Pharmacology, Toxicology and Environmental Health Commons^™

Differing Functions Of Atr Kinase In Human Epidermal Keratinocytes Exposed To Ultraviolet B Radiation, Kavya Shaj

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Ataxia-telangiectasia and Rad-3 related (ATR) is a DNA damage response protein kinase that is upregulated in various cancer cell types and has key roles in cell cycle progression, DNA repair and apoptosis. Small molecule ATR kinase inhibitors are of importance as antineoplastic agents because they sensitize cancer cells to DNA damaging chemotherapy drugs. However, only a few studies have looked at the effects of ATR kinase inhibitors on non-replicating cells, which constitute the majority of cells in the human body and have suggested an opposite, pro-apoptotic role for ATR kinase signaling in non-replicating cells in comparison to a pro-survival function …

Zolpidem Facilitated Sexual Assaults: A Hair Method Validation, Danielle N. Chasworth

Student Theses

A liquid chromatography tandem mass spectrometry (LC-MSMS) method was developed and validated to detect for the presence of zolpidem in human hair samples. Zolpidem is a sedative hypnotic whose adverse effects make it a common drug found in drug facilitated crimes (DFC). It is important to be able to detect and quantitate the drug after a long period of time due to the victim’s delayed reporting of the crime. Hair’s long window of detection makes it a useful matrix for DFC investigations. The linear range of the assay was targeted at 2 pg/mg to 1,000 pg/mg and experiments designed to …

The Combined Effects Of Atrazine And Tetracycline On Primary Producers And Zooplankton In Freshwater Microcosms, Madison R. Kelly

Honors College Theses

Widespread use of agrochemicals such as herbicides and antibiotics increases their likelihood of entering aquatic systems in mixture. Despite different modes of action, atrazine (herbicide) and tetracycline (antibiotic) adversely affect non-target photosynthetic organisms, such algae and macrophytes, with the potential to reduce food availability to higher trophic levels. However, the effects of simultaneous exposure to both contaminants have yet to be determined. I hypothesized that a mixture of atrazine and tetracycline affects freshwater communities differently than each compound alone. A microcosm experiment was conducted to test effects of environmentally relevant concentrations of atrazine (1 μg L^-1) and tetracycline …

Maternal Engineered Nanomaterial Inhalation During Gestation Alters The Fetal Transcriptome, P.A. Stapleton, Q.A. Hathaway, C.E. Nichols, A.B. Abukabda, M.V. Pinti, D.L. Shepherd, C.R. Mcbride, J. Yi, V.C. Castranova, J.M Hollander, Timothy Robert Nurkiewicz

Faculty & Staff Scholarship

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. …

Impact Of Physico-Chemical Properties Of Manufactured Nanomaterials On Plant Uptake And Trophic Transfer, Jieran Li

Theses and Dissertations--Toxicology and Cancer Biology

Large quantities of manufactured nanomaterials (MNM) are released into the environment by human activity each year. The entry of MNM into the terrestrial food webs, which has the potential for far-reaching impacts, begins with the uptake by plant species from the soil. These processes can be affected by MNM physico-chemical properties such as size, chemical composition, surface charge, etc., of which our knowledge is still incomplete. To bridge some of the gaps in our understanding of these processes and, specifically, to determine whether the physico-chemical properties of the MNM are predictive of their behavior in terrestrial food chains, we conducted …

The Influence Of Physiological And Abiotic Factors On The Sensitivity Of The Sea Lamprey (Petromyzon Marinus) To The Lampricide 3-Trifluoromethyl-4-Nitrophenol (Tfm), Alexandra Muhametsafina

Theses and Dissertations (Comprehensive)

Invasive sea lamprey (Petromyzon marinus) in the Great Lakes are controlled using the pesticide (lampricide) 3-trifluoromethyl-4-nitrophenol (TFM), which is applied to nursery streams containing larval lamprey. The toxicity of TFM to lamprey is affected by various environmental and physiological factors, which can lead to residual lamprey that survive TFM treatment. The goal of this study was to investigate how abiotic (season and temperature) factors interacted with physiological parameters (whole body and tissue energy reserves) to influence TFM sensitivity in sea lamprey. Toxicity tests were conducted at different times of the year (spring, early and late summer, fall) and …

Protein Participants Of Cytosolic Internalization Of The Ouabain-Bound Na⁺/K⁺Atpase Receptor In Human B-3 Lens Epithelial Cells, Joshua Lysle Stricker

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The primary function of Na⁺/K⁺ATPase (NKA) discovered by Jens Christian Skou in 1958, through electrogenic exchange of 3 Na⁺ for 2 K⁺ ions (Robert L Post, 1958), is the homeostatic preservation of their electrochemical gradient across the plasma membrane (PM) of almost all species and their derived cell lines. Cardiotonic steroids (CTS), such as cardenolides or bufadienolides, are well established inhibitors of NKA. Fox glove plant extracts containing CTS, including digitalis, were first described by William Withering (1744-91) for their positive inotropic effect in heart failure patients. Later research identified the mechanism of their action through direct inhibition of NKA …

