Pharmacology, Toxicology and Environmental Health Commons^™

Integration Of Biological Effects, Fish Histopathology And Contaminant Measurements For The Assessment Of Fish Health: A Pilot Application In Irish Marine Waters, Michelle Giltrap, Jenny Ronan, John Bignell, Brett Lyons, Evelyn Collins, Heather Rochford, Brendan Mchugh, Evin Mcgovern, Lorraine Bull, James Wilson

Articles

This study investigates the use of a weight of evidence (WOE) approach to evaluate fish health status and biological effects (BEs) of contaminants for assessment of ecosystem health and discusses its potential application in support of the Marine Strategy Framework Directive (MSFD). External fish disease, liver histopathology and several BEs of contaminant exposure including 7-ethoxy resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites, vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two flatfish species from four locations in Ireland. Contaminant levels in fish were generally low with PCBs in fish liver below OSPAR environmental assessment criteria (EAC). There were …

Mercury Bioaccumulation In Three Popular Subsistence And Recreational Estuarine Fishes From Southeastern U.S.A., Taylor Cannon

Theses and Dissertations

A rising concern in recent years has occurred over the presence of methylmercury in seafood, particularly fishes, and its impact on human health. However, fish also provide many health benefits, including improved cardiovascular health and neurodevelopment. Because fishes are the main source of methylmercury exposure to humans, and are such an integral part of the human diet, understanding the risks versus the benefits of fish consumption is imperative in allowing the public to make healthy, educated choices. One way that state and federal governments attempt to do this is through issuing fish consumption advisories. Unfortunately, these advisories do not always …

A Study Of Hepatic Purinergic Receptor X7 Molecular Mechanisms In Ectopic Intestinal Inflammation In Environmental Nafld, Varun Chandrashekaran

Theses and Dissertations

Due to the increased consumption of unhealthy foods rich in sugar and fat along with a highly sedentary lifestyle the prevalence of obesity has steadily increased in the United States and the rest of the world. In America about one third of the adult population is obese putting them at a greater risk for diseases such as cancer, cardio-vascular disorders, inflammation and metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD can be classified into two major categories non-alcoholic fatty liver (NAFL) and non-alcoholic steato-hepatitis depending on the extent of damage which ranges from simple fat accumulation …

Chronic Effects Of Lead Exposure On Atherinops Affinis (Topsmelt): Influence Of Salinity And Organism Age, Erik Joseph Reynolds

Master's Theses

Pb (lead) appears in the environment as a consequence of both natural and anthropogenic processes. Mining, smelting, coal burning, lead acid batteries, and cement manufacturing substantially release Pb into aquatic environments. The goal of this study was to determine the influence of salinity and organism age on chronic toxicity of Pb to Atherinops affinis (topsmelt) in support of development of a species sensitivity distribution (SSD). Species sensitivity distributions assist in ecological risk assessments and establishing quality criteria for contaminants. Three chronic exposure studies were conducted for 28 days in a water flow-through testing system. Survival, standard length, dry weight, and …

Three Dimensional Homology Modeling Of Organic Cation Transporter 3 To Identify Structural Elements Mediating Transporter-Substrate Interactions, Hebing Liu

Theses and Dissertations

Organic cation transporters (OCTs) play a pivotal role in the absorption, tissue distribution, and excretion of a diverse array of substances, and currently the nature of the biochemical interactions between substrate and OCTs are unknown. Therefore, identifying which amino acid residues are critical for OCT-substrate interactions is of central importance to understanding and predicting interactions between drugs and OCTs. A three-dimensional (3-D) homology model of human OCT3 was generated using the crystal structure of a high affinity phosphate transporter from Piriformospora indica (PiPT) as template, and putative binding pocket for the prototypical hOCT3 ligand 1-methyl-4-phenylpyridinium (MPP⁺) was identified …

Alpha6 Beta2 Subunit Containing Nicotinic Acetylcholine Receptor Contributions To Abuse-Related Effects Of Nicotine And Alcohol, Alexandra M. Stafford

Theses and Dissertations

Pharmacotherapies for tobacco and alcohol cessation are only modestly successful, so it is important to better understand mechanisms underlying their use and abuse. The overarching goal of this research is to assess a6b2 subunit containing nicotinic acetylcholine receptor (a6b2*nAChR; *denotes possible assembly with other subunits) contributions to abuse-related effects of nicotine and alcohol. In the absence of a6b2*nAChR-selective agonists, a6b2*nAChR gain-of-function (a6L9’S) mice provide a tool for selective activation of a6b2*nAChRs. Using the a6L9’S mice together with nicotine doses sub-threshold for stimulation of native nAChRs, these studies tested the hypothesis that activation of a6b2*nAChRs is sufficient to promote neurochemical and …

