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https://www.readbyqxmd.com/read/29140753/a-mutated-recombinant-subunit-vaccine-protects-mice-and-guinea-pigs-against-botulinum-type-a-intoxication
#1
Chi Ho Yu, Dong Hyun Song, Jun Young Choi, Hae Eun Joe, Woo Hyeon Jeong, Gyeung Haeng Hur, Young Kee Shin, Seong Tae Jeong
Botulinum neurotoxins (BoNTs) are the most potent toxins to mammals. A toxoid vaccine was previously used for prevention of botulinum intoxication; however, this vaccine is no longer available. Currently, no approved botulinum vaccines are available from the Food and Drug Administration (FDA). Recently, a recombinant host cell receptor-binding subunit created for use as a potential vaccine completed phase 2 clinical trials. The current study designed a vaccine candidate against BoNT type A (BoNT/A) using a structural design...
November 15, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29140511/two-fatal-cases-involving-cardiovascular-drugs-diltiazem-and-amlodipine
#2
Luca Morini, Matteo Moretti, Francesca Brandolini, Antonio Marco Maria Osculati, Angelo Groppi, Claudia Vignali
A liquid chromatographic tandem mass spectrometric method for the identification and quantification of 18 cardiovascular drugs was developed in order to evaluate two cases of fatal intoxication involving diltiazem and amlodipine respectively. Samples were simply diluted and centrifuged using a three-steps procedure with methanol, acetonitrile and mobile phase. The method proved to be selective and all the validation parameters fulfilled the acceptance criteria. In particular, linearity was studied in the range limits of quantitation (LOQ)-1,000 ng/mL (LOQ ranging from 0...
November 13, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29138563/squarticles-as-the-nanoantidotes-to-sequester-the-overdosed-antidepressant-for-detoxification
#3
Chun-Han Chen, Tse-Hung Huang, Ahmed O Elzoghby, Pei-Wen Wang, Chia-Wen Chang, Jia-You Fang
The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29138448/antimicrobial-peptides-in-frog-poisons-constitute-a-molecular-toxin-delivery-system-against-predators
#4
Constantijn Raaymakers, Elin Verbrugghe, Sophie Hernot, Tom Hellebuyck, Cecilia Betti, Cindy Peleman, Myriam Claeys, Wim Bert, Vicky Caveliers, Steven Ballet, An Martel, Frank Pasmans, Kim Roelants
Animals using toxic peptides and proteins for predation or defense typically depend on specialized morphological structures, like fangs, spines, or a stinger, for effective intoxication. Here we show that amphibian poisons instead incorporate their own molecular system for toxin delivery to attacking predators. Skin-secreted peptides, generally considered part of the amphibian immune system, permeabilize oral epithelial tissue and enable fast access of cosecreted toxins to the predator's bloodstream and organs...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137047/massive-neonatal-intracranial-hemorrhage-caused-by-bromadiolone-a-case-report
#5
Mingsheng Ma, Mengqi Zhang, Xiaoyan Tang, Zhenghong Li
RATIONALE: Bromadiolone, often called a super-warfarin, is a potent rodenticide with long half-life. Skin and mucosal bleeding is the most common clinical manifestations of its intoxication. Bromadiolone intoxications in adults and children have been reported, but this phenomenon is rarely seen in fetuses. This paper presents a case of neonate with massive intracranial hemorrhage mediated by bromadiolone intoxication, highlighting that the bromadiolone is potentially lethal to the fetus...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136314/syncope-prognosis-based-on-emergency-department-diagnosis-a-prospective-cohort-study
#6
Cristian Toarta, Muhammad Mukarram, Kirtana Arcot, Soo-Min Kim, Sarah Gaudet, Marco L A Sivilotti, Brian H Rowe, Venkatesh Thiruganasambandamoorthy
OBJECTIVE: Relatively little is known about outcomes after disposition among syncope patients assigned various diagnostic categories during emergency department (ED) evaluation. We sought to measure the outcomes among these groups within 30 days of the initial ED visit. METHODS: We prospectively enrolled adult syncope patients at six EDs and excluded patients with pre-syncope, persistent mental status changes, intoxication, seizure, and major trauma. Patient characteristics, ED management, diagnostic impression (presumed vasovagal, orthostatic, cardiac, or other/unknown) at the end of the ED visit and physicians' confidence in assigning the etiology were collected...
November 14, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/29135925/membrane-active-properties-of-an-amphitropic-peptide-from-the-cyaa-toxin-translocation-region
#7
Alexis Voegele, Orso Subrini, Nicolas Sapay, Daniel Ladant, Alexandre Chenal
The adenylate cyclase toxin CyaA is involved in the early stages of infection by Bordetella pertussis, the causative agent of whooping cough. CyaA intoxicates target cells by a direct translocation of its catalytic domain (AC) across the plasma membrane and produces supraphysiological levels of cAMP, leading to cell death. The molecular process of AC translocation remains largely unknown, however. We have previously shown that deletion of residues 375-485 of CyaA selectively abrogates AC translocation into eukaryotic cells...
