Pharmacology, Toxicology and Environmental Health Commons^™

Long-Distance Phasing Of A Tentative "Enhancer" Single-Nucleotide Polymorphism With Yp2d6 Star Allele Definitions, Erin C. Boone, Wendy Y. Wang, R Gaedigk, Mariana Cherner, Anick Bérard, J Steven Leeder, Neil A. Miller, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

Background: The CYP2D6 gene locus has been extensively studied over decades, yet a portion of variability in CYP2D6 activity cannot be explained by known sequence variations within the gene, copy number variation, or structural rearrangements. It was proposed that rs5758550, located 116 kb downstream of the CYP2D6 gene locus, increases gene expression and thus contributes to variability in CYP2D6 activity. This finding has, however, not been validated. The purpose of the study was to address a major technological barrier, i.e., experimentally linking rs5758550, also referred to as the "enhancer" single-nucleotide polymorphism (SNP), to CYP2D6 haplotypes >100 kb away. To overcome …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

The Influence Of Climate Change On Disease And Public Health, Natalie Petruzelli

The Review: A Journal of Undergraduate Student Research

This paper attempts to analyze the growing influence of climate change on the spread and development of diseases, as well as how this continues to affect public health and medical administrations around the world. The prevalence of airborne, waterborne, and vector-borne diseases have been found to be exacerbated as a result of climate change. In addition to this, the paper addresses the reemergence of eliminated diseases and ancient pathogens due to changing temperatures and weather patterns. Finally, the effect of these different conditions on national and international public health organizations and policies is analyzed, including projections on what can be …

Optimization Of Dna Extraction From Human Milk, Cassandra Z. Rutherford

Graduate Theses

Background: Techniques are emerging for determining the best and most cost-effective way to test for human milk adulteration. Currently, the literature is focused on the use of qPCR testing, a technique used to isolate and amplify pieces of DNA for analysis. However, no recommendation currently exists on the best DNA extraction kit to use to achieve optimal DNA yield or purity from human milk samples for downstream qPCR use. Thus, the objective of this study is to assess and compare two DNA extraction kits for use with human milk samples for future DNA-based analysis in the testing for bovine milk …

Per- And Polyfluoroalkyl Substances In Consumable Fish & Surface Waters Near Sites Using Aqueous Film-Forming Foams: Potential Risks, Suggested Regulatory Standards And Policy Approaches For Massachusetts, Tachalla Gibeau

Sustainability and Social Justice

Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants of concern with potential for adverse effects on both human and environmental health. Hence, long-chain PFAS compounds used in legacy aqueous film-forming foams (AFFFs) are being phased out, resulting in the stockpiling of them at various commercial installations. PFAS contaminated runoff from these facilities has the potential to contaminate nearby surface water bodies and the fish inhabiting them. An analytical approach was used to identify surface water bodies in Massachusetts that are habitats for fish susceptible to PFAS contamination and where said fish are also popularly consumed by locals – thereby representing …

Cluster Determinant 44 (Cd44) Receptor And Gout: Mechanistic Role In Pathogenesis And Therapeutic Targets, Emira Bousoik

Pharmaceutical Sciences (PhD) Dissertations

Gout is considered one of the most common forms of arthritis. It is characterized by sudden, severe attacks of pain, redness, and swelling in the joints. Management of acute gout attacks remains suboptimal, and hospitalizations due to poorly controlled flares have significantly increased over the past two decades. Colchicine is considered one of the first-line treatments for the relief of the symptoms associated with gout attacks. However, the use of colchicine for gout therapy has limitations due to the severe adverse effects, including fatalities. Acute gout is caused by deposition of monosodium urate (MSU) crystals in peripheral joints and surrounding …

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 …

Hexadecane Petroleum, And Biofuel Utilization In Marine Bacteria Isolated From Ballast Tanks, Alex Yashchenko

Graduate Theses

This study characterized the growth of bacteria isolated from ballast tank fluids in hexadecane, petroleum, plant, and algae-derived fuels. The study was performed to explore the capacity of ballast tank isolates to survive and grow within fuels that may be stored within ballast tanks. Results of the hexadecane analysis indicated that most isolates had higher viable cell counts in media supplemented with hexadecane. Members of Alteromonas, Pseudoalteromonas, and a single Brevundimonas species had viable cell counts that were one or several orders ofmagnitude greater than that of controls. Results offuel analysis indicated higher viable cell counts in pure JP-5 and …

