Estrabismo após toxina botulínica para fins estéticos

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Marta Halfeld Ferrari Alves Lacordia

2011-06-01

Full Text Available RESUMO Nas últimas décadas, a toxina botulínica tem sido aplicada para fins terapêuticos em inúmeras afecções. A toxina do tipo A foi aprovada primeiramente em 1989 para o uso em estrabismo, blefaroespasmo e espasmo hemifacial de pacientes maiores que 12 anos de idade. A observação de que pacientes tratados de blefaroespasmo com toxina botulínica apresentavam um efeito adicional de diminuição das rugas de expressão inspirou estudos sobre a aplicação cosmética da toxina. Recentemente, a toxina botulínica do tipo A foi aprovada para fins estéticos. Este trabalho relata um caso de ocorrência de estrabismo após aplicação de toxina botulínica na face para fins estéticos.

[A case of foodborne botulism in the province of Viterbo

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Flavia Verginelli

2016-06-01

The present article follows the diagnostic therapeutic pathway of the patient, highlighting the critical points not only related to the clinic but also to the ministerial procedures for reporting a case of botulism. This case provides an opportunity to emphasize the need for greater awareness about how to prevent and correctly manage the cases of botulism, both by the general population and by physicians who faced a patient with suspected poisoning by Botulinum toxin. [Article in Italian

Fatal outbreak of botulism in Greenland

DEFF Research Database (Denmark)

Hammer, Tóra Hedinsdottir; Jespersen, Sanne; Kanstrup, Jakob

2015-01-01

respiratory muscle paralysis. We present five cases of foodborne botulism occurring in Greenland, two with fatal outcome, caused by ingestion of tradionally preserved eider fowl. In the cases of the survivors, antitoxin and supportive care, including mechanical ventilation, were administered. In these cases...

[Botulism. Therapeutic management. Apropos of 36 cases].

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Sudre, Y; Becq-Giraudon, B; Boutaud, P h

1975-03-08

Botulism is relatively common in the Vienne department as we have observed 36 cases over a peroid of 7 years. Other French cases, published over the last 10 years, included 10 to 19 cases in the largest series. In a total of 10 series, there were 105 cases. Botulism is caused, in most cases, by eating ham prepared on the farm. It gives rise to the usual clinical picture including paralysis of accommodation, dysphagia, digestive symptoms with abdominal pain and constipation and finally, bladder paralysis. The mild forms are fairly common. We did not observe any severe cases. Our patients were treated in two homogeneous series of 17 cases each ; two patients were given no treatment. Patients treated by sero-anatoxin therapy according to classical methods, evolved towards a cure within 21 days on average. Patients treated by sulfguanidin were cured within 24 days. This study permitted us to confirm that sero-anatoxin therapy is not essential. The disadvantages are the number of injections, the possibility of sometimes fatal hyper-sensitive reactions which, in the opinion of many authors, justifies routine cover with cortisone. This attitude does not seem to us justified owing to the usually benign nature of the botulism. The treatment with sulfaguanidin is well tolerated and is not of any risk to the patient.

Botulism associated with commercially canned chili sauce--Texas and Indiana, July 2007.

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2007-08-03

On July 7 and July 11, 2007, public health officials in Texas and Indiana, respectively, reported to CDC four suspected cases of foodborne botulism, two in each state. Investigations conducted by state and local health departments revealed that all four patients had eaten brands of Castleberry's hot dog chili sauce before illness began. Botulinum toxin type A was detected in the serum of one Indiana patient and in a leftover chili mixture obtained from his home. CDC informed the Food and Drug Administration (FDA) of the apparent link between illness and consumption of the chili sauce. On July 18, FDA issued a consumer advisory, and the manufacturer, Castleberry's Food Company (Augusta, Georgia), subsequently recalled the implicated brand and several other products produced in the same set of retorts (commercial-scale pressure cookers for processing canned foods) at the same canning facility. Examination of the canning facility in Georgia during the outbreak investigation had identified deficiencies in the canning process. On July 19, the U.S. Department of Agriculture Food Safety and Inspection Service (FSIS) issued a press release that announced a recall of chili and certain meat products from the Castleberry canning facility and provided recommendations to consumers. That recall was expanded on July 21 to include additional canned products. A fifth case of botulism potentially linked to one of the recalled products is under investigation in California. This report describes the ongoing investigation by members of OutbreakNet and others and the measures undertaken to control the outbreak, which is the first outbreak of foodborne botulism in the United States associated with a commercial canning facility in approximately 30 years. Clinicians should be vigilant for symptoms of botulism, including symmetric cranial nerve palsies, especially if accompanied by descending flaccid paralysis. Consumers should not eat any of the recalled chili sauce or other recalled

Cluster of botulism among Dutch tourists in Turkey, June 2008.

