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Emergency Toxicology

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https://www.readbyqxmd.com/read/28922086/assessment-of-ah-receptor-transcriptional-activity-mediated-by-halogenated-dibenzo-p-dioxins-and-dibenzofurans-pxdd-fs-in-human-and-mouse-cell-systems
#1
Kari L Organtini, Troy D Hubbard, Gary H Perdew, Frank L Dorman
Polybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health is incomplete. Here we utilized human and mouse hepatocellular carcinoma cell lines to examine the ability of differentially halogenated PXDD/F congeners to induce aryl hydrocarbon receptor (AHR)-mediated transcriptional activity. Dose-response experiments in reporter cell lines identified varied potencies among differentially halogenated PXDD/F isomers by comparison of EC50 values relative to the prototypical AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...
September 18, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28915823/patients-with-acute-poisoning-presenting-to-an-urban-emergency-department-of-a-tertiary-hospital-in-tanzania
#2
Ghaniya S Mbarouk, Hendry R Sawe, Juma A Mfinanga, John Stein, Shankar Levin, Victor Mwafongo, Michael S Runyon, Teri A Reynolds, Kent R Olson
BACKGROUND: Poisoning is a major public health concern in sub-Saharan Africa, affecting patients of all age groups. Poisoned patients often present to the emergency department (ED) and prompt evaluation and appropriate management are imperative to ensure optimal outcomes. Unfortunately, little is known about the specific presentations of poisoned patients in East Africa. We describe the clinical and epidemiological features of patients presenting to the Muhimbili National Hospital (MNH) ED with suspected toxicological syndromes...
September 16, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28913001/methamphetamine-use-and-emergency-department-utilization-20-years-later
#3
John R Richards, Sheiva Hamidi, Connor D Grant, Colin G Wang, Nabil Tabish, Samuel D Turnipseed, Robert W Derlet
BACKGROUND: Methamphetamine (MAP) users present to the emergency department (ED) for myriad reasons, including trauma, chest pain, and psychosis. The purpose of this study is to determine how their prevalence, demographics, and resource utilization have changed. METHODS: Retrospective review of MAP patients over 3 months in 2016. Demographics, mode of arrival, presenting complaints, disposition, and concomitant cocaine/ethanol use were compared to a 1996 study at the same ED...
2017: Journal of Addiction
https://www.readbyqxmd.com/read/28911631/new-psychoactive-substances-of-natural-origin-a%C3%A2-brief-review
#4
REVIEW
Ling-Yi Feng, Altansuvd Battulga, Eunyoung Han, Heesun Chung, Jih-Heng Li
Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28903775/nonclinical-and-clinical-pharmacology-evidence-for-cardiovascular-safety-of-saxagliptin
#5
REVIEW
Pia S Pollack, Kristina D Chadwick, David M Smith, Martin Billger, Boaz Hirshberg, Nayyar Iqbal, David W Boulton
BACKGROUND: In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin...
September 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28894772/epidemiologic-features-and-outcomes-of-caustic-ingestions-a-10-year-cross-sectional-study
#6
Athena Alipour Faz, Fahimeh Arsan, Hassan Peyvandi, Mahbobeh Oroei, Omid Shafagh, Maryam Peyvandi, Maryam Yousefi
INTRODUCTION: Caustic ingestions are among the most prevalent causes of toxic exposure. The present 10-year survey aimed to evaluate the epidemiologic features and outcomes of caustic ingestion cases presenting to emergency department. METHODS: This is a retrospective cross-sectional study on patients who were admitted to a referral toxicology center during 2004 to 2014, following caustic ingestion. Baseline characteristics, presenting chief complaint, severity of mucosal injury, complications, imaging and laboratory findings as well as outcomes (need for ICU admission, need for surgery, mortality) were recorded, reviewing patients' medical profile, and analyzed using SPSS 22...
2017: Emergency (Tehran, Iran)
https://www.readbyqxmd.com/read/28893587/current-nonclinical-testing-paradigm-enables-safe-entry-to-first-in-human-clinical-trials-the-iq-consortium-nonclinical-to-clinical-translational-database
#7
Thomas M Monticello, Thomas W Jones, Donna M Dambach, David M Potter, Michael W Bolt, Maggie Liu, Douglas A Keller, Timothy K Hart, Vivek J Kadambi
The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis...
