Pharmacology, Toxicology and Environmental Health Commons^™

Investigating Stormwater Parameters From Runoff On East Tennessee State University Campus, Abby Mciver, Dr. Joseph R. Bidwell

Undergraduate Honors Theses

Climate change has caused an increase in extreme rain events and flooding in certain regions across the globe. During rain events, water flows over impervious surfaces structures such as roads and sidewalks, picking up contaminants such as metals, fertilizers and other nutrients, and various organics that which may impact organisms in such as streams, river, and lakes. Previous work has found significant differences in survival of organisms that were exposed to contaminated stormwater runoff. This study investigated stormwater chemistry parameters at collection sites on the East Tennessee State University campus. Sites were selected based on the extent of human interaction …

Validation Of The 40 Hz Auditory Steady State Response As A Pharmacodynamic Biomarker Of Evoked Neural Synchrony, Muhammad Ummear Raza

Electronic Theses and Dissertations

Schizophrenia is a troubling and severe mental illness that is only incompletely treated by currently available drugs. New drug development is hindered by a scarcity of functionally relevant pharmacodynamic biomarkers that are translatable across preclinical and human subjects. Although psychosis is a major feature of schizophrenia, cognitive and negative symptoms determine the long-term functional outcomes for patients. Stimulus-evoked neural synchrony at gamma (~ 40 Hz) frequency plays an important role in the processing and integration of sensory information. Not surprisingly, schizophrenia patients show deficits in gamma oscillations. NMDA receptor (NMDAR) activation on fast-spiking parvalbumin-positive interneurons is deemed important for the …

Dibutyl Amine Detection, Quantification, And Removal With Iron(Ii)Tetrasulfophthalocyanine (Fetspc), Kyle Bittner

Electronic Theses and Dissertations

Pesticide testing is of practical interest in various areas of today’s world due to their prevalence and toxicity. These areas include agriculture, environmental, chemical plants, and many others. Herbicides, like Roundup, contain secondary amines such as glyphosate. The ability to detect secondary amines could offer a method for glyphosate detection in agricultural and environmental samples. Secondary amines can interact with metal complexes through electron charge transfer. Such interactions can cause a change in the metal’s electron configuration and energy state and can be seen in the UV-Vis spectrum. Metal phthalocyanines (MPc’s) and other organometallic complexes have been of interest for …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Operatic Mysticisms: Mountains, Deserts, Waterscapes, Andrew Demczuk

Electronic Theses and Dissertations

Operatic Mysticisms: Mountains, Deserts, Waterscapes examines the ways we encounter environments as readers/viewers of operas, literature, film, and sound recordings, and how each medium requires different detail-gathering techniques. Respective to the previously mentioned mediums, Sun & Sea (2017), Mount Analogue (1952), El Mar La Mar (2017), and Energy Field (2010) are analyzed by engaging with environmental media studies and invention. Reflecting the nature of each landscape—summits of mountains, aporias of deserts, and mysteries of waterscapes—an elemental approach is taken in investigating how these spaces may be noticed, internalized, recorded, and traversed by both the artist and viewer. …

Behavioral Effects And Neurobiological Mechanisms Of 3-Aminobenzimide In A Rodent Model Of Chronic Psychological Stress, Liza Wills

Electronic Theses and Dissertations

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent …

Effects Of Respiratory Perturbations On Aging And Healthspan In Daphnia Magna, Millicent Nkiruka Ekwudo

Electronic Theses and Dissertations

Aging is a degenerative process characterized by a decline in physiological functions and cellular activities. Environmental and pharmacological interventions affecting longevity pathways have been extensively studied in model organisms. This study investigated the effect of chronic mild intermittent hypoxia (4 mg O2/L) or mild mitochondrial uncoupling with three doses of 0 (control), 0.1, 1, and 5 μM of 2,4-Dinitrophenol (DNP), on life history and gene expression in four clones of Daphnia magna. Interestingly, clones from intermittent ponds displayed better tolerance to hypoxia and DNP. Although neither treatments extended longevity, hypoxia increased fecundity and body size, and decreased food consumption and …

Potential Toxicity Of Silver Nanoparticles To Microbial Communities And Macroinvertebrates, Joseph Kusi

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) are the most common nanomaterials incorporated in commercial products due to their antimicrobial activity. Recently, AgNPs were detected in surface waters suggesting the potential for bioavailability in the aquatic receptor organisms. This dissertation research attempts to understand the potential toxicity of AgNPs on water quality indicators, focusing on the microbial community and amphipods. This study evaluated whether: (1) the antimicrobial properties of AgNPs pose potential risks to microbial communities in pathogen impaired streams; (2) AgNPs can cause a shift in functional diversity and metabolic fingerprinting of microbial communities; (3) survival and growth of Hyalella azteca (amphipods) could …

