Pharmacology, Toxicology and Environmental Health Commons^™

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …

Poison In Pink, Sydney V. Cook

Graduate Student Theses, Dissertations, & Professional Papers

Humans slather, spray, mist, and cleanse their bodies with personal care products like lotion, hairspray, cologne, and shampoo every day. Our cupboards are stocked full of them, but few of us understand what is in those jars and bottles. We trust that if it’s on the shelf at the store, it’s safe. However, this is not always the case, and many personal care products contain chemicals that are harmful to human and environmental health.

My multi-disciplinary Environmental Studies thesis project combines evidenced-based research, interviews, nonfiction narrative, and science communication to create part of a book manuscript intended to educate general …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Immunotherapy Against Drugs Of Abuse, Gianna Raimondi (Class Of 2017)

Writing Across the Curriculum

Current treatments for drug addiction involve classical pharmacological therapy, involving the use of competitive or noncompetitive agonists (full, partial, or inverse) and antagonists. Drugs of abuse enter the brain after crossing the blood-brain barrier rapidly and binding to the proper receptor(s). They are able to do so because they are small and lipid soluble, and produce reinforcing effects by increasing levels of dopamine in brain areas associated with reward. This occurs in specific systems associated with addiction. In the mesolimbic system, neuron cell bodies originate in the ventral tegmental area (VTA) and project to the nucleus accumbens (NAc), amygdala, hippocampus, …

Determination Of Potency Of Tetanus Immunoglobulin Products By Commercial Tetanus Anti-Toxoid Test Kits, Wichuda Jariyapan, Kanitta Puwanardnaranuban, Saywarul Jadoonkittnan

The Thai Journal of Pharmaceutical Sciences

Replacement of using experimental animals in scientific research with alternative methods is encouraged, according to the ‘3Rs’ principles (replacement, reduction and refinement). This study presented results for determination of potency of tetanus i...

New Fluorinated Chalcone And Pyrazolines Analogues: Synthesis, Docking And Molecular Dynamic Studies As Anticancer Agents, Jasril Jasril

The Thai Journal of Pharmaceutical Sciences

Some of chalcones and pyrazolines analogues are known to have a good potency as anticancer agents. In this work, a fluorinated chalcone and two pyrazolines were successfully synthesized under microwave irradiation. Molecular docking and molecular dynamic.

Influence Of Disease-Related Knowledge And Personality Traits On Parkinson’S Patient Empowerment, Pramon Viwattanakulvanid, Tanattha Kittisopee

The Thai Journal of Pharmaceutical Sciences

Background: Parkinson’s disease (PD), a neurodegenerative disorder, has an impact on both the physical and mental functions of persons with Parkinson’s (PwP), who tend to lose their sense of empowerment, cognitive state of perceived competence and pe...

Stability Determination Of An Alternative Approach To Use Of Liquid Drug Substance As Oil Phase In Microemulsion Formulations: Methyl Salicylate, Warunee Leesajakul, Sunee Channarong, Pathamaporn Chuetee

The Thai Journal of Pharmaceutical Sciences

The objective of this study was to investigate the stability of microemulsions using methyl salicylate as oil phase in the presence and the absence of hydrophobic additives and/or drug after six-month storage at ambient temperature. The investigated addi.

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice, Rucha Fadnavis

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Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice., Rucha Fadnavis

Browse all Theses and Dissertations

Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Axonal Transport, Parkin, And Α-Synuclein; Novel Therapeutic Targets To Treat Methamphetamine Neurotoxicity, Bryan Andrew Killinger

Wayne State University Dissertations

Methamphetamine (METH) is a commonly abuse psychostimulant. Exposure to chronic high doses of METH can result in neurotoxicity primarily characterized by damage to striatal dopaminergic (DAergic) axons. There are currently no therapeutic interventions for METH neurotoxicity. To some extent damage to striatal DAergic axons is reversible and DAergic axon function may return following abstinence from METH. The reversible nature of METH neurotoxicity suggests that normal striatal function could be restored following exposure to METH. However, potential targets to treat METH neurotoxicity are needed. Axonal transport is required for restoration of DAergic axon components damaged or lost following METH. Here we …

Underlying Mechanisms Of Arsenic-Induced Tumorigenesis: From Epigenetics To Malignancy, Lingzhi Li

Wayne State University Dissertations

Arsenic is a well-recognized environmental health threat with the capability of inducing a number of human diseases, including cancer. The aim of this dissertation is to unveil the mechanisms underlying the carcinogenic activities of environmental arsenic. The biological functions of arsenic had been studied for decades. However, there are still many questions that remain to be fully answered, such as whether and how arsenic contributes to the epigenetic regulations and migration or metastasis control of the cancer cells. In this regard, we focused our attention on both histone modifications and miRNA regulations in the arsenic-induced malignant transformation of the cells, …