November 14, 2017: Toxins
https://www.readbyqxmd.com/read/29135894/deferoxamine-preconditioning-of-irradiated-tissue-improves-perfusion-and-fat-graft-retention
#8
John Flacco, Natalie Chung, Charles P Blackshear, Dre Irizarry, Arash Momeni, Gordon K Lee, Dung Nguyen, Geoffrey C Gurtner, Michael T Longaker, Derrick C Wan
BACKGROUND: Radiation therapy is a mainstay in the treatment of many malignancies, but collateral damage to surrounding tissue, with resultant hypovascularity, fibrosis, and atrophy, can be difficult to reconstruct. Fat grafting has been shown to improve the quality of irradiated skin, but volume retention of the graft is significantly decreased. Deferoxamine (DFO) is a FDA-approved iron-chelating medication for acute iron intoxication and chronic iron overload that has also been shown to increase angiogenesis...
November 8, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#9
Linda Feldbrügge, Z Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Stephanie Tran, Eric U Yee, Sonja Rothweiler, Kahini A Vaid, Jean Sévigny, Moritz Schmelzle, Yury V Popov, Simon C Robson
Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice...
November 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29133010/three-fatalities-associated-with-the-synthetic-cannabinoids-5f-adb-5f-pb-22-and-ab-chminaca
#10
V Angerer, S Jacobi, F Franz, V Auwärter, J Pietsch
The use of synthetic cannabinoids (SC) has been widespread in certain groups of drug users for many years. In the scientific literature many intoxication cases and a number of fatalities after the use of synthetic cannabinoids were reported. In this paper three death cases are described with involvement of the synthetic cannabinoids 5F-PB-22, AB-CHMINACA, and 5F-ADB. The three cases occurred in the eastern region of Germany, which is known as a region of high methamphetamine abuse. All decedents were male, between 25 and 41 years old, and had a known history of drug use...
November 7, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29131112/spurious-hyperchloremia-in-the-presence-of-elevated-plasma-salicylate-a-cohort-study
#11
Kianoush B Kashani, Jon H Steuernagle Iv, Qi Qian
BACKGROUND: Acute metabolic acidosis is rarely associated with a reduced or negative anion gap (AG), but several case reports have described such an abnormality occurring in the setting of acute salicylate intoxication. The underlying cause of this phenomenon is unclear. METHODS: In this retrospective cohort study, we reviewed our institutional database to identify all patients admitted for salicylate intoxication at Mayo Clinic (Rochester, MN, USA) from January 2010 through December 2012...
November 9, 2017: Nephron
https://www.readbyqxmd.com/read/29129797/microglia-and-alcohol-meet-at-the-crossroads-microglia-as-critical-modulators-of-alcohol-neurotoxicity
#12
REVIEW
Joana F Henriques, Camila C Portugal, Teresa Canedo, João B Relvas, Teresa Summavielle, Renato Socodato
Alcohol use disorders affect millions of people worldwide causing huge social and economic burden on modern society. Excessive alcohol consumption or intoxication provokes severe damage to the body inducing immune suppression, liver damage and neurological disorder. In the central nervous system (CNS), alcohol exposure can lead to neuronal loss, cognitive decline, motor dysfunction, inflammation and impairment of neuroimmune responses. Glial cells, from which microglia represent roughly 10-15%, are primary modulators of the neuroimmune responses and inflammation in the CNS...
November 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29128925/transcriptome-profile-analysis-reveals-cardiotoxicity-of-maduramicin-in-primary-chicken-myocardial-cells
#13
Xiuge Gao, Lin Peng, Xiangchun Ruan, Xin Chen, Hui Ji, Junxiao Ma, Han Ni, Shanxiang Jiang, Dawei Guo
Maduramicin, an excellent ionophore antibiotic, is extensively used to control coccidiosis in poultry. Numerous maduramicin intoxications have been reported in farm animal and human due to its relatively narrow safety range, with necrosis or degeneration of cardiac and skeletal muscles as hallmark. To date, the mechanisms of maduramicin-induced cardiotoxicity remain unclear in chicken and other animals. Maduramicin (5 µg/mL)-treated primary chicken myocardial cells were used for RNA sequencing (RNA-Seq) and bioinformatics analysis in this study...
November 11, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29128652/differences-in-combinations-and-concentrations-of-drugs-of-abuse-in-fatal-intoxication-and-driving-under-the-influence-cases
#14
Hilde Erøy Edvardsen, Torill Tverborgvik, Joachim Frost, Sidsel Rogde, Inge Morild, Helge Waal, Thomas Clausen, Lars Slørdal, Vigdis Vindenes
BACKGROUND: In toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users - in terms of demographics and drug exposure patterns...