Therapeutic Drug Monitoring Of Apixaban Using Chromogenic Kits, Brooke Vogel

Undergraduate Honors Theses

Apixaban is a novel oral anticoagulant that prevents clotting by directly inhibiting Factor Xa in the coagulation cascade. Due to its different pharmacokinetics, previous standards for testing anticoagulant concentrations are ineffective at measuring apixaban. In this study, Hyphen Biomed Biophen Direct Xa Inhibitor and Biophen Heparin chromogenic kits from Aniara Diagnostica were used along with a NanoDrop™ One/One^C Microvolume UV-Vis Spectrophotometer to see if either of these kits provide acceptable precision and accuracy for the quantification of apixaban in plasma samples, as well as if there is a significant difference in these two kits at varying concentrations of apixaban. …

Levels Of Parp1-Immunoreactivity In The Human Brain In Major Depressive Disorder, Aamir Shaikh

Undergraduate Honors Theses

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search …

The Chelation Of Metal Ions By Vicibactin, A Siderophore Produced By Rhizobium Leguminosarum Atcc 14479, Joshua Stinnett

Undergraduate Honors Theses

Vicibactin is a small, high-affinity iron chelator produced by Rhizobium leguminosarum ATCC 14479. Previous work has shown that vicibactin is produced and secreted from the cell to sequester ferric iron from the environment during iron-deplete conditions. This ferric iron is then transported into the cell to be converted into ferrous iron. This study uses UV-Vis spectroscopy as well as ion trap-time of flight mass spectroscopy to determine that vicibactin does form a complex with copper(II) ions, however, at a much lower affinity than for iron(III). Stability tests have shown that the copper(II)-vicibactin complex is stable over time. The results of …

The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat

Electronic Theses and Dissertations

Cadmium is present in food and groundwater. Tobacco smoking and occupational exposure are also major sources for cadmium. Cadmium is primarily accumulated in liver, a major organ metabolizing exogenous chemicals. Chemical metabolism may cause detoxification, but it can also cause bio-activation resulting in liver damage. Cytochrome P450s (CYP) are major liver metabolism enzymes, and cadmium chloride (CdCl2) can induce CYP2A5 in mice. We examined the effect of CYP2A5 on CdCl2-induced liver injury using CYP2A5-knockout (cyp2a5-/-) mice. The cyp2a5-/- mice and their control WT mice were injected CdCl2 intraperitoneally at 5 mg/kg body weight, respectively, to induce liver injury. …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

The Combined Neuropharmacology And Toxicology Of Major 'Bath Salts' Constituents Mdpv, Mephedrone, And Methylone, Serena Allen

Electronic Theses and Dissertations

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the …

Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown Phd, Alexei Gonzalez-Estrada Md

Appalachian Student Research Forum

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.

Results: The results …

Enemy Exacerbation: Effects Of Predator Stress On Sulfate Lethality In Freshwater Amphipods (Gammarus Minus), Trevor Chapman

Electronic Theses and Dissertations

Predator cues can influence how aquatic organisms respond to anthropogenic contaminants. This study examined the effects of predator cues on behavior, metabolic rate, and sulfate (as Na₂SO₄) toxicity in amphipods (Gammarus minus). Predator cues included alarm cue (macerated conspecifics) and kairomone from mosquitofish (Gambusia affinis). Amphipods decreased activity and increased time in refuge when exposed to alarm cue, and increased time in refuge when exposed to kairomone. While median lethal concentrations (96-h LC₅₀) were not influenced by predator cues, analysis of dose response curves indicated that kairomone exposure increased amphipod …

Range-Wide Prevalence And Impacts Of Pseudocercosporella Inconspicua On Lilium Grayi And An Assessment Of L. Superbum And L. Michauxii As Reservoirs, Cindy L. Barrett

Electronic Theses and Dissertations

Lilium grayi (Gray’s Lily), a southern Appalachian endemic species, is threatened by a Lilium-specific fungal pathogen, Pseudocercosporella inconspicua. The disease is characterized by tan lesions that can cause early senescence, while also lowering seed production and viability. This project tested for P. inconspicua conidia and accessed health at nine locations. The disease was present and ubiquitous across the range of L. grayi. Through identification of P. inconspicua conidia in the field, L. superbum (Turk’s Cap Lily) was identified as an additional host, while L. michauxii (Michaux’s Lily) was disease-free. However, infection was inducible in both species. With …

Salmonella And Aeromonas Contamination In A 303(D) Listed Water Body Compared To Fecal Indicators & Water Quality Parameters, Elizabeth M. Morgan Ms.

