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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/28220863/engineering-botulinum-neurotoxin-c1-as-a-molecular-vehicle-for-intra-neuronal-drug-delivery
#1
Edwin J Vazquez-Cintron, Phillip H Beske, Luis Tenezaca, Bao Q Tran, Jonathan M Oyler, Elliot J Glotfelty, Christopher A Angeles, Aurelia Syngkon, Jean Mukherjee, Suzanne R Kalb, Philip A Band, Patrick M McNutt, Charles B Shoemaker, Konstantin Ichtchenko
Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181679/mechanism-of-motor-coordination-of-masseter-and-temporalis-muscles-for-increased-masticatory-efficiency-in-mice
#2
Tomoko Yoshimi, Yoshiyuki Koga, Aya Nakamura, Ayumi Fujishita, Haruka Kohara, Emi Moriuchi, Keiko Yoshimi, Chi-Yang Tsai, Noriaki Yoshida
The demand for the use of mice as animal models for elucidating the pathophysiologies and pathogeneses of oral motor disorders has been increasing in recent years, as more and more kinds of genetically modified mice that express functional disorders of the stomatognathic system become available. However, the fundamental characteristics of mouse jaw movements during mastication have yet to be fully elucidated. The purpose of this study was to investigate the roles of the masseter and temporalis muscles, and the mechanisms of motor coordination of these muscles for increasing masticatory efficiency in the closing phase in mice...
February 9, 2017: Journal of Oral Rehabilitation
https://www.readbyqxmd.com/read/28137423/mechanism-of-inhibition-of-botulinum-neurotoxin-type-a-light-chain-by-two-quinolinol-compounds
#3
Yacoba V T Minnow, Ronald Goldberg, Sreedhar R Tummalapalli, David P Rotella, Nina M Goodey
Quinolinol-based compounds are a promising starting point for discovery of effective inhibitors of the clostridial neurotoxin, botulinum neurotoxin type A light chain (BoNT/A LC). Insights into the mechanism of inhibition by quinolinol compounds facilitate interpretation of docking data and inhibitor optimization. In this study, a fluorogenic substrate of BoNT/A, SNAPtide, was used to study the mechanism by which two new quinolinol compounds, MSU58 and MSU84, with IC50 values of 3.3 μM and 5.8 μM, respectively, inhibit BoNT/A LC...
January 28, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28118733/safety-and-efficacy-of-letibotulinumtoxina-botulax%C3%A2-in-treatment-of-post-stroke-upper-limb-spasticity-a-randomized-double-blind-multi-center-phase-iii-clinical-trial
#4
Kyung Hee Do, Min Ho Chun, Nam-Jong Paik, Yoon Ghil Park, Shi-Uk Lee, Min-Wook Kim, Don-Kyu Kim
OBJECTIVE: To investigate a new botulinum neurotoxin type A, termed letibotulinumtoxinA(Botulax(®)) and compare its efficacy and safety for post-stroke upper limb spasticity with that of onabotulinumtoxinA(Botox(®)). DESIGN: A prospective, double-blinded, multicenter, randomized controlled clinical study. SETTING: Six university hospitals in Korea. SUBJECTS: A total of 187 stroke participants with upper limb spasticity...
January 1, 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28093167/re-retrograde-transport-of-radiolabelled-botulinum-neurotoxin-type-a-to-the-cns-after-intradetrusor-injection-in-rats
#5
Alan J Wein
No abstract text is available yet for this article.
February 2017: Journal of Urology
https://www.readbyqxmd.com/read/28090659/the-effect-of-intradetrusor-botulinum-neurotoxin-type-a-on-urinary-ngf-tgf-beta-1-timp-2-levels-in-children-with-neurogenic-detrusor-overactivity-due-to-myelodysplasia
#6
Tuncay Top, Cagri Akin Sekerci, Banu Isbilen-Basok, Yiloren Tanidir, Ilker Tinay, Ferruh Kemal Isman, Cem Akbal, Ferruh Simsek, Tufan Tarcan
AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA)...
January 16, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28076405/development-and-validation-of-a-new-reliable-method-for-the-diagnosis-of-avian-botulism
#7
Caroline Le Maréchal, Sandra Rouxel, Valentine Ballan, Emmanuelle Houard, Typhaine Poezevara, Marie-Hélène Bayon-Auboyer, Rozenn Souillard, Hervé Morvan, Marie-Agnès Baudouard, Cédric Woudstra, Christelle Mazuet, Sophie Le Bouquin, Patrick Fach, Michel Popoff, Marianne Chemaly
Liver is a reliable matrix for laboratory confirmation of avian botulism using real-time PCR. Here, we developed, optimized, and validated the analytical steps preceding PCR to maximize the detection of Clostridium botulinum group III in avian liver. These pre-PCR steps included enrichment incubation of the whole liver (maximum 25 g) at 37°C for at least 24 h in an anaerobic chamber and DNA extraction using an enzymatic digestion step followed by a DNA purification step. Conditions of sample storage before analysis appear to have a strong effect on the detection of group III C...
2017: PloS One
https://www.readbyqxmd.com/read/28043867/bont-ab-hybrid-maintains-similar-duration-of-paresis-as-bont-a-wild-type-in-murine-running-wheel-assay
#8
Anna Kutschenko, Marie-Christine Reinert, Nadja Krez, David Liebetanz, Andreas Rummel
The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50kDa cell binding domain of BoNT/B...
