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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/28445195/protective-effect-of-botulinum-toxin-type-a-against-atopic-dermatitis-like-skin-lesions-in-nc-nga-mice
#1
Sang Bum Han, Hyeree Kim, Sang Hyun Cho, Jin Ho Chung, Hei Sung Kim
BACKGROUND: Botulinum neurotoxin (BTX) A possesses various biological activities, including anti-inflammatory and antipruritic actions. Human and animal studies have shown that BTX is effective in treating histamine-induced itch, lichen simplex chronicus, psoriasis, rosacea, allergic rhinitis, and scar prevention. However, its effect on atopic dermatitis (AD) has not been studied yet. OBJECTIVE: To examine the effect of BTX on AD using a mouse model. The primary outcome was skin thickness and transepidermal water loss (TEWL), and the secondary outcome was the alteration in skin severity scores, histological, and laboratory test results...
April 24, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#2
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427139/-advances-in-the-research-of-mechanism-in-prevention-and-treatment-of-scar-with-botulinum-toxin-type-a-and-its-clinical-application
#3
Y H Li, J Q Liu, D Xiao, W Zhang, D H Hu
Scar is a common complication in wound healing process, and how to effectively prevent and treat it is a hot and difficult problem in burns and plastic surgery field. Botulinum toxin type A is a neurotoxin that has been widely and effectively used in the cosmetic surgery field such as anti-wrinkle and thin face. In recent years, botulinum toxin type A has been applied in prevention and treatment of scar, which causes a great concern. Nowadays, the relevant reports have gradually increased, and the mechanisms have been explored more deeply...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28410268/long-term-anti-itch-effect-of-botulinum-neurotoxin-a-is-associated-with-downregulation-of-trpv1-and-trpa1-in-the-dorsal-root-ganglia-in-mice
#4
Lei-Fang Cao, Meng Si, Ya Huang, Li-Hua Chen, Xiao-Yan Peng, Ya-Qin Qin, Teng-Teng Liu, Yan Zhou, Tong Liu, Wei-Feng Luo
Itch is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-itch effects of the botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in mice...
April 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28389376/botulinum-neurotoxin-type-a-cleaved-snap25-is-confined-to-primary-motor-neurons-and-localized-on-the-plasma-membrane-following-intramuscular-toxin-injection
#5
Brian B Cai, Joseph Francis, Mitchell F Brin, Ron S Broide
The mechanism of action of botulinum neurotoxin type A (BoNT/A) is well characterized, but some published evidence suggests the potential for neuronal retrograde transport and cell-to-cell transfer (transcytosis) under certain experimental conditions. The present study evaluated the potential for these processes using a highly selective antibody for the BoNT/A-cleaved substrate (SNAP25197) combined with 3-dimensional imaging. SNAP25197 was characterized in a rat motor neuron (MN) pathway following toxin intramuscular injections at various doses to determine whether SNAP25197 is confined to MNs or also found in neighboring cells or nerve fibers within spinal cord (SC)...
April 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28385185/antibody-responses-to-botulinum-neurotoxin-type-a-of-toxin-treated-spastic-equinus-children-with-cerebral-palsy-a-randomized-clinical-trial-comparing-two-injection-schedules
#6
Minako Oshima, Philip Deitiker, Tandy Hastings-Ison, K Roger Aoki, H Kerr Graham, M Zouhair Atassi
We have conducted a 26-month-long comparative study involving young patients (2-6years old) with a clinical diagnosis of spastic equinus secondary to cerebral palsy who have been treated with BoNT/A (BOTOX®, Allergan) tri-annually or annually. Serum samples were obtained to determine the presence or absence of blocking antibodies (Abs) by a mouse protection assay (MPA) and levels of anti-BoNT/A Abs by radioimmune assay (RIA). HLA DQ alleles were typed using blood samples to determine the possible association of certain HLA type(s) with the disease or with the Ab status...
May 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28359137/an-ultrasensitive-gold-nanoparticle-based-lateral-flow-test-for-the-detection-of-active-botulinum-neurotoxin-type-a
#7
Jing Liu, Shan Gao, Lin Kang, Bin Ji, Wenwen Xin, Jingjing Kang, Ping Li, Jie Gao, Hanbin Wang, Jinglin Wang, Hao Yang
Botulism is a severe and potentially lethal paralytic disease caused by several botulinum neurotoxin-producing Clostridia spp. In China, the majority of the cases caused by botulism were from less-developed rural areas. Here, we designed specific substrate peptides and reconfigured gold nanoparticle-based lateral flow test strip (LFTS) to develop an endopeptidase-based lateral flow assay for the diagnosis of botulism. We performed this lateral flow assay on botulinum neurotoxin-spiked human serum samples. The as-prepared LFTS had excellent performance in the detection of botulinum neurotoxin using only 1 μL of simulated serum, and its sensitivity and specificity were comparable to that of mouse lethality assay...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28356439/botulinum-neurotoxins-biology-pharmacology-and-toxicology
#8
REVIEW
Marco Pirazzini, Ornella Rossetto, Roberto Eleopra, Cesare Montecucco
The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28347837/a-novel-therapeutic-with-two-snap-25-inactivating-proteases-shows-long-lasting-anti-hyperalgesic-activity-in-a-rat-model-of-neuropathic-pain
#9
Jiafu Wang, Laura Casals-Diaz, Tomas Zurawski, Jianghui Meng, Orla Moriarty, John Nealon, Om Prakash Edupuganti, Oliver Dolly
A pressing need exists for long-acting, non-addictive medicines to treat chronic pain, a major societal burden. Botulinum neurotoxin type A (BoNT/A) complex - a potent, specific and prolonged inhibitor of neuro-exocytosis - gives some relief in several pain disorders, but not for all patients. Our study objective was to modify BoNT/A to overcome its inability to block transmitter release elicited by high [Ca(2+)]i and increase its limited analgesic effects. This was achieved by fusing a BoNT/A gene to that for the light chain (LC) of type/E...
March 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28324318/botulinum-neurotoxin-type-a-for-the-treatment-of-pain-not-just-in-migraine-and-trigeminal-neuralgia
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28264432/electrophysiological-characterization-of-the-antarease-metalloprotease-from-tityus-serrulatus-venom
#17
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
#18
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...
May 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
#19
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
#20
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
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