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Toxicologic Emergencies

Céline Laurencé, Narimane Zeghbib, Michael Rivard, Sonia Lehri-Boufala, Isabelle Lachaise, Caroline Barau, Philippe Le Corvoisier, Thierry Martens, Laure Garrigue-Antar, Christophe Morin
Pharmaceuticals and their by-products are increasingly a matter of concern, because of their unknown impacts on human health and ecosystems. The lack of information on these transformation products, which toxicity may exceed that of their parent molecules, makes their detection and toxicological evaluation impossible. Recently we characterized the Pyridinium of furosemide (PoF), a new transformation product of furosemide, the most widely used diuretic and an emerging pollutant. Here, we reveal PoF toxicity in SH-SY5Y cells leading to alpha-synuclein accumulation, reactive oxygen species generation, and apoptosis...
December 8, 2018: Biochemical Pharmacology
Claudia Teodora Judea-Pusta, Gabriela Muţiu, Andrei Vasile Paşcalău, Camelia Liana Buhaş, Adina Nicoleta Ciursaş, Carmen Delia Nistor-Cseppento, Alina Bodea, Adrian Sorin Judea, Răzvan Marius Vicaş, Luciana Dobjanschi, Ovidiu Laurean Pop
Ethylene glycol is a toxic alcohol that is mainly introduced into an organism through the digestive pathway. Its priority toxic metabolites are glycolic acid and oxalic acid. We present the case of a young person, of the male persuasion, without any personal pathological history, found unconscious and presenting signs of violence. The patient is emergency hospitalized presenting coma, convulsive syndrome, severe metabolic acidosis and a positive result for alcoholism. Anamnestic data is extremely poor. The results of the clinical and paraclinical examinations suggest a possible poisoning with toxic alcohols...
2018: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Luke F Hartje, Christopher D Snow
The porosity, order, biocompatibility, and chirality of protein crystals has motivated interest from diverse research domains including materials science, biotechnology, and medicine. Porous protein crystals have the unusual potential to organize guest molecules within highly ordered scaffolds, enabling applications ranging from biotemplating and catalysis to biosensing and drug delivery. Significant research has therefore been directed toward characterizing protein crystal materials in hopes of optimizing crystallization, scaffold stability, and application efficacy...
November 28, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
Melissa Van Bossuyt, Els Van Hoeck, Tamara Vanhaecke, Vera Rogiers, Birgit Mertens
Due to the exponentially growing number of substances requiring safety evaluation, efficient prioritisation strategies are needed to identify those of highest concern. To limit unnecessary animal testing, such strategies should respect the 3R principles (Replacement, Reduction, Refinement). In the present study, a strategy based on non-animal approaches was developed to prioritize non-evaluated printed paper and board food contact material (FCM) substances for further in-depth safety evaluation. Within the strategy, focus was put on genotoxicity, a key toxicological endpoint when evaluating safety...
November 28, 2018: ALTEX
Jamie C DeWitt, Sarah J Blossom, Laurel A Schaider
In this perspective, we evaluate key and emerging epidemiological and toxicological data concerning immunotoxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) and seek to reconcile conflicting conclusions from two reviews published in 2016. We summarize ways that immunosuppression and immunoenhancement are defined and explain how specific outcomes are used to evaluate immunotoxicity in humans and experimental animals. We observe that different approaches to defining immunotoxicological outcomes, particularly those that do not produce clinical disease, may lead to different conclusions from epidemiological and toxicological studies...
November 27, 2018: Journal of Exposure Science & Environmental Epidemiology
Lilian H J Richter, Andreas Beck, Veit Flockerzi, Hans H Maurer, Markus R Meyer
New psychoactive substances (NPS) are still an emerging issue in clinical and forensic toxicology. Information about their cytotoxic potential is limited or even unavailable before distribution and thus their intake can be of high risk for consumers. The aim of the presented study was to develop a strategy to identify cytotoxic potential of NPS based on a high content screening assay (HCSA) using HepG2 cell line and four fluorescent dyes, namely Hoechst33342, TMRM, CAL-520, and TOTO-3. The HCSA was optimized to work without an automated analyzer by using the model compounds fluvastatin, paracetamol, propranolol, and simvastatin...
November 19, 2018: Toxicology Letters
Tuang Yeow Poh, Nur A'tikah Binte Mohamed Ali, Micheál Mac Aogáin, Mustafa Hussain Kathawala, Magdiel Inggrid Setyawati, Kee Woei Ng, Sanjay Haresh Chotirmall
Our development and usage of engineered nanomaterials has grown exponentially despite concerns about their unfavourable cardiorespiratory consequence, one that parallels ambient ultrafine particle exposure from vehicle emissions. Most research in the field has so far focused on airway inflammation in response to nanoparticle inhalation, however, little is known about nanoparticle-microbiome interaction in the human airway and the environment. Emerging evidence illustrates that the airway, even in its healthy state, is not sterile...