Analysis Of Cannabinoids In Serum By Gc-Ms/Ms, Christie Cannarozzi

Student Theses

Due to recent changes in federal and state legislations, the availability and consumption of cannabis products have increased in the United States. The expanded use of recreational and medicinal cannabis products increases the importance of implementing sensitive and selective instrumental methods in toxicological laboratories, as legal implications may arise in forensic cases, such as driving under the influence of drugs (DUID). The purpose of this study was to perform a cross-validation for the quantitative analysis of cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, cannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol) in serum by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GCTQ). This method was fully …

California Drought Projections Based On Climate Change Models’ Effects On Water Availability, Lauren Lynam

Student Scholar Symposium Abstracts and Posters

Future streamflow in California, as predicted by eight climate projections models, and their effects on water availability are discussed in this paper. The unimpaired projected streamflow for eleven California rivers, collected from Cal-Adapt Streamflow are compared with their unimpaired historical flows (1950-2015) using eight climate model projections (2020-2099) developed by Scripps Institution of Oceanography’s Routed Streamflow Projections; Warm Dry RCP 4.5, Average RCP 4.5, Cool Wet RCP 4.5, Other RCP 4.5, Warm Dry RCP 8.5, Average RCP 8.5, Cool Wet RCP 8.5, Other RCP 8.5. Projected drought quantities, durations, and intensities are statistically tested against historical values to determine significance …

Phospholipid Remodeling Via Exogenous Polyunsaturated Fatty Acid Uptake Modulates Stress Resistance In Vibrio Cholerae, William Strike

Honors Theses

Antibiotic-resistant pathogens represent an escalating threat to public health worldwide, substantially increasing the burden of healthcare and community-acquired infections. Several factors contribute to the emergence and spread of this threat, including but not limited to improper antibiotic use and prescriptions in health-care settings and the community, increasing global travel and migration from countries that have higher levels of antibiotic-resistant pathogens, and a lack of new antibiotics under development. According to the World Health Organization, rising rates of resistance among Gram-negative bacteria (such as Vibrio cholerae) are of particular concern. These bacteria have evolved a number of endogenous membrane remodeling strategies …

Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle

Electronic Theses and Dissertations

BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …

Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson

Electronic Theses and Dissertations

Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …

The Role Of Slc7a11 In Controlling Extracellular And Intracellular Redox Environments Of Lung Fibroblasts - Potential Targets For Intervention In Aging And Idiopathic Pulmonary Fibrosis., Yuxuan Zheng

Electronic Theses and Dissertations

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (E_h) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular E_h(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system X_c^-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 …

The Cardiovascular Effects Of Tobacco Product-Derived Aldehydes: Contribution Of Transient Receptor Potential Ankyrin-1., Lexiao Jin

Electronic Theses and Dissertations

Cardiovascular diseases (CVD) are the leading cause of death in most countries and are significant health and financial burden worldwide. Smoking contributes to more than 480,000 premature deaths annually -- accounting for one of every five deaths in the United States each year. Numerous studies have shown that smoking increases the risk of factors including endothelial dysfunction, thrombosis, and atherosclerosis, which may lead to an incidence of myocardial infarction, coronary artery disease, and stroke. Electronic cigarettes (e-cigarettes) are a new kind of tobacco product, and some studies show that e-cigarettes also could induce CVD since both e-cigarettes and conventional tobacco …

Identification And Quantification Of Classic, Prescription, And Synthetic Opioids In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc/Ms/Ms), Natalia A. Platosz

Student Theses

The current use and misuse of synthetic and prescription opioids in the US has reached epidemic status. According to the US Department of Health and Human Services, every day more than 130 people in the US die after overdosing on opioids, and 2.1 million had an opioid use disorder in 2016. Hair is becoming an alternative matrix of increasing interest in forensic toxicology to investigate drug use and abuse patterns due to its long window of detection. The focus of this project was to develop and validate a method that simultaneously detects and quantifies 27 classic, prescription and synthetic opioids …

