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https://www.readbyqxmd.com/read/27908630/non-linear-dose-response-of-aluminium-hydroxide-adjuvant-particles-selective-low-dose-neurotoxicity
#1
Guillemette Crépeaux, Housam Eidi, Marie-Odile David, Yasmine Baba-Amer, Eleni Tzavara, Bruno Giros, François-Jérôme Authier, Christopher Exley, Christopher A Shaw, Josette Cadusseau, Romain K Gherardi
Aluminium (Al) oxyhydroxide (Alhydrogel(®)), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain...
November 28, 2016: Toxicology
https://www.readbyqxmd.com/read/27908258/neurotoxicity-induced-by-mephedrone-an-up-to-date-review
#2
Flaminia Pantano, Roberta Tittarelli, Giulio Mannocchi, Roberta Pacifici, Alessandro di Luca, Francesco Paolo Busardò, Enrico Marinelli
Mephedrone is a β-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. The aim of this review was to examine the emerging scientific literature on the possible mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental studies, mainly carried on animal models. Relevant scientific articles were identified from international literature databases (Medline, Scopus, etc...
November 30, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27905399/cellular-reactions-to-long-term-volatile-organic-compound-voc-exposures
#3
Johanna M Gostner, Johannes Zeisler, Mohammad Tauqeer Alam, Peter Gruber, Dietmar Fuchs, Kathrin Becker, Kerstin Neubert, Markus Kleinhappl, Stefan Martini, Florian Überall
Investigations of cellular processes initiated by volatile organic compounds (VOCs) are limited when modelling realistic long-term exposure scenarios at low concentrations. Exposure to indoor VOCs is associated with a range of adverse effects, but data on molecular changes at regulatory threshold limits are lacking. Activity analysis of VOC in vitro can be a valuable complement to inhalation toxicological evaluations. We developed an exposure platform that generates a stable VOC atmosphere and allows the exposure of cells for longer periods...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901621/perfluorooctanoic-acid-induces-mitochondrial-dysfunction-in-mc3t3-e1-osteoblast-cells
#4
Eun Mi Choi, Kwang Sik Suh, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Young Seol Kim, Youngmi Kim Pak, Suk Chon
Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells...
November 30, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27899215/toxicology-in-international-drug-control-prioritizing-the-most-harmful-persistent-and-prevalent-substances
#5
Susan C Ifeagwu, Martin Raithelhuber, Conor Crean, Dimitri Gerostamoulos, Heesun Chung, Justice N Tettey
The nature of the global drugs market has evolved rapidly and has become more complex with the emergence of new psychoactive substances (NPS), some of which have been associated with increased abuse, hospital emergency admissions and sometimes fatalities. NPS are characterized by geographic heterogeneity, with some only transient in nature and others not satisfying the criteria for harm required for international control. Consequently, a pragmatic response of the international community is to prioritize the most harmful, persistent and prevalent substances for action - an objective, which is hampered by the paucity of data on harms...
November 20, 2016: Forensic Science International
https://www.readbyqxmd.com/read/27864543/long-non-coding-rnas-a-novel-paradigm-for-toxicology
#6
REVIEW
Joseph L Dempsey, Julia Yue Cui
Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are transcribed from the mammalian genome in a tissue-specific and developmentally regulated pattern. There is growing recognition that lncRNAs are novel biomarkers and/or key regulators of toxicological responses in humans and animal models. Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad of transcriptional regulatory functions that include cis and trans gene expression, transcription factor activity, chromatin remodeling, imprinting, and enhancer up-regulation...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27860548/mitochondrial-dysfunction-and-myocardial-ischemia-reperfusion-implications-for-novel-therapies
#7
Edward J Lesnefsky, Qun Chen, Bernard Tandler, Charles L Hoppel
Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#8
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27856027/a-case-of-strychnine-poisoning-from-a-southeast-asian-herbal-remedy
#9
Terry Singhapricha, Adam C Pomerleau
BACKGROUND: Strychnine is a highly toxic alkaloid found in both naturally occurring compounds and commercial products. Extracts of fruits from the strychnine plant have been used in Southeast Asia as remedies for various illnesses. We describe strychnine poisoning from ingestion of a Southeast Asian herbal supplement quantitatively confirmed by serum and urine analysis. CASE REPORT: A 40-year-old Cambodian woman presented to the emergency department with a complaint of jaw pain and spasms...
November 14, 2016: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27855972/transformation-products-in-the-water-cycle-and-the-unsolved-problem-of-their-proactive-assessment-a-combined-in-vitro-in-silico-approach
#10
Jakob Menz, Anju Priya Toolaram, Tushar Rastogi, Christoph Leder, Oliver Olsson, Klaus Kümmerer, Mandy Schneider
Transformation products (TPs) emerging from incomplete degradation of micropollutants in aquatic systems can retain the biological activity of the parent compound, or may even possess new unexpected toxic properties. The chemical identities of these substances remain largely unknown, and consequently, the risks caused by their presence in the water cycle cannot be assessed thoroughly. In this study, a combined approach for the proactive identification of hazardous elements in the chemical structures of TPs, comprising analytical, bioanalytical and computational methods, was assessed by the example of the pharmaceutically active micropollutant propranolol (PPL)...
