collaborative work between different forensic disciplines, especially with regards to pathology, toxicology, and entomology. This dissertation investigates the effects of designer opioids on the development of blow fly (Lucilia sericata) larvae and the ability to detect and quantify the drugs and/or metabolites present in each stage of the fly’s life cycle. Therefore, we evaluated human tissue fortified with fentanyl at four treatment concentrations, and blow fly larvae were placed to feed on the drug infused tissue. A quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method was developed, validated, and applied to extract …

Effects Of Acute And Chronic Nicotine Administration On Choice Of Probabilistic Outcomes, Katya A. Nolder

Graduate Theses, Dissertations, and Problem Reports

Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer. Research suggests smokers engage in more risky or maladaptive decisions when compared to nonsmokers. The relation between nicotine and risky choice could benefit from further investigation, since nicotine is the active substance of tobacco products that maintains tobacco addiction. Acute nicotine administration has shown to alter risky choice; however, since the everyday smoker uses nicotine repeatedly, more research on chronic administration is warranted and would allow for assessment of tolerance or sensitization of these effects. The present study investigated effects of …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

In Vitro Assessment Of Deleterious Impacts Of Organomodified Nanoclays And Their Incinerated Byproducts On Human Cells, Andrew Philip White

Graduate Theses, Dissertations, and Problem Reports

Organomodified nanoclays (ONCs: i.e., smectite clays with different organic coatings), act as nanofillers in applications ranging from automotive, to aerospace, and biomedical implementations. Because of their large utilization, ONC industry is projected to be a U.S. $3.3 billion industry by 2023. However, emerging studies showed that ONCs and ONC-nanocomposites could harbor health risks upon pulmonary exposure and along their life cycle, namely during synthesis, handling, use, manipulation, and disposal. Specifically, the potential for exposure and adverse effects on human health primarily includes release of dry particulate during handling, manipulation, release during use, and release during the end-of-life disposal or recycling …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …

Environmental Contaminants, Parasitism, And Neoplasia In White Perch Morone Americana From Chesapeake Bay, Usa, Mark Arnold Matsche

Graduate Theses, Dissertations, and Problem Reports

White perch are an abundant demersal fish species in freshwater and oligohaline habitats of the Chesapeake Bay. An avoidance of salinity > 12-15 ppt generally restricts the distribution and movements of fish to within tributaries in the mid to lower Bay, which over time has resulted in the formation of at least three separate stocks in Chesapeake Bay. Sub-populations of white perch that are partially isolated may serve as sentinels of the conditions or stressors in the tributaries in which they reside. Fish are exposed to a variety of environmental contaminants and other anthropogenic stressors that can vary in magnitude based …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

The Acute Effect Of Propanil On Reproductive Hormones, Ovarian Gene Expression And Splenic Cells In C57bl/6 Female Mice, Malia Danielle Berg

Graduate Theses, Dissertations, and Problem Reports

Earlier evidence indicates exposure to propanil, a post-emergent herbicide used on rice and wheat fields, increases the number of antibody-secreting cells (ASC) in the spleen of mice after immunization with heat-killed Streptococcus pneumoniae (HKSP, 2x10⁸ CFU). Interestingly, an intact hypothalamic-pituitary-gonadal (HPG) axis is required for this immune response assessed on day 7-10 after immunization in female mice. Hence, an overarching premise is that propanil arbitrates the connection between the reproductive and immune system by altering the concentration of hormones involved in the HPG axis, which may then affect the populations of splenic cells. Hypotheses were tested with C57Bl/6 female …

Effects Of E-Cigarette Flavoring Chemicals On Human Macrophages And Bronchial Epithelial Cells, Anna Manzi Morris

Graduate Theses, Dissertations, and Problem Reports

E-cigarettes and vapes are relatively new devices which are popular among young adults and teens. These devices vaporize an “e-liquid” for the user to inhale, which typically contains a mixture of propylene glycol (PG), vegetable glycerin (VG), varying concentrations of nicotine, and flavoring chemicals. Due to these flavoring chemicals being intended for ingestion as a food additive, their respiratory health effects are not well understood. Thousands of e-cigarette flavors are available on the market, many of which have the potential for toxicity. The majority of e-liquid flavoring chemicals (ELFCs) have not been tested for inhalation safety. In this study, we …