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Swaan, C M; van Ouwerkerk, I M; Roest, H J

2010-04-08

In June 2008, three Dutch tourists participating in a mini-cruise in Turkey needed urgent repatriation for antitoxin treatment because of symptoms of botulism. Because there was a shortage of antitoxin in the Netherlands, an emergency delivery was requested from the manufacturer in Germany. An outbreak investigation was initiated into all nine cruise members, eight of whom developed symptoms. C. botulinum type B was isolated in stool culture from four of them. No other patients were notified locally. Food histories revealed locally purchased unprocessed black olives, consumed on board of the ship, as most likely source, but no left-overs were available for investigation. C. botulinum type D was detected in locally purchased canned peas, and whilst type D is not known to be a cause of human intoxication, its presence in a canned food product indicates an inadequate preserving process. With increasing tourism to areas where food-borne botulism is reported regularly special requests for botulism antitoxin may become necessary. Preparing an inventory of available reserve stock in Europe would appear to be a necessary and valuable undertaking.

Three outbreaks of foodborne botulism caused by unsafe home canning of vegetables--Ohio and Washington, 2008 and 2009.

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Date, Kashmira; Fagan, Ryan; Crossland, Sandra; Maceachern, Dorothy; Pyper, Brian; Bokanyi, Rick; Houze, Yolanda; Andress, Elizabeth; Tauxe, Robert

2011-12-01

Foodborne botulism is a potentially fatal paralytic illness caused by ingestion of neurotoxin produced by the spore-forming bacterium Clostridium botulinum. Historically, home-canned vegetables have been the most common cause of botulism outbreaks in the United States. During 2008 and 2009, the Centers for Disease Control and Prevention (CDC) and state and local health departments in Ohio and Washington State investigated three outbreaks caused by unsafe home canning of vegetables. We analyzed CDC surveillance data for background on food vehicles that caused botulism outbreaks from 1999 to 2008. For the three outbreaks described, patients and their family members were interviewed and foods were collected. Laboratory testing of clinical and food samples was done at the respective state public health laboratories. From 1999 to 2008, 116 outbreaks of foodborne botulism were reported. Of the 48 outbreaks caused by home-prepared foods from the contiguous United States, 38% (18) were from home-canned vegetables. Three outbreaks of Type A botulism occurred in Ohio and Washington in September 2008, January 2009, and June 2009. Home-canned vegetables (green beans, green bean and carrot blend, and asparagus) served at family meals were confirmed as the source of each outbreak. In each instance, home canners did not follow canning instructions, did not use pressure cookers, ignored signs of food spoilage, and were unaware of the risk of botulism from consuming improperly preserved vegetables. Home-canned vegetables remain a leading cause of foodborne botulism. These outbreaks illustrate critical areas of concern in current home canning and food preparation knowledge and practices. Similar gaps were identified in a 2005 national survey of U.S. adults. Botulism prevention efforts should include targeted educational outreach to home canners.

Management of animal botulism outbreaks: from clinical suspicion to practical countermeasures to prevent or minimize outbreaks

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Anniballi, F.; Fiore, A.; Löfström, Ch.; Skarin, H.; Auricchio, B.; Woudstra, C.; Bano, L.; Segerman, B.; Koene, M.G.J.

2013-01-01

Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded animals, and some fishes. The disease is caused by exposure to toxins produced by Clostridium botulinum and other botulinum toxin–producing clostridia. Botulism in animals represents a severe environmental and economic