Ethanol Reversal Of Oxycodone Tolerances, Joanna C. Jacob

Theses and Dissertations

Oxycodone is a semi-synthetic opioid originally developed as a safer alternative to morphine. It is commonly prescribed for its pain-relieving effects, but has recently been implicated as a major underlying cause of the current opioid epidemic due to its clinical limitations that include tolerance, dependence and a high abuse liability. Simultaneous consumption of opioids and ethanol has been shown to increase the risk of overdose and death from opioids in opioid-tolerant individuals. We hypothesized that ethanol reversed opioid tolerance and previous studies showed that ethanol reversed morphine tolerance. This dissertation investigated whether ethanol reversed tolerance to other opioids in mice, …

From Disposable Culture To Disposable People: Teaching About The Unintended Consequences Of Plastics, Sasha Adkins

Antioch University Dissertations & Theses

Plastics, the epitome of disposable culture, pose both a toxicological and a spiritual problem. This dissertation examines plastics at a molecular level using the discourse of endocrine disruption, and at a sociological level using the discourses of eco-theology and environmental justice. Adding to the literature on the adsorption of toxicants to plastic marine debris, I demonstrate that certain types of plastic -- those containing mercaptans, such as styrene butadiene block copolymer -- efficiently concentrate methyl mercury from seawater. Further, samples of polycarbonate contributed mercury to seawater. I propose the term plastic-mediated magnification to describe the phenomenon that plastics, along with …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …

Contributing Factors To Child Stunting In Guatemala: A Systems Analysis Focused On Enteric Disease Transmission And Mycotoxin Exposure, Lee Emerson Voth-Gaeddert

Doctoral Dissertations

"Child stunting -- low height-for-age -- is a United Nation's indicator for chronic malnutrition that has been linked to both acute and chronic health problems. Data from Guatemala suggests for children under five years of age, 49% are classified as stunted. This dissertation tests the following hypotheses, among children in Guatemala 1) environmental enteric dysfunction (EED) is correlated with height-for-age, 2) aflatoxin B (AFB) exposure is correlated with height-for-age, and 3) AFB exposure is correlated with EED. A network analysis was conducted on data from the US Agency for International Development (USAID) collected in 2012 to identify trends in a …

Review: Epidemiological Evidence Of Groundwater Contribution To Global Enteric Disease, 1948–2015, Heather Murphy, Morgan Prioleau, Mark Borchardt, Paul Hynds

Articles

Globally, approximately 2.2 billion people rely on groundwater for daily consumption. It is widely accepted that groundwater is more pristine than surface water but while this assumption is frequently the case, groundwater is not ubiquitously free of contaminants; accordingly, this presumption can result in an unfounded and potentially hazardous sense of security among owners, operators and users. The current paper presents a review of published literature providing epidemiological evidence of the contribution of groundwater to global human enteric infection. An emphasis is placed on enteric pathogens transmitted via the faecal-oral route, and specifically those associated with acute gastrointestinal illness (AGI). …

Folate Receptor Alpha Targeted Delivery And Characterization Of Polyethyleneimine-Graft-Polycaprolactone-Block-Poly(Ethylene Glycol) Containing Sirna Micelleplexes, Steven Jones

Wayne State University Dissertations

This dissertation focuses on the ability of polyethyleneimine-graft-polycaprolactone-block-poly(ethylene glycol) (PEI-g-PCL-b-PEG-Fol) folate decorated tri-block copolymers ability to deliver a targeted dose of siRNA. The micelleplexes that are formed upon electrostatic interaction with siRNA are used to deliver siRNA in a targeted manner to ovarian cancer cells that over-express Folate Receptor-α (FRα). Each conjugate showed suitable sizes below 200 nm with full siRNA condensation ability. Furthermore, flow cytometry and western blot analysis demonstrated that the best FRα targeted polymer was able to effectively deliver siRNA which resulted in protein knockdown of Toll-like receptor 4 (TLR4). Consequently, TLR4 knock down within SKOV-3 cells …

Approach Towards The Development Of Novel Disease Modifying Therapeutics For Parkinson's Disease, Dan Luo

