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https://www.readbyqxmd.com/read/29168766/tityus-serrulatus-scorpion-venom-in-vitro-tests-and-their-correlation-with-in-vivo-lethal-dose-assay
#1
Daniela Cajado-Carvalho, Juliana Galvão, Alexandre K Kuniyoshi, Patrícia Dos Santos Carneiro, Adriana Franco Paes Leme, Bianca Alves Pauletti, Eliana Blini Marengo, Fernanda V Portaro
Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO) recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD50 determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD50 results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom...
November 23, 2017: Toxins
https://www.readbyqxmd.com/read/29167427/scallop-genome-reveals-molecular-adaptations-to-semi-sessile-life-and-neurotoxins
#2
Yuli Li, Xiaoqing Sun, Xiaoli Hu, Xiaogang Xun, Jinbo Zhang, Ximing Guo, Wenqian Jiao, Lingling Zhang, Weizhi Liu, Jing Wang, Ji Li, Yan Sun, Yan Miao, Xiaokang Zhang, Taoran Cheng, Guoliang Xu, Xiaoteng Fu, Yangfan Wang, Xinran Yu, Xiaoting Huang, Wei Lu, Jia Lv, Chuang Mu, Dawei Wang, Xu Li, Yu Xia, Yajuan Li, Zhihui Yang, Fengliang Wang, Lu Zhang, Qiang Xing, Huaiqian Dou, Xianhui Ning, Jinzhuang Dou, Yangping Li, Dexu Kong, Yaran Liu, Zhi Jiang, Ruiqiang Li, Shi Wang, Zhenmin Bao
Bivalve molluscs are descendants of an early-Cambrian lineage superbly adapted to benthic filter feeding. Adaptations in form and behavior are well recognized, but the underlying molecular mechanisms are largely unknown. Here, we investigate the genome, various transcriptomes, and proteomes of the scallop Chlamys farreri, a semi-sessile bivalve with well-developed adductor muscle, sophisticated eyes, and remarkable neurotoxin resistance. The scallop's large striated muscle is energy-dynamic but not fully differentiated from smooth muscle...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29166654/therapeutic-efficacy-of-equine-botulism-antitoxin-in-rhesus-macaques
#3
Shantha Kodihalli, Andrew Emanuel, Teresa Takla, Yi Hua, Charles Hobbs, Ross LeClaire, Denise C O'Donnell
BACKGROUND: There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques...
2017: PloS One
https://www.readbyqxmd.com/read/29161446/microglia-activation-and-gene-expression-alteration-of-neurotrophins-in-the-hippocampus-following-early-life-exposure-to-e-cigarette-aerosols-in-a-murine-model
#4
Judith T Zelikoff, Nancy Parmalee, Kevin Corbett, Terry Gordon, Catherine B Klein, Michael Aschner
Recent epidemiological data indicate that the popularity of electronic cigarettes (e-cigarettes), and consequently nicotine use, is rising in both adolescent and adult populations. As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages. Despite this, few studies have evaluated the toxicity of e-cigarettes on the developing central nervous system (CNS). The goal of this study was to assess neurotoxicity resulting from early life exposure to electronic cigarette aerosols in an in vivo model...
November 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29159335/protective-effects-of-lipoic-acid-against-acrylamide-induced-neurotoxicity-involvement-of-mitochondrial-energy-metabolism-and-autophagy
#5
Ge Song, Zhigang Liu, Luanfeng Wang, Renjie Shi, Chuanqi Chu, Man Xiang, Qi Tian, Xuebo Liu
Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway...
