Toxicology Commons^™

Developmental Ethanol Exposure Causes Central Nervous System Dysfunction And May Slow The Aging Process In A Drosophila Model Of Fetal Alcohol Spectrum Disorder, Khaoula Belhorma, Nahed Darwish, Elizabeth Benn-Hirsch, Annalisa Duenas, Hillary Gates, Navneet Sanghera, Jodie Wu, Rachael L. French

Faculty Research, Scholarly, and Creative Activity

Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, …

Stress, Alcohol Use, And Punitive Parenting During The Covid-19 Pandemic, Jennifer Price Wolf, Bridget Freisthler, Caileigh Chadwick

Faculty Research, Scholarly, and Creative Activity

Background
Emerging research suggests that parents are experiencing heightened stress during the COVID-19 pandemic. Parental stress is a risk factor for harsh or punitive parenting, and this association may be exacerbated by the use of alcohol.
Objective
We examine whether parental stress is associated with use of punitive parenting, as well as whether this association is modified by drinking pattern.
Participants & setting
We used advertisements and word-of-mouth to recruit 342 parents living in Central Ohio during the initial stay-at-home order for COVID-19.
Methods
We used geographic ecological momentary assessment (gEMA) to measure parental stress and punitive parenting during three …

David S. Miller: Scientist, Mentor, Friend--A Tribute And Thank You, Björn Bauer, J. Larry Renfro, Karl J. Karnaky, Rosalinde Masereeuw, Gert Fricker, Ron E. Cannon, Anika M. S. Hartz

Pharmaceutical Sciences Faculty Publications

David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood-CSF and blood-brain barriers, from fish, amphibians and birds to …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Association Of Long-Term Consumption Of Repeatedly Heated Mix Vegetable Oils In Different Doses And Hepatic Toxicity Through Fat Accumulation, Gul Ambreen, Afshan Siddiq, Kashif Hussain

Department of Biological & Biomedical Sciences

Background: Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with …

Natural Sources And Bioactivities Of 2,4-Di-Tert-Butylphenol And Its Analogs, Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su, Shiyou Li

NCPC Publications and Patents

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, …

Postmortem Toxicology Of New Synthetic Opiods, Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper

Publications and Research

One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies. This article reviews the current knowledge of postmortem toxicology of synthetic opioids and the …

The Effects Of Heart Medication On The Heart Rates Of Drosophila Melanogaster, Felicia A. Baer

Honors Program Projects

Background

Current animal models of human cardiac disease may be similar in anatomy and physiology but are often expensive and tedious to work with. The current need is for a model organism that is more efficient to work with in the lab but that still provides an accurate model of human cardiac disease. Drosophila melanogaster (D. mel) is such a candidate. While 74% of the genes coding for protein are conserved between D. mel and human hearts, it is unknown if cardiac medication used in humans, such as atropine and propranolol hydrochloride, similarly affect heart rate. I hypothesized that …

Rxtx And Micromedex, Shawn Hendrikx, Kelly Hatch

Western Libraries Publications

No abstract provided.

Evaluation Of Perfluorohexane Sulfonate (Pfhxs) Exposure To Risk Of Liver Disease Caused By High Fat Fructose Diet, Dwight C. Anderson

Senior Honors Projects

Perfluorohexane sulfonate (PFHxS) has been used in products as surfactants[AS1] . These products include fluoropolymers and as protective and water-resistant coatings to different materials such as carpets, paper, and textiles. Also, evidence of PFHxS exposure has been reported in firefighters who use certain film forming foams. Current investigations have shown widespread exposure to PFHxS in the environment, specifically in drinking water. There has also been evidence of PFHxS accumulation in humans, with a half-life lasting several years.

PFHxS is one of several perfluoronated alkyl substances (PFAS). Other PFASs are considered to be hepatotoxic in rodents and potentially in humans. Studies …

Immunotherapy Against Drugs Of Abuse, Gianna Raimondi (Class Of 2017)

Writing Across the Curriculum

Current treatments for drug addiction involve classical pharmacological therapy, involving the use of competitive or noncompetitive agonists (full, partial, or inverse) and antagonists. Drugs of abuse enter the brain after crossing the blood-brain barrier rapidly and binding to the proper receptor(s). They are able to do so because they are small and lipid soluble, and produce reinforcing effects by increasing levels of dopamine in brain areas associated with reward. This occurs in specific systems associated with addiction. In the mesolimbic system, neuron cell bodies originate in the ventral tegmental area (VTA) and project to the nucleus accumbens (NAc), amygdala, hippocampus, …

The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach

Internal Medicine Faculty Publications

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These …

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, …

Importance Of Clinical Toxicology Teaching And Its Impact In Improving, Nadeem Ullah Khan, Jabeen Fayyaz, Uzma R. Khan, Asher Feroze

Department of Emergency Medicine

Objective: To assess the impact of a one-day clinical toxicology workshop in improving knowledge.
Methods: A one-day clinical toxicology workshop was conducted as a pre-conference workshop of the Annual Emergency Medicine Conference at the Aga Khan University Hospital, Karachi, in April 2012. The course was composed of poisoning-related common clinical scenarios. The pre-test and post-test understanding was used to assess the impact of the course in improving knowledge. The participants also evaluated the workshop as a whole thorough written evaluation forms. SPSS 19 was ued for statistical analysis of the data.
Result: There were 22 participants in the course. The …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

Study Of Charge-Dependent Transport And Toxicity Of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos And Single Nanoparticle Plasmonic Spectroscopy, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs^+ζ), negatively (Ag-CALNNS NPs^−2ζ), and more negatively charged NPs (Ag-CALNNE NPs^−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as …

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.

Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi

Department for Educational Development

No abstract provided.