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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/28816652/reoccurrence-of-botulinum-neurotoxin-subtype-a3-inducing-food-borne-botulism-slovakia-2015
#1
Lucia Mad'arová, Brigitte G Dorner, Lars Schaade, Vladimír Donáth, Mária Avdičová, Milota Fatkulinová, Jozef Strhársky, Ivana Sedliačiková, Cyril Klement, Martin B Dorner
A case of food-borne botulism occurred in Slovakia in 2015. Clostridium botulinum type A was isolated from three nearly empty commercial hummus tubes. The product, which was sold in Slovakia and the Czech Republic, was withdrawn from the market and a warning was issued immediately through the European Commission's Rapid Alert System for Food and Feed (RASFF). Further investigation revealed the presence of botulinum neurotoxin (BoNT) subtype BoNT/A3, a very rare subtype implicated in only one previous outbreak (Loch Maree in Scotland, 1922)...
August 10, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28809452/neurotoxin-synthesis-is-positively-regulated-by-the-sporulation-transcription-factor-spo0a-in-clostridium-botulinum-type-e
#2
Gerald Mascher, Anna Mertaoja, Hannu Korkeala, Miia Lindström
Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls...
August 15, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28802703/identification-and-characterization-of-clostridium-botulinum-group-iii-field-strains-by-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry-maldi-tof-ms
#3
Luca Bano, Ilenia Drigo, Elena Tonon, Simone Pascoletti, Cinzia Puiatti, Fabrizio Anniballi, Bruna Auricchio, Florigio Lista, Cesare Montecucco, Fabrizio Agnoletti
Animal botulism is primarily due to botulinum neurotoxin (BoNT) types C, D or their chimeric variants C/D or D/C, produced by Clostridium botulinum group III, which appears to include the genetically indistinguishable Clostridium haemolyticum and Clostridium novyi. In the present study, we used matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI TOF MS) to identify and characterize 81 BoNT-producing Clostridia isolated in 47 episodes of animal botulism. The instrument's default database, containing no entries for Clostridium botulinum, permitted reliable identification of 26 strains at the genus level...
August 9, 2017: Anaerobe
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#4
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800585/comparative-pathogenomics-of-clostridium-tetani
#5
Jonathan E Cohen, Rong Wang, Rong-Fong Shen, Wells W Wu, James E Keller
Clostridium tetani and Clostridium botulinum produce two of the most potent neurotoxins known, tetanus neurotoxin and botulinum neurotoxin, respectively. Extensive biochemical and genetic investigation has been devoted to identifying and characterizing various C. botulinum strains. Less effort has been focused on studying C. tetani likely because recently sequenced strains of C. tetani show much less genetic diversity than C. botulinum strains and because widespread vaccination efforts have reduced the public health threat from tetanus...
2017: PloS One
https://www.readbyqxmd.com/read/28783115/a-novel-surface-plasmon-resonance-biosensor-for-the-rapid-detection-of-botulinum-neurotoxins
#6
Kruti Patel, Shmuel Halevi, Paul Melman, John Schwartz, Shuowei Cai, Bal Ram Singh
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD50 of 1-2 ng/kg body weight), cause fatal flaccid paralysis by blocking neurotransmitter release. The current gold standard detection method, the mouse-bioassay, often takes days to confirm botulism. Furthermore, there are no effective antidotes known to reverse the symptoms of botulism, and as a result, patients with severe botulism often require meticulous care during the prolonged paralytic illness...
August 7, 2017: Biosensors
https://www.readbyqxmd.com/read/28770389/long-term-stability-of-reconstituted-incobotulinumtoxina-how-can-we-reduce-costs-of-botulinum-toxin-therapy
#7
Dirk Dressler, Hans Bigalke
Botulinum neurotoxin (BNT), the biologically active component of botulinum toxin (BT), is a large double-stranded protein susceptible to various physical and chemical influences. All BT type A (BT-A) drugs are stored as powders allowing shelf lives from 24 to 36 months. After reconstitution, the specified shelf life is reduced to 8-24 h. Some studies, however, suggest longer shelf life. We wanted to test the long-term stability of reconstituted BT-A drugs in the hemidiaphragm assay (HDA), a high quality BT potency test...
August 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28733282/differentiating-botulinum-neurotoxin-producing-clostridia-with-a-simple-multiplex-pcr-assay
#8
Charles H D Williamson, Adam J Vazquez, Karen Hill, Theresa J Smith, Roxanne Nottingham, Nathan E Stone, Colin J Sobek, Jill H Cocking, Rafael A Fernández, Patricia A Caballero, Owen P Leiser, Paul Keim, Jason W Sahl
Diverse members of the genus clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum Groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This study introduces a multiplex polymerase chain reaction (PCR) assay for differentiating members of C. botulinum Group I, C...