November 20, 2018: Particle and Fibre Toxicology
Daniël J van Hoving, Luke D Hunter, Rachel Elre J Gerber, Hendrick J Lategan, Carine J Marks
Introduction: Intentional self-poisoning is a significant part of the toxicological burden experienced by emergency centres. The aim of this study was to describe all adults presenting with intentional self-poisoning over a six-month period to the resuscitation unit of Khayelitsha Hospital, Cape Town. Methods: Adult patients with a diagnosis of intentional self-poisoning between 1 November 2014 and 30 April 2015 were retrospectively analysed after eligible patients were obtained from the Khayelitsha Hospital Emergency Centre database...
September 2018: African Journal of Emergency Medicine Revue Africaine de la Médecine D'urgence
Melissa Hobbs, Nicola J Kalk, Paul D Morrison, James M Stone
Synthetic cannabinoid receptor agonists (SCRAs) are suggested to have increased potential to induce psychosis compared to natural cannabis (NC). In this review we synthesise current knowledge about the association of SCRA use with psychotic symptoms. Following a literature search we identified 2 toxicology reports, 4 case-control studies, 3 cross-sectional studies and 15 case reports. In each of the case reports, we identified the presence or absence of symptoms based on the items of the Postitive and Negative Syndrome Scele (PANSS)...
November 16, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Seyed Mostafa Monzavi, Reza Afshari, Ali Reza Khoshdel, Mahmoud Mahmoudi, Amir Ahmad Salarian, Farhad Samieimanesh, Elham Shirmast, Azam Mihandoust
Snakebite is an important toxicologic emergency with the potential of triggering local and systemic inflammation. Antivenom has remained the mainstay of treatment for snakebite envenomation. In this study we sought to investigate the effectiveness of Iranian antivenom in a series of 44 viper envenomed patients through analysis of changes in clinical severity and the levels of inflammatory markers. Clinical envenomation severity assessed by snakebite severity score (SSS) and laboratory exams of the patients were recorded before (baseline visit) and after antivenom therapy...
November 16, 2018: Toxicon: Official Journal of the International Society on Toxinology
Camille Richeval, Jean-Michel Gaulier, Ludovic Romeuf, Delphine Allorge, Yvan Gaillard
Today, new psychoactive substances (NPS) producers increasingly appear to be targeting new synthetic opioids (NSOs), and the recent emergence of NSOs is causing considerable concern in North America and in Europe. For toxicologists, NSO detection in a forensic context presents three additional difficulties to the general NPS analytical detection challenge: (i) high frequency of new products, (ii) low concentrations (in μg/L range and under) in biological samples related to their high opioid potency, and (iii) extensive metabolism...
November 15, 2018: International Journal of Legal Medicine
Eleonora Guzzetti, Antoni Sureda, Silvia Tejada, Caterina Faggio
Microplastics are tiny ubiquitous plastic particles present in marine environments. They are not an individual entity, but constitute a cocktail of polymers and additives that can absorb substances from the surrounding environment, including living substances, nutrients and marine pollutants. Given their small size (< 5 μm), microplastics can be ingested by a wide range of marine organisms with the potential to cause harms. Microplastics are a growing threat for marine biota and ecosystem. For organisms, the risks associated with microplastic ingestion are not only due to the material itself, but also to its ability to absorb and concentrate environmental contaminants in seawater and subsequently transfer them through food chains...
December 2018: Environmental Toxicology and Pharmacology
Michalis Koutinas, Marlen I Vasquez, Euthimia Nicolaou, Petros Pashali, Eleni Kyriakou, Elena Loizou, Aikaterini Papadaki, Apostolis A Koutinas, Ioannis Vyrides
Ionic liquids (ILs) have been characterized as contaminants of emerging concern (CEC) that often resist biodegradation and impose toxicity upon environmental release. Sphingomonas sp. MKIV has been isolated as an extreme microorganism capable for biodegradation of major classes of ILs. Six imidazolium-, pyridinium- and ammonium-based ILs (pyridinium trifluoromethanesulfonate [Py][CF3 SO3 ], 1-(4-pyridyl)pyridinium chloride [1-4PPy][Cl], 1-butyl-3-methylimidazolium bromide [BMIM][Br], 1-butyl-3-methylimidazolium methanesulfonate [BMIM][MeSO4 ], tetrabutylammonium iodide [n-Bu4 N][I] and tetrabutylammonium hexafluorophosphate [n-Bu4 N][PF6 ]) were used for microbial growth...