Undergraduate Honors Theses

Since the passage of the Clean Water Act, concern about surface water quality has increased. Reducing exposure to pathogens and adverse impacts on human health because of contact with surface waters has become the focus of many regulatory agencies. Fecal pollution is often a cause of surface water impairment. Fecal indicators, such as fecal coliforms and Escherichia coli, are used as surrogates to evaluate the presence or absence of fecal pollution. However, a growing body of research has shown that these species lack key characteristics necessary to be adequate indicators. As such, explorations into the efficacy of indicator species …

Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted

Electronic Theses and Dissertations

Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as well as determine target tissue concentration. These included the …

Assessing Public Health Burden Associated With Exposure To Ambient Black Carbon In The United States, Ying Li, Daven K. Henze, Darby Jack, Barron H. Henderson, Patrick L. Kinney

ETSU Faculty Works

Black carbon (BC) is a significant component of fine particulate matter (PM_2.5) air pollution, which has been linked to a series of adverse health effects, in particular premature mortality. Recent scientific research indicates that BC also plays an important role in climate change. Therefore, controlling black carbon emissions provides an opportunity for a double dividend. This study quantifies the national burden of mortality and morbidity attributable to exposure to ambient BC in the United States (US). We use GEOS–Chem, a global 3-D model of atmospheric composition to estimate the 2010 annual average BC levels at 0.5 x 0.667° …

An Analysis Of The Interaction Of Methylphenidate And Nicotine In Adolescent Rats: Effects On Bdnf, Elizabeth D. Freeman

Electronic Theses and Dissertations

This investigation was an analysis of the interaction of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine sensitization and conditioned place preference (CPP) in a rodent model and underlying mechanisms of this effect. Animals were treated IP with 1 mg/kg MPH or saline using a ―school day‖ regimen of five days on, two days off, from postnatal day (P) 28-50. During the final two weeks of MPH treatment, animals were either behaviorally sensitized to nicotine (0.5 mg/kg free base) or saline for 10 days, or conditioned to nicotine or saline using the CPP behavioral paradigm. In addition, three …

Evaluation Of Colloidal Stability And Ecotoxicity Of Metal-Based Nanoparticles In The Aquatic And Terrestrial Systems, Lok R. Pokhrel

Electronic Theses and Dissertations

Intrinsic to the many nano-enabled products are atomic-size multifunctional engineered nanomaterials, which upon release contaminate the environments, raising considerable health and safety concerns. This Ph.D. dissertation is designed to investigate (i) whether metals or oxide nanoparticles are more toxic than ions, and if MetPLATE^TM bioassay is applicable as a rapid nanotoxicity screening tool; (ii) how variable water chemistry (dissolved organic carbon (DOC), pH, and hardness) and organic compounds (cysteine, humic acid, and trolox) modulate colloidal stability, ion release, and aquatic toxicity of silver nanoparticles (AgNP); and (iii) the developmental responses of crop plants exposed to Ag- or ZnO- (zinc …

Application Of Multivariate Statistical Methodology To Model Factors Influencing Fate And Transport Of Fecal Pollution In Surface Waters, Kimberlee K. Hall

Electronic Theses and Dissertations

Degraded surface water quality is a growing public health concern. While indicator organisms are frequently used as a surrogate measure of pathogen contamination, poor correlation is often observed between indicators and pathogens. Because of adverse health effects associated with poor water quality, an assessment of the factors influencing the fate and transport of fecal pollution is necessary to identify sources and effectively design and implement Best Management Practices (BMPs) to protect and restore surface water quality. Sinking Creek is listed on the State of Tennessee’s 303D list as impaired due to pathogen contamination. The need to address the listing of …

Localization And Expression Of Gfrα2 Receptors In Neonatal And Adolescent Mouse Heart., Bryan Gunter

Undergraduate Honors Theses

Neurturin (NRTN), a member of the glial cell-line derived neurotrophic factor(GDNF) family, is required in the development of parasympathetic cholinergic neurons. It signals through binding to a glycosyl-phophatidyl inositol (GPI)-linked receptor, GDNF family receptor α2 (GFRα2), which couples to Ret tyrosine kinase. Studies of NRTN knockout mice have shown that NRTN is essential for normal cholinergic innervation of the heart, but the precise role of NRTN remains unknown. For NRTN to evoke a biological response, GFRα2 must be localized to the surface of target neurons. The aim of this study was to determine the expression and localization of GFRα2 at …