November 21, 2017: Food & Function
https://www.readbyqxmd.com/read/29158500/use-dependent-potentiation-of-voltage-gated-calcium-channels-rescues-neurotransmission-in-nerve-terminals-intoxicated-by-botulinum-neurotoxin-serotype-a
#6
Phillip H Beske, Katie M Hoffman, James B Machamer, Margaret R Eisen, Patrick M McNutt
Botulinum neurotoxins (BoNTs) are highly potent toxins that cleave neuronal SNARE proteins required for neurotransmission, causing flaccid paralysis and death by asphyxiation. Currently, there are no clinical treatments to delay or reverse BoNT-induced blockade of neuromuscular transmission. While aminopyridines have demonstrated varying efficacy in transiently reducing paralysis following BoNT poisoning, the precise mechanisms by which aminopyridines symptomatically treat botulism are not understood. Here we found that activity-dependent potentiation of presynaptic voltage-gated calcium channels (VGCCs) underlies 3,4-diaminopyridine (3,4-DAP)-mediated rescue of neurotransmission in central nervous system synapses and mouse diaphragm neuromuscular junctions fully intoxicated by BoNT serotype A...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158482/structural-basis-for-the-unique-ganglioside-and-cell-membrane-recognition-mechanism-of-botulinum-neurotoxin-dc
#7
Sicai Zhang, Ronnie P-A Berntsson, William H Tepp, Liang Tao, Eric A Johnson, Pål Stenmark, Min Dong
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29154270/ubisol-q10-a-nanomicellar-water-soluble-formulation-of-coq10-treatment-inhibits-alzheimer-type-behavioral-and-pathological-symptoms-in-a-double-transgenic%C3%A2-mouse%C3%A2-tgapeswe-%C3%A2-psen1de9-model-of-alzheimer-s-disease
#8
Krithika Muthukumaran, Annie Kanwar, Caleb Vegh, Alexandra Marginean, Austin Elliott, Nicholas Guilbeault, Alexander Badour, Marianna Sikorska, Jerome Cohen, Siyaram Pandey
 Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29151990/robot-embodied-neuronal-networks-as-an-interactive-model-of-learning
#9
Abraham M Shultz, Sangmook Lee, Mary Guaraldi, Thomas B Shea, Holly C Yanco
Background and Objective: The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form an ex vivo network capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarify in situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neurons in vivo...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29151073/effect-of-the-different-doses-of-acrylamide-on-acetylocholinoesterase-activity-thiol-groups-malondialdehyde-concentrations-in-hypothalamus-and-selected-muscles-of-mice
#10
M Kopanska, J Czech, P Zagata, L Dobrek, P Thor, G Formicki
Acrylamide is a chemical compound that typically forms in starchy food products during high-temperature cooking, including frying, baking and roasting. Acrylamide is a known lethal neurotoxin. Its discovery in some cooked starchy foods in 2002 prompted concerns about the carcinogenicity of those foods. Little is known about acrylamide's influence on the peripheral nerves. In our research we measured acrylamide's influence on the acetylcholinesterase activity in hypothalamus, heart muscle, skeletal muscles of the thigh and smooth muscle of the small intestine (males, Swiss strain) in relation to the thiol groups and malondialdehyde concentration...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29150919/a-focus-on-the-beneficial-effects-of-alpha-synuclein-and-a-re-appraisal-of-synucleinopathies
#11
Larisa Ryskalin, Carla L Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella, Francesco Fornai
Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owing an abnormal structure (as occurring following point gene mutations)...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#12
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150520/dopaminergic-neurotoxins-induce-cell-death-by-attenuating-nf-%C3%AE%C2%BAb-mediated-regulation-of-trpc1-expression-and-autophagy
#13
Pramod Sukumaran, Yuyang Sun, Neil Antonson, Brij B Singh
Alterations in Ca(2+) homeostasis affect neuronal survival. However, the identity of Ca(2+) channels and the mechanisms underlying neurotoxin-induced neuronal degeneration are not well understood. In this study, the dopaminergic neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl -4-phenylpyridium ions (MPP(+)/MPTP), which mimic Parkinson's disease (PD), induced neuronal degeneration by decreasing store-mediated Ca(2+) entry. The function of the transient receptor potential canonical (TRPC)-1 channel was decreased upon exposure to the neurotoxins, followed by a decrease in TRPC1 expression...
