Pharmacology, Toxicology and Environmental Health Commons^™

A Quantitative Analysis Of The Effects Of Urbanization, Mesophication And Prescribed Burns On Oak Woodlands In The Chicago Metropolitan Area, Chad Populorum

Celebration of Learning

Urban expansion has had devastating impacts on forest ecosystems, especially within the past century. Human attempts to dominate nature have diminished natural disturbance regimes, which have maintained the biodiversity and historic composition of these ecosystems. Fires have been a prominent force in maintaining the structure of oak, hickory and other heliophytic (sun loving and fire-adapted) forest systems. Human induced fire suppression has led to mesophication across North America. Mesophication is the transition from drier conditions with open canopies to wetter conditions with closed canopies. These new conditions decrease the survival rates of these important species and begin to favor mesophytic …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Examining The Roles Of Genetic And Environmental Factors In Drosophila Melanogaster Hematopoiesis And Innate Immune System, Minkyung Lee

Student Theses and Dissertations

Nearly 24 million people are affected by autoimmune diseases in the United States. Main causes of autoimmune diseases have been attributed to genetic predisposition and environmental exposure to chemicals such as hormones and pesticides. Due to the large population that are affected by autoimmune diseases, it is critical to understand the mechanisms behind them. In this study, we sought to explore both genetic and environmental factors that affect hematopoiesis, or the formation of specific blood cells, and immune system in Drosophila melanogaster. As Drosophila melanogaster have conserved pathways of hematopoiesis as humans, they were used as the model organism …

Systematic Pan-Cancer Analysis Of Somatic Allele Frequency., Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in …

Combined Mtor And Mek Inhibition Is An Effective Therapy In A Novel Mouse Model For Angiosarcoma, Michelle L. Chadwick, Adam Lane, Dana Thomas, Amanda R. Smith, Angela R. White, Dominique Davidson, Benjamin Feng, Elisa Boscolo, Yi Zheng, Denise M. Adams, Anita Gupta, Andre Veillette, Lionel M L Chow

Peer Reviewed Articles

Angiosarcoma is an aggressive malignancy of vascular origin that occurs de novo or in the context of previous cancer therapy. Despite multi-modal aggressive treatment including surgical resection, chemotherapy, and radiation, five-year overall survival remains poor at 35%. Due to its rarity, little is known about its molecular pathology and clinical trials have been extremely difficult to conduct. Development of animal models for rare diseases like angiosarcoma is critical to improve our understanding of tumorigenesis and to test novel treatment regimens. A genetically engineered mouse model for angiosarcoma was generated by conditional deletion of Trp53, Pten, and Ptpn12 in …

An Examination Of The Community And Environmental Impact Of A Las Vegas Convention Food Rescue Program, Samantha H. To

UNLV Theses, Dissertations, Professional Papers, and Capstones

Food insecurity affects millions of Americans each year, inflicting negative consequences on the physical and mental health outcomes at all ages. Concurrently, millions of tons of leftover edible foods are sent to landfill each year. Not only does this pose a question of ethics, but increasingly harms the environment by misusing resources and increasing the release of

greenhouse gases.

Food rescue advisory meetings highlighted the need for more focused research to be conducted that assessed the impacts of donating rescued convention food on local environmental and community health. A mixed-method approach was used to detail the food rescue process between …

Investigating The Role Of Genomic Variation In Susceptibility To Environmental Chemicals Across Populations, Lindsay Adrian Holden

Dissertations and Theses

No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)--large (>1 Kb) duplications or deletions across the genome--on the toxicant-susceptibility phenotype.

Herein copy number variants were characterized across three commonly used laboratory strains of zebrafish (Danio rerio) and mRNA expression phenotypes were identified in the same strains. It was found that …

Science, Advocacy, Policy, Planning: Tools For Advancing Transportation Equity, Garrett S. Mcallister

Graduate Student Portfolios, Professional Papers, and Capstone Projects

The theme of this portfolio is how different tools and approaches can be used for advancing transportation equity. Broadly defined, transportation equity is about fairness in transportation. There are a number of ways this fairness can be assessed. The most common way to assess transportation equity is by looking at the fairness of outcomes, distributed geographically, socially, or even by mode of transportation. Equity can also be defined by the fairness of processes. The first half of the portfolio illustrates some of the problems with the current transportation system and how it is unhealthy (Piece 1) and unjust (Piece 2). …

