Pharmacology, Toxicology and Environmental Health Commons^™

Effects Of Short-Term Pesticides Exposure On Swimming Behavior, Tissue Morphology, Oxidative-Nitrative Stress, Antioxidant Expression, And Cellular Apoptosis In Kidneys Of Goldfish, Esmirna Cantú

Theses and Dissertations

The prevalence of pesticides in the aquatic environment continues to increase due to anthropogenic activities and poses a threat to aquatic organisms. The aim of this study was to determine the short-term exposure (one-week) of pesticide mixtures (metolachlor, linuron, isoproturon, tebucanazole, alconifen, atrazine, pendimethalin; azinphos-methyl) on swimming behaviors, kidney morphology, and expression of nitrotyrosine protein (NTP), dinitrophenyl protein (DNP), superoxide dismutase (SOD), catalase (CAT), renin, and cellular apoptosis in goldfish (Carassius auratus). Results indicated that both low- and high-dose pesticide mixtures decreased the distance swimming behavior. Histological analysis showed pesticide exposure alters kidney morphology. DNP, NTP, and renin expressions, and …

Parent Perspectives On Barriers And Facilitators To Optimal Healthcare And Medical Screenings For Children With Down Syndrome In South Carolina, Vinita Oberoi Leedom

Theses and Dissertations

Children with Down syndrome (DS) often have co-occurring conditions affecting vision, hearing, sleeping, and more. Screenings, as recommended by the American Academy of Pediatrics (AAP), can help prevent secondary disability, and allow children to thrive. Studies have evaluated the receipt of recommended screenings, but barriers and facilitators surrounding access to screenings and care have not been described.

Parents of 24 children with DS in SC were recruited through schools and family support groups. One-hour long interviews were conducted in English and Spanish. Information was collected on health, healthcare quality, respiratory concerns, pandemic effects, access to care, and knowledge about AAP …

Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar

Theses and Dissertations

The ethylene bisdithiocarbamate pesticides, a subclass of the dithiocarbamate pesticides, are broad spectrum organometallic fungicides used on a variety of crops. The fungicide Mancozeb is comprised of an ethylene bisdithiocarbamate backbone complexed to the metals manganese and zinc. Ingestion of food containing pesticide residue and occupational exposure are common routes of Mancozeb exposure. Previous work demonstrated that Mancozeb exposure to HT-29 colon cancer cells resulted in cytotoxicity, apoptosis, and disruption of mitochondrial complex I, II, and V activity. The current study investigated the effect of Mancozeb exposure on mitochondrial complex III and IV activity and oxidative stress parameters in the …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

Effects Of Microcystin-Lr On Channel Catfish (Ictalurus Punctatus) Susceptibility To Microbial Pathogens (Aeromonas Hydrophila And Edwardsiella Piscicida), Alison Marchant

Theses and Dissertations

Microcystin-LR is a hepatotoxin produced by cyanobacteria. Aeromonas hydrophila and Edwardsiella piscicida infections are leading causes of losses in market-sized channel catfish (Ictalurus punctatus). These older fish should have natural immunity in place and a predisposing factor is likely a prerequisite for these disease outbreaks. While microcystin-LR rarely causes mortality in warm-water aquaculture, we believe it may be a predisposing factor that leads to bacterial disease outbreaks during the summer months due to its ability to damage the liver. Our study investigated microcystin-LR’s effects on channel catfish susceptibility to these pathogens. We found that a sublethal dose of microcystin-LR induced …

The Evergreen Challenges Of Healing: An Evaluation Of Urban Green Space In Harambee, Kacee Ochalek

Theses and Dissertations

Urban green space initiatives have emerged in low- and middle-income cities as a solution to disinvestment, the production of more positive public health metrics, and a tool of community engagement. While the production of urban greening provides ample room for applause, The City of Milwaukee’s Healing Spaces Initiative model regarding the ongoing construction of green space and the implementation of maintenance creates challenges that perpetuate racist capitalistic notions of the neoliberal project. This paper presents reports from participant observation, document analysis, and 17 qualitative interviews with representatives of the City of Milwaukee, community partners, garden leaders, and residents. The data …

Understanding Effect Of Ionic Liquid On Metalloproteins: Laccase And Azurin, Aashka Y. Patel

Theses and Dissertations

Interactions between ionic liquids and biomolecules have been of great interest due to the intrinsic properties of ionic liquids and the flexibility to mix and match cations and anions to create unique ionic liquids. A number of ionic liquid-biomolecule studies have focused on the interactions with proteins, including industrially relevant enzymes. One of these, laccase from Trametes versicolor, is a naturally derived enzyme used in the breakdown of phenolic compounds in a wide variety of industries, especially useful in breakdown of lignocellulosic materials. Here, a combination of experiments and molecular dynamics (MD) simulations were used to investigate the interactions …