December 30, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/28042813/the-anatomical-basis-of-paradoxical-masseteric-bulging-after-botulinum-neurotoxin-type-a-injection
#9
Hyung-Jin Lee, In-Won Kang, Kyle K Seo, You-Jin Choi, Seong-Taek Kim, Kyung-Seok Hu, Hee-Jin Kim
The aim of this study was to determine the detailed anatomical structures of the superficial part of the masseter and to elucidate the boundaries and locations of the deep tendon structure within the superficial part of the masseter. Forty-four hemifaces from Korean and Thai embalmed cadavers were used in this study. The deep tendon structure was located deep in the lower third of the superficial part of the masseter. It was observed in all specimens and was designated as a deep inferior tendon (DIT). The relationship between the masseter and DIT could be classified into three types according to the coverage pattern: Type A, in which areas IV and V were covered by the DIT (27%, 12/44); Type B, in which areas V and VI were covered by the DIT (23%, 10/44); and Type C, in which areas IV, V, and VI were covered by the DIT (50%, 22/44)...
December 30, 2016: Toxins
https://www.readbyqxmd.com/read/27915984/structure-function-and-evolution-of-clostridium-botulinum-c2-and-c3-toxins-insight-to-poultry-and-veterinary-vaccines
#10
P Chellapandi, A Prisilla
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines...
December 1, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27884737/botulinum-neurotoxin-type-a-alleviates-mechanical-hypersensitivity-associated-with-infraorbital-nerve-constriction-injury-in-rats
#11
Noboru Noma, Kosuke Watanabe, Yuka Sato, Yoshiki Imamura, Yumiko Yamamoto, Reio Ito, Mitsuru Maruno, Kohei Shimizu, Koichi Iwata
We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical allodynia and hyperalgesia associated with infraorbital nerve constriction (ION-CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the whisker pad area on day 7 postoperatively and underwent pain assessment on days 14 and 21 postoperatively. Rats were assigned to one of four treatment groups (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively...
January 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27855161/an-integrative-approach-to-computational-modelling-of-the-gene-regulatory-network-controlling-clostridium-botulinum-type-a1-toxin-production
#12
Adaoha E C Ihekwaba, Ivan Mura, John Walshaw, Michael W Peck, Gary C Barker
Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27806874/submolecular-recognition-regions-of-the-hn-domain-of-the-heavy-chain-of-botulinum-neurotoxin-type-a-by-t-cells-from-toxin-treated-cervical-dystonia-patients
#13
Minako Oshima, Philip Deitiker, Joseph Jankovic, M Zouhair Atassi
We have recently reported the submolecular T-cell recognition profile of the C-terminal half (HC, residues 855-1296) of the heavy (H) chain of botulinum neurotoxin type A (BoNT/A) with peripheral blood lymphocytes (PBL) from 25 BoNT-treated cervical dystonia (CD) patients. In the current study, we describe the mapping of the T-cell responses of the patients to the N-terminal half (HN, residues 449-859) of the heavy chain by using 29 synthetic overlapping peptides encompassing the entire HN domain of BoNT/A...
November 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27773588/differences-in-active-range-of-motion-measurements-in-the-upper-extremity-of-patients-with-writer-s-cramp-compared-with-healthy-controls
#14
Prachaya Srivanitchapoom, Ejaz A Shamim, Pierre Diomi, Takaaki Hattori, Sanjay Pandey, Sherry Vorbach, Jung E Park, Tianxia Wu, Sungyoung Auh, Mark Hallett
STUDY DESIGN: Exploratory case-control study. INTRODUCTION: Writer's cramp (WC) is a type of focal hand dystonia. The central nervous system plays a role in its pathophysiology, but abnormalities in the affected musculoskeletal components may also be relevant. PURPOSE OF THE STUDY: We compared the active range of motion (ROM) in patients with WC and healthy volunteers (HVs) and correlated the findings with disease duration and severity. METHODS: Affected limb joints were measured with goniometers...
October 2016: Journal of Hand Therapy: Official Journal of the American Society of Hand Therapists
https://www.readbyqxmd.com/read/27764971/effect-of-electrical-stimulation-as-an-adjunct-to-botulinum-toxin-type-a-in-the-treatment-of-adult-spasticity-a-systematic-review
#15
Domenico Intiso, Andrea Santamato, Filomena Di Rienzo
OBJECTIVE: To investigate whether electrical stimulation (ES) as an adjunct to BTX-A boosts botulinum activity and whether the combined therapeutic procedure is more effective than BTX-A alone in reducing spasticity in adult subjects. DATA SOURCES: A search was conducted in PubMed, EMBASE, Cochrane Central Register, and CINAHL from January 1966 to January 2016. STUDY SELECTION: Only randomized controlled studies (RCT) involving the combination of BTX-A and ES were considered...
October 21, 2016: Disability and Rehabilitation
https://www.readbyqxmd.com/read/27709895/multiplex-biosensing-based-on-highly-sensitive-magnetic-nanolabel-quantification-rapid-detection-of-botulinum-neurotoxins-a-b-and-e-in-liquids
#16
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
https://www.readbyqxmd.com/read/27682175/adverse-drug-reactions-of-botulinum-neurotoxin-type-a-in-children-with-cerebral-palsy-a-pharmaco-epidemiological-study-in-vigibase
#17
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)...
March 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/27669303/development-of-an-innovative-in-vitro-potency-assay-for-anti-botulinum-antitoxins
#18
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...
September 24, 2016: Toxins
https://www.readbyqxmd.com/read/27646276/the-munc18-1-domain-3a-hinge-loop-controls-syntaxin-1a-nanodomain-assembly-and-engagement-with-the-snare-complex-during-secretory-vesicle-priming
#19
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
https://www.readbyqxmd.com/read/27626446/neutralization-of-botulinum-neurotoxin-type-e-by-a-humanized-antibody
#20
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)...
September 12, 2016: Toxins
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