Botulism (type A in a horse - case report

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Sevim Kasap

2016-01-01

Full Text Available This paper presents the case of a six year-old, male, thoroughbred horse with clinical signs of inappetence, weakness, and incoordination when walking. Clinical examination showed that the horse staggered and leaned to the left side. Feedstuff was present inside and around its mouth. Salivation was increased and there was no reflex at the palpebrae and tongue. The horse had difficulty swallowing and the tone of its tail was reduced. Botulism was diagnosed based on the clinical signs. Antibiotic (ceftiofur and fluid-electrolyte treatment was commenced. Next day, neostigmin was added to the horse’s treatment, and it became recumbent. The horse’s palpebral, tongue and tail reflexes returned partially after neostigmine methylsulphate treatment on the same day and it stood up on day four. However, it could not swallow anything during the whole week, so after getting permission from the owner, the horse was euthanized on day 10. Samples of the colonic content and blood serum were sent by courier to the laboratory for toxin neutralization, however, botulinum neurotoxins could not be detected. After that, serum samples from days 6 and 10 were sent to another laboratory for testing for botulinum neurotoxin antibodies by ELISA. Specific antibodies against botulinum neurotoxin type A were measured, indicating a previous, immuno-relevant contact with the toxin. This seroconversion for type A supports the clinical botulism diagnosis. Type A botulism is rarely seen in Europe and has been detected in a horse in Turkey for the first time.

A Family Outbreak of Foodborne Botulism Following Consumption of Home-Canned Doogh in Hamadan, West of Iran

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Hashemi

2015-02-01

Full Text Available Background Food-borne botulism is one of the potentially fatal forms of food poisoning, usually caused by ingestion of home-canned vegetables, fruits and fish products. Objectives The aim of this study was to report an outbreak of botulism due to homemade doogh in Hamadan, Iran. Patients and Methods During an outbreak, 10 members of a family referred to the hospital because of food poisoning. All patients had a history of consumption of doogh, a traditional drink. After careful physical examination, all of them were hospitalized. Botulism was suspected in all patients except for the first patient. Results The first patient was a 76-year-old man who died after 12 hours of admission due to respiratory distress. Nine subsequent patients were diagnosed as botulism with the following symptoms: diplopia (90%, dizziness (70%, nausea and vomiting (80%, ptosis (60%, symmetric weakness of extremities (60%, dysarthria (30%, chest discomfort (30%, mydriasis (20%, dysphasia (20% and dry mouth (20%. All of the nine patients received botulinum antitoxin and improved during 5-15 days of hospitalization. Conclusions Immediate diagnosis based on careful history and physical examination are essential for management of botulism. People should be notified about proper food handling and preparation of traditional homemade foods.

The Short-Lived Epidemic of Botulism From Commercially Canned Foods in the United States, 1919 to 1925.

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Kazanjian, Powel

2018-04-17

In 1919, three deadly outbreaks of botulism caused by consumption of canned olives packed in California captured national headlines. In all of the outbreaks, which occurred in separate locales, unsuspecting people died after consuming tainted food during a banquet or family meal. The press's sensational portrayal of canned food as hazardous aroused alarm among consumers at a time when commercial canning was becoming more common. Intent on restoring the image of their product as safe and wholesome, canning industry leaders funded a "botulism commission" of scientific experts in 1919 to investigate how to systematically eliminate the threat of botulism that had imperiled their business. The commissioners identified the scientific reasons for the outbreaks, and on the basis of their findings, the California Department of Public Health issued explicit recommendations for sterilization procedures intended to ensure safety. However, the department did not mandate inspections for all canneries. When commercially packed fruits and vegetables continued to cause botulism, industry leaders voluntarily backed a cannery inspection act to legally require all California canners to possess appropriate equipment and follow scientifically validated sterilization procedures. After the California legislature approved the act in 1925, canneries were inspected, regulations were enforced, and no further outbreaks occurred. This botulism epidemic is an example of a disease outbreak that was controlled when business interests became aligned with public health goals. The press's portrayal of afflicted persons as innocent victims and worthy citizens galvanized businessmen to implement safeguards to protect consumers from botulism intoxication. To preserve their customer base and salvage their corporations, leaders of the canning industry acknowledged the public health threat of their unregulated procedures and acted on the recommendations of scientists.

Nanotechnology Laboratory Collaborates with Army to Develop Botulism Vaccine | FNLCR

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The Nanotechnology Characterization Laboratory (NCL) is collaborating with the Army to develop a candidate vaccine against botulism. Under a collaboration agreement between the National Cancer Institute and the U.S. Army Medical Research Institute of

Foodborne botulism in southwest Romania during the post-communism period 1990-2007.

