Medical Toxicology Commons^™

The Intersection Of Herbicide Policy, Exposure, And Health At The University Of Connecticut, Katherine Hayward

Honors Scholar Theses

Pesticides play an extremely complicated role in our everyday lives. From the water you use to make your coffee, to the breastmilk your neighbor provides for their child, to the lake your dog swims in, chemical pesticides or their byproducts have been found in nearly every corner of our lives. The chemicals used in synthetic herbicides, a subcategory of pesticides, have far reaching negative impacts on human health, biodiversity, and water quality. Despite there being numerous published studies on the relationships between pesticide exposures and health, there is still ongoing discord and controversy surrounding their role in our lives. After …

Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker

Doctoral Dissertations

Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …

Developmental Behavioral Alterations Following Lead (Pb) Exposure In The Zebrafish Model System, Jenny Chen

The Journal of Purdue Undergraduate Research

No abstract provided.

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 …

Evaluation Of Biochemical And Pathological Parameters At Different Doses Of Cisplatin In Experimental Animal Model: Toxicological Study On An Antineoplastic Drug, Farhana Sultana, Muhammed Mohibul Islam, Mohammad Nurul Amin, Nusrat Jahan, Asma Kabir, Talha Bin Emran, Bibek Chandra Sutradhar, Sujan Banik

Makara Journal of Health Research

Background: This study aimed to assess the effect of cisplatin-induced toxicities on biochemical and pathological parameters such as body, liver, and kidney weights, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and blood cells (RBCs and WBCs) in white Swiss albino mice.

Methods: Cisplatin’s potential toxic effects on body, liver, and kidney weights were evaluated using standard laboratory methods. Blood biochemical levels such as BUN, creatinine, and ALT levels were determined by an auto-hemolyzer using commercial diagnostic kits. Blood cells (RBCs and WBCs) were counted under a microscope by a hemocytometer.

Results: Cisplatin’s potential toxic effects on …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Formation, Antimicrobial Activity, And Biomedical Performance Of Plant-Based Nanoparticles: A Review, Ngoan Thi Thao Nguyen, Luan Minh Nguyen, Thuy Thi Thanh Nguyen, Thuong Thi Nguyen, Duyen Thi Cam Nguyen, Thuan Van Tran

Journal Articles

Because many engineered nanoparticles are toxic, there is a need for methods to fabricate safe nanoparticles such as plant-based nanoparticles. Indeed, plant extracts contain flavonoids, amino acids, proteins, polysaccharides, enzymes, polyphenols, steroids, and reducing sugars that facilitate the reduction, formation, and stabilization of nanoparticles. Moreover, synthesizing nanoparticles from plant extracts is fast, safe, and cost-effective because it does not consume much energy, and non-toxic derivatives are generated. These nanoparticles have diverse and unique properties of interest for applications in many fields. Here, we review the synthesis of metal/metal oxide nanoparticles with plant extracts. These nanoparticles display antibacterial, antifungal, anticancer, and …

Occurrence, Toxicity And Adsorptive Removal Of The Chloramphenicol Antibiotic In Water: A Review, Luan Minh Nguyen, Ngoan Thi Thao Nguyen, Thuy Thi Thanh Nguyen, Thuong Thi Nguyen, Duyen Thi Cam Nguyen, Thuan Van Tran

Journal Articles

Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, …

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …

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. …

An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron

Theses and Dissertations--Toxicology and Cancer Biology

The reversible oxidation of cysteine by reactive oxygen species (ROS) is both a mechanism for cellular protein signaling as well as a cause of cellular injury and death through the generation of oxidative stress. The study of cysteine oxidation is complicated by the methodology currently available to isolate and enrich oxidized-cysteine containing proteins. We sought to simplify this process by reducing the time needed to process samples and reducing sample loss and contamination risk.

We accomplished this by eliminating precipitation steps needed for the protocol by (a) introducing an in-solution NEM-quenching step prior to reduction and (b) replacing soluble dithiothreitol …

Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo

Gyongyi Szabo

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, have …

Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson

Publications and Research

The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …

Identification Of Activities Involved In Cag/Ctg Repeat Instability, Nelson Lap Shun Chan

University of Kentucky Doctoral Dissertations

CAG/CTG repeat instability is associated with at least 14 neurological disorders, including Huntington’s disease and Myotonic dystrophy type 1. In vitro and in vivo studies have showed that CAG/CTG repeats form a stable hairpin that is believed to be the intermediate for repeat expansion and contraction.

Addition of extra DNA is essential for repeat expansion, so DNA synthesis is one of the keys for repeat expansion. In vivo studies reveal that 3’ CTG slippage with subsequent hairpin formation (henceforth called the 3’ CTG slippage hairpin) occurs during DNA synthesis. It is proposed that hairpin tolerance machinery is activated because prolonged …

Mycotoxins In Grains – Causes, Prevention And Control, Hester F. Vismer

INTSORMIL Presentations

Discusses mycotoxins, their effect on grain, mitigation considerations, and resulting human toxicology.

Do Recent Data From The Seychelles Islands Alter The Conclusions Of The Nrc Report On The Toxicological Effects Of Methylmercury?, Alan H. Stern, Joseph L. Jacobson, Louise Ryan, Thomas A. Burke

Wayne State University Associated BioMed Central Scholarship

Abstract

In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to …

Review Of: Lewis' Dictionary Of Toxicology (Robert A. Lewis, Ed.; Lewis Publishers 1998), Dana E. Evans

RISK: Health, Safety & Environment (1990-2002)

Review of the book: Lewis' Dictionary of Toxicology (Robert A. Lewis, ed.; Lewis Publishers 1998). About the author, acknowledgments, alphabetical listing of terms defined. ISBN 1-56670-223-2; [1127 pp. $84.95. Hardbound. 2000 Corporate Blvd. N.W., Boca Raton, FL 33431.]

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