An Evaluation Of Coating Material Dependent Toxicity Of Silver Nanoparticles, Thilini Upekshika Silva

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) synthesized using numerous types of coating materials may exhibit different toxicity effects. The study evaluated coating material dependent toxicity by selecting 3 types of AgNP synthesis methods with different coating materials (citrate, polyvinyl pyrrolidone, and branched polyethyleneimine, coated AgNPs as citrate-AgNPs, PVP-AgNPs, and BPEI-AgNPs respectively). Two acute aquatic toxicity tests were performed; 48hr D. magna and MetPLATE E. coli toxicity tests. Significantly different toxicity effects were observed in D. magna test exhibiting lethal median concentrations (LC50) for citrate-AgNPs, PVP-AgNPs, and BPEI AgNPs respectively as, 2.7, 11.2, and 0.57μg/L. Median inhibitory concentrations (EC50) for MetPLATE tests were 1.27, …

Urinary Excretion Of (1-3)-Beta-D-Glucans., Debra K. Head

Electronic Theses and Dissertations

(1→3)-β-D-Glucans are carbohydrate polymers that are present in the cell wall of various fungi and bacteria; they are pathogen associated molecular patterns that circulate during infection and modulate immunity. Our laboratory has previously established the pharmacokinetics of intravenously and orally administered glucans; the present studies investigated the renal excretion of (1→3)-β-D-glucans following intravenous and oral administration. Three fluorescently-labeled glucans were administered to adult male rats in the presence or absence of toxic challenge. Urine specimens were collected and analyzed by fluorescence spectroscopy, size-exclusion chromatography and GPC/MALLS. 71 ± 3% of fluorescence remained in the >5K MWCO fraction; this fraction showed …

Previous Spatial Memory Training And Nicotine Administration Alleviates Cognitive Deficits Produced By Medial Frontal Cortex Lesions In Rats., Rachel L. Norris

Electronic Theses and Dissertations

Rats were administered nicotine (0.3 mg/kg) for 11 consecutive days before and after an electrolytic medial frontal cortex lesion. Behavioral testing was arranged so that the rats were tested on the RAM 1 day after drug administration followed by behavioral testing on the MWT 19 days after drug treatment, or tested on the MWT 1 day after drug administration followed by testing on the RAM4 days after drug treatment. Results of MWT testing showed that regardless of the drug/behavioral testing interval, lesioned rats given nicotine demonstrated enhancement relative to saline-treated animals. Results of RAM testing showed that nicotine improved performance …

Signaling Mechanisms For Muscarinic Receptor-Mediated Coronary Vasoconstriction In Isolated Rat Hearts, Yi Zhang

Electronic Theses and Dissertations

The signaling mechanisms for muscarinic receptor-mediated vasoconstriction in coronary resistance arteries were studied in KCl-arrested isolated rat hearts perfused at a constant flow rate. The cholinergic agonists acetylcholine and bethanechol were given by bolus injection or constant infusion. The coronary vascular resistance was monitored by measuring the changes in perfusion pressure. The selective muscarinic agonist bethanechol caused a similar vasoconstrictor response as ACh, but with less potency and efficacy. Bolus injection of bethanechol evoked a phasic vasoconstriction in a dose-dependent manner, while infusion of bethanechol evoked a tonic vasoconstriction without producing tachyphylaxis. Coronary vascular responses to bethanechol were further examined …

In Vitro Assessment Of The Toxicity Of Cocaine And Its Metabolites In The Human Umbilical Artery, Tessa L. Long

Electronic Theses and Dissertations

An in vitro model was used to assess the effect of cocaine and its metabolites on the umbilical artery. Objectives were to pharmacologically confirm the presence of adrenergic innervation using tyramine, evaluate the ability of cocaine, benzoylecgonine, norcocaine and cocaethylene to potentiate vasoconstriction by serotonin and norepinephrine, examine the ability of ketanserin to block the enhanced vasoconstriction produced by cocaine, and determine displacement of 3 H-ketanserin by serotonin, norepinephrine, tyramine and mianserin. The vasoconstrictive effect of tyramine (100 μM) was enhanced in the presence of cocaine by 257%. Vasoconstrictive effects of serotonin and norepinephrine were significantly enhanced by cocaine by …

Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu

Electronic Theses and Dissertations

$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by isoproterenol, AlF$\sb4\sp-$, forskolin, and PGE$\sb1$. Isometric recording was used to …