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Neghina, Adriana Maria; Marincu, Iosif; Moldovan, Roxana; Iacobiciu, Ioan; Neghina, Raul

2010-02-01

This study was a retrospective investigation of botulism cases over a period of 18 years following major political and economic changes, addressing the question of whether this disease is still an important health concern in southwest Romania. The medical records of botulism cases were used as the source of data. Patients from five southwest Romanian counties were hospitalized at Victor Babes Hospital of Infectious Diseases in Timisoara during the period 1990-2007. The median annual incidence of botulism cases in southwest Romania decreased from 0.1 per 100 000 persons during 1990-1998, to 0.05 per 100 000 persons during 1999-2007. Most of the cases (18.6%) were diagnosed in 1990, immediately following the communism period. The median age of the patients was 38 years (range 16-73 years); 24 (55.8%) were male; the case fatality rate was 2.3%. A significantly higher incidence rate of 2.7 cases per 100 000 persons occurred in rural areas, even though most of the cases (53.5%) were inhabitants of urban areas. The clinical pattern included: difficulty swallowing (79.1%), double and/or blurred vision (69.8%), dry mouth (60.5%), drooping eyelids (51.2%), vomiting (39.5%), mydriasis (37.2%), constipation (27.9%), abdominal pain (23.3%), and slurred speech (18.6%). All cases were attributed to contaminated food sources, mainly home-prepared traditional pork products. Although the botulism cases decreased over the study period in southwest Romania, this life-threatening disease continues to be an important concern. A strategy addressing individual behaviors in the home is needed to improve food safety. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Type C botulism in pelicans and other fish-eating birds at the Salton Sea

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Rocke, T.E.; Nol, P.; Pelizza, C.; Sturm, K.K.

2004-01-01

In 1996, type C avian botulism killed over 10,000 pelicans and nearly 10,000 other fish-eating birds at the Salton Sea in southern California. Although botulism had been previously documented in waterbirds at the Sea, this die-off was unusual in that it involved primarily fish-eating birds. The American White Pelican (Pelecanus erythrorynchos) was the species with the greatest mortality in 1996. Since 1996, mortality has recurred every year but losses have declined (Salton Sea, but the source of toxin for fish is unknown.

A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons

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Sreenivasan, Nandini; Person, Bobbie; Shew, Mark; Wheeler, Daniel; Hall, Julia; Bogdanow, Linda; Leniek, Karyn; Rao, Agam

2015-01-01

Objectives. Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. Methods. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. Results. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. Conclusions. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks. PMID:26378846

Cluster of Botulism among dutch tourists in Turkey, june 2008

NARCIS (Netherlands)

Swaan, C.M.; Ouwerkerk, van M.; Roest, H.I.J.

2010-01-01

In June 2008, three Dutch tourists participating in a mini-cruise in Turkey needed urgent repatriation for antitoxin treatment because of symptoms of botulism. Because there was a shortage of antitoxin in the Netherlands, an emergency delivery was requested from the manufacturer in Germany. An

BOTULISM E IN LAKE ERIE: ECOLOGY AND LOWER FOOD WEB TRANSFER

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This project will determine the environmental conditions that favor botulism Type E bacteria in Lake Erie and explore whether quagga mussels are altering bottom sediment conditions to favor C. botulinum growth. Analysis of environmental parameters, including water chemistry, alg...

Investigation of a type C/D botulism outbreak in free-range laying hens in France.

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Souillard, R; Le Maréchal, C; Ballan, V; Rouxel, S; Léon, D; Balaine, L; Poëzevara, T; Houard, E; Robineau, B; Robinault, C; Chemaly, M; Le Bouquin, S

2017-04-01

In 2014, a botulism outbreak in a flock of laying hens was investigated in France. In the flock of 5020 hens, clinical signs of botulism occurred at 46 weeks of age. A type C/D botulism outbreak was confirmed using the mouse lethality assay for detection of botulinum toxin in serum and a real-time PCR test to detect Clostridium botulinum in intestinal contents. The disease lasted one week with a mortality rate of 2.6% without recurrence. Botulism in laying hens has rarely been reported. Five monthly visits were made to the farm between December 2014 and May 2015 for a longitudinal study of the persistence of C. botulinum in the poultry house after the outbreak, and to assess egg contamination by C. botulinum. Several samples were collected on each visit: in the house (from the ventilation circuit, the egg circuit, water and feed, droppings) and the surrounding area. Thirty clean and 30 dirty eggs were also swabbed at each visit. In addition, 12 dirty and 12 clean eggs were collected to analyse eggshell and egg content. The samples were analysed using real-time PCR to detect type C/D C. botulinum. The bacterium was still detected in the house more than 5 months after the outbreak, mostly on the walls and in the egg circuit. Regarding egg contamination, the bacteria were detected only on the shell but not in the content of the eggs. Control measures should therefore be implemented throughout the egg production period to avoid dissemination of the bacteria, particularly during egg collection.