Forensic Markers Of Lampricide Toxicity In Oncorhynchsus Mykiss, Chris White

Theses and Dissertations (Comprehensive)

The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) has been used for decades to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, normally with little harm to other fish populations. However, due to the nature of lampricide treatments and the chemical properties of TFM, adverse effects to non-target fishes and non-target mortality occasionally occur. However, investigations of non-target mortality can be complex, particularly if fish deaths are not noticed immediately, due to decomposition of the carcasses. The objectives of this thesis were to expose rainbow trout (Oncorhynchsus mykiss) to TFM in order to: (i) identify forensic markers …

Mercury Concentrations In Snowy Plovers And Sediments Of Their Breeding Environments In The Southern Great Plains, Laura Duffie

Electronic Theses and Dissertations

Western snowy plovers (Charadrius nivosus) are philopatric shorebirds sporadically distributed during the breeding season at saline lake and alkali flat breeding environments of the Southern Great Plains (SGP) of Oklahoma, New Mexico, and Texas. The major conservation threat to interior snowy plovers breeding on the SGP derives from anthropogenic modification of breeding environments. The SGP is one of the most intensively cultivated regions in the world, and excessive groundwater mining and resulting deterioration of artesian spring flows reduces site quantity and quality critical for regional successful nesting. Most saline lakes now primarily receive freshwater inputs via irregular precipitation …

Poison In Pink, Sydney V. Cook

Graduate Student Theses, Dissertations, & Professional Papers

Humans slather, spray, mist, and cleanse their bodies with personal care products like lotion, hairspray, cologne, and shampoo every day. Our cupboards are stocked full of them, but few of us understand what is in those jars and bottles. We trust that if it’s on the shelf at the store, it’s safe. However, this is not always the case, and many personal care products contain chemicals that are harmful to human and environmental health.

My multi-disciplinary Environmental Studies thesis project combines evidenced-based research, interviews, nonfiction narrative, and science communication to create part of a book manuscript intended to educate general …

Molecular Measurement Of Toxicity In Fish; Case Examples And Policy Implications, Jessica A. Freedman

Senior Honors Projects

Stormwater and oil are common urban contaminants that can be harmful to fish species. One way of recognizing exposed and impaired fish is by monitoring gene expression and gene induction. This study focused on the identification and validation of reference genes for measuring contaminant-induced changes in gene expression due to urban influence. In this study, reference genes (which are genes used to normalize data and remain consistent in varying exposures regardless of organism and tissue type) were established. Six genes were identified as reference genes (ef1a, wdtc1, mtm1, spop, rxrba and tuba1) from a longer list of potential …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Consequences Of Developmental Lead (Pb2+) Exposure On Reproductive Strategies In Drosophila, Elizabeth Kathleen Peterson

Legacy Theses & Dissertations (2009 - 2024)

Anthropogenic lead (Pb) pollution is ubiquitous in the environment and a risk factor for both human and wildlife health. Pb exposure has the potential to alter reproductive strategies with respect to mate choice and reproductive output. This could be especially deleterious if these changes disrupt adaptive behavioral and reproductive life history strategies. Therefore, the overall aim of this body of work was to examine the consequences of developmental Pb exposure on reproductive strategies, using Drosophila melanogaster as a model system. In all experiments, D. melanogaster were reared from egg stage to adulthood in either control or leaded medium and were …

Development Of Culturing Methods For Native Mayfly Taxa For Use In Laboratory Toxicity Testing, Kevin Nicholas Rowsey

Theses, Dissertations and Capstones

Salinity is increasing in freshwaters throughout the world due to anthropogenic impacts with the implication of the increases to biological communities only now being realized. Declining mayfly populations in Appalachian streams have generated increased interest in elevated dissolved solids in that region and their effect on benthic macroinvertebrates, particularly the sensitive Ephemeroptera taxa. Field and laboratory evaluations have indicated high sensitivity of mayflies to elevated dissolved solids. The research described herein is part of an ongoing effort to provide opportunity for toxicity testing with native mayflies in the laboratory. A successful endeavor would establish mayfly sensitivity to total dissolved solids …

Behavior Of Gold Nanoparticles In Physiological Environment And The Role Of Agglomeration And Fractal Dimension, Rose Cooper

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The Present study was designed to examine the role of agglomeration, density and the resulting fractal dimension of nanomaterials in cell culture media. Studies were completed on the kinetics and the process of agglomeration, as well as how to calculate fractal dimensions. The correlation of such complex agglomeration patterns of nanomaterials in culture media, their translocation into cells, and toxic effects were observed. Our results showed that smaller primary particles agglomerated at an accelerated rate when compared to the larger primary particles. They also demonstrated increased cellular uptake, but exhibited lower fractal dimensions. The larger primary particle agglomerates displayed obvious …