An In Silico Study Of The Delta Opioid Receptor Using Small Molecules, Emily Dean

Theses and Dissertations

The DOR is the least studied out of the three opioid receptors (Mu, Kappa, and Delta). The most is known of the Mu Opioid receptor (MOR) and the drugs that target it have led to the global opioid epidemic due to their adverse effects of tolerance and addiction. The DOR is not known for the same adverse effects and therefore, is a promising pharmacological target for the development of new opioid ligands. In this thesis, molecular modeling, simulations and other computational methods are introduced in Chapter 1 where these methods are used to study the activation mechanism of DOR (Chapter …

Coastal Stormwater Pond Pollutants And The Potential For Development Of Antimicrobial Resistance In Vibrio And Enterococcus Bacteria, Cassandra L. Horton

Theses and Dissertations

The Southeastern coastal plain is the most rapidly urbanizing region in the United States. Associated landscape changes which increase imperviousness lead to hydrological cycle alterations, increasing runoff of nonpoint source (NPS) pollution. Urban and agricultural NPS runoff is generally discharged into stormwater ponds, which sequester chemical contaminants, nutrients, and microbes to reduce loading into coastal ecosystems. Studies of these ponds have indicated elevated levels of trace metals, antimicrobial compounds, and bacterial contamination (SCSGC 2018).

Interactions of aquatic pathogens Vibrio vulnificus and Enterococcus faecium with trace metals (arsenic, copper, zinc) and clinically relevant antimicrobials (triclosan, ciprofloxacin, oxytetracycline) commonly found in coastal …

Xenobiotic Exposures On Women’S Reproductive Health, Maria Zubizarreta Mcclam

Theses and Dissertations

Environmental and chemical exposures are continually introduced into our bodies. The female reproductive cycle is complex and particularly sensitive to toxic substances. A recent rise in infertility and reproductive diseases and cancers make reproductive toxicity a public health concern. The overall purpose of this dissertation is to explore how environmental and chemical exposures impact women’s reproductive health and overall wellbeing. To do this, a variety of topics related to women’s reproductive health are explored, including how environmental exposures can impact reproduction, methods for studying reproductive dysfunctions, fertility preservation among cancer patients, and the overall wellbeing of female cancer patients.

The …

Monitoring Titanium Dioxide Engineered Particles In Rural And Urban Surface Waters, Md Mahmudun Nabi

Theses and Dissertations

Quantifying and characterizing engineered particles in environmental systems is key for assessing their risk but remains challenging and requires the distinction between natural and engineered particles. The Ph.D. dissertation research described in this thesis contributes to the current attempts to improve environmental nanoparticle analysis and better understand nanoparticle behavior in natural systems, with the focus being on natural streams, and the application of single particle inductively coupled plasma-time of flight-mass spectrometry (SP-ICP-TOF-MS) for distinguishing and tracing the origins of environmental nanoparticles. The objective of this dissertation is to characterize and quantify the concentrations of titanium dioxide engineered particles in urban …

Detection Of Microcystin Aerosol Particles, Alexis D. Dabney

Theses and Dissertations

Harmful Algal Blooms (HABs) are a growing global concern due to their increased prevalence and magnitude, frequency, and duration in affecting both aquatic ecosystems and human health (Brooks et al. 2015). In a series of experiments, lab-generated aerosol particles containing Microcystis and Microseira were captured using filters to analyze for concentrations of Microcystin, Saxitoxin, and Lyngbya toxins. The solutions were found to contain aerosols but did not contain detectable levels of Microcystin, Saxitoxin, and Lyngbya toxins following analysis by HPLC-MS. While the techniques for generating aerosols were shown to be effective, the generation and analysis of toxins did not produce …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

Evaluating Soil Health Changes Following Cover Crop And No-Till Integration Into A Soybean (Glycine Max) Cropping System In The Mississippi Alluvial Valley, Alexandra Gwin Firth

Theses and Dissertations

The transition of natural landscapes to intensive agricultural uses has resulted in severe loss of soil organic carbon (SOC), increased CO₂ emissions, river depletion, and groundwater overdraft. Despite negative documented effects of agricultural land use (i.e., soil erosion, nutrient runoff) on critical natural resources (i.e., water, soil), food production must increase to meet the demands of a rising human population. Given the environmental and agricultural productivity concerns of intensely managed soils, it is critical to implement conservation practices that mitigate the negative effects of crop production and enhance environmental integrity. In the Mississippi Alluvial Valley (MAV) region of Mississippi, USA, …

Improving Nutrition And Food Safety Knowledge Of Small-Scale Fish Processors In Delta State, Nigeria, Grace Adeola Adegoye

Theses and Dissertations

Introduction: Fish is an affordable animal source food that provides nutrition and serves as a source of income for many people especially women in Nigeria. Smoking and sun drying are the processing methods in practice that expose the fish products to possible contaminants which may consequentially negate their nutritive value.

