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https://www.readbyqxmd.com/read/28617306/characterization-of-hemagglutinin-negative-botulinum-progenitor-toxins
#1
Suzanne R Kalb, Jakub Baudys, Theresa J Smith, Leonard A Smith, John R Barr
Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs), toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC), alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs) to cause hemagglutination...
June 15, 2017: Toxins
https://www.readbyqxmd.com/read/28597722/foodborne-botulism-in-the-faroe-islands-in-atwo-decade-period
#2
Anirban Nandy, Høgni Djurhuus, Shahin Gaini
No abstract text is available yet for this article.
June 9, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28584101/deubiquitinating-enzyme-vcip135-dictates-the-duration-of-botulinum-neurotoxin-type-a-intoxication
#3
Yien Che Tsai, Archana Kotiya, Erkan Kiris, Mei Yang, Sina Bavari, Lino Tessarollo, George A Oyler, Allan M Weissman
Botulism is characterized by flaccid paralysis, which can be caused by intoxication with any of the seven known serotypes of botulinum neurotoxin (BoNT), all of which disrupt synaptic transmission by endoproteolytic cleavage of SNARE proteins. BoNT serotype A (BoNT/A) has the most prolonged or persistent effects, which can last several months, and exerts its effects by specifically cleaving and inactivating SNAP25. A major factor contributing to the persistence of intoxication is the long half-life of the catalytic light chain, which remains enzymatically active months after entry into cells...
June 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28573317/further-optimization-of-peptide-substrate-enhanced-assay-performance-for-bont-a-detection-by-maldi-tof-mass-spectrometry
#4
Dongxia Wang, Jakub Baudys, Kaitlin M Hoyt, John R Barr, Suzanne R Kalb
Rapid and sensitive detection of botulinum neurotoxins (BoNTs), which cause botulism, is essential in a public health emergency or bioterrorism event. We have previously developed a mass spectrometry (MS)-based functional method, Endopep-MS assay, for the fast detection and differentiation of all BoNT serotypes by affinity enriching the toxin and detecting the serotype-specific cleavage products of peptide substrates derived from the in vivo targets. To improve the performance of the Endopep-MS assay, we report here the further optimization of the peptide substrate for the detection of serotype A botulinum neurotoxins...
June 2, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28569348/black-tar-heroin-skin-popping-as-a-cause-of-wound-botulism
#5
Ihtesham A Qureshi, Mohtashim A Qureshi, Mohammad Rauf Afzal, Alberto Maud, Gustavo J Rodriguez, Salvador Cruz-Flores, Darine Kassar
BACKGROUND: Botulism is a rare potentially fatal and treatable disorder caused by a bacteria-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. It is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. We present our observations with a descriptive case series of wound botulism secondary to black tar heroin (BTH) injection. METHODS: We report a retrospective single-center case series of 15 consecutive cases of wound botulism presenting to University Medical Center of El Paso...
May 31, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28555060/role-of-homologous-fc-fragment-in-the-potency-and-efficacy-of-anti-botulinum-antibody-preparations
#6
Amram Torgeman, Eyal Ozeri, Alon Ben David, Eran Diamant, Osnat Rosen, Arieh Schwartz, Ada Barnea, Arik Makovitzki, Avishai Mimran, Ran Zichel
The only approved treatment for botulism relies on passive immunity which is mostly based on antibody preparations collected from hyper-immune horses. The IgG Fc fragment is commonly removed from these heterologous preparations to reduce the incidence of hyper-sensitivity reactions. New-generation therapies entering the pipeline are based on a combination of humanized monoclonal antibodies (MAbs), which exhibit improved safety and pharmacokinetics. In the current study, a systematic and quantitative approach was applied to measure the direct contribution of homologous Fc to the potency of monoclonal and polyclonal antitoxin preparations in mice...
May 29, 2017: Toxins
https://www.readbyqxmd.com/read/28534855/rbc-adherence-of-immune-complexes-containing-botulinum-toxin-improves-neutralization-and-macrophage-uptake
#7
Fetweh H Al-Saleem, Rashmi Sharma, Rama Devudu Puligedda, Md Elias, Chandana Devi Kattala, Paul M Simon, Lance L Simpson, Scott K Dessain
In the paralytic disease botulism, the botulinum neurotoxin (BoNT) passes through the bloodstream to reach and inactivate neuromuscular junctions. Monoclonal antibodies (mAbs) may be useful BoNT countermeasures, as mAb combinations can rapidly clear BoNT from the blood circulation. We have previously shown that the BoNT-neutralizing potency of mAbs can be improved through red blood cell (RBC) immunoadherence. For example, a fusion protein (FP) that adheres biotinylated mAbs to the RBC surface enabled a pair of mAbs to neutralize 5000 LD50 BoNT/A in the mouse protection assay...