Human Kinome In Skeletal Muscle Insulin Resistance, Yue Qi

Wayne State University Dissertations

Protein kinases play fundamental roles in regulation of biological processes and functions, such as insulin signaling and glucose metabolism. Dysregulation of protein kinases may cause impaired cell signaling and human diseases, such as metabolic syndrome and type 2 diabetes (T2D). Skeletal muscle is the main site responsible for insulin-stimulated glucose disposal, and insulin resistance in skeletal muscle is one of the key features of the pathogenesis of T2D. Therefore, malfunction of protein kinases and their interaction proteins may contribute to the molecular mechanism of insulin resistance in human skeletal muscle. However, no large scale profiling study has been reported to …

G-Quadruplexes As Molecular Targets For Transcriptional Control, Rhianna Kyelle Morgan

Electronic Theses and Dissertations

DNA G-quadruplexes (G4s) have gained interest in modern drug discovery efforts. The majority of G4 research, including the mass of this research, heavily focuses on cancer therapeutic development, as G4s are more pronounced in oncogenic promoters compared to the rest of the genome, our efforts extend towards neuroprotection as well. In particular, this work covers G4s in the promoters of MYC, VEGF, kRAS, and Bcl-2. MYC and VEGF harbor the two most well described promoter G4s to date, and their stabilization cultivates transcriptional silencing. Downregulation of MYC reduces cell growth and alters cell energetics; it is promising for a variety …

Does Timing Of Herbicide Use Influence Rates Of Germination Or Seedling Biomass Of Native Plants Used For Restoration?, Christine Mcmanamen

Graduate Student Theses, Dissertations, & Professional Papers

Invasive plants can negatively impact native grasslands by changing their species composition, productivity, and function. Managers commonly use herbicides as a control method; however, this practice can lead to secondary invasion by other non-native invasive plants, unless measures are taken to promote natives. Because of this, managers often seed native plants after spraying herbicides. There is evidence, however, that chemical control of invasive plants may reduce the effectiveness of subsequent seed-addition treatments, but there is currently little quantitative information on optimal timing between spraying and seeding or on variation in herbicide sensitivity among native plants commonly used in seed mixes. …

Thermal Burn Injury Induced Microvesicle Particle Release, Katherine Erin Fahy

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Microvesicle particles (MVP) are found to be important for cellular communication because they contain many bioactive proteins, lipids, cytokines, and nucleic acids. We have previously found that ultraviolet B radiation (UVB) and a Platelet-activating factor agonist (CPAF) can stimulate the release of MVP in keratinocytes. We hypothesized that there may also be an increase in MVP released after thermal burn and that could be involved in pathogenesis of the systemic effects found in some patients. In this thesis various keratinocyte cell lines, mice and human ex vivo skin were used as model systems to test our hypotheses. It was determined …

Extracellular Microvesicles As A Novel Biomarker For Wound Healing, Walid Omran Mari

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Introduction: Wound healing is a sophisticated dynamic process that involves complex coordination among a variety of resident cells in a suitable extracellular environment. Chronic wounds are defined as wounds that fail to heal within a period of 3 months. Negative pressure wound therapy (NPWT) is a closed suction drainage system is used to enable mass transport of fluid from the body as an adjunct to surgical procedures. (Oasis-ultra) is a triple layer extracellular matrix containing different types of glycosaminoglycans (GAGs) like heparin sulfate, hyaluronic acid and chondroitin sulfate. In addition, it has adhesion molecule such as fibronectin and laminin along …

Investigating The Modulation And Mechanisms Of Α7 Nicotinic Acetylcholine Receptors In Nicotine Dependence, Asti Jackson

Theses and Dissertations

Tobacco dependence dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. Nicotine, the main addictive component of tobacco, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). The homomeric α7 nAChR is one of the most abundant receptors found in the brain and has unique features in comparison to other nAChR subtypes such as high calcium permeability, low probability of channel opening, and a rapid desensitization rate. α7 nAChR agonists reduce nicotine's rewarding properties in the conditioned place preference (CPP) test and i.v. self-administration. Recently, the peroxisome proliferator-activated receptor …

Altered Gut Microbiome In A Mouse Model Of Gulf War Illness Causes Neuroinflammation And Intestinal Injury Via Leaky Gut And Tlr4 Activation, Firas Alhasson, Suvarthi Das, Ratanesh K. Seth, Diptadip Dattaroy, Varun Chandrashekaran, Caitlin N. Ryan, Luisa S. Chan, Traci Testerman, James Burch, Lorne J. Hofseth, Ronnie Horner, Mitzi Nagarkatti, Prakash Nagarkatti, Stephen M. Lasley, Saurabh Chatterjee

Faculty Publications

Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease …

Atp-Sensitive Inwardly Rectifying Potassium Channel Modulators Alter Cardiac Function In Honey Bees, Scott T. O'Neal, Daniel R. Swale, Jeffrey R. Bloomquist, Troy D. Anderson

Department of Entomology: Faculty Publications

ATP-sensitive inwardly rectifying potassium (KATP) channels couple cellular metabolism to the membrane potential of the cell and play an important role in a variety of tissue types, including the insect dorsal vessel, making them a subject of interest not only for understanding invertebrate physiology, but also as a potential target for novel insecticides. Most of what is known about these ion channels is the result of work performed in mammalian systems, with insect studies being limited to only a few species and physiological systems. The goal of this study was to investigate the role that K_ATP channels play in …