Pharmacology, Toxicology and Environmental Health Commons^™

Inhibition Of Aflatoxin Biosynthesis With Vibrio Gazogenes, Phani Madhuri Gummadidala

Theses and Dissertations

Aflatoxin, a mycotoxin, is one of the world’s most potent carcinogen. It contaminates major food products such as milk, grains, nuts, corn, etc., leading to greater than $ 1 billion in economic losses and when ingested causes hepatocellular carcinoma (HCC). It is the primary risk factor for 75% HCC cases in the developing world and 3% HCC cases in developed world. Most common methods used in agriculture to reduce aflatoxin contamination are expensive, time consuming and have low efficiency with limited success rates where as biological controls were proven to be most effective in inhibiting aflatoxins and aflatoxin producing fungi. …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

Undergraduate Research Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

Design, Synthesis And Biological Evaluation Of Inhibitors Against Both Human And Mouse Microsomal Prostaglandin E2 Synthase-1 Enzymes, Kai Ding

Theses and Dissertations--Chemistry

As the principal pro-inflammatory prostanoid, prostaglandin E₂ (PGE₂) serves as mediator of pain and fever in inflammatory reactions. The biosynthesis of PGE₂ starts from arachidonic acid (AA). Cyclooxygenase (COX)-1 and/or COX-2 converts AA to prostaglandin H₂ (PGH₂), and PGE₂ synthases transform PGH₂ to PGE₂. Current mainstream approach for treating inflammation-related symptoms remains the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). As both categories shut down the biosynthesis of all downstream prostanoids, their application renders several deleterious effects including gastrointestinalulceration and cardiovascular risk. Microsomal prostaglandin …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron

Theses and Dissertations--Toxicology and Cancer Biology

The reversible oxidation of cysteine by reactive oxygen species (ROS) is both a mechanism for cellular protein signaling as well as a cause of cellular injury and death through the generation of oxidative stress. The study of cysteine oxidation is complicated by the methodology currently available to isolate and enrich oxidized-cysteine containing proteins. We sought to simplify this process by reducing the time needed to process samples and reducing sample loss and contamination risk.

We accomplished this by eliminating precipitation steps needed for the protocol by (a) introducing an in-solution NEM-quenching step prior to reduction and (b) replacing soluble dithiothreitol …

Tumor Multicomponent Targeting Polymer-Lipid Hybrid Nanoparticles To Overcome Drug Resistance In Renal Cell Carcinoma, Hashem Obaid Alsaab

Wayne State University Dissertations

Renal Cell Carcinoma (RCC) contributes to more than 90% of the most common form of kidney tumor and remains one of the ten leading causes of cancer death in the United States. Although surgery remains an option for operable tumors, high metastatic index and resistance to radiation and chemotherapies prompted recent development of therapeutics that target the RCC angiogenesis and cell proliferation pathways. Tyrosine kinase inhibitors or TKIs (Cabozantinib, Axitinib, Sorafenib, and Sunitinib) and mammalian target of rapamycin (mTOR) inhibitors (Temsirolimus and Everolimus) have increased the therapeutic options for treating RCC. Although the impact towards decreasing disease progression is encouraging, …

Drug Delivery Strategies For The Treatment Of Advanced Lung Cancer And Various Lung Metastases, Elizabeth Bielski

Wayne State University Dissertations

Lung cancer remains the leading cause of cancer-related deaths in the United States. Secondary lung tumors metastasized from other cancer sites also remains highly prevalent, in which most metastatic tumors cannot be cured with existing therapies. Chemoresistance (multi drug resistance – MDR) that develops intrinsically or acquired is one of the key factors leading to fatality in these patients. MDR develops form a variety of resistance mechanisms that can occur consecutively or concurrently, therefore, making most current treatments unsuccessful. Current therapies have known to slow tumor growth, but rarely provide a cure. Immunotherapy has seen some promise, including the use …