November 6, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29128314/early-changes-in-m2-muscarinic-acetylcholine-receptors-machrs-induced-by-sarin-intoxication-may-be-linked-to-long-lasting-neurological-effects
#15
Zipora Pittel, Shlomi Lazar, Rellie Gez, Shira Chapman
The effect of sarin on the binding parameters (KD & Bmax) of M2 muscarinic acetylcholine receptor (mAChR) was studied 24h and 1 week post exposure. Male & female Sprague-Daweley rats were poisoned with 1XLD50 sarin (80μg/kg, im) followed by treatment of trimedoxime bromide and atropine (7.5:5mg/kg, im) 1min later. Brains were removed and analyzed for M2 mAChR binding, using [(3)H]AFDX384, an M2 selective antagonist. A significant increase in KD of M2 mAChR was found in the cortex 24h post poisoning, displaying elevation from 4...
November 8, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29127761/seizure-vulnerability-and-anxiety-responses-following-chronic-co-administration-and-acute-withdrawal-of-caffeine-and-ethanol-in-a-rat-model
#16
Daniel Matovu, Paul E Alele
BACKGROUND: Caffeine antagonizes the intoxicating effects of alcohol. Consequently, there has been a dramatic global increase in the consumption of caffeinated drinks together with alcohol, especially among young adults. We assessed the seizure vulnerability and anxiety responses following the chronic co-administration of, and withdrawal from, caffeine and ethanol in male rats. METHODS: The rats were randomly assigned to six groups consisting of 10 animals each: 10 mg/kg of caffeine, 20 mg/kg of caffeine, 4 g/kg of 20% ethanol, combined caffeine (20 mg/kg) and ethanol (4 g/kg of 20%), 4 mL/kg distilled water, and an untreated control group...
November 11, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29127660/exposure-to-a-sublethal-concentration-of-imidacloprid-and-the-side-effects-on-target-and-nontarget-organs-of-apis-mellifera-hymenoptera-apidae
#17
Aline Fernanda Catae, Thaisa Cristina Roat, Marcel Pratavieira, Anally Ribeiro da Silva Menegasso, Mario Sergio Palma, Osmar Malaspina
The use of insecticides has become increasingly frequent, and studies indicate that these compounds are involved in the intoxication of bees. Imidacloprid is a widely used neonicotinoid; thus, we have highlighted the importance of assessing its oral toxicity to Africanized bees and used transmission electron microscopy to investigate the sublethal effects in the brain, the target organ, and the midgut, responsible for the digestion/absorption of food. In addition, the distribution of proteins involved in important biological processes in the brain were evaluated on the 1st day of exposure by MALDI-imaging analysis...
November 10, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/29127449/determining-a-threshold-sub-acute-dose-leading-to-minimal-physiological-alterations-following-prolonged-exposure-to-the-nerve-agent-vx-in-rats
#18
E Bloch-Shilderman, I Rabinovitz, I Egoz, G Yacov, N Allon, U Nili
VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure...
November 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29126365/suicidal-ideation-suicide-attempts-and-psychological-distress-among-intoxicated-adolescents-in-the-pediatric-emergency-department
#19
Varpu Puuskari, Terhi Aalto-Setälä, Erkki Komulainen, Mauri Marttunen
BACKGROUND: Studies have emphasized screening for psychiatric disorders, especially suicide risk in emergency departments. Psychiatric disorders and experimentation with alcohol increase in adolescence and intoxications among patients challenge the staff in emergency departments. AIMS: This study examined the degree of suicidal ideation (SI) and suicidal behavior in adolescents, and the extent to which they differed from non-suicidal patients in terms of alcohol use, psychological distress, self-esteem, and perceived social support...
November 10, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/29125985/cadmium-toxicity-and-its-amelioration-by-kinetin-in-tomato-seedlings-vis-%C3%A3-vis-ascorbate-glutathione-cycle
#20
Shikha Singh, Anita Singh, Prabhat Kumar Srivastava, Sheo Mohan Prasad
The supplementation of plant hormones may enhance the tolerance capacity of plants against certain environmental stresses by increasing their physiological functioning and detoxification capacity. To answer the question that whether a phytohormone 'kinetin' (KN, 6-furfuylaminopurine), one of the artificial cytokinins could ameliorate the cadmium induced toxicity in tomato seedlings, the effect of KN was assessed in differentially cadmium (Cd1: 3mgkg(-1) sand and Cd2: 9mgkg(-1) sand) intoxicated tomato seedlings by estimating the changes in reactive oxygen species (ROS, viz...
October 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
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