Melatonin-Micronutrients Osteopenia Treatment Study (Mots): A Translational Study Assessing The Effects Of Melatonin, Strontium Citrate, Vitamin D3 And Vitamin K2 On Bone Density, Bone Turnover Markers And Health-Related Quality Of Life In Postmenopausal Osteopenic Women Following A One-Year Double-Blind Randomized Placebo-Controlled Trial And On Osteoblast-Osteoclast Co-Cultures, Sifat Maria

Electronic Theses and Dissertations

Objective: The purpose of this study was to assess if a novel combination of melatonin and three other natural bone-aiding micronutrients: strontium citrate, vitamins D₃ and K₂ (MSDK) could improve bone health by modulating the activity of osteoblasts and osteoclasts in favor of balanced bone remodeling and by improving the overall health-related quality of life in postmenopausal osteopenic women.

Methods: The Melatonin-micronutrients Osteopenia Treatment Study (MOTS) is a translational research study that used both clinical and in vitro approaches to assess the efficacy of MSDK on bone health in women and to identify potential mechanisms for its effects. …

Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack

Pharmacology and Physiology Faculty Publications

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat …

Cloning And Characterization Of A Pyrethroid Pesticide Decomposing Esterase Gene, Est3385, From Rhodopseudomonas Palustris Psb-S, Xiangwen Luo, Deyong Zhang, Xuguo Zhou, Jiao Du, Songbai Zhang, Yong Liu

Entomology Faculty Publications

Full length open reading frame of pyrethroid detoxification gene, Est3385, contains 963 nucleotides. This gene was identified and cloned based on the genome sequence of Rhodopseudomonas palustris PSB-S available at the GneBank. The predicted amino acid sequence of Est3385 shared moderate identities (30–46%) with the known homologous esterases. Phylogenetic analysis revealed that Est3385 was a member in the esterase family I. Recombinant Est3385 was heterologous expressed in E. coli, purified and characterized for its substrate specificity, kinetics and stability under various conditions. The optimal temperature and pH for Est3385 were 35 °C and 6.0, respectively. This enzyme could …

Levels Of Heavy Metals In Drinking Water, Cosmetics And Fruit Juices From Selected Areas In Dar Es Salaam, Tanzania, John Am Mahugija

Tanzania Journal of Science

Heavy metals were determined in samples of drinking water, cosmetics (nail polish, lip glosses and hair dye) and fresh fruit juices in Dar es Salaam. The samples were analyzed using Atomic Absorption Spectrometry (AAS) after digestion with concentrated acids, filtration and dilution. Lead, zinc and iron were detected in the water samples and the concentration ranges were below detection limit (BDL) to 0.114, 0.01 to 1.47 and 0.027 to 0.39 mg/L, respectively, whereas cadmium was not detected. The concentrations of lead in 70.83% of the samples exceeded the WHO permissible limit, implying that the water in most of the areas …

Heavy Metals And Cyanide Distribution In The Villages Surrounding Buzwagi Gold Mine In Tanzania, Edwin Sifuel Gomezulu, Agnes Mwakaje, Jamidu, H.Y. Katima

Tanzania Journal of Science

The study aimed at assessing the levels of heavy metals and cyanide in water and sediments in villages surrounding Buzwagi gold mine, both during wet and dry seasons.  A total of 56 samples of water (28 from each season) and 44 samples of sediments (22 from each season) were collected from the wells in the area and were analyzed for total cyanide and heavy metals.  The total cyanide was analyzed spectrophotometrically whilst the heavy metals were analyzed by an Inductively Coupled Plasma (ICP). The Pb and Fe levels in water were found to exceed 10 µg/L and 2000 µg/L respectively, …

Status Of Selected Heavy Metals Dispersion From Top Soil In And Around Automobile Workshop Areas In Zanzibar Municipality, Tanzania, John Am Mahugija, Hawa M Sheikh

Tanzania Journal of Science

The distributions of selected heavy metals in top soil in areas with and without automobile workshops in Zanzibar municipality were investigated. Sampling was done during dry and rainy seasons. The samples were digested with aqua regia (HCl and HNO3, 3:1) and analysed by Atomic Absorption Spectrophotometry. The concentrations of zinc, copper and lead in the samples ranged 0.27–419.2, 0.10–167 and 0.02–271 mg/kg dry weight, respectively. The concentrations were higher in areas with automobile workshops than those without. The concentrations of the heavy metals were highest at point sources and decreased with increase in distance during the dry season. The concentrations …

Assessment Of Heavy Metal And Radioactivity Levels In Spinach (Spinacia Oleracea) Grown At Bahi Wetlands In Dodoma Region, Najat K. Mohammed, Boniface Haule