July 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28727388/lysozyme-gene-treatment-in-testosterone-induced-benign-prostate-hyperplasia-rat-model-and-comparasion-of-its-effectiveness-with-botulinum-toxin-injection
#9
Osman Ergün, Pinar Aslan Koşar, İbrahim Onaran, Hakan Darici, Alim Koşar
OBJECTIVES: To compare the effects and histopathological changes of botulinum neurotoxin type A and lysozyme gene injections into prostate tissue within a testosterone induced benign prostate hyperplasia rat model. MATERIALS AND METHODS: 40 male Wistar rats were randomized into four Groups. Group-1: Control, Group-2: Testosterone replacement, Group-3: Testosterone+botulinum neurotoxin type A, Group-4: Testosterone+plazmid DNA/liposome complex. RESULTS: Estimated prostate volume of the testosterone injected Groups were higher than the control (p <0...
July 20, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28705271/molecular-and-epidemiological-characterization-of-infant-botulism-in-beijing-china
#10
Yin Ping Dong, Wei Wang, Tao Jiang, Jin Xu, Chun Hui Han, Shao Fei Yan, Séamus Fanning, Ying Li, Xiao Chen Ma, Di Zhang, Yao Zhao, Biao Zeng, Feng Qin Li
Laboratory-based pathogen isolation, identification, and toxicity determination were performed on samples from a suspected case of infant botulism. Mice injected with cultures generated from the enema sample and ingested Powered infant formula (PIF) presented typical signs of botulism. Antitoxins to polyvalent botulinum neurotoxins (BoNTs) and monovalent BoNT type B antitoxin had protective effects. Clostridium botulinum isolated from the enema and residual PIF samples were positive for type B toxin. Pulsed-field gel electrophoresis (PFGE) revealed that the two strains of C...
June 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28692343/pulsotype-diversity-of-clostridium-botulinum-strains-containing-serotypes-a-and-or-b-genes
#11
Jessica L Halpin, Lavin Joseph, Janet K Dykes, Loretta McCroskey, Elise Smith, Denise Toney, Steven Stroika, Kelley Hise, Susan Maslanka, Carolina Lúquez
Clostridium botulinum strains are prevalent in the environment and produce a potent neurotoxin that causes botulism, a rare but serious paralytic disease. In 2010, a national PulseNet database was established to curate C. botulinum pulsotypes and facilitate epidemiological investigations, particularly for serotypes A and B strains frequently associated with botulism cases in the United States. Between 2010 and 2014 we performed pulsed-field gel electrophoresis (PFGE) using a PulseNet protocol, uploaded the resulting PFGE patterns into a national database, and analyzed data according to PulseNet criteria (UPGMA clustering, Dice coefficient, 1...
July 10, 2017: Foodborne Pathogens and Disease
https://www.readbyqxmd.com/read/28685363/the-role-of-endoscopic-intra-gastric-botulinum-toxin-a-for-obesity-treatment
#12
REVIEW
Hadya Elshakh, Khalid El-Ejji, Shahrad Taheri
Obesity prevalence has been increasing with devastating health and economic consequences. Botulinum toxin type A (BTX-A), a neurotoxin, is used clinically for conditions characterized by prolonged muscular contraction. Its inhibitory effects on gastric smooth muscles, in theory, make it a potential agent for obesity treatment through delayed gastric emptying and increased satiety. This review aims to examine the evidence for the use of endoscopic BTX-A injection for treating obesity. The literature search identified 60 articles with 11 primary studies as relevant for the scope of the review...
July 6, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28684374/investigating-crispr-cas-systems-in-clostridium-botulinum-via-bioinformatics-tools
#13
Manica Negahdaripour, Navid Nezafat, Nasim Hajighahramani, Seyyed Soheil Rahmatabadi, Younes Ghasemi
The Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a type of innate immunity found in some prokaryotes, which protect them against alien genetic elements by targeting foreign nucleic acids. Some other functions are also attributed to these systems. Clostridium botulinum bacteria produce botulinum neurotoxins (BoNT), one of the deadliest known toxins for humans and some animals. Food poisoning due to these bacteria is still a challenge in food industries. On the other hand, BoNT has been widely investigated for therapeutic applications including different muscle disorders...
July 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28674381/engineered-botulinum-neurotoxin-b-with-improved-efficacy-for-targeting-human-receptors
#14
Liang Tao, Lisheng Peng, Ronnie P-A Berntsson, Sai Man Liu, SunHyun Park, Feifan Yu, Christopher Boone, Shilpa Palan, Matthew Beard, Pierre-Etienne Chabrier, Pål Stenmark, Johannes Krupp, Min Dong
Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B's therapeutic efficacy and reduce adverse effects. Here we utilized the bacterial adenylate cyclase two-hybrid method and carried out a saturation mutagenesis screen in the Syt II-binding pocket of botulinum neurotoxin B...
July 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28614091/injectable-daxibotulinumtoxina-for-the-treatment-of-glabellar-lines-a-phase-2-randomized-dose-ranging-double-blind-multicenter-comparison-with-onabotulinumtoxina-and-placebo
#15
Jean Carruthers, Nowell Solish, Shannon Humphrey, Nathan Rosen, Channy Muhn, Vince Bertucci, Arthur Swift, Andrei Metelitsa, Roman G Rubio, Jacob Waugh, John Quiring, Gill Shears, Alastair Carruthers
BACKGROUND: Injectable daxibotulinumtoxinA (RT002) is an investigational botulinum toxin Type A in clinical development. It is formulated with a proprietary peptide and offers the potential of a longer acting neurotoxin therapy. OBJECTIVE: To compare the safety, efficacy, and duration of response of daxibotulinumtoxinA with onabotulinumtoxinA and placebo [www.clinicaltrials.gov NCT02303002]. METHODS: In this Phase 2, randomized, dose-ranging, parallel-group, double-blind, multicenter study, subjects with moderate or severe glabellar lines at maximum frown were randomly assigned to 20U, 40U, or 60U daxibotulinumtoxinA, 20U onabotulinumtoxinA, or placebo...
June 12, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28596838/botulinum-neurotoxins-serotypes-a-and-b-induce-paralysis-of-mouse-striated-and-smooth-muscles-with-different-potencies
#16
Jacquie Maignel-Ludop, Marion Huchet, Johannes Krupp
To address the scarcity of direct comparison of botulinum neurotoxin serotypes activity on smooth versus striatal muscle, we have studied the action of BoNT/A1 and BoNT/B1 on ex vivo preparations of both muscle types. We have set up and characterized a model of neurogenic contractions in the isolated mouse bladder, and used this model to explore the effects of the two serotypes on contractions evoked by electrical field stimulation. Both toxins were also tested in the mouse phrenic nerve hemidiaphragm assay, to compare their potency in smooth versus striated muscle...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28587791/evaluation-of-anti-botulinum-neurotoxin-single-domain-antibodies-with-additional-optimization-for-improved-production-and-stability
#17
Lisa C Shriver-Lake, Dan Zabetakis, Ellen R Goldman, George P Anderson
Botulinum neurotoxin (BoNT) is a highly potent and lethal toxin, which even in minute quantities can lead to death. BoNT occurs in seven well described serotypes, A-G, and it is critical to not only detect the presence of BoNT, but also to determine the serotype to which a person has been exposed, as the degree of toxicity and persistence of symptoms varies greatly between the various types. Recently, Conway et al. 2010 developed single domain antibodies (sdAb), the recombinant variable domains of heavy-chain-only antibodies derived from camelids, for the detection of all seven serotypes of BoNT; identifying pairs of sdAb for each serotype they demonstrated the sensitive detection of each toxin...
June 3, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28584101/deubiquitinating-enzyme-vcip135-dictates-the-duration-of-botulinum-neurotoxin-type-a-intoxication
#18
Yien Che Tsai, Archana Kotiya, Erkan Kiris, Mei Yang, Sina Bavari, Lino Tessarollo, George A Oyler, Allan M Weissman
Botulism is characterized by flaccid paralysis, which can be caused by intoxication with any of the seven known serotypes of botulinum neurotoxin (BoNT), all of which disrupt synaptic transmission by endoproteolytic cleavage of SNARE proteins. BoNT serotype A (BoNT/A) has the most prolonged or persistent effects, which can last several months, and exerts its effects by specifically cleaving and inactivating SNAP25. A major factor contributing to the persistence of intoxication is the long half-life of the catalytic light chain, which remains enzymatically active months after entry into cells...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28566161/long-term-safety-of-repeated-high-doses-of-incobotulinumtoxina-injections-for-the-treatment-of-upper-and-lower-limb-spasticity-after-stroke
#19
Andrea Santamato, Francesco Panza, Domenico Intiso, Alessio Baricich, Alessandro Picelli, Nicola Smania, Francesca Fortunato, Davide Seripa, Pietro Fiore, Maurizio Ranieri
Current guidelines suggested a dosage up to 600units (U) of botulinum toxin type A (BoNT-A) (onabotulinumtoxinA or incobotulinumtoxinA) in reducing spastic hypertonia with low prevalence of complications, although a growing body of evidence showed efficacy with the use of high doses (>800U). The available evidence mainly referred to a single set of injections evaluating the efficacy and safety of the neurotoxin 30days after the treatment. In a prospective, non-randomized, open-label study, we studied the safety of repeated higher doses of incobotulinumtoxinA in post-stroke upper and lower limb spasticity...
July 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28556093/recovery-of-rat-muscle-size-but-not-function-more-than-1-year-after-a-single-botulinum-toxin-injection
#20
Samuel R Ward, Viviane B Minamoto, Kentaro P Suzuki, Jonah B Hulst, Shannon N Bremner, Richard L Lieber
INTRODUCTION: Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin-injected adult rat skeletal muscle over nearly the entire lifespan. METHODS: Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT-A); Allergan, Irvine, California] or saline solution injection. Neurotoxin-injected animals (n = 90) were analyzed at different time-points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months...
May 26, 2017: Muscle & Nerve
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