September 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28889270/uranium-and-the-central-nervous-system-what-should-we-learn-from-recent-new-tools-and-findings
#8
Céline Dinocourt
Increasing industrial and military use of uranium has led to environmental pollution, which may result in uranium reaching the brain and causing cerebral dysfunction. A recent literature review has discussed data published over the last 10 years on uranium and its effects on brain function (Dinocourt C, Legrand M, Dublineau I, et al., Toxicology 337:58-71, 2015). New models of uranium exposure during neonatal brain development and the emergence of new technologies (omics and epigenetics) are of value in identifying new specific targets of uranium...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28889247/guidelines-for-autopsy-investigation-of-sudden-cardiac-death-2017-update-from-the-association-for-european-cardiovascular-pathology
#9
Cristina Basso, Beatriz Aguilera, Jytte Banner, Stephan Cohle, Giulia d'Amati, Rosa Henriques de Gouveia, Cira di Gioia, Aurelie Fabre, Patrick J Gallagher, Ornella Leone, Joaquin Lucena, Lubov Mitrofanova, Pilar Molina, Sarah Parsons, Stefania Rizzo, Mary N Sheppard, Maria Paz Suárez Mier, S Kim Suvarna, Gaetano Thiene, Allard van der Wal, Aryan Vink, Katarzyna Michaud
Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task...
September 9, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28889024/the-toxicology-of-mercury-current-research-and-emerging-trends
#10
REVIEW
Geir Bjørklund, Maryam Dadar, Joachim Mutter, Jan Aaseth
Mercury (Hg) is a persistent bio-accumulative toxic metal with unique physicochemical properties of public health concern since their natural and anthropogenic diffusions still induce high risk to human and environmental health. The goal of this review was to analyze scientific literature evaluating the role of global concerns over Hg exposure due to human exposure to ingestion of contaminated seafood (methyl-Hg) as well as elemental Hg levels of dental amalgam fillings (metallic Hg), vaccines (ethyl-Hg) and contaminated water and air (Hg chloride)...
September 7, 2017: Environmental Research
https://www.readbyqxmd.com/read/28886207/the-biological-effects-of-kambo-is-there-a-relationship-between-its-administration-and-sudden-death
#11
Isabella Aquila, Santo Gratteri, Matteo A Sacco, Vittorio Fineschi, Simona Magi, Pasqualina Castaldo, Graziella Viscomi, Salvatore Amoroso, Pietrantonio Ricci
Kambo is a substance obtained from the skin secretions of a frog, Phyllomedusa bicolor, popular in the Amazon region, which is administered via the transdermal route. We report a case of 42-year-old man found dead in his house. Near the corpse, a plastic box labeled as "Kambo sticks" was found. The man was a chronic consumer of Kambo and no previous pathology or genetic disease emerged in clinical history from the declaration of his general practitioner. Autopsy investigations and toxicological analysis were performed...
September 8, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28874109/prospects-and-frontiers-of-stem-cell-toxicology
#12
Shuyu Liu, Nuoya Yin, Francesco Faiola
The development of stem cell biology has revolutionized regenerative medicine and its clinical applications. Another aspect through which stem cells would benefit human health, is their use in toxicology. In fact, owing to their ability to differentiate into all the lineages of the human body, including germ cells, stem cells and in particular pluripotent stem cells, can be utilized for the assessment, in vitro, of embryonic, developmental, reproductive, organ and functional toxicities, relevant to human physiology, without employing live animal tests and with the possibility of high throughput applications...
September 6, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28859050/overdose-deaths-related-to-fentanyl-and-its-analogs-ohio-january-february-2017
#13
Raminta Daniulaityte, Matthew P Juhascik, Kraig E Strayer, Ioana E Sizemore, Kent E Harshbarger, Heather M Antonides, Robert R Carlson
Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050...
September 1, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28855114/mitochondrial-epigenetic-crosstalk-in-environmental-toxicology
#14
Caren Weinhouse
Crosstalk between the nuclear epigenome and mitochondria, both in normal physiological function and in responses to environmental toxicant exposures, is a developing sub-field of interest in environmental and molecular toxicology. The majority (∼99%) of mitochondrial proteins are encoded in the nuclear genome, so programmed communication among nuclear, cytoplasmic, and mitochondrial compartments is essential for maintaining cellular health. In this review, we will focus on correlative and mechanistic evidence for direct impacts of each system on the other, discuss demonstrated or potential crosstalk in the context of chemical insult, and highlight biological research questions for future study...