Wayne State University Dissertations

Parkinson’s disease (PD) is an age-related neurodegenerative disease, which is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of intraneuronal proteinaceous deposits named Lewy bodies (LBs) or Lewy neurites (LNs). A broad spectrum of motor and non-motor symptoms has been observed in PD, with bradykinesia, resting tremor, rigidity, and postural instability as its key clinical features. Although the etiology of PD is still not well-understood, multiple pathological factors including oxidative stress, mitochondrial dysfunction, α-synuclein (αSN) protein aggregation, as well as genetic and environmental aspects are strongly implicated in the disease …

Valproic Acid: A Neural Outgrowth Model For The Autism Spectrum Disorder, Hannah M. Bergan

Dissertations and Theses @ UNI

Autism spectrum disorder has been dramatically on the rise since the early 1990s, with one in forty-five children being diagnosed in 2014. It is known that contributing factors to autism spectrum disorder may have genetic and epigenetic origins, as well as environmental triggers. What is still unclear, however, is the impact of teratogenic drugs, consumed by the mother, have on a developing fetus in utero. How can they lead to the child developing autistic-like behaviors? The current study documents the effects of one teratogenic drug Valproic acid, a known histone deacetylase inhibitor. It establishes the role it plays on developing …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Knockout Of Sphingosine Kinase 1 Attenuates Renal Interstitial Fibrosis In Unilateral Ureteral Obstruction (Uuo) Model, Xiwen Zhang

Theses and Dissertations

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and an important signaling molecule that plays a significant role in fibrosis. S1P synthesis is catalyzed by sphingosine kinases (SphKs), which phosphorylate sphingosine into S1P. The present study tested the hypothesis that SphK1-S1P signaling pathway participates in the kidney damage in unilateral ureteral obstruction (UUO) model. Wild type and SphK1 knockout mice were subjected to UUO for 7 days or 14 days and then four groups of kidneys were collected: wild type control group (WT-C), wild type UUO group (WT-UUO), SphK1-/- control group (KO-C) and SphK1-/- UUO group (KO-UUO). The mRNA level of …

Investigating The Sources And Dynamics Of Escherichia Coli In A Missouri Ozarks Watershed, Kaleb Bassett

Masters Theses

"Escherichia coli, an intestinal bacterium, can serve as an indication of the presence of pathogenic microorganisms in water systems used by humans for recreation, agriculture, or drinking water. Many aquatic systems in the United States exceed the E. coli standard, set by the Environmental Protection Agency, for safe drinking water and recreational use. During 2016, a water sampling program was established in the Mill Creek watershed, a rural watershed located near the city of Newburg in Phelps County, Missouri. Water samples were collected before, during, and after storms throughout the year to examine the relationship between E. coli …

Roles Of Community Pharmacists In Improving Oral Health Awareness In Plateau State, Northern Nigeria, Olaniyi O. Taiwo

Walden Dissertations and Doctoral Studies

There is poor oral health awareness in Nigeria. This is mainly attributed to limited access to correct information on oral health as well as a lack of oral health care providers. The impact of the poor oral health awareness is worse in Northern Nigeria due to the uneven distribution of oral health care workers and training facilities. The purpose of this cross-sectional study was to describe the roles of community pharmacists (CPs) in Plateau State, Nigeria as sources of oral health information. Theoretical framework for this study was the theory of planned behavior (TPB). Background knowledge and practices of oral …

The Effects Of Metolachlor Exposure On The Thp-1 Alveolar Monocyte And Macrophage Function, Jared S. Parmater

Dissertations and Theses @ UNI

The use of additive chemicals such as pesticides has become commonplace in agricultural practices in the Midwestern United States. Metolachlor, an herbicide used to regulate broadleaf weeds in corn and soybeans, is a widely utilized pesticide in the United States. This herbicide is effective in killing broadleaf weeds but has detrimental effects and consequences in non-target organisms. It is a frequent contaminant of ground water due to post application run-off and the air.