Outbreak of Type C Botulism in Commercial Layer Chickens.

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Sato, Yuko; Wigle, William L; Gallagher, Susan; Johnson, Amy L; Sweeney, Raymond W; Wakenell, Patricia S

2016-03-01

This report describes an outbreak of type C botulism in two organic, free-range commercial layer farms in the Midwest. Hens affected were 64-wk-old Hy-Line brown hens and 34-wk-old Hy-Line brown hens owned by the same company, but housed on different premises, with approximately 20,000 birds per house. Mortality over the 2 wk of investigation was estimated to be up to 8% and 2.8%, respectively, with birds acting listless, lethargic, and depressed. Clinical signs consisted of progressive paralysis, and severely affected birds were moribund and laterally recumbent. Hens had ruffled feathers that easily epilated, with loss of muscular tone in the neck, tail, and wings. Hens had closed eyes and were reluctant to move. There were no significant gross or histopathologic lesions. Intestinal samples were submitted to the University of Pennsylvania Botulism Diagnostic Laboratory for real-time PCR and were positive for Clostridium botulinum organisms containing the Type C neurotoxin gene. Speculations on the source of the botulinum toxins include poor mortality removal leading to cannibalism of decomposing carcasses, as well as birds on the farm having access to putrid carcasses in the compost pile from a hole in their outdoor access fence.

National outbreak of type a foodborne botulism associated with a widely distributed commercially canned hot dog chili sauce.

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Juliao, Patricia C; Maslanka, Susan; Dykes, Janet; Gaul, Linda; Bagdure, Satish; Granzow-Kibiger, Lynae; Salehi, Ellen; Zink, Donald; Neligan, Robert P; Barton-Behravesh, Casey; Lúquez, Carolina; Biggerstaff, Matthew; Lynch, Michael; Olson, Christine; Williams, Ian; Barzilay, Ezra J

2013-02-01

On 7 and 11 July 2007, health officials in Texas and Indiana, respectively, reported 4 possible cases of type A foodborne botulism to the US Centers for Disease Control and Prevention. Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin. Investigators reviewed patients' medical charts and food histories. Clinical specimens and food samples were tested for botulinum toxin and neurotoxin-producing Clostridium species. Investigators conducted inspections of the cannery that produced the implicated product. Eight confirmed outbreak associated cases were identified from Indiana (n = 2), Texas (n = 3), and Ohio (n = 3). Botulinum toxin type A was identified in leftover chili sauce consumed by the Indiana patients and 1 of the Ohio patients. Cannery inspectors found violations of federal canned-food regulations that could have led to survival of Clostridium botulinum spores during sterilization. The company recalled 39 million cans of chili. Following the outbreak, the US Food and Drug Administration inspected other canneries with similar canning systems and issued warnings to the industry about the danger of C. botulinum and the importance of compliance with canned food manufacturing regulations. Commercially produced hot dog chili sauce caused these cases of type A botulism. This is the first US foodborne botulism outbreak involving a commercial cannery in >30 years. Sharing of epidemiologic and laboratory findings allowed for the rapid identification of implicated food items and swift removal of potentially deadly products from the market by US food regulatory authorities.

Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach

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Wanpen Chaicumpa

2011-05-01

Full Text Available Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT derived from heterologous species (immunized animal or mouse hybridoma together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80% to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP, the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme.

Cortical recovery of swallowing function in wound botulism

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Ringelstein Erich B

2008-05-01

Full Text Available Abstract Background Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. Methods In this study, we applied whole-head magnetoencephalography (MEG in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM. Results The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC. In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. Conclusion These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.

Early, Real-Time Medical Diagnosis of Botulism by Endopeptidase-Mass Spectrometry.

