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https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#1
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/28306178/effective-treatment-of-infant-botulism-on-day-13-after-symptom-onset-with-human-botulism-antitoxin
#2
Anita J Campbell, Geoff Knight, Peter Walsh, Asha C Bowen
No abstract text is available yet for this article.
March 17, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/28296078/botulinum-neurotoxin-type-b-uses-a-distinct-entry-pathway-mediated-by-cdc42-into-intestinal-cells-versus-neuronal-cells
#3
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/28282873/crystal-structure-of-the-receptor-binding-domain-of-botulinum-neurotoxin-type-ha-also-known-as-type-fa-or-h
#4
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/28280466/embryonic-stem-cell-derived-neurons-grown-on-multi-electrode-arrays-as-a-novel-in-vitro-bioassay-for-the-detection-of-clostridium-botulinum-neurotoxins
#5
Stephen P Jenkinson, Denis Grandgirard, Martina Heidemann, Anne Tscherter, Marc-André Avondet, Stephen L Leib
Clostridium botulinum neurotoxins (BoNTs) are the most poisonous naturally occurring protein toxins known to mankind and are the causative agents of the severe and potentially life-threatening disease botulism. They are also known for their application as cosmetics and as unique bio-pharmaceuticals to treat an increasing number of neurological and non-neurological disorders. Currently, the potency of biologically active BoNT for therapeutic use is mainly monitored by the murine LD50-assay, an ethically disputable test causing suffering and death of a considerable number of mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28273554/head-drop-after-botox-electrodiagnostic-evaluation-of-iatrogenic-botulinum-toxicity
#6
Eliza Szuch, James B Caress, Bandhu Paudyal, Allison Brashear, Michael S Cartwright, Roy E Strowd
BACKGROUND: Botulinum is a potent neurotoxin with increasing indications for neurologic disorders. While clinical benefit manifests primarily due to local actions at the neuromuscular junction, regional and systemic effects do occur. Rarely, systemic symptoms including weakness, dysarthria, dysphagia and other side effects occur as a result of iatrogenic botulinum neurotoxicity. CASE: A 72 year-old female with right leg dystonia developed head drop, bulbar and systemic weakness following right lower extremity botulinum toxin injection...
March 5, 2017: Clinical Neurology and Neurosurgery
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/28260503/in-vivo-neutralization-of-botulinum-neurotoxin-serotype-e-using-rabbit-polyclonal-antibody-developed-against-bont-e-light-chain
#9
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/28252640/crystal-structure-of-the-bont-a2-receptor-binding-domain-in-complex-with-the-luminal-domain-of-its-neuronal-receptor-sv2c
#10
Roger M Benoit, Martin A Schärer, Mara M Wieser, Xiaodan Li, Daniel Frey, Richard A Kammerer
A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with the luminal domain (LD) of its neuronal receptor SV2C revealed only few specific side-chain - side-chain interactions that are important for binding. Notably, two BoNT/A1 residues, Arg 1156 and Arg 1294, that are crucial for the interaction with SV2, are not conserved among subtypes...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174033/acute-hypotonia-in-an-infant
#11
Jimme Sierakowski, Jason Arthur, Todd Wylie
BACKGROUND: Acute flaccid myelitis (AFM) is increasing in incidence in the United States and presenting to emergency departments (EDs) across the country. This clinical entity presents as acute paralysis, with magnetic resonance imaging changes in the gray matter only in children younger than 21 years of age. The etiology is unknown, although preceding viral illnesses are common. There are no consensus guidelines regarding treatment. CASE REPORT: A 4-month-old girl presented with decreased bilateral arm movement...
February 4, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28166935/toxicoses-of-the-ruminant-nervous-system
#12
REVIEW
Gene A Niles
This article discusses the etiology, mechanism of action, clinical signs, and diagnostic tests used to identify toxic agents that affect the nervous system of ruminants. The article is not intended to be an exhaustive review of each agent, but a reference for establishing a differential diagnosis when toxic agents are suspected as the cause of central nervous system disease in ruminants. The initial focus of the article is on agents that cause brain lesions consistent with polioencephalomalacia. Other neurotoxic disease agents include bovine bonkers, urea, organophosphate, organochlorine, cyanobacteria, zinc, aluminum, phosphide, metaldehyde, strychnine, botulism, tetanus, clostridium perfringens, and poisonous plants...
March 2017: Veterinary Clinics of North America. Food Animal Practice
https://www.readbyqxmd.com/read/28076405/development-and-validation-of-a-new-reliable-method-for-the-diagnosis-of-avian-botulism
#13
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/28065740/bacterial-signaling-to-the-nervous-system-through-toxins-and-metabolites
#14
REVIEW
Nicole J Yang, Isaac M Chiu
Mammalian hosts interface intimately with commensal and pathogenic bacteria. It is increasingly clear that molecular interactions between the nervous system and microbes contribute to health and disease. Both commensal and pathogenic bacteria are capable of producing molecules that act on neurons and affect essential aspects of host physiology. Here we highlight several classes of physiologically important molecular interactions that occur between bacteria and the nervous system. First, clostridial neurotoxins block neurotransmission to or from neurons by targeting the SNARE complex, causing the characteristic paralyses of botulism and tetanus during bacterial infection...