Inhalation constitutes one route of exposure, in addition to ingestion, adding to the list of unintended targets and consequences. This route of exposure creates an argument for …

The Highs And Lows Of Making A Bucket List - Quantifying Potential Mosquito Breeding Habitats In Metropolitan Backyards, Ram Sharan Lamichhane, Peter J. Neville, Jacques Oosthuizen, Kim Clark, Maria Fatouros, Shelley Beatty

Research outputs 2014 to 2021

While the development of land for residential housing along the Swan and Canning Rivers in Perth, WA, Australia has reduced natural mosquito breeding sites, the role of backyard container breeding remains a relatively unknown factor. Local Governments responsible for these areas focus management and control efforts on low lying, tidally driven mosquito habitats to control Aedes vigilax (Skuse) and Aedes camptorhynchus (Thomson) mosquitoes in an effort to reduce both the nuisance and disease risk to residents. In spite of their efforts, Local Governments continue to receive complaints regarding mosquito nuisance, even when environmental conditions do not favor hatching and development …

Exploring Knowledge, Beliefs And Practices Of Radon Gas Exposure Among Public Health Workers, Paschal Nwako

Seton Hall University Dissertations and Theses (ETDs)

Radon gas exposure is the highest cause of lung cancer among people that never smoked in the United States. People exposed to elevated levels of radon had a higher risk of developing lung cancer. Achieving the long term goal of the Indoor Radon Abatement Act (IRAA) of 1988 require a combined efforts of government agencies. Public health workers are change agents and their role in protecting and improving the health of their communities are well documented. This study created and utilized a multi question survey, the Public Health Workers Radon Assessment Instrument (PHWRAI) to explore knowledge, beliefs, personal and professional …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

An Assessment Of Data Related To Inspections Of Risk Factors For Public Swimming Pools, Shanita Shack, Maurice Redmond, R. Christopher Rustin

Environmental Health Sciences: Faculty Publications

Background: The Georgia Department of Public Health (DPH) is mandated to ensure that public swimming pools are safe for those who use them. This mandate is carried out by the DPH and local environmental health professionals through regulations and inspections. In 2015, legislation was introduced proposing to reduce the authority of the DPH to inspect certain pool types (apartments, subdivision, condominiums) and thus reduce regulatory protections in place for swimmers. To ensure that the DPH had current information on the risks associated with pools, the EH team, with assistance from a graduate student, analyzed inspection data to evaluate risk factors …

A Preliminary Examination Of Elevated Blood Lead Levels In A Rural Georgia County, R. Christopher Rustin, Yu Sun, Chris Calhoun, Christy Kuriatnyk

Environmental Health Sciences: Faculty Publications

Background: Rural areas are often viewed as lower risk for lead poisoning and toxic exposures seriously impacting development of the brain and central nervous system; this report examines the prevalence of elevated blood lead levels for children <6 years of age in rural Ben Hill County, GA.

Methods: Lead surveillance data from the Georgia Department of Public Health (DPH) were analyzed using SAS®v-9.3 to calculate the prevalence of elevated blood lead levels (≥5ug/dL) among those children in Ben Hill County who had been tested for lead; the results were compared to Georgia and national data.

Results: A preliminary analysis of 2010-2015 screening data for Ben Hill County indicates that 8.73% …

Vectored Intracerebral Immunization With The Anti-Tau Monoclonal Antibody Phf1 Markedly Reduces Tau Pathology In Mutant Tau Transgenic Mice, Wencheng Liu, Lingzhi Zhao, Brittany Blackman, Mayur Parmar, Man Ying Wong, Thomas Woo, Fangmin Yu, Maria J. Chiuchiolo, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal, Steven M. Paul

HPD Articles

UNLABELLED: Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic …

Sneaky Salt Contributes To High Blood Pressure, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

The Relationship Between Lead In Groundwater And Elementary School Students' Academic Performance In Missouri, Lynnette Xiangling Li

Graduate Theses/Dissertations

Lead exposure can come from various sources, e.g., lead mines, industrial areas, and lead based paint. Missouri has more than 4,128 lead mines. Lead is a neurotoxin. The objectives of the study were to investigate i) the spatial relationship between lead mines and lead distribution in groundwater, ii) the statistical impact of lead in groundwater on students' Missouri Assessment Program (MAP) scores, and iii) the geographic variations of lead's impact on students' MAP scores. Geographic Information Science spatial analysis tools were used to analyze the concentration of lead in groundwater within school districts in Missouri. Regression analysis was utilized to …

Rapamycin Increases Length And Mechanosensory Function Of Primary Cilia In Renal Eptihelial And Vascular Endothelial Cells, Rinzhin T. Sherpa, Kimberly F. Atkinson, Viviana P. Ferreira, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia arebiophysically-sensitive organelles responsible for sensing fluid-flow and transducing this stimulus into intracellular responses. Previous studies have shown that the primary cilia mediate flow-induced calcium influx, and sensitivity of cilia function to flow is correlated to cilia length. Cells with abnormal cilia length or function can lead to a host of diseases that are collectively termed as ciliopathies. Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Here we look …