May 19, 2017: Toxins
https://www.readbyqxmd.com/read/28524037/-clinical-analysis-of-53-patients-with-clostridium-botulinum-food-poisoning
#8
Peng Zhang, Jianguang Dong, Lili Bai, Zewu Qiu
OBJECTIVE: To analyze the epidemiologic data of patients with Clostridium botulinum food poisoning, and to improve the understanding, diagnosis and treatment of food borne botulism. METHODS: A retrospective study was conducted. Fifty-three patients with Clostridium botulinum food poisoning admitted to Chinese PLA Center of Poisoning and Treatment from January 2009 to December 2016 were enrolled, and they were divided into mild, moderate, and severe groups according to the severity of disease...
May 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28522711/draft-genome-sequences-of-five-brazilian-clostridium-botulinum-group-iii-type-d-c-strains
#9
Cédric Woudstra, Roseane B Brito, Antônio A Fonseca Júnior, Rodrigo O S Silva, Francisco C F Lobato, Patrick Fach
Animal botulism is mainly associated with Clostridium botulinum group III-producing neurotoxin types C, C/D, D, and D/C. In this report, we present the draft genome sequences of the first five strains of Clostridium botulinum type D/C isolated in Brazil and used for vaccination purposes.
May 18, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28500638/adult-intestinal-colonization-botulism-mimicking-brain-death
#10
Brin Freund, Lindsey Hayes, Lucia Rivera-Lara, Charlotte Sumner, Vinay Chaudhry, Kevin Chatham-Stephens, Katharine Benedict, Suzanne Kalb, David Blythe, Richard Brooks, John C Probasco
No abstract text is available yet for this article.
May 13, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28489146/acute-muscular-weakness-in-children
#11
REVIEW
Ricardo Pablo Javier Erazo Torricelli
Acute muscle weakness in children is a pediatric emergency. During the diagnostic approach, it is crucial to obtain a detailed case history, including: onset of weakness, history of associated febrile states, ingestion of toxic substances/toxins, immunizations, and family history. Neurological examination must be meticulous as well. In this review, we describe the most common diseases related to acute muscle weakness, grouped into the site of origin (from the upper motor neuron to the motor unit). Early detection of hyperCKemia may lead to a myositis diagnosis, and hypokalemia points to the diagnosis of periodic paralysis...
April 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/28480790/wound-botulism-its-neurological-manifestations-treatment-and-outcomes-a-case-series-from-the-glasgow-outbreak-2015
#12
Sarah-Jane Martin, Gillian Penrice, Corinne Amar, Kathie Grant, George H Gorrie
Background and aims We examined the neurological manifestations, treatment and outcomes of a subset of 25 patients within the largest ever outbreak of wound botulism in Europe. Methods and results All 25 cases were intravenous drug users. The most common presenting symptom was dysarthria in 19/25 (76%), followed by dysphagia in 12/25 (48%), blurred vision in 10/25 (40%) and double vision in 8/25 (32%). Microbiological analysis confirmed the diagnosis in nine cases (36%). Duration of admission positively correlated with time to antitoxin, time to wound debridement and female sex...
January 1, 2017: Scottish Medical Journal
https://www.readbyqxmd.com/read/28478747/creation-of-a-virtual-antidotes-network-between-pharmacy-departments-of-catalan-hospitals
#13
Raquel Aguilar-Salmerón, Edurne Fernández de Gamarra-Martínez, Milagros García-Peláez, Antoni Broto-Sumalla, Lidia Martínez-Sánchez, Santiago Nogué-Xarau
Objetive: To design a virtual antidote network between hospitals that could help to locate on-line those hospitals that stocked those antidotes with the highest difficulty in terms of availability, and ensured that the medication was loaned in case of necessity. METHODS: The application was developed by four hospital pharmacists and two clinical toxicologists with the support of a Healthcare Informatics Consultant Company. RESULTS: The antidotes network in Catalonia, Spain, was launched in July 2015...