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Rosen, Osnat; Feldberg, Liron; Gura, Sigalit; Brosh-Nissimov, Tal; Guri, Alex; Zimhony, Oren; Shapiro, Eli; Beth-Din, Adi; Stein, Dana; Ozeri, Eyal; Barnea, Ada; Turgeman, Amram; Ben David, Alon; Schwartz, Arieh; Elhanany, Eytan; Diamant, Eran; Yitzhaki, Shmuel; Zichel, Ran

2015-12-15

Botulinum toxin was detected in patient serum using Endopeptidase-mass-spectrometry assay, although all conventional tests provided negative results. Antitoxin was administered, resulting in patient improvement. Implementing this highly sensitive and rapid assay will improve preparedness for foodborne botulism and deliberate exposure. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Botulism in Brazil, 2000-2008: epidemiology, clinical findings and laboratorial diagnosis Botulismo no Brasil, 2000-2008: epidemiologia, achados clínicos e diagnóstico laboratorial

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Ruth Estela Gravato Rowlands

2010-08-01

Full Text Available Botulism is a rare and potentially lethal illness caused by Clostridium botulinum neurotoxin. We describe the findings of a laboratorial investigation of 117 suspected cases of botulism reported to the surveillance system in Brazil from January 2000 to October 2008. Data on the number and type of samples analyzed, type of toxins identified, reporting of the number of botulism cases and transmission sources are discussed. A total of 193 clinical samples and 81 food samples were analyzed for detection and identification of the botulism neurotoxin. Among the clinical samples, 22 (11.4% presented the toxin (nine type A, five type AB and eight with an unidentified type; in food samples, eight (9.9% were positive for the toxin (five type A, one type AB and two with an unidentified type. Of the 38 cases of suspected botulism in Brazil, 27 were confirmed by a mouse bioassay. Laboratorial botulism diagnosis is an important procedure to elucidate cases, especially food-borne botulism, to confirm clinical diagnosis and to identify toxins in food, helping sanitary control measures.Botulismo é uma doença rara e potencialmente letal, resultante da ação de uma neurotoxina produzida pelo Clostridium botulinum. No presente estudo, estão descritos os resultados da investigação laboratorial de 117 casos suspeitos de botulismo notificados ao sistema de vigilância, ocorridos no Brasil no período de janeiro de 2000 a outubro de 2008. Os dados obtidos sobre as fontes de transmissão, os tipos de toxina identificados e de amostras analisadas serão discutidos. Foram analisadas 193 amostras clínicas e 81 amostras de alimentos para detecção e identificação de neurotoxina botulínica. Entre as amostras clínicas, 22 (11,4% amostras apresentaram resultado positivo para toxina (nove do tipo A, cinco do tipo AB e em oito o tipo não foi identificado e entre as amostras de alimentos, oito (9,9% foram positivas (cinco do tipo A, uma do tipo AB e em duas o tipo n

Qualidade de vida e custos diretos em pacientes com blefaroespasmo essencial e espasmo hemifacial, tratados com toxina botulínica-A

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Osaki Midori Hentona

2004-01-01

Full Text Available OBJETIVO: Avaliar os custos e a qualidade de vida dos pacientes com blefaroespasmo essencial e espasmo hemifacial, submetidos à terapia com a toxina botulínica-A. MÉTODOS: Vinte e oito pacientes, sendo 16 com blefaroespasmo essencial e 12 com espasmo hemifacial, tratados com toxina botulínica-A, foram avaliados por meio de dois instrumentos: o SF-36 e a Escala de Disfunção de Blefaroespasmo. Os custos foram calculados segundo o número de unidades da toxina utilizadas por cada paciente no período de um ano. RESULTADOS: O custo total direto foi estimado em 1081,62 reais por ano (±89,39 para blefaroespasmo essencial e 618,06 reais por ano (±60,06 para espasmo hemifacial, para tratamento ambulatorial (p<0,001. Antes do tratamento, todos os domínios do SF-36 foram significantemente piores em ambas as doenças. Sob tratamento efetivo com toxina botulínica-A, os aumentos nos índices do SF-36 evidenciaram mudanças nas taxas de saúde geral da população em estudo, com diferença estatisticamente significante entre as respostas pré e pós-tratamento (p<0,05. Relacionando-se o SF-36 com Escala de Disfunção de Blefaroespasmo, foram observadas nos casos de blefaroespasmo essencial, relações significantes positivas (capacidade funcional, estado geral, aspecto emocional e aspectos sociais, ao passo que nos pacientes com espasmo hemifacial não foi encontrada nenhuma correlação. CONCLUSÃO: Este estudo demonstra notável impacto negativo das doenças na qualidade de vida desses pacientes, e uma significante melhora em ambas as doenças após tratamento com toxina botulínica-A. Além disso, os dados fornecem subsídios para justificar o alto custo da aquisição da toxina botulínica-A, devido a seus consideráveis benefícios para a qualidade de vida.

