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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/28324318/botulinum-neurotoxin-type-a-for-the-treatment-of-pain-not-just-in-migraine-and-trigeminal-neuralgia
#1
Giorgio Sandrini, Roberto De Icco, Cristina Tassorelli, Nicola Smania, Stefano Tamburin
BACKGROUND: Despite their huge epidemiological impact, primary headaches, trigeminal neuralgia and other chronic pain conditions still receive suboptimal medical approach, even in developed countries. The limited efficacy of current pain-killers and prophylactic treatments stands among the main reasons for this phenomenon. Botulinum neurotoxin (BoNT) represents a well-established and licensed treatment for chronic migraine, but also an emerging treatment for other types of primary headache, trigeminal neuralgia, neuropathic pain, and an increasing number of pain conditions...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#2
Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J Smith, Leonard A Smith, James D Marks
Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4...
2017: PloS One
https://www.readbyqxmd.com/read/28299552/the-history-of-botulinum-toxin-from-poison-to-beauty
#3
Katlein França, Anagha Kumar, Massimo Fioranelli, Torello Lotti, Michael Tirant, Maria Grazia Roccia
Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine...
March 15, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28296078/botulinum-neurotoxin-type-b-uses-a-distinct-entry-pathway-mediated-by-cdc42-into-intestinal-cells-versus-neuronal-cells
#4
Chloé Connan, Marie Voillequin, Carolina Varela Chavez, Christelle Mazuet, Christian Leveque, Sandrine Vitry, Alain Vandewalle, Michel R Popoff
Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT/B most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonization such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa...
March 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28295026/neuronal-entry-and-high-neurotoxicity-of-botulinum-neurotoxin-a-require-its-n-terminal-binding-sub-domain
#5
Jiafu Wang, Jianghui Meng, Marc Nugent, Minhong Tang, J Oliver Dolly
Botulinum neurotoxins (BoNTs) are the most toxic proteins known, due to inhibiting the neuronal release of acetylcholine and causing flaccid paralysis. Most BoNT serotypes target neurons by binding to synaptic vesicle proteins and gangliosides via a C-terminal binding sub-domain (HCC). However, the role of their conserved N-terminal sub-domain (HCN) has not been established. Herein, we created a mutant form of recombinant BoNT/A lacking HCN (rAΔHCN) and showed that the lethality of this mutant is reduced 3...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28282873/crystal-structure-of-the-receptor-binding-domain-of-botulinum-neurotoxin-type-ha-also-known-as-type-fa-or-h
#6
Guorui Yao, Kwok-Ho Lam, Kay Perry, Jasmin Weisemann, Andreas Rummel, Rongsheng Jin
Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently...
March 8, 2017: Toxins
https://www.readbyqxmd.com/read/28271909/challenges-in-searching-for-therapeutics-against-botulinum-neurotoxins
#7
Marco Pirazzini, Ornella Rossetto
Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes...
March 8, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28264432/electrophysiological-characterization-of-the-antarease-metalloprotease-from-tityus-serrulatus-venom
#8
Irene Zornetta, Michele Scorzeto, Pablo Victor Mendes Dos Reis, Maria E De Lima, Cesare Montecucco, Aram Megighian, Ornella Rossetto
Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction...
February 27, 2017: Toxins
https://www.readbyqxmd.com/read/28263010/bilateral-analgesic-effects-of-abobotulinumtoxina-dysport-%C3%A2-following-unilateral-administration-in-the-rat
#9
C Favre-Guilmard, P-E Chabrier, M Kalinichev
BACKGROUND: In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel-induced polyneuropathy, abobotulinumtoxinA (aboBoNT-A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non-injected paw. METHODS: Here, we assessed bilateral analgesic effects of unilateral aboBoNT-A in several chronic pain models in Sprague-Dawley rats...
March 6, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28260503/in-vivo-neutralization-of-botulinum-neurotoxin-serotype-e-using-rabbit-polyclonal-antibody-developed-against-bont-e-light-chain
#10
Sarita Sarita, Ponmariappan Sarkaraisamy, Arti Sharma, D V Kamboj, A K Jain
Clostridium botulinum is an obligate anaerobic, Gram positive bacterium that secretes extremely toxic substances known as botulinum neurotoxins (BoNTs) that cause serious paralytic illness called botulism. Based upon the serological properties, these neurotoxin have been classified into seven serotypes designated from A to G. Due to extreme toxicity of BoNTs, these neurotoxins have been designated as category A biowarfare agents. There is no commercial neutralizing antibody available for the treatment of botulism...
March 1, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28220863/engineering-botulinum-neurotoxin-c1-as-a-molecular-vehicle-for-intra-neuronal-drug-delivery
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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