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Behavioral Impairment Following Gestational Exposure To Titanium Dioxide Nanomaterial Aerosols In Male And Female Rats, Matthew Leland Eckard

Graduate Theses, Dissertations, and Problem Reports

Engineered nanomaterials (ENMs) are beginning to be recognized as hazardous to human and animal health. Titanium dioxide (TiO2) is primarily used as a whitening agent in paints, plastics, and sunscreens. While relatively inert in its bulk form, nano-TiO2 (diameter) can produce prolonged inflammation and oxidative stress in target tissue. Recently, the potential for nano-TiO2 to cause neuroinflammation and damage has heightened concerns about its continued use. One important concern is that nano-TiO2, and other metal oxide ENMs, may affect fetal neurodevelopment. Accordingly, it is imperative to screen ENMs, like TiO2, for possible neurotoxicity following developmental exposures. The current set of …

Electrochemical Detection Of Fentanyl Using Screen-Printed Carbon Electrodes With Confirmatory Analysis Of Fentanyl And Its Analogs In Oral Fluid Using Liquid Chromatography-Tandem Mass Spectrometry, Colby E. Ott

Graduate Theses, Dissertations, and Problem Reports

Utilizing screen-printed carbon electrodes (SPCEs), a fast, simple, and sensitive approach toward the detection, identification, and quasi-quantitation of fentanyl was achieved both in an electrochemical cell and as a drop on the electrode surface. Electro-oxidation of fentanyl at the electrode was demonstrated using adsorptive stripping square-wave voltammetry between -0.5 V and +1.6 V with 100 mM Tris-HCl buffer at pH 8.5 as supporting electrolyte. Parameter optimization was conducted during method development to include supporting electrolyte and pH, electrochemical technique, pre-treatment and equilibration time, and various surface modifications. The simplest method utilizing an unmodified SPCE was determined to be appropriate for …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Metal Nanomaterials: Immune Effects And Implications Of Physicochemical Properties On Sensitization, Elicitation, And Augmentation Of Allergic Disease, Katherine Adair Roach

Graduate Theses, Dissertations, and Problem Reports

Many allergenic metals are being manufactured in nanoparticulate forms. Although the decreased size profile of metal nanomaterials has been consistently associated with more pronounced lung toxicity compared to larger materials, it is unclear if metal-induced immunotoxic effects exhibit a similar size-dependency.

The central hypothesis of these studies was that metal nanoparticles cause more pronounced immunomodulatory effects on allergic processes than larger forms of respective metals. Moreover, it was anticipated that, similar to their inflammatory potential in airways, the magnitude of these responses would correlate best with the dose metric of surface area.

The first set of studies utilized fine and …

Ground Ingredients: Analysis Of Lead Exposure In The California Condor’S (Gymnogyps Californianus) Ground Foraging Habitat, Evan Michael Mcwreath

Graduate Theses, Dissertations, and Problem Reports

The California Condor (Gymnogyps californianus) is a critically endangered species that reached its nadir in 1987 with a population of 27 birds in the wild. Intensive management efforts have been implemented to aid the condors’ recovery, however, anthropogenic factors, like use of lead ammunition, continue to cause fatalities in this vulnerable population. Lead toxicosis, which is responsible for approximately 40% of all condor deaths since 1992, is one of the most significant threats to condors. In birds lead poisoning leads to neurological dysfunction, reproductive impairment, immune suppression, gastrointestinal disturbance, anemia, and ultimately increased vulnerability to predation, starvation, and infection. For …

Delay Discounting And Cannabinoid Enzyme Inhibitors, Devin Andrew Galdieri

Graduate Theses, Dissertations, and Problem Reports

Delay discounting is a measure of impulsive choice that is correlated with maladaptive behavior and psychological disorders. Disruptions to serotonin and dopamine pathways can cause changes in delay discounting, as can lesions to the prefrontal cortex and nucleus accumbens. The endocannabinoid system modulates other neurotransmitter systems, including dopamine and serotonin pathways. Cannabinoid receptors type 1 are found in relatively high concentrations in the nucleus accumbens and the prefrontal cortex. These receptors are activated by endogenous cannabinoids, which are synthesized on demand and broken down by catabolic enzymes. The action of these enzymes can be inhibited by a class of drugs …