Toxina botulínica y su empleo en la patología oral y maxilofacial Botulinum toxin and its use in oral and maxillofacial pathology

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D. Martínez-Pérez

2004-06-01

Full Text Available Resumen: Las toxinas botulínicas son exotoxinas de la bacteria formadora de esporas Clostridim botulinum y los agentes causantes del botulismo. Cuando se inyecta en el músculo produce una parálisis flácida. El efecto clínico está directamente relacionado con la dosis y debe ajustarse para cada caso concreto. La Toxina botulínica ha demostrado en los más de veinte años en que se está utilizando que es un fármaco seguro. Las indicaciones de la toxina botulínica en la actualidad incluyen todas aquellas patologías que resultan de la hiperfunción muscular y la disfunción autonómica.Abstract: Botilinum toxins are exotoxins of the bacteria that form the Clostridium botulinum spores and the causative agents of botulism. When injected into the muscle flaccid paralysis is produced. The clinical effect is directly related with the dose and is should be adjusted for each particular case. over the last twenty years that it has been in use, the botulinum toxin has shown itself to be a reliable drug. Current indications for the use of botulinum toxin include all those pathologies which are the results of muscle hyperfunction and autonomic dysfunction.

Toxina botulínica para além da cosmética

OpenAIRE

Duarte, Maria José da Silva

2015-01-01

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015 As neurotoxinas produzidas a partir da bactéria Clostridium botulinum são potentes inibidores dos neurotransmissores que se encontram entre os neurónios e o músculo, inibindo também a sinalização entre os neurónios. Dos sete serótipos pertencentes à neurotoxina botulínic...

Fatal course of foodborne botulism in an eigth-month old Infant

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Davide Lonati

2011-12-01

Full Text Available An 8-month old girl, weighing 9 kg, was brought by her parents at 8.15 am to the Emergency Department (ED for a progressive worsening of weakness and acute respiratory failure. On admission, the baby presented with poor oral intake, a weak cry and extremely weak muscular body control. Poor gag and suck, unreactive mydriasis, hypotonia, lethargy and absence of peristalsis were noted. Laboratory data showed severe respiratory acidosis. Chest X-ray, electroencephalography, encephalic CT scan and MRI were all normal, as were cerebrospinal fluid analysis and viral tests. Orotracheal intubation and continuous mechanical ventilation were applied. The patient received fluids, corticosteroids, aerosol therapy, large-spectrum antibiotics and enteral- nutrition. Further investigation revealed ingestion of an improperly prepared homecanned homogenized turkey meal. Type A botulinum neurotoxin was identified. Trivalent botulinum antitoxin, prostigmine and oral activated charcoal were administered. Generalized flaccid paralysis, areflexic bilateral mydriasis, gastric stasis and deep coma persisted for the duration of the hospital stay, and the patient died of severe respiratory failure and cardiac arrest 12 days after ED admission. Botulism poisoning should be suspected in any infant presenting with feeding difficulties, constipation, descendent paralysis or acute respiratory failure. Supportive treatment and antidotal therapy should be performed as soon as a clinical diagnosis is made. We describe a case of foodborne botulism in an 8-month old infant caused by ingestion of an improperly prepared home-canned homogenized turkey meal, representing the youngest fatal case reported in medical literature.

An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

National Research Council Canada - National Science Library

Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

2008-01-01

... incompatible vaccine mixtures. Intradermally administered arrays of vaccines for protection from anthrax, botulism, plague, and staphylococcal toxic shock were biocompatible in vivo, retained potent antibody responses...

Avaliação da fenda palpebral após aplicação de toxina botulínica tipo A em pacientes com distonias faciais

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Mariana Eleonora Pereira Cunial

2012-12-01

Full Text Available OBJETIVO: Avaliar a medida da fenda palpebral em pacientes com blefaroespasmo essencial benigno (BEB e espasmo hemifacial (EHF após a aplicação periocular de toxina botulínica tipo A. MÉTODOS: Foram estudados pacientes portadores de BEB e EHF submetidos à injeção periocular de toxina botulínica tipo A pela técnica inner orbital de aplicação. Os pacientes foram fotografados em PPO antes da aplicação e catorze dias depois dela. A fenda palpebral foi mensurada nestas imagens por meio de processamento computadorizado de imagens, utilizando o programa ImageJ. As alterações da fenda palpebral foram observadas comparando-se as medidas obtidas no pré e pós-aplicação. RESULTADOS: Comparando-se as imagens obtidas com o programa ImageJ, houve aumento estatisticamente significante (p<0,001 da fenda palpebral em 14 olhos (51,8% após a aplicação de injeção periocular da toxina botulínica e nenhuma das imagens analisadas apresentou diminuição da fenda palpebral. CONCLUSÃO: No presente estudo, os pacientes portadores de distonias faciais apresentaram aumento de fenda palpebral estatisticamente significante após aplicação periocular de toxina botulínica tipo A.