Effects Of Nanosilver And Silver Nitrate Exposure On Fathead Minnows (Pimephales Promelas) And Zebrafish (Danio Rerio), Adam D. Hawkins

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) due to their unique antimicrobial properties are among the most widely utilized nanoparticle. Because of the nature of the products that utilize AgNPs, environmental release of AgNPs is inevitable. At greatest risk is the aquatic ecosystem due to known toxicity of the Ag + ion to aquatic organisms. Our goal was to use two fish models, fathead minnows (Pimephales promelas; FHMs) and zebrafish ( Danio rerio; ZFs), to study the effects of AgNPs on gill histopathology, Na+/K+-ATPase immunoreactivity, mucus production, bioaccumulation, particle uptake characterization, gill gene expression, and lethality in varying water parameters in comparison to the …

Enhanced Angiotensin Ii-Induced Cardiac And Aortic Remodeling In Ace2 Knockout Mice, Mahmoud Alghamri

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Activation of the renin angiotensin system (RAS) is a well-known driving force, governing the aggravation and progression of CVD and associated target organ damage. Angiotensin (Ang) converting enzyme 2 (ACE2), a new member within the RAS family, was first cloned from the ventricle of patient with heart failure. ACE2 was shown to be upregulated under pathological conditions. We hypothesize that loss of ACE2 negatively affects cardiac function and exacerbates hypertrophic cardiomyopathy and aortic remodeling in response to Ang II. Eight weeks old ACE2 knock out (KO) and wild type (WT) mice were infused with Ang II s.c. (1000 ng/kg/min for …

Causes, Extent, And Consequences Of Lead-Pellet Ingestion By Chukars (Alectoris Chukar) In Western Utah: Examining Habitat, Search Images, And Toxicology, R. Justin Bingham

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Lead ingestion adversely affects humans and over 130 species of wildlife. Wild chukars (Alectoris chukar) are documented to ingest lead, but the causes and consequences of this ingestion are poorly understood. The objectives of this research were to 1) examine the influence of habitat use, the hunting season, and seasonal climate on the extent and severity of lead ingestion by chukars in western Utah, 2) assess the effects of habitat use, feeding behaviors, and lead density on the causes of lead-pellet ingestion in captive and wild chukars, and 3) investigate the consequences of lead-pellet ingestion in captive chukars as a …

Response Of Monovalent Cation Transporters To Pro-Apoptotic Protein Kinase C Modulators In Human Lens Epithelial Cells, Michael Anthony Lepera

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Protein kinase inhibition by staurosporine causes apoptotic volume decrease involving potassium (K) channels in immortalized human B3 lens epithelial cells (LECs). Here, the effect of two pro-apoptotic protein kinase C (PKC) inhibitors [12-O-tetradecanoyl-phorbol-13-acetate (TPA) and chelerythrine (CET)] were studied on membrane K transport in a fetal human LEC line (FHL124) by western blotting, immunofluorescence, ion flux, ATP, apoptosis, and biotinylation assays. Long term TPA exposure (0-6 h) inhibited 75% of Na-K-2Cl cotransport (NKCC). In contrast, short term (0-20 min) exposure to 50 μM CET reduced Na/K pump and NKCC by >90% and >70%, respectively, without retrieval from the membrane into …

Differentiation Of Megakaryocytes/Platelets And Neurons From Human Endometrial Stromal Progenitor Cells, Jinju Wang

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Human endometrium is a high dynamic tissue that contains stem/progenitor cells. These endometrial stromal progenitor cells (hESCs) have been differentiated into a number of mesodermal lineages. There is limited information on differentiating hESCs into neurons, and no information on differentiating hESCs into megakaryocytes (MKs) and platelets (PLTs). The aim of this work was to investigate the possibility of differentiating hESCs into two distinct lineages: MKs, with subsequent PLT formation, and neurons.

We isolated hESCs from human endometrial tissue and cultured the cells for 4-6 passages. Before each differentiation experiment, the purity of hESCs was confirmed by flow cytometry analysis which …

Aluminium Phosphide Poisoning: A Case Report, Shela Akbar Ali Hirani, Arshalooz Rahman

School of Nursing & Midwifery

This paper reports the case of a family in which three children were presented at Emergency Room (ER) with poisoning after the use of a pesticide at home. Initially, the cases were managed as routine cases of organophosphorus poisoning; however, the death of two children made the health team members realise that the poison's effects were delayed and devastating. Later, the compound was identified as Aluminium Phosphide (ALP), and the life of the last surviving child in the family was saved.