Aim: To improve the knowledge of fish processors on nutrition and safe fish handling.

Methodology: A 3-day participatory training was organized to train 122 fish processors, 95 women, and 25 men. The training was conducted in the three senatorial districts in Delta State, Nigeria. Knowledge was assessed using the pre …

Towards Environmental Sustainability Of Nanotechnology Through Improved Evaluations Of Impact And Risk To Aquatic Species: Cross-Species Comparisons From The Laboratory And Environmentally Realistic Exposure Scenarios In The Field, Becky J. Curtis

Theses and Dissertations

Engineered nanomaterials (ENMs) are utilized in a wide variety of applications and products, including everything from toothpaste and personal care products to industries such as aerospace, defense, medicine, electronics, and agriculture. Depending on the application, release of ENMs to the environment may occur through both unintentional and deliberate routes. High surface-area-to-volume ratios make ENMs more volatile than bulk counterparts, and their small size allows translocation within biological systems that would not be possible with larger materials. These and other characteristics make ENM-biological system interactions unpredictable, creating uncertainty about their potential risks to environmental health. The purpose of this research is …

Molecular And Behavioral Impacts Of Treated Wastewater Effluent On Fish, Peter Schumann

Theses and Dissertations

Currently, most studies that focus on the sublethal impacts of contaminants of emerging concern (CECs) such as pharmaceuticals utilize a single-compound approach, whereas these compounds always occur as complex mixtures in the environment. Wastewater treatment plants (WWTPs) are a major contributor to the formation of these mixtures as current treatment technologies inadequately remove many chemical pollutants. There is a paucity of knowledge on the neurological impacts due to exposure to complex CEC mixtures resulting from the discharge of treated WWTP effluent into aquatic environments. This knowledge gap leaves incomplete assessments of the hazards and risks from exposure to treated effluent …

Removal Of Arsenic (Iii) And Arsenic (V) From Aqueous Solution Via Common Sunflower Helianthus Annuus By Phytoremediation, Irving A. Vazquez Hurtado

Theses and Dissertations

Phytoremediation provides a cost-effective, non-invasive technique to remove contaminants from the soil and groundwater. Sunflowers are fast growing and have a showed effective at removing various pollutants from soil, including lead and other heavy metals. Health issues related to arsenic are mainly attributed to exposure of arsenite, whereas arsenate is much less toxic. The common sunflower Helianthus annuus was the species used to remove both arsenic (III) and As(V) ions from hydroponics solutions. In the present study sunflower seeds were germinated for a week, placed under the sun for a day and subsequently placed in a nutrient solution to aid …

Describing The Impact Of The Sales Of Antibiotics On The Environment And In Population Health, Andrés Gaviria-Figueroa

Theses and Dissertations

The role of antibiotics in human health is of significant importance in the advancement of the medical field. It has contributed to an improvement of the quality of life and the age expectancy of the population. Antibiotic resistance is an expected consequence of the use of antibiotics. Bacteria have developed biological mechanisms that would help them become resistant to antibiotics. The uncontrolled use of antibiotics is significantly contributing to the ability of bacteria to become resistant to those antibiotics. This study, using the model of the Socio-Ecological Coupling of Antibiotic Resistance, explains how social and environmental factors interact and impact …

Comparative Assessment Of The Fate And Toxicity Of Chemically And Biologically Synthesized Silver Nanoparticles Toward Juvenile Clams, Mercenaria Mercenaria, Amar Yasser Al-Rshim

Theses and Dissertations

Engineered nanomaterials (ENMs) with unique nanoscale properties, including novel optical behavior and superparamagnetic, are continually being developed for biomedical and industrial applications. In specific biomedical applications, ENMs are surface-functionalized using polymers, proteins, and other stabilizing agents to facilitate their resistance to salt-induced aggregation. Since their colloidal stability in high ionic-strength matrices, functionalized ENMs are anticipated to be persistent aquatic contaminants. Despite their potential environmental significance, the persistence of surface-functionalized ENMs as individually stabilized nanoparticles in marine environments is largely unknown. Further, few studies have investigated the fundamental factors that influence ENMs uptake and fate/transport processes in ecologically susceptible aquatic biota, …