May 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28478553/electrochemical-aptamer-scaffold-biosensors-for-detection-of-botulism-and-ricin-proteins
#14
Jessica Daniel, Lisa Fetter, Susan Jett, Teisha J Rowland, Andrew J Bonham
Electrochemical DNA (E-DNA) biosensors enable the detection and quantification of a variety of molecular targets, including oligonucleotides, small molecules, heavy metals, antibodies, and proteins. Here we describe the design, electrode preparation and sensor attachment, and voltammetry conditions needed to generate and perform measurements using E-DNA biosensors against two protein targets, the biological toxins ricin and botulinum neurotoxin. This method can be applied to generate E-DNA biosensors for the detection of many other protein targets, with potential advantages over other systems including sensitive detection limits typically in the nanomolar range, real-time monitoring, and reusable biosensors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28475321/metal-ions-effectively-ablate-the-action-of-botulinum-neurotoxin-a
#15
Paul T Bremer, Sabine Pellett, James P Carolan, William H Tepp, Lisa M Eubanks, Karen N Allen, Eric A Johnson, Kim D Janda
Botulinum neurotoxin serotype A (BoNT/A) causes a debilitating and potentially fatal illness known as botulism. The toxin is also a bioterrorism threat, yet no pharmacological antagonist to counteract its effects has reached clinical approval. Existing strategies to negate BoNT/A intoxication have looked to antibodies, peptides, or organic small molecules as potential therapeutics. In this work, a departure from the traditional drug discovery mindset was pursued, in which the enzyme's susceptibility to metal ions was exploited...
May 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28465161/assessment-of-elisa-as-endpoint-in-neuronal-cell-based-assay-for-bont-detection-using-hipsc-derived-neurons
#16
Sabine Pellett, William H Tepp, Eric A Johnson, Dorothea Sesardic
INTRODUCTION: Botulinum neurotoxins (BoNTs), the causative agents of botulism, are widely used as powerful bio-pharmaceuticals to treat neuro-muscular disorders. Due to the high potency and potential lethality of BoNTs, careful monitoring of the biologic activity of BoNT-based pharmaceuticals is required to ensure safe usage. For decades, the only approved method for potency determination of pharmaceutical BoNTs was the mouse bioassay (MBA), but in recent years improvements in cell-assay technologies have enabled MBA replacement by cell-based assays for specific product evaluations...
April 29, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28464023/heat-shock-and-prolonged-heat-stress-attenuate-neurotoxin-and-sporulation-gene-expression-in-group-i-clostridium-botulinum-strain-atcc-3502
#17
Katja Selby, Gerald Mascher, Panu Somervuo, Miia Lindström, Hannu Korkeala
Foodborne pathogenic bacteria are exposed to a number of environmental stresses during food processing, storage, and preparation, and in the human body. In order to improve the safety of food, the understanding of molecular stress response mechanisms foodborne pathogens employ is essential. Many response mechanisms that are activated during heat shock may cross-protect bacteria against other environmental stresses. To better understand the molecular mechanisms Clostridium botulinum, the causative agent of botulism, utilizes during acute heat stress and during adaptation to stressfully high temperature, the C...
2017: PloS One
https://www.readbyqxmd.com/read/28455330/regulation-of-botulinum-neurotoxin-synthesis-and-toxin-complex-formation-by-arginine-and-glucose-in-clostridium-botulinum-atcc-3502
#18
Chase M Fredrick, Guangyun Lin, Eric A Johnson
Botulinum neurotoxin (BoNT) produced by neurotoxigenic clostridia is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation are not well studied. Previous studies indicated that growth and BoNT formation was affected by arginine and glucose in C. botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine, glucose and three products of arginine metabolism, citrulline, proline and ornithine...
April 28, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28450682/clinical-serum-therapy-benefits-cautions-and-potential-applications
#19
Toru Hifumi, Akihiko Yamamoto, Manabu Ato, Kyoko Sawabe, Kazunori Morokuma, Nobuya Morine, Yutaka Kondo, Eiichiro Noda, Atsushi Sakai, Jin Takahashi, Kazuo Umezawa
Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use...
April 28, 2017: Keio Journal of Medicine
https://www.readbyqxmd.com/read/28441004/insights-into-the-mechanisms-by-which-clostridial-neurotoxins-discriminate-between-gangliosides
#20
Joshua R Burns, Gregory S Lambert, Michael R Baldwin
Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the causative agents of the paralytic diseases botulism and tetanus, respectively. Entry of toxins into neurons is mediated through initial interactions with gangliosides, followed by binding to a protein co-receptor. Herein, we aimed to understand the mechanism through which individual neurotoxins recognize the carbohydrate motif of gangliosides. Using cell-based and in vitro binding assays, in conjunction with structure-driven site-directed mutagenesis, a conserved hydrophobic residue within the BoNTs that contributes to both affinity and specificity toward Sia5-containing gangliosides was identified...
May 9, 2017: Biochemistry
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