November 15, 2016: Environment International
https://www.readbyqxmd.com/read/27850512/874-impact-of-an-emergency-critical-care-unit-on-the-disposition-of-critically-ill-toxicology-patients
#11
Ronny Otero, Benjamin Long, Cemal Sozener, Benjamin Bassin, Kyle Gunnerson, James Cranford
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27847220/occurrence-and-toxicity-of-musks-and-uv-filters-in-the-marine-environment
#12
Rainieri S, Barranco A, Primec M, Langerholc T
Emerging chemical contaminants in the marine ecosystem represent a threat to the environment and also to human health due to insufficient knowledge about their toxicity and bioaccumulation in the food chain. Consequently, many of them are not regulated. In this review we focus on musks and organic UV filters. For both groups of compounds we describe occurrence in the marine environment, toxic effects identified so far and methods used to identify such effects. The final objective of this work is to identify gaps in the understanding of their toxicology...
November 12, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27842783/liquid-chromatography-tandem-mass-spectrometry-an-emerging-technology-in-the-toxicology-laboratory
#13
REVIEW
Yan Victoria Zhang, Bin Wei, Yu Zhu, Yanhua Zhang, Martin H Bluth
In the last decade, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in routine toxicology laboratories. LC-MS/MS offers significant advantages over other traditional testing, such as immunoassay and gas chromatography-mass spectrometry methodologies. Major strengths of LC-MS/MS include improvement in specificity, flexibility, and sample throughput when compared with other technologies. Here, the basic principles of LC-MS/MS technology are reviewed, followed by advantages and disadvantages of this technology compared with other traditional techniques...
December 2016: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/27836646/localized-delivery-of-carbon-monoxide
#14
Christoph Steiger, Cornelius Hermann, Lorenz Meinel
The heme oxygenase (HO) / carbon monoxide (CO) system is a physiological feedback loop orchestrating various cell-protective effects in response to cellular stress. The therapeutic use of CO is impeded by safety challenges as a result of high CO-Hemoglobin formation following non-targeted, systemic administration jeopardizing successful CO therapies as of this biological barrier. Another caveat is the use of CO-Releasing Molecules containing toxicologically critical transition metals. An emerging number of local delivery approaches addressing these issues have recently been introduced and provide exciting new starting points for translating the fascinating preclinical potential of CO into a clinical setting...
November 8, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27829332/in-vitro-metabolite-profiling-of-adb-fubinaca-a-new-synthetic-cannabinoid
#15
Jeremy Carlier, Xingxing Diao, Ariane Wohlfarth, Karl Scheidweiler, Marilyn A Huestis
Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable. We aimed to determine optimal markers for identifying ADB-FUBINACA intake. Metabolic stability was evaluated with human liver microsome incubations. Metabolites were identified after 1 and 3 h incubation with pooled human hepatocytes, liquid chromatography- high resolution mass spectrometry in positive-ion mode (5600+ TripleTOF®, Sciex) and several data mining approaches (MetabolitePilot™, Sciex)...
November 8, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27825741/global-occurrence-of-pyrethroid-insecticides-in-sediment-and-the-associated-toxicological-effects-on-benthic-invertebrates-an-overview
#16
REVIEW
Huizhen Li, Fei Cheng, Yanli Wei, Michael J Lydy, Jing You
Pyrethroids are the third most applied group of insecticides worldwide and are extensively used in agricultural and non-agricultural applications. Pyrethroids exhibit low toxicity to mammals, but have extremely high toxicity to fish and non-target invertebrates. Their high hydrophobicity, along with pseudo-persistence due to continuous input, indicates that pyrethroids will accumulate in sediment, pose long-term exposure concerns to benthic invertebrates and ultimately cause significant risk to benthic communities and aquatic ecosystems...
October 25, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27824267/the-impact-of-online-toxicology-training-on-fijian-emergency-doctors-knowledge-the-global-educational-toxicology-uniting-project-getup
#17
A Wong, A Stolbach, A H Dawson, R Vohra
No abstract text is available yet for this article.
November 8, 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/27814027/harnessing-big-data-for-systems-pharmacology
#18
Lei Xie, Eli J Draizen, Philip E Bourne
Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets...
October 13, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27810537/eco-toxicological-risk-and-impact-of-pesticides-on-important-parasitoids-of-cabbage-butterflies-in-cruciferous-ecosystem
#19
D M Firake, D P Thubru, G T Behere
Eco-toxicological risk and impact of pesticides was estimated on three important parasitoids of butterflies viz., Hyposoter ebeninus, Cotesia glomerata and Pteromalus puparum. Four commonly used pesticides were evaluated using standard protocol (of IOBC/WPRS-group). In laboratory tests, the survival of the female wasps decreased significantly on fresh contact and ingestion of deltamethrin, spinosad and azadirachtin; whereas Bacillus thuringiensis var kurstaki (Btk) was found harmless pesticide. Under semi-field conditions, parasitoid mortality decreased significantly on fresh contact with the pesticides...
October 27, 2016: Chemosphere
https://www.readbyqxmd.com/read/27808109/trends-for-isolated-amino-acids-and-dipeptides-conformation-divalent-ion-binding-and-remarkable-similarity-of-binding-to-calcium-and-lead
#20
M Ropo, V Blum, C Baldauf
We derive structural and binding energy trends for twenty amino acids, their dipeptides, and their interactions with the divalent cations Ca(2+), Ba(2+), Sr(2+), Cd(2+), Pb(2+), and Hg(2+). The underlying data set consists of more than 45,000 first-principles predicted conformers with relative energies up to ~4 eV (~400 kJ/mol). We show that only very few distinct backbone structures of isolated amino acids and their dipeptides emerge as lowest-energy conformers. The isolated amino acids predominantly adopt structures that involve an acidic proton shared between the carboxy and amino function...
November 3, 2016: Scientific Reports
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