Behavioral And Physiological Effects Of Heavy Metals On Fish: A Review And Preliminary Results, Diana V. Morales

Theses and Dissertations

Pollution, specifically heavy metal pollution, in various bodies of water has been a significant issue for decades. Research has been conducted on heavy metals and their effects on the environment, larger fish species, and humans since the 1970s (Skidmore, 1964; Adeniyi et al., 2007; Adeosun et al., 2015; Bawuro et al., 2018). It is known that zinc is a neurotoxin in some species and causes harm to the environment. It is also known that it causes harm to people if it is ingested or if they are exposed to it for long periods of time (Mahurpawar, 2015; Mizuno and Kawahara, …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson

Theses and Dissertations

Mancozeb (MZ), an ethylene bis-dithiocarbamate complexed with the metals manganese and zinc, is a broad-spectrum fungicide used primarily on orchards and vineyards. Disulfiram (DS, Antabuse®), a diethyldithiocarbamate, is an FDA-approved drug used for alcohol aversion therapy. Both dithiocarbamates (DTCs) have shown neurological effects including motor impairment, muscle weakness, and hind-limb paralysis, although the mechanism of toxicity is not understood. The purpose of this study is to determine how these neurotoxic compounds are damaging striated muscle of rats. Adult, male Long-Evans rats were administered either 250mg/kg MZ or 750mg/kg DS via oral gavage 3x/week for four weeks. Animals were euthanized 24 …

The Role Of Human Dopamine Transporter Threonine 261 And Serine 262 In Amphetamine Regulation Of Transporter Function And Surface Expression, Sina Abdollahi

Theses and Dissertations

Amphetamine (AMPH) has been used clinically and recreationally around the world for years. A 2021 study reports a 67.5% rise in AMPH use from 2010-2017 across all fifty states. Study also shows that 30% of patients with AMPH-induced psychosis end up with primary psychosis over time. AMPH works by inhibiting monoamine (Norepinephrine (NE), Serotonin (5-HT), and Dopamine (DA) reuptake followed by triggering transporter mediated monoamine release and consequently increases monoamine concentrations in extracellular synaptic space. AMPH also works as a substrate for monoamine transporters, enters the neuron, and once its inside the neuron, it will prevent the storage of monoamines …

Using Molecularly Imprinted Polymers For The Selective Extraction Of Analytes, Haley A. Mulder

Theses and Dissertations

Sample preparation is a critical steps in bioanalysis. Traditional methods such as solid-phase extraction and liquid-liquid extraction are laborious and ultimately incapable of properly separating target analytes from matrix and interferents. The co-extraction of these components interferes with the analytical instrument’s ability to properly detect and quantitate analytes. Molecularly imprinted polymers (MIPs) are synthetic polymers that have been “imprinted” with a template analyte in a co-polymer system. MIPs are capable of selectively extracting analytes from complex biological matrices and can be employed in off-line, benchtop extractions or for on/in-line instrument extractions. MIPs offer faster and more selective sample preparation, leading …

Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird

Theses and Dissertations

The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 …

Mechanisms And Treatment Of Pain-Depressed Behavior In Male And Female Mice, Clare M. Diester

Theses and Dissertations

One of the largest discrepancies between preclinical and clinical assessment of pain and analgesia is the type of behavioral endpoint used. Although most preclinical research has historically focused on drug effectiveness to block reflexive withdrawal behaviors stimulated by a noxious stimulus, increasing evidence shows that drug-induced restoration of pain-depressed behaviors provides increased clinical translation with decreased susceptibility to false-positives. Accordingly, the first portion of this dissertation designed a behavioral battery that featured pain-depressed behaviors as well as more conventional pain-stimulated behaviors for testing candidate analgesics in male and female mice. The main findings are as follows. (1) Intraperitoneal injection of …

Modulating Ketamine’S Locomotor Activating And Reinforcing Effects Through Drug Combinations, Tegshjargal Baasansukh

Theses and Dissertations

Major Depressive Disorder (MDD) affects approximately 280 million people worldwide. The standard of care for pharmacological treatment of MDD has been monoaminergic antidepressants (MAA). However, MAAs have serious clinical limitations including a relatively slow onset of action and up to 40% of patients failing to respond and being diagnosed as “treatment resistant”. Ketamine, an N-methyl-D-aspartate antagonist, was originally approved for use as an injectable anesthetic. In addition, ketamine has been shown to rapidly improve depressive symptoms in patients with treatment resistant depression. In 2019, (S)-ketamine was approved as a nasal spray (Spravato®) for patients with MDD and treatment-resistant depression in …