Tanzania Journal of Science

This study reports on the levels of heavy metals and radionuclides in Spinach (Spinacia oleracea) grown in Bahi wetlands in Dodoma Region. The farm soil in Bahi wetland has been reported to contain elevated concentrations of 238U, 232Th and 40K due to the existence of shallow uranium deposit in the area. In this study, spinach (Spinacia oleracea) grown in three zones of Bahi district were analyzed for heavy metals and radioactivity associated with the uranium deposit in the area. The concentrations of elements were determined by Energy Dispersive X-ray Analysis (EDXRF) of Tanzania Atomic Energy Commission, Arusha. The activities of …

Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells, Ryker Penn

Theses & Dissertations

The purpose of this study was to investigate the development of chemotherapeutic resistance to paclitaxel in ovarian cancer cells after treatment with drugs that are substrates for P-glycoprotein (PGP). A core concept of this experiment was to identify if PGP substrate drugs could also act as PGP inducers after prolonged treatment in SKOV-3 ovarian cancer cells. In order to test this, SKOV-3 cells were exposed to either fexofenadine, a PGP substrate used as an antihistamine, or the chemotherapeutic drug vinblastine. After 42 days of drug treatment, ABCB1 gene expression was measured by qRT-PCR. Analysis of ABCB1 expression in treated cells …

Amylin And Diabetic Cardiomyopathy – Amylin-Induced Sarcolemmal Ca2+ Leak Is Independent Of Diabetic Remodeling Of Myocardium, Miao Liu, Amanda Hoskins, Nirmal Verma, Donald M. Bers, Sanda Despa, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca²⁺ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the …

Enhancement Of Nafld Risk By Vinyl Chloride : Role Of Adipose Tissue In A Mouse Model., Brenna R. Kaelin

College of Arts & Sciences Senior Theses

Background: Vinyl chloride (VC), an environmental contaminant, is directly hepatotoxic at high concentrations. However, our group has recently demonstrated that VC and the VC metabolite chloroethanol (CE), at concentrations that are not considered hepatotoxic, enhanced liver injury caused by high-fat diet (HFD). These data therefore suggest that the impact of VC exposure on hepatic tissue may be enhanced with underlying metabolic syndrome and/or liver injury. It is known that there is an axis between adipose and hepatic tissue in non-alcoholic fatty liver disease (NAFLD), with the former impacting pathology in the hepatic tissue via release of pro-inflammatory cytokines and/or lipolysis. …

Lead, Copper, And Iron In University Tap Water, Alison Mclendon

Honors Theses

This study observed concentrations of lead, copper, and iron in university tap water over an eight-week span during and between the summer and fall semesters. First draw and 30s flush samples were taken after overnight stagnation from the Honor House, College Hall, J. B. George Building, and International Center bathrooms and analyzed with an inductively-coupled plasma mass spectrometer (ICPMS). There was no obvious correlation between time in the semester and metal concentrations. Relative iron levels rose and fell at the same time in all buildings, but there was little correlation between buildings for lead and copper concentrations. The Honor House …

A Model To Study The Effects Of Whole Life Chronic Exposure To Arsenic Or Cadmium On The Development Of Adult Metabolic Syndrome : Initial Characterization Of Hepatic Changes., Jamie L. Young

Electronic Theses and Dissertations

Metabolic syndrome (MetS) is a group of diseases affecting < 30% of adults. Although obesity is a major risk for the development of MetS, it does not account for all cases, suggesting contribution of other risk factors. We hypothesized that early life exposure to arsenic (As) or cadmium (Cd) may represent such a risk. The purpose of this study was to characterize a model to discern the effects of early life exposures to Cd and As on high fat diet (HFD)-induced MetS. Adult C57BL/6J mice were exposed to control or metals containing drinking water. Pregnant dams and offspring were continuously exposed to the same toxicants as their parents. At weaning, offspring were fed LFD or HFD and sacrificed 10 or 24 weeks later. Metal exposure caused time- and sex-dependent alterations in HFD-induced variables of liver damage. The initial results suggest that these toxicants enhanced obesity-induced liver injury.

Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael Mccarthy

Dissertations and Theses (Open Access)

RAS, one of the most well characterized membrane-associated small GTPases, is a notorious oncogene with >15% of all tumors harboring RAS mutations. When RAS is mutated it becomes constitutively active sending cell growth, survival and proliferation into overdrive, which subsequently leads to cancer. Although, RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules …

The Effects Of Polychlorinated Biphenyls Exposure On Non-Alcoholic Fatty Liver Disease : Role Of Aryl Hydrocarbon Receptor., Hongxue Shi

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are detectable in serum of 100% of adults in US, and has been associated with fatty liver disease in epidemiological studies. PCBs are classified as either dioxin-like (DL) or non-dioxin-like (NDL) PCB based on their ability to activate the aryl hydrocarbon receptor (AhR). We used exposures that reflect human bioaccumulation patterns, which resembles Aroclor 1260 with a low level of the DL-PCB, PCB 126. Our aim was to determine if this exposure will activate the human and mouse AhR and examine if receptor activation influences these steatotic responses due to PCB exposures. DL-PCBs exposure-induced AhR activation in …

Vinyl Chloride Enhances Diet-Induced Liver Injury Via Metabolic Dyshomeostasis : Critical Role Of Mitochondria., Anna L. Lang

Electronic Theses and Dissertations

Background. Vinyl chloride (VC) is an environmental toxicant and has been shown to be directly hepatotoxic at high exposures. However, recent studies suggest low-level toxicant exposure can cause subtle changes to the liver. Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the United States, it is important to determine the impact of low-level toxicant exposure on the progression of underlying liver injury when combined with other factors. Therefore, the overarching goal of this dissertation was to develop a model of VC co-exposure with high-fat diet (HFD) and to determine the mechanisms by which VC contributes to the …

Protocol Development In The Or: Lessons Learned, Megan Sims

Doctor of Nursing Practice Projects

The management of pain in those undergoing a laparoscopic cholecystectomy is complex and challenging. There have been advances in the understanding of the physiology of pain and a wide variety of treatment options are now available. Establishing a preventative multi-modal protocol with different types of pain medications that work on a variety of receptors along the pain pathway is imperative. Through an exhaustive literature review, a preventative multi-modal approach was established and introduced at a small hospital in Central Illinois available for all laparoscopic cholecystectomy patients undergoing surgery over a 10 week implementation period. There was only one completed case …

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

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 …

Effects Of Copper Sulfate On Mortality Rates Of Daphnia Magna, Grace Vilem

Honors Projects

Many reservoirs used for drinking water end up growing algae that needs to be removed. Copper sulfate (CuSO₄) can be used to reduce the growth of algae, however this chemical has been shown to have negative effects on invertebrates living in aquatic environment. This experiment exposed Daphnia magna, an aquatic zooplankton, to various concentrations of CuSO₄ for 48 hours to determine an LC50 value. Six sets of data were collected and averaged, finding an LC50 value of 36 ug/L. Further testing is needed to determine effects of CuSO₄ on fecundity between generations of Daphnia, as …

Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart

University Scholar Projects

Bacterial and fungal strains are growing resistance to antibiotics and antifungal agents at an alarming rate. According to the Centers for Disease Control and Prevention, over two million people in the United States in 2016 were diagnosed with an infection resistant to antibiotics. As such, there has been increased interest in natural products as sources of novel compounds that are essential to the development of new drugs and treatment methods. Within the environment, there are various host-microbe symbioses, one of which is the Trachymyrmex septentrionalis leaf-cutter ant community. The microbes in symbioses like the T. septentrionalis community are hypothesized to …

Comparison Of Habitat And Water Quality In The Blue River's South And Salem Forks In Southern Indiana To Support Watershed Management, Erin Crone

Undergraduate Theses

A stream’s habitat and water quality are heavily influenced by land use and geology within its watershed. Pollutants and sediment loading from watershed drainage can make streams less habitable for certain species, reducing biodiversity. Watershed management strategies, such as the promotion of best management practices in agriculture, can help to combat stream degradation from watershed inputs. The upper Blue River in southern Indiana is a biodiversity hotspot but is experiencing degradation and biodiversity loss due to watershed inputs. This is exemplified by the disappearance of the eastern hellbender salamander, an indicator species, from this area. Fine sediment loading is particularly …

Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart

Honors Scholar Theses

Bacterial and fungal strains are growing resistance to antibiotics and antifungal agents at an alarming rate. According to the Centers for Disease Control and Prevention, over two million people in the United States in 2016 were diagnosed with an infection resistant to antibiotics. As such, there has been increased interest in natural products as sources of novel compounds that are essential to the development of new drugs and treatment methods. Within the environment, there are various host-microbe symbioses, one of which is the Trachymyrmex septentrionalis leaf-cutter ant community. The microbes in symbioses like the T. septentrionalis community are hypothesized to …