August 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28853901/pharmacological-physiochemical-and-drug-relevant-biological-properties-of-short-chain-fatty-acid-hexosamine-analogs-used-in-metabolic-glycoengineering
#15
Christopher Saeui, Lingshu Liu, Esteban Urias, Justin Morrissette-McAlmon, Rahul Bhattacharya, Kevin J Yarema
In this study, we catalog structure activity relationships (SAR) of several short chain fatty acid (SCFA)-modified hexosamine analogues used in metabolic glycoengineering (MGE) by comparing in silico and experimental measurements of physiochemical properties important in drug design. We then describe the impact of these compounds on selected biological parameters that influence the pharmacological properties and safety of drug candidates by monitoring P-glycoprotein (Pgp) efflux, inhibition of cytochrome P450 3A4 (CYP3A4), hERG channel inhibition, and cardiomyocyte cytotoxicity...
August 30, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28842581/a-first-in-human-study-of-the-novel-hiv-fusion-inhibitor-c34-peg4-chol
#16
Killian Quinn, Cinzia Traboni, Sujan Dily Penchala, Georgios Bouliotis, Nicki Doyle, Vincenzo Libri, Saye Khoo, Deborah Ashby, Jonathan Weber, Alfredo Nicosia, Riccardo Cortese, Antonello Pessi, Alan Winston
Long-acting injectable antiretroviral (LA-ARV) drugs with low toxicity profiles and propensity for drug-drug interactions are a goal for future ARV regimens. C34-PEG4-Chol is a novel cholesterol tagged LA HIV-fusion-inhibitor (FI). We assessed pre-clinical toxicology and first-in-human administration of C34-PEG4-Chol. Pre-clinical toxicology was conducted in 2 species. HIV-positive men were randomised to a single subcutaneous dose of C34-PEG4-Chol at incrementing doses or placebo. Detailed clinical (including injection site reaction (ISR) grading), plasma pharmacokinetic (time-to-minimum-effective-concentration (MEC, 25 ng/mL) and pharmacodynamic (plasma HIV RNA) parameters were assessed...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842010/a-novel-high-throughput-screening-assay-for-binding-affinities-of-perfluoroalkyl-iodide-for-estrogen-receptor-alpha-and-beta-isoforms
#17
Wenting Song, Lixia Zhao, Zhendong Sun, Xiaoxi Yang, Qunfang Zhou, Guibin Jiang
Contaminants of emerging concern are continuously increasing, which makes it important to develop high throughput screening techniques for the evaluation of their potential biological effects, especially endocrine disrupting effects, which would directly influence the population dynamics in environment. A novel competitive binding assay based on enzyme fragmentation complementation technology was established to screen the binding affinities of emerging chemicals for estrogen receptor (ER) α or β isoforms...
December 1, 2017: Talanta
https://www.readbyqxmd.com/read/28834579/topical-flurbiprofen-toxicosis-in-a-cat
#18
Elizabeth M Yi, Elizabeth Leech
OBJECTIVE: To describe the clinical presentation and treatment of a cat with flurbiprofen toxicosis due to topical cream exposure. CASE SUMMARY: A 3-year-old castrated male domestic shorthair cat presented to an emergency and referral center for acute lethargy, hematemesis, and anemia. Severe azotemia was observed on serum biochemistry panel. The patient's anemia was treated with packed RBC transfusion, and treatment with crystalloid fluids, famotidine, pantoprazole, ampicillin, and sucralfate were begun on presentation...
August 23, 2017: Journal of Veterinary Emergency and Critical Care
https://www.readbyqxmd.com/read/28830120/detection-of-carfentanil-by-lc-ms-ms-and-reports-of-associated-fatalities-in-the-usa
#19
Kevin G Shanks, George S Behonick
Carfentanil is a mu (μ) opioid receptor agonist and is estimated to be ~10,000 times more potent than morphine in animal (non-human) models. It is not approved for human use and is only used to immobilize large exotic animals in veterinary medicine. In mid-2016, carfentanil emerged as a contaminant in street heroin in the USA and was central to a large number of emergency department visits and deaths. We describe an analytical method for the detection and quantification of carfentanil in whole blood specimens via a protein precipitation extraction with acetonitrile and liquid chromatography with triple quadrupole mass spectrometry...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28830119/confirmation-of-carfentanil-u-47700-and-other-synthetic-opioids-in-a-human-performance-case-by-lc-ms-ms
#20
Joshua Seither, Lisa Reidy
Recently, it has been documented that there has been a rise in synthetic opioid abuse. Synthetic opioids are compounds that were created to act as agonists for the opioid receptors. Like synthetic cannabinoids, most of these compounds were created by research groups or pharmaceutical companies in an attempt to find compounds that have medicinal use. Synthetic opioids have severe health implications when abused that can include hospitalization and death. Due to the high potency and the low dose required to produce the desired effects for these compounds, it was hypothesized that they may not be detectable in human performance case samples...
July 1, 2017: Journal of Analytical Toxicology
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