A bibliography of references to avian botulism

Science.gov (United States)

Allen, Jack E.; Wilson, Sonoma S.

1977-01-01

This bibliography, first compiled in 1970 in response to many requests for information on avian botulism, has been updated to include the literature published through 1975.In general, only articles dealing primarily with the avian disease are included, as opposed to those concerned with various aspects of the biology of Clostridium botulinum, either type C or type E. A few exceptions, such as Bengton’s report of the first isolation and description of the type C organism, are included for their historical interest. Progress reports and other administrative documents not available for distribution or request are excluded, as are textbook accounts, which are generally summaries of work published elsewhere.Although Mr. Allen and Mrs. Wilson have attempted to list every important reference, they make no claim to complete coverage of the published literature. The authors will be grateful to users of the bibliography who call attention to errors or omissions.

Regional variations in home canning practices and the risk of foodborne botulism in the Republic of Georgia, 2003.

Science.gov (United States)

Tarkhashvili, N; Chokheli, M; Chubinidze, M; Abazashvili, N; Chakvetadze, N; Imnadze, P; Kretsinger, K; Varma, J; Sobel, J

2015-04-01

Foodborne botulism is a severe, paralytic illness caused by ingestion of preformed neurotoxins produced by Clostridium botulinum. In 2003, we conducted a population-based household survey of home canning practices to explore marked regional variations in botulism incidence in the Republic of Georgia (ROG). We designed a cluster sampling scheme and subdivided each of the 10 regions of the ROG into a variable number of strata. Households were selected from each stratum using a two-step cluster sampling methodology. We administered a questionnaire about home canning practices to household members responsible for food preparation. Using multivariate logistic regression analysis, we modeled high (eastern ROG) against low (western ROG) incidence areas. Overall, we surveyed 2,742 households nationwide. Home canning with a capping device hermetically sealing the lid covering the jar was practiced by 1,909 households (65.9%; 95% confidence interval [CI]: 59.8 to 72.1%). Canning was more prevalent in regions of low botulism incidence (34 versus 32%; P canning vegetables and consuming them (adjusted odds ratio [aOR] = 2.1; 95% CI: 1.3 to 3.5) and adding any of the following ingredients to the jar at time of preparation: >1 tablespoon of salt per liter (aOR = 5.1; 95% CI: 1.2 to 22.6); vinegar (aOR = 2.2; 95% CI: 1.3 to 3.7), and greens (aOR = 5.6; 95% CI: 1.7 to 18.2). The following practices were associated with a decreased risk in high-botulism areas: >57 jars canned per household annually (aOR = 0.5; 95% CI: 0.3 to 0.9), covering or immersing vegetables in boiling water before placing them into the jar (aOR = 0.3 95% CI: 0.2 to 0.6), covering or immersing vegetables in boiling water after placing them into the jar (aOR = 0.4; 95% CI: 0.2 to 0.9), or adding garlic (aOR = 0.2; 95% CI: 0.1 to 0.5) or aspirin (aOR = 0.1; 95% CI: 0.1 to 0.2) to the jar at the time of preparation.

Toxina botulínica como tratamento para fobia social generalizada com hiperidrose

OpenAIRE

Lessa,Larissa da Rocha; Fontenelle,Leonardo F.

2011-01-01

CONTEXTO: Enrubescimento, tremores e transpiração excessiva são fenômenos frequentemente observados na fobia social. OBJETIVOS: Descrever a resposta de um paciente com o tipo generalizado de fobia social e hiperidrose à terapia cognitivo-comportamental aliada à toxina botulínica. MÉTODO: Relato de caso único. RESULTADOS: O Sr. A, 20 anos, estudante universitário, procurou tratamento por apresentar sintomas compatíveis com os diagnósticos de fobia social e depressão. O Sr. A também apresentava...

Type C botulism in swine fed on restaurant waste

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Djeison L. Raymundo

2012-11-01