March 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28062435/flaccid-paralysis-in-an-infant-associated-with-a-dirty-wound-and-application-of-honey
#15
Charlotte Jane Joseph, Teik Beng Khoo, Keng Yee Lee
An infant, who was born preterm at 36 weeks, presented with fever and ulcer at umbilical region which progressed to necrotising fasciitis of anterior abdominal wall. He was treated with intravenous penicillin, intravenous cloxacillin and local application of medicated honey. Subsequently, he required wound debridement. Postoperatively, he required prolonged invasive ventilation due to poor respiratory effort which was associated with hypotonia and areflexia. Nerve conduction study revealed absent responses...
January 6, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28058209/impact-of-clostridium-botulinum-genomic-diversity-on-food-safety
#16
REVIEW
Michael W Peck, Arnoud Hm van Vliet
The deadly botulinum neurotoxin formed by Clostridium botulinum is the causative agent of foodborne botulism. The increasing availability of C. botulinum genome sequences is starting to allow the genomic diversity of C. botulinum Groups I and II and their neurotoxins to be characterised. This information will impact on microbiological food safety through improved surveillance and tracing/tracking during outbreaks, and a better characterisation of C. botulinum Groups I and II, including the risk presented, and new insights into their biology, food chain transmission, and evolution...
August 2016: Current Opinion in Food Science
https://www.readbyqxmd.com/read/28056003/notes-from-the-field-botulism-outbreak-from-drinking-prison-made-illicit-alcohol-in-a-federal-correctional-facility-mississippi-june-2016
#17
Lindsey McCrickard, Mariel Marlow, Julie L Self, Louise Francois Watkins, Kevin Chatham-Stephens, Jannifer Anderson, Sheryl Hand, Kathryn Taylor, Jennifer Hanson, Keiundria Patrick, Carolina Luquez, Janet Dykes, Suzanne R Kalb, Kaitlin Hoyt, John R Barr, Todd Crawford, Anthony Chambers, Brian Douthit, Robert Cox, Matt Craig, John Spurzem, Joseph Doherty, Michael Allswede, Paul Byers, Thomas Dobbs
No abstract text is available yet for this article.
January 6, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28041655/trends-in-outcomes-and-hospitalization-charges-of-infant-botulism-in-the-united-states-a-comparative-analysis-between-kids-inpatient-database-and-national-inpatient-sample
#18
Tamara Opila, Asha George, Mohammad El-Ghanem, Nizar Souayah
BACKGROUND: New therapeutic strategies, including immune globulin intravenous, have emerged in the past two decades for the management of botulism. However, impact on outcomes and hospitalization charges among infants (aged ≤1 year) with botulism in the United States is unknown. METHODS: We analyzed the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) for in-hospital outcomes and charges for infant botulism cases from 1997 to 2009. Demographics, discharge status, mortality, length of stay, and hospitalization charges were reported from the two databases and compared...
February 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/27989928/anti-botulism-single-shot-vaccine-using-chitosan-for-protein-encapsulation-by-simple-coacervation
#19
Roger S Sari, Anna Christina de Almeida, Alex S R Cangussu, Edson V Jorge, Otto D Mozzer, Hércules Otacílio Santos, Wagner Quintilio, Igor Viana Brandi, Viviane Aguiar Andrade, Angelo Samir M Miguel, Eliane M Sobrinho Santos
The aim of the present study was to compare the potency and safety of vaccines against Clostridium botulinum (C. botulinum) type C and D formulated with chitosan as controlled release matrix and vaccines formulated in conventional manner using aluminum hydroxide. Parameters were established for the development of chitosan microspheres, using simple coacervation to standardize the use of this polymer in protein encapsulation for vaccine formulation. To formulate a single shot vaccine inactivated antigens of C...
October 27, 2016: Anaerobe
https://www.readbyqxmd.com/read/27966961/newly-designed-quinolinol-inhibitors-mitigate-the-effects-of-botulinum-neurotoxin-a-in-enzymatic-cell-based-and-ex-vivo-assays
#20
Paul T Bremer, Michael Adler, Cecilia H Phung, Ajay K Singh, Kim D Janda
Botulinum neurotoxin A (BoNT/A) is one of the most deadly toxins and is the etiological agent of the potentially fatal condition, botulism. Herein, we investigated 8-hydroxyquinoline (quinolin-8-ol) as a potential inhibitor scaffold for preventing the deadly neurochemical effects of the toxin. Quinolinols are known chelators that can disrupt the BoNT/A metalloprotease zinc-containing active site, thus impeding its proteolysis of the endogenous protein substrate, synaptosomal-associated protein 25 (SNAP-25)...
January 12, 2017: Journal of Medicinal Chemistry
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