November 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29150503/carbon-amendments-alter-microbial-community-structure-and-net-mercury-methylation-potential-in-sediments
#14
Geoff A Christensen, Anil C Somenahally, James G Moberly, Carrie M Miller, Andrew J King, Cynthia C Gilmour, Steven D Brown, Mircea Podar, Craig C Brandt, Scott C Brooks, Anthony V Palumbo, Judy D Wall, Dwayne A Elias
Neurotoxic methylmercury (MeHg) is produced by anaerobic Bacteria and Archaea possessing the genes hgcAB, but it is unknown how organic substrate and electron acceptor availability impact the distribution and abundance of these organisms. We evaluated the impact of organic substrate amendments on mercury (Hg) methylation rates, microbial community structure, and the distribution of hgcAB(+) microbes with sediments. Sediment slurries were amended with short-chain fatty acids, alcohols, or a polysaccharide. Minimal increases in MeHg were observed following lactate, ethanol and methanol amendments while a significant decrease (∼70%) was observed with cellobiose incubations...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150297/prolonged-stretching-of-the-ankle-plantarflexors-elicits-muscle-tendon-adaptations-relevant-to-ankle-gait-kinetics-in-children-with-spastic-cerebral-palsy
#15
Teresa Martín Lorenzo, Eduardo Rocon, Ignacio Martínez Caballero, Ana Ramírez Barragán, Sergio Lerma Lara
Tissue related ankle hyper-resistance has been reported to contribute to equinus gait in children with spastic cerebral palsy. Hence, ankle plantarflexor stretching programs have been developed in order to restore passive ankle dorsiflexion. Despite high quality evidence on the limited effects of stretching on passive joint mobility, further muscle-tendon adaptations have been reported which may impact gait performance. As such, children with spastic cerebral palsy subject to long-term manual static stretching achieved dorsiflexion gains through the reduction of muscle and fascicle strain whilst preserving tendon strain, and prolonged use of ankle-foot orthoses achieved similar dorsiflexion gains through increased tendon strain whilst preserving muscle and fascicle strain...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149813/structural-analysis-of-cd59-of-chinese-tree-shrew-a-new-reference-molecule-for-human-immune-system-specific-cd59-drug-discovery
#16
Subhamay Panda, Leena Kumari, Santamay Panda
BACKGROUND: Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquires shared common as well as unique characteristics, and hence offers a genetic basis for employing this animal as a prospective model for biomedical research...
November 17, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29142416/protective-effect-of-pluchea-lanceolata-against-aluminum-chloride-induced-neurotoxicity-in-swiss-albino-mice
#17
Ravi Mundugaru, Senthilkumar Sivanesan, Padmaja Udaykumar, Niranjan Rao, Naveen Chandra
Background: Aluminum chloride (AlCl3) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb Pluchea lanceolata is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine. Objective: To evaluate the neuroprotective activity of hydroalcoholic extract of P. lanceolata in chronic AlCl3-induced neurotoxicity in Swiss albino mice. Materials and Methods: Albino mice were categorized into four different groups; Group 1served as vehicle control, Group 2 mice were administered with AlCl3, 40 mg/kg body weight by intraperitoneal route for 45 consecutive days...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29140753/a-mutated-recombinant-subunit-vaccine-protects-mice-and-guinea-pigs-against-botulinum-type-a-intoxication
#18
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/29135566/management-of-hypertonia-in-cerebral-palsy
#19
Nickolas J Nahm, H Kerr Graham, Mark E Gormley, Andrew G Georgiadis
PURPOSE OF REVIEW: The review provides an update on the treatment of hypertonia in cerebral palsy, including physical management, pharmacotherapy, neurosurgical, and orthopedic procedures. RECENT FINDINGS: Serial casting potentiates the effect of Botulinum neurotoxin A injections for spasticity. Deep brain stimulation, intraventricular baclofen, and ventral and dorsal rhizotomy are emerging tools for the treatment of dystonia and/or mixed tone. The long-term results of selective dorsal rhizotomy and the timing of orthopedic surgery represent recent advances in the surgical management of hypertonia...
November 11, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29133849/canonical-germinant-receptor-is-dispensable-for-spore-germination-in-clostridium-botulinum-group-ii-strain-nctc-11219
#20
Charlien Clauwers, Cédric Lood, Vera van Noort, Chris W Michiels
Clostridium botulinum is an anaerobic sporeforming bacterium that is notorious for producing a potent neurotoxin. Spores of C. botulinum can survive mild food processing treatments and subsequently germinate, multiply, produce toxin and cause botulism. Control of spore germination and outgrowth is therefore essential for the safety of mildly processed foods. However, little is known about the process of spore germination in group II C. botulinum (gIICb), which are a major concern in chilled foods because they are psychrotrophic...
November 13, 2017: Scientific Reports
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