Discovery Of Piperlongumine Derivatives As Anti-Leukemic And Anti-Prostate Cancer Agents, Yi Liao

Wayne State University Dissertations

Piperlongumine (PL) is an electrophilic anti-cancer natural product. Through non-covalent or covalent interactions with cellular targets, PL inactivates multiple oncogenic pathways and suppresses key components of cellular anti-oxidant/anti-electrophile defense systems. These actions result in pleiotropic anticancer effects and are expected to be effective to heterogeneous acute myeloid leukemia (AML) and prostate cancer (PCa). We applied two approaches to enhance the anticancer potency of PL: 1) To design PL-histone deacetylase inhibitor hybrid drugs (PL-HDACis; e.g., 1-58), and 2) To dimerize PL pharmacophore to generate a dimeric PL (DiPL) warhead that is suitable for further conjugation (e.g., 5-17). Both 1-58 and 5-17 …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Organochloride Pesticides Present In Animal Fur, Soil, And Streambed In An Agricultural Region Of Southeastern Arkansas, Matthew E. Grilliot, John L. Hunt, Christopher G. Sims

Journal of the Arkansas Academy of Science

Animals in agricultural settings may be subject to bioaccumulation of toxins. For the last several years, we collected hair samples from bats and rodents in an agricultural area near Bayou Bartholomew in Drew County, Arkansas. Samples were submitted to the Center of Environmental Sciences and Engineering at the University of Connecticut for wide-screen toxin analysis. Several of these samples contained measurable amounts of organochloride pesticides or their metabolites, including some that have been banned for decades, such as dichlorodiphenyltrichloroethane (DDT) and chlordane. In addition, we collected several samples of soil from within an agricultural field, from adjacent edge habitat, from …

Understanding The Impact Of Land Use On Microbial Water Quality To Support Decisions For A Future Land Use Plan, Mohammed Tawfiq Aljassim

Theses and Dissertations

May River meandering through the Town of Bluffton, South Carolina has been known for its high level of water quality. The May River is one of the major sources of shellfish harvesting in South Carolina. Due to the non-point source pollution of fecal coliform, the water quality of the May River became degraded. As a result, shellfish harvesting classification in the May River was downgraded for the first time in its history. The rapid growth of the Town has led to a change in land use, which might be related to the increased levels of fecal coliform in the stream …

The Effects Of 5-Ht4 Receptor Agonists On Interleukin-10 Knockout Mice, Quentin Mylie

Graduate College Dissertations and Theses

Recent studies have demonstrated that activation of the 5-HT4 receptors in the colonic mucosa can have healing and protective actions in experimental models of colitis. These actions include increased mucus secretion, increased epithelial proliferation, and enhanced epithelial migration. Since these studies involved chemically induced models of colitis, the current investigation was conducted to test whether a protective action of 5-HT4 receptor stimulation could be detected in Interleukin-10 knockout (IL-10 KO), which develop colitis spontaneously due to the absence of the anti-inflammatory cytokine, interleukin-10.

Upon weaning, the IL-10 knockout mice were separated into two groups: an agonist group and a vehicle …

Arsenic In Groundwater In South West Ireland - Occurrence, Controls, And Hydrochemistry, Ellen R. Mcgrory, Emma Holian, Alberto Alvarez-Iglesias, Norma Bargary, Eoin Mcgillicuddy, Henry Tiernan, Liam Morrison

Articles

Globally numerous regions have been identified with elevated arsenic within groundwater which can result in potential adverse health risks. In Ireland, a previous national-scale research assessment of groundwater identified isolated clusters of elevated arsenic and indicated that lithology was a major controlling factor on arsenic in groundwater. Complementary comparisons of national-scale and regional-scale groundwater assessments of arsenic are lacking in Europe when compared to other global regions. The aims of this study were to demonstrate the value of a regional-scale groundwater hydrochemistry dataset with an existing national-scale approach, describe anomalies that can become the focus of attention for public health …