In Vitro Bioactivities Of Single Or Combined Extracts From Three Selected Asian Vegetables, Mahmud Norfaizah

Student Works (2020-2029)

Three underutilized folklore oriental-based vegetables Acalypha indica (AI), Centella asiatica (CA), and Sesbania grandiflora (SG) have been investigated for pharmacological activities relevant to wound healing process and synergistic actions. Single and combination of aqueous (A) and methanol (M) extracts of the three vegetables namely AI-A, CA-A, SG-A, AI-M, CA-M, SG-M, AI-A+CA-A, AI-A+SG-A, CA-A+SG-A, AI-M+CA-M, AI-M+SG-M, and CA-M+SG-M were assessed for stimulation of wound closure by normal human dermal fibroblast (NHDF) cells, antioxidant, protection against hydrogen peroxide (H2O2), stimulation of nitric oxide (NO) from RAW264.7 macrophages and antimicrobial activities. The combined vegetable extracts AI-A+CA-A (90.76%) showed the highest percentage of wound …

Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

Synthesis, Cytotoxicity And Apoptosis Studies On Nickel And Zinc Derivatives Of Testosterone-N4-Substituted-Thiosemicarbazones, Mok Piew Heng

Student Works (2020-2029)

The side effects of cisplatin such as toxicities are mainly due to the lack of selectivity of this chemotherapeutic agent. In order to increase the selectivity of an anticancer agent, hormone molecule that targets a specific receptor may be utilized. This research aimed to prepare cytotoxic Schiff base compounds (and their nickel and zinc complexes) with testosterone and derivatives of thiosemicarbazide, which are potentially selective towards cancerous cells. Three Schiff base ligands (TM, TF, and TP) were made from the conjugation of testosterone with three derivatives of thiosemicarbazide (N4= methyl, fluorophenyl, and ethylphenyl) and their respective nickel (NM, NF, and …

Baclofen-Induced Changes In The Resting Brain Modulate Smoking Cue Reactivity: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study In Cigarette Smokers, Ariel Ketcherside, Kanchana Jagannathan, Sudipto Dolui, Nathan Hager, Nathaniel Spilka, Chaela Nutor, Hengyi Rao, Teresa Franklin, Reagan Wetherill

Psychology Faculty Publications

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure.

Methods: In this longitudinal, …

Impact Of Slco1b1 Genetic Variation On Rosuvastatin Systemic Exposure In Pediatric Hypercholesterolemia., Jonathan B. Wagner, Susan M. Abdel-Rahman, Andrea Gaedigk, R Gaedigk, Geetha Raghuveer, Vincent S. Staggs, Leon Van Haandel, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC

The Relationship Between Tree Canopy And Social Capital On Physical Activity In Unlv Students, Melissa Bartshe

UNLV Theses, Dissertations, Professional Papers, and Capstones

Despite the numerous health benefits, rates of physical activity are low, especially among the college student population. Neighborhood tree canopy is one aspect of the built environment that has been shown to positively impact physical activity. Social capital has also been correlated with higher rates of physical activity. The sprawling urban design and arid desert climate of Las Vegas pose unique challenges to both tree canopy and social capital. Additionally, the relationship between tree canopy, social capital, and physical activity is understudied in the college student population. The purpose of this study was to assess the relationship of tree canopy …

Investigating The Effects Of Temperature On Lesser Celandine, Regina Bellian

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

This paper explores invasive species Ficaria verna (Lesser celandine) and the effects of temperature on its growth. Trials were completed with two treatments, 13OC cold temperature and 20OC ambient temperature. Germinated bulbils of Lesser celandine were planted on February 15, 2017 and placed in their respective growing chambers. The plants were watered weekly and monitored for growth until harvest on March 29, 2017. Upon harvest, the plants’ height, largest leaf diameter and biomass were measured after extraction from soil and the removal of the leftover soil debris. Average height was found to be 11.66cm for the cold treatment and 5.14cm …

Understanding The Toxicity Of Single Hydrocarbons, Oil, And Dispersed Oil: A Species Sensitivity Assessment For Five Atlantic Coral Species, Nicholas R. Turner