Curated Exhibit: Absolute Poison, Laura J. Hall

Posters and Presentations

The Absolute Poison exhibit, curated by Laura J. Hall, MFA, delved into the fascinating and deadly world of poisons. From the ancient Sumerian goddess Gula, to Shakespeare’s Hamlet, and the infamous cyanide-laced Tylenol case of 1982, poisons have long held a place in our collective imagination. The exhibit explored the history, symbolism, and cultural impact of poisons, featuring materials such as Albrecht Dürer’s Adam and Eve with its skull and crossbones motif symbolizing death. On display from September 2010 to August 2011 at the UNM Domenici Center, the exhibit examined how poisons have shaped narratives of danger and mystery. September …

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 …

Toxin Producing Phytoplankton In Chesapeake Bay, Harold G. Marshall

Biological Sciences Faculty Publications

Three diatoms and nine dinoflagellates, known to be associated with toxin production, have been identified within Chesapeake Bay. Over the past several decades this number has increased to its present level so that they now represent approximately 1.7% the total number of phytoplankton species reported for the Bay.

Indomethacin Reduces Splenic Red Pulp Macrophage Populations In Female New Zealand White Rabbits, Thane S. Thurmond

Electronic Theses and Dissertations

In an effort to elucidate the mechanism by which indomethacin (IN) attenuates the stimulatory effect of estradiol (E$\sb2$) on rabbit splenic red pulp macrophages (RPM), thirty-nine female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX), OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX), SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2, OVX/25 mg E$\sb2$/IN at 0.1 and 5.0 mg/kg bw/day; intact Control. Quantitative changes in RPM population in response to the treatments were measured using a 0 to 4 histologic grading scale. Estradiol treatment resulted in increased RPM grade when compared …

The Effect Of Trimethyltin On The Cholinergic System Of The Rat Hippocampus, Richard L. Cannon

Electronic Theses and Dissertations

Trimethyltin (TMT) is a neurotoxin occurring in the environment. Exposure to (TMT) is known to destroy specific neuronal components of the hippocampus in the rat and to cause clinical symptoms in exposed humans, including mnemonic deficits, that indicate hippocampal involvement. In addition to hippocampal cell loss TMT causes significant increases in cholinergic markers such as acetylcholinesterase (AChE) stain density and choline acetyltransferase (ChAT) activity in the hippocampus of rats. However, despite these observations the effect of TMT on hippocampal cholinergic system has not been investigated in detail. The purpose of the present study was to elucidate more fully the consequences …

Nitrogen Dioxide Reaction With Proteins: Evidence For Peptide Bond Cleavage At Lysine Residues, Darryl B. Hood

Electronic Theses and Dissertations

Nitrogen dioxide (NO$\sb2$), an air pollutant produced by burning fossil fuels and a component of cigarette smoke, is thought to contribute to the pathogenesis of pulmonary diseases, such as emphysema. To gain information on the mechanism by which NO$\sb2$ damages the lung, in vitro exposures of $\alpha\sb1$-proteinase inhibitor ($\alpha\sb1$-PI), elastin, bovine serum albumin (BSA), human serum albumin (HSA) and synthetic poly-L-lysine were performed. A genetic deficiency of $\alpha\sb1$-PI predisposes humans to emphysema and NO$\sb2$ has been hypothesized to damage $\alpha\sb1$-PI, which would leave proteases such as human neutrophil elastase, (HNE) free to attack lung structural proteins. The ability of $\alpha\sb1$-PI …

Policy For Identifying And Assessing The Health Risks Of Toxic Substances, Maine Bureau Of Health

Maine Collection

Policy for Identifying and Assessing the Health Risks of Toxic Substances

by Norman T. Anderson, Environmental Toxicology Program, Division of Disease Control, Bureau of Health (February, 1988).

Contents: Section I: Introduction / Section II: Methods / Section III: Exposure Assessment / Section IV: Hazard Identification / Section V: Hazard Assessment / Section VI: Risk Characterization / List of Figures / List of Tables

Brisket Disease: Elemental And Oxalate Contents Of Cattle Forages On Two Utah Cattle Allotments, Raga Hafez I. Abaza

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

It was hypothesized that the hypocalcemia, hyperphosphoremia, hyperkalemia and the mild hypochromic microcytic anemia which existed in cattle afflicted with brisket disease could be due, at least in part, to nutritional disturbances. A chemical composition study was made of seven monocotyledonous plant species that comprise a major part of the diet and nine dicotyledonous plant species consumed by cattle and known or suspected of being poisonous. The plants analyzed were collected from two cattle grazing allotments, 7-mile and UM, in the Fishlake District, Fishlake National Forest, Utah, where brisket disease incidence is high. In each species the percentages on dry …

The Water Supply Of Minneapolis, James A. Dodge, C. L. Herrick, C. W. Hall

Journal of the Minnesota Academy of Science

No abstract provided.