October 23, 2018: Journal of Hazardous Materials
Daniel G Rudmann
Microphysiological systems (MPS), commonly known as organs-on-chips, are a rapidly advancing technology that promises to impact many areas of medical and toxicological pathology. In this minireview, the history of MPS and its potential utility in safety assessment are described with the toxicologic pathologist in mind. Several MPS development focus areas are defined, and recent progress in the area is highlighted. MPS will likely become an important tool for the toxicologic pathologist as part of our role in the safety assessment process within the pharmaceutical, biotechnology, medical device, and cosmetic and agrichemical industries...
November 8, 2018: Toxicologic Pathology
Gal Barel, Ralf Herwig
Toxicogenomics is the study of the molecular effects of chemical, biological and physical agents in biological systems, with the aim of elucidating toxicological mechanisms, building predictive models and improving diagnostics. The vast majority of toxicogenomics data has been generated at the transcriptome level, including RNA-seq and microarrays, and large quantities of drug-treatment data have been made publicly available through databases and repositories. Besides the identification of differentially expressed genes (DEGs) from case-control studies or drug treatment time series studies, bioinformatics methods have emerged that infer gene expression data at the molecular network and pathway level in order to reveal mechanistic information...
2018: Frontiers in Genetics
Manal H Saad, Candace L Savonen, Matthew Rumschlag, Sokol V Todi, Carl J Schmidt, Michael J Bannon
Opioid abuse is now the primary cause of accidental deaths in the United States. Studies over several decades established the cyclical nature of abused drugs of choice, with a current resurgence of heroin abuse and, more recently, fentanyl's emergence as a major precipitant of drug-related deaths. To better understand abuse trends and to explore the potential lethality of specific drug-drug interactions, we conducted statistical analyses of forensic toxicological data from the Wayne County Medical Examiner's Office from 2012-2016...
2018: Frontiers in Neuroscience
Ana Capitão, Mónica Lopes-Marques, Yoichiro Ishii, Raquel Ruivo, Elza Fonseca, Inês Páscoa, Rodolfo Jorge, Mélanie Barbosa, Youhei Hiromori, Takayuki Miyagi, Tsuyoshi Nakanishi, Miguel Santos, L Filipe C Castro
Globally persistent man-made chemicals display ever-growing ecosystemic consequences, a hallmark of the Anthropocene. In this context, the assessment of how lineage-specific gene repertoires influence organism sensitivity towards endocrine disruptors is a central question in toxicology. A striking example highlights the role of a group of compounds known as obesogens. In mammals, most examples involve the modulation of the nuclear receptor, peroxisome proliferator-activated receptor  (PPAR). To address the structural and biological determinants of PPARγ exploitation by a model obesogen, tributyltin (TBT), in chordates, we employed comparative genomics, transactivation and ligand binding assays, homology modeling and site-directed-mutagenesis...
November 6, 2018: Environmental Science & Technology
Christian Kubitza, Florian Bittner, Carsten Ginsel, Antje Havemeyer, Bernd Clement, Axel J Scheidig
Biotransformation enzymes ensure a viable homeostasis by regulating reversible cycles of oxidative and reductive reactions. The metabolism of nitrogen-containing compounds is of high pharmaceutical and toxicological relevance because N-oxygenated metabolites derived from reactions mediated by cytochrome P450 enzymes or flavin-dependent monooxygenases are in some cases highly toxic or mutagenic. The molybdenum-dependent mitochondrial amidoxime-reducing component (mARC) was found to be an extremely efficient counterpart, which is able to reduce the full range of N-oxygenated compounds and thereby mediates detoxification reactions...
November 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
John Pierce Wise, James T F Wise, Catherine F Wise, Sandra S Wise, Cairong Zhu, Cynthia L Browning, Tongzhang Zheng, Christopher Perkins, Christy Gianios, Hong Xie, John Pierce Wise
One Environmental Health has emerged as an important area of research that considers the interconnectedness of human, animal and ecosystem health with a focus on toxicology. The great whales in the Gulf of Maine are important species for ecosystem health, for the economies of the Eastern seaboard of the United States, and as sentinels for human health. The Gulf of Maine is an area with heavy coastal development, industry, and marine traffic, all of which contribute chronic exposures to environmental chemicals that can bioaccumulate in tissues and may gradually diminish an individual whale's or a population's fitness...
February 2019: Chemosphere
Lijuan Zhou, Xianqi Zhang, Ralf Paus, Zhongfa Lu
Human skin organ culture (hSOC) is a simple but highly instructive and clinically relevant skin research method. It has been used for decades to study the development, differentiation, and function as well as the response to wounding or test agents of intact human skin in the presence of its appendages and all resident cell populations. hSOC has also proven useful in toxicological and oncological studies and studies of skin aging (both chronological aging and photoaging), skin energy metabolism, skin immunology, pigmentation biology, and cutaneous (neuro-)endocrinology and neurobiology...
October 16, 2018: Differentiation; Research in Biological Diversity
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