Pharmacology, Toxicology and Environmental Health Commons^™

Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …

The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall

Electronic Theses and Dissertations

Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …

Wastewater-Informed Public Health Intervention Playbook

Sustain Magazine

As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

An Interdisciplinary Discussion On Climate Change, Aamira Shah, Jaley F. Adkins, Kelsey Littrell, Priyadarshini Chandrashekhar

The Cardinal Edge

No abstract provided.

Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun

Electronic Theses and Dissertations

Cannabidiol (CBD) is the most abundant non-psychotropic cannabinoid constituent of Cannabis sativa. CBD is potentially therapeutic for the eye through antioxidant, anti-inflammatory, and neuroprotective effects. However, the effect of CBD on intraocular pressure (IOP)- the major risk factor for glaucoma- is controversial and large variability exists in the literature. IOP is regulated through aqueous humor (AH) dynamics in trabecular meshwork (TM) tissues. Measurement of CBD in AH and correlation with effects on IOP would clarify what concentrations mediate changes to IOP. Therefore, the overall goal of this dissertation is to measure CBD in ocular tissues and correlate concentrations with …

Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan

Electronic Theses and Dissertations

Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt

Electronic Theses and Dissertations

Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …

Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams

Electronic Theses and Dissertations

Hexavalent Chromium [Cr(VI)] is a known human lung carcinogen and general health hazard. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the major theory in its carcinogenic mechanism. Homologous recombination (HR) repair is a DNA repair pathway that prevents CIN by repairing DNA double-strand breaks. RAD51, a key mediator protein of HR repair, along with the RAD51 paralogs (RAD51B, C, D, XRCC2, and 3) are required for HR repair. During HR, RAD51 loads and forms a helical nucleoprotein filament structure to promote DNA strand exchange and stimulate pairing activity of DNA. Cr(VI) exposures have been shown …

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

Surveillance Of Rnase P, Pmmov, And Crassphage In Wastewater As Indicators Of Human Fecal Concentration Across Urban Sewer Neighborhoods, Louisville, Kentucky, R. H. Holm, M. Nagarkar, R. A. Yeager, D. Talley, A. C. Chaney, J. P. Rai, A. Mukherjee, S. N. Rai, A. Bhatnagar, T. Smith

Faculty Scholarship

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase …