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botulinum neurotoxin type A

Alexey V Orlov, Sergey L Znoyko, Vladimir R Cherkasov, Maxim Petrovich Nikitin, Petr I Nikitin
We present a multiplex quantitative lateral flow (LF) assay for simultaneous on-site detection of botulinum neurotoxin (BoNT) types A, B and E in complex matrices, which is innovative by virtually no sacrifice in performance while transition from the single-plex assays and by characteristics on the level of laboratory quantitative methods. The novel approach to easy multiplexing is realized via joining an on-demand set of single-plex LF strips, which employ magnetic nanolabels, into a miniature cylinder cartridge that mimics LF strip during all assay stages...
October 6, 2016: Analytical Chemistry
Jeanne Montastruc, Philippe Marque, Florence Moulis, Véronique Bourg, Valérie Lambert, Geneviève Durrieu, Jean-Louis Montastruc, François Montastruc
AIM: The aim of this study was to assess the risk of adverse drug reactions (ADRs) with botulinum neurotoxin type A (BoNT-A) in children with cerebral palsy (CP) using the World Health Organization global individual case safety report (ICSR) database, VigiBase. METHOD: We extracted all children ICSRs for ADRs with BoNT-A used as anti-spastic drug in CP recorded between 1995 and 2015 in VigiBase. We also performed a case/non-case method (disproportionality analysis) to assess the link between exposure to BoNT-A and each ADR of interest in children and adults, calculating reporting odds ratios (RORs)...
September 28, 2016: Developmental Medicine and Child Neurology
Osnat Rosen, Eyal Ozeri, Ada Barnea, Alon Ben David, Ran Zichel
Botulinum neurotoxins are bacterial proteins that cause botulism, a life-threatening disease. Therapy relies mostly on post-intoxication antibody treatment. The only accepted method to measure the potency of, and to approve, antitoxin preparations is the mouse lethality neutralization bioassay. However, this assay is time-consuming, labor-intensive, costly, and raises ethical issues related to the large numbers of laboratory animals needed. Until now, all efforts to develop an alternative in vitro assay have not provided a valid replacement to the mouse potency assay...
2016: Toxins
Ravikiran Kasula, Ye Jin Chai, Adekunle T Bademosi, Callista B Harper, Rachel S Gormal, Isabel C Morrow, Eric Hosy, Brett M Collins, Daniel Choquet, Andreas Papadopulos, Frédéric A Meunier
Munc18-1 and syntaxin-1A control SNARE-dependent neuroexocytosis and are organized in nanodomains on the plasma membrane of neurons and neurosecretory cells. Deciphering the intra- and intermolecular steps via which they prepare secretory vesicles (SVs) for fusion is key to understanding neuronal and hormonal communication. Here, we demonstrate that expression of a priming-deficient mutant lacking 17 residues of the domain 3a hinge-loop (Munc18-1(Δ317-333)) in PC12 cells engineered to knockdown Munc18-1/2 markedly prolonged SV docking...
September 26, 2016: Journal of Cell Biology
Yağmur Derman, Katja Selby, Sebastian Miethe, André Frenzel, Yvonne Liu, Christine Rasetti-Escargueil, Arnaud Avril, Thibaut Pelat, Remi Urbain, Alexandre Fontayne, Philippe Thullier, Dorothea Sesardic, Miia Lindström, Michael Hust, Hannu Korkeala
Botulinum neurotoxins (BoNTs) cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential use as bioweapons. To counter bio-threat and naturally-occurring botulism cases, well-tolerated antibodies by humans that neutralize BoNTs are relevant. In our previous work, we showed the neutralizing potential of macaque (Macaca fascicularis)-derived scFv-Fc (scFv-Fc ELC18) by in vitro endopeptidase immunoassay and ex vivo mouse phrenic nerve-hemidiaphragm assay by targeting the light chain of the botulinum neurotoxin type E (BoNT/E)...
2016: Toxins
Mallory Jackman, Mehdi Delrobaei, Fariborz Rahimi, S Farokh Atashzar, Mahya Shahbazi, Rajni Patel, Mandar Jog
INTRODUCTION: Writer's cramp is a specific focal hand dystonia causing abnormal posturing and tremor in the upper limb. The most popular medical intervention, botulinum neurotoxin type A (BoNT-A) therapy, is variably effective for 50-70% of patients. BoNT-A non-responders undergo ineffective treatment and may experience significant side effects. Various assessments have been used to determine response prediction to BoNT-A, but not in the same population of patients. METHODS: A comprehensive assessment was employed to measure various symptom aspects...
2016: Tremor and Other Hyperkinetic Movements
Jason D Bloom, Jeremy B Green, Whitney Bowe, Erika von Grote, Alessandra Nogueira
The proportion of men seeking facial rejuvenation with botulinum neurotoxin type A (BoNTA) products is increasing. The number of male patients treated in the 5-year period between 2009 and 2014 grew by 25%. There is little clinical data supporting gender-specific efficacy with regard to dosing and injection placement in men. To nurture the confidence associated with treatment of male patients, clinicians are in need of more informational materials to develop their evaluation and treatment strategies. Three BoNTA products are currently available in the United States (US) for treatment of the upper face...
September 1, 2016: Journal of Drugs in Dermatology: JDD
Stefano Paolucci, Andrea Martinuzzi, Giorgio Scivoletto, Nicola Smania, Claudio Solaro, Irene Aprile, Michela Armando, Roberto Bergamaschi, Eliana Berra, Giulia Berto, Elena Carraro, Monica Cella, Marialuisa Gandolfi, Marcella Masciullo, Marco Molinari, Emanuela Pagliano, Cristiano Pecchioli, Laura Roncari, Monica Torre, Erika Trabucco, Gabriella Vallies, Paolo Zerbinati, Stefano Tamburin
Pain is a common and disabling symptom in patients with stroke, multiple sclerosis (MS), cerebral palsy (CP), spinal cord injury (SCI) and other conditions associated with spasticity, but data on its prevalence, and natural history, as well as guidelines on its assessment and treatment in the field of neurorehabilitation, are largely lacking. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) searched and evaluated current evidence on the frequency, evolution, predictors, assessment, and pharmacological and non-pharmacological treatment of pain in patients with stroke, MS, CP, SCI and other conditions associated with spasticity...
August 31, 2016: European Journal of Physical and Rehabilitation Medicine
Marie E Noland, Donald H Lalonde, G Jackie Yee, Rod J Rohrich
LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Recognize the various types of botulinum toxins and their differences. 2. Identify current indications, both approved and off-label. 3. Inject botulinum toxin to counteract various natural aging processes, including facial descent and rhytides. SUMMARY: Botulinum neurotoxin is a naturally synthesized microbial protein that has been applied in the management of various disorders...
September 2016: Plastic and Reconstructive Surgery
Adam Bobkiewicz, Wojciech Francuzik, Lukasz Krokowicz, Adam Studniarek, Witold Ledwosiński, Jacek Paszkowski, Michal Drews, Tomasz Banasiewicz
BACKGROUND: Chronic anal fissure (CAF) is a linear split of the anoderm. The minimally invasive management of CAF such as botulinum toxin (BT) injection is recommended. However, the exact efficient dose of BT, number of injections per session and the injection sites are still debatable. The aim of this analysis was to assess the dose-dependent efficiency of botulinum toxin injection for CAF. METHODS: PubMed and Web of Science databases were searched for terms: "anal fissure" AND "botulinum toxin...
August 18, 2016: World Journal of Surgery
Yvette N Lamb, Lesley J Scott
Intramuscular incobotulinumtoxinA (Xeomin(®)) is indicated for the treatment or improvement of adult patients with upper limb spasticity (featured indication), cervical dystonia, blepharospasm and glabellar lines. It is a highly purified formulation of botulinum toxin type A that inhibits acetylcholine signalling at neuromuscular junctions, reducing muscle hypertonia. This narrative review discusses the clinical use of incobotulinumtoxinA in adults with upper limb spasticity and summarizes its pharmacological properties...
September 2016: Drugs
P Caballero, M Troncoso, S I Patterson, C López Gómez, R Fernandez, M A Sosa
The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain...
October 2016: Toxicon: Official Journal of the International Society on Toxinology
Edwin Vazquez-Cintron, Luis Tenezaca, Christopher Angeles, Aurelia Syngkon, Victoria Liublinska, Konstantin Ichtchenko, Philip Band
Cyto-012 is a recombinant derivative of Botulinum neurotoxin Type A (BoNT/A). It primarily differs from wild type (wt) BoNT/A1 in that it incorporates two amino acid substitutions in the catalytic domain of the light chain (LC) metalloprotease (E224 > A and Y366 > A), designed to provide a safer clinical profile. Cyto-012 is specifically internalized into rat cortical and hippocampal neurons, and cleaves Synaptosomal-Associated Protein 25 (SNAP-25), the substrate of wt BoNT/A, but exhibits slower cleavage kinetics and therefore requires a higher absolute dose to exhibit pharmacologic activity...
2016: Scientific Reports
Ewelina Wachnicka, Sandra C Stringer, Gary C Barker, Michael W Peck
UNLABELLED: Heat treatment is an important controlling factor that, in combination with other hurdles (e.g., pH, aw), is used to reduce numbers and prevent the growth of and associated neurotoxin formation by nonproteolytic C. botulinum in chilled foods. It is generally agreed that a heating process that reduces the spore concentration by a factor of 10(6) is an acceptable barrier in relation to this hazard. The purposes of the present study were to review the available data relating to heat resistance properties of nonproteolytic C...
October 1, 2016: Applied and Environmental Microbiology
John Fezza, John Burns, Julie Woodward, Daniel Truong, Thomas Hedges, Amit Verma
To characterize satisfaction with current standard-of-care botulinum neurotoxin type A (BoNT/A) treatment for blepharospasm, we performed a cross-sectional, structured survey in subjects with blepharospasm who had received ≥2 BoNT/A cycles. Subjects were interviewed immediately before re-injection to evaluate treatment satisfaction, time course of treatment effects, preferred injection intervals, Jankovic Rating Scale (JRS), and Blepharospasm Disability Index (BSDI). Subjects' (n=114) last treatment was onabotulinumtoxinA (n=78), incobotulinumtoxinA (n=35), or abobotulinumtoxinA (n=1)...
August 15, 2016: Journal of the Neurological Sciences
Jessica Warnink-Kavelaars, R Jeroen Vermeulen, Annemieke I Buizer, Jules G Becher
AIM: To validate a detailed intramuscular needle placement protocol using passive muscle stretching and relaxing for botulinum neurotoxin type A (BoNT-A) treatment in the lower extremity of children with spastic cerebral palsy (CP), with verification by electrical stimulation. METHOD: A prospective observational study was performed in 75 children with spastic CP who received regular BoNT-A treatment under general anaesthesia (52 males, 23 females; mean age 8y 9mo, SD 3y 7mo, range 4-18y; mean body mass index 16...
July 6, 2016: Developmental Medicine and Child Neurology
Eva-Maria Hansbauer, Martin Skiba, Tanja Endermann, Jasmin Weisemann, Daniel Stern, Martin B Dorner, Friedrich Finkenwirth, Jessica Wolf, Werner Luginbühl, Ute Messelhäußer, Laurent Bellanger, Cédric Woudstra, Andreas Rummel, Patrick Fach, Brigitte G Dorner
Botulinum neurotoxin (BoNT) serotypes C and D and their mosaic variants CD and DC cause severe cases of botulism in animal husbandry and wildlife. Epidemiological data on the exact serotype or toxin variant causing outbreaks are rarely available, mainly because of their high sequence identity and the lack of fast and specific screening tools to detect and differentiate the four similar toxins. To fill this gap, we developed four highly specific sandwich enzyme-linked immunosorbent assays (ELISAs) able to detect and differentiate botulinum neurotoxins type BoNT/C, D, CD, and DC based on four distinct combinations of specific monoclonal antibodies targeting both conserved and divergent subdomains of the four toxins...
September 21, 2016: Analyst
Elcio J Piovesan, Michael Oshinsky, Stephen Silberstein, Pedro Andre Kowacs, Edison Matos Novak, Lineu Cesar Werneck
METHOD: Neuropathic pain was induced by surgical constriction of the infraorbital nerve in rats. A control group underwent a sham procedure consisting of surgical exposure of the nerve. Subgroups of each group received either BoNT/A or isotonic saline solution. The clinical response was assessed with the -20°C test. Animals that underwent nerve constriction developed sensitization; the sham group did not. RESULTS: The sensitization was reversed by BoNT/A treatment evident 24 hours following application...
June 2016: Arquivos de Neuro-psiquiatria
Stefan Mahrhold, Tomas Bergström, Daniel Stern, Brigitte G Dorner, Crister Åstot, Andreas Rummel
The extraordinary potency of botulinum neurotoxins (BoNTs) is mediated by their high neurospecificity, targeting peripheral cholinergic motoneurons leading to flaccid paralysis and successive respiratory failure. Complex polysialo gangliosides accumulate BoNTs on the plasma membrane and facilitate subsequent binding to synaptic vesicle membrane proteins which results in toxin endocytosis. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 (SV2) isoforms A-C mediates uptake of the clinically most relevant serotype BoNT/A1...
September 1, 2016: Biochemical Journal
Sabine Pellett, William H Tepp, Marite Bradshaw, Suzanne R Kalb, Janet K Dykes, Guangyun Lin, Erin M Nawrocki, Christina L Pier, John R Barr, Susan E Maslanka, Eric A Johnson
Botulinum neurotoxins (BoNTs), produced by neurotoxigenic clostridial species, are the cause of the severe disease botulism in humans and animals. Early research on BoNTs has led to their classification into seven serotypes (serotypes A to G) based upon the selective neutralization of their toxicity in mice by homologous antibodies. Recently, a report of a potential eighth serotype of BoNT, designated "type H," has been controversial. This novel BoNT was produced together with BoNT/B2 in a dual-toxin-producing Clostridium botulinum strain...
January 2016: MSphere
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