HCNSO Student Theses and Dissertations

Coral reefs are keystone coastal ecosystems that are at risk of exposure to petroleum hydrocarbons from a range of sources, including oil spill incidents and chronic runoff, and are usually one of the highest valued natural resources for protection in Net Environmental Benefit Analysis (NEBA)/Spill Impact Mitigation Assessment (SIMA) of response methods and environmental damage. Previous research evaluating hydrocarbon impacts to corals has resulted in no clear characterization of sensitivity, as work has generally focused on higher-level effects, compounded by significant variability in experimental methodology. This represents an important knowledge gap in oil spill preparedness and response as it relates …

Antinéoplasiques En Milieu Hospitalier : Étude Pilote Sur L’Exposition Potentielle Du Personnel D’Hygiène Et De Salubrité, France Labrèche, Capucine Ouellet, Brigitte Roberge, Ahmed Yennek, Nicolas Caron

Rapports de recherche scientifique

Certains antinéoplasiques (ANP), utilisés pour le traitement du cancer, sont eux-mêmes classés cancérogènes et peuvent avoir d’autres effets toxiques chez des travailleurs qui les manipulent. L’incidence du cancer et le nombre de personnes vivant avec le cancer ne cessent d’augmenter, ce qui permet d’envisager une augmentation des quantités d’ANP utilisées et du nombre de travailleurs potentiellement exposés. Une étude menée par l’Unité de recherche en pratique pharmaceutique du Centre hospitalier universitaire Ste-Justine a montré que plusieurs prélèvements effectués sur des surfaces touchées par le personnel infirmier et par celui de la pharmacie montraient des résidus d’ANP. Il n’y a cependant …

The Influence Of Acidification And Copper Exposure On Copper Accumulation And Anti-Oxidant Enzyme Responses In The Pond Snail, Lymnaea Stagnalis, Gretchen K. Bielmyer-Fraser, Francis Alip, Ruth Adeyemi, Nolan Carney, Fasinia Santiago, Kyla Siemen, Kiley Donaghy

Georgia Journal of Science

Atmospheric carbon dioxide is rising at an accelerated rated due to increased anthropogenic activities. Metals have also been a noted problem; however, little research has addressed combined exposure of both pollutants to sensitive, calcifying organisms in freshwater habitats. This study examined copper accumulation (over 7 d) and activity of the antioxidant enzymes, catalase and glutathione peroxidase (over 2 d), in the freshwater common pond snail, Lymnaea stagnalis, after exposure to ambient and increased (2000 µatm) CO₂ and copper (control, 5, and 20 µg/L). Results demonstrated increased copper accumulation in soft tissue of snails exposed to copper; however, exposure to …

Assessment Of The Toxicological Effects Of Cnt-Ab In Mice Followed By Microwave Hyperthermia 14 Days Post Treatment., Andrew C. Mixson

Honors College Theses

Serious side effects and treatment resistance are the main impediments to successful cancer therapy. A variety of nanoparticles have been used for localized, site-specific treatment that prevent or circumvent these impediments. Microwaves alone have been previously used for thermal ablation of various tumors, setting precedence for their successful use in live organisms. In cell culture studies, it has been observed that multiwall carbon nanotubes (MWCNTs) instantly and efficiently absorb microwaves, causing hyperthermia of cells in direct contact with them with unnoticed harm to other cells. It is hypothesized that a treatment can be developed based on a safe microwave heating …

Investigating The Toxicology Of Intramuscular Injected Cnt-Ab In Mice Followed By Microwave Hyperthermia., Conner Clark

Honors College Theses

The advent of carbon nanotubes (CNTs) has led to a wide range of research in various fields including cancer therapy for targeting specific localized and site-specific treatment. Carbon nanotubes bound to tumor specific antibodies (Ab) offers specific treatment for cancer cells without affecting surrounding tissue. This treatment makes use of infrared absorptive properties of nanotubes to incinerate both the nanotube and its associated tumor in vivo. We seek to affirm the initial results of CNT in cancer therapy by investigating the toxicological effect in mice injected with CNT-Ab followed by microwave hypothermia. After 1-week post-injection, mice were sacrificed followed …