Impacts Of Trace Metal Pollution, Urbanization And Aquifer Recharge On Spokane River Macroinvertebrates, Carolyn K. Connelly

EWU Masters Thesis Collection

This study analyzed macroinvertebrate communities of the Spokane River to determine: 1) accumulation of toxic trace metals in macroinvertebrate tissue, 2) effects of aquifer recharge, and 3) impact of urbanization. I predicted that aquifer inflows of cold, clean water would mitigate effects of pollution, and that reaches above the City of Spokane would be less negatively affected by urbanization; both were unsupported. I also predicted that effects of toxic trace metals would decrease within distance downstream; this prediction was supported. I sampled 12 riffles of the Spokane River between the Washington/Idaho border and Riverside State Park in late summer 2010. …

Environmental Impacts On Enterococcus In Shem Creek, South Carolina, And Characterization Of Changing Land Use, Maria Elizabeth Zubizarreta

Theses and Dissertations

Zoning and land-use practices have a direct influence on hydrologic systems and can impact water resources. Linkages between change in land uses and degradation of water quality in stream and watershed environments have been well established. Shem Creek, located in Mount Pleasant, SC, has a history of fecal indicator bacteria levels that exceed the Environmental Protection Agency’s recreational water quality standards. With recent coastal population and development trends, proper management and the sustainability of beach and estuary environments are a rising public health concern. The objective of this study is to determine what climatic and water quality parameters are associated …

I Have Never Stepped In The Same River Twice, Madison Hailey Emond

Senior Projects Spring 2018

“No man ever steps in the same river twice, for it’s not the same river and he’s not the same man.” – Heraclitus

I never knew that I would learn to walk the Sawkill River in moonlight, that I would come to know its contours and the depths of its waters so well. I never expected that the tree roots and rocks that lay in my path to its banks would know my gait so fully.

This project began as a reaction to the hurricanes that struck the Caribbean last fall. It felt apt to question landscape imagery and how …

Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan

Theses and Dissertations (Comprehensive)

This study investigated ovarian development in Fundulus heteroclitus (mummichog), through molecular characterization of key mediators in the ovarian steroidogenic pathway; these included ovarian StAR (steroidogenic acute regulatory protein), cytochrome P450 enzymes, estrogen receptors (ERα, ERβ1 and ERβ2), and gonadotropin receptors (FSHr and LHr); additionally, hepatic vitellogenin (VTG1) and ERs, and brain P450 aromatase (P450arom; CYP19b) were studied. Fish were staged into cortical alveolus, vitellogenic, early mature, late mature, and ovulating stages of maturation; blood (plasma), ovary (tissue and isolated ovarian follicles per stage), liver, and brains were collected. Testosterone (T), 17β-estradiol (E₂) and maturation inducing steroid (MIS), measured …

Forensic Markers Of Lampricide Toxicity In Oncorhynchsus Mykiss, Chris White

Theses and Dissertations (Comprehensive)

The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) has been used for decades to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, normally with little harm to other fish populations. However, due to the nature of lampricide treatments and the chemical properties of TFM, adverse effects to non-target fishes and non-target mortality occasionally occur. However, investigations of non-target mortality can be complex, particularly if fish deaths are not noticed immediately, due to decomposition of the carcasses. The objectives of this thesis were to expose rainbow trout (Oncorhynchsus mykiss) to TFM in order to: (i) identify forensic markers …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

Watered Down: The Challenges Of Managing Water Resources In Montana, Beau E. Baker

Graduate Student Theses, Dissertations, & Professional Papers

Like much of the American West, Montana sits in the cross hairs of climate change. State drought resiliency projects and cooperative watershed management are on the rise in the face of decreased snowpack, early runoff, precipitation variability and lower seasonal stream flows. Population growth, land use practices, recreation and tourism all contribute to pressures on state water supplies.

Montana is faced with the arrival of invasive species that threaten the ecological health of its lakes, rivers and streams. State budget constraints and depressed agency capacity are hurting our ability to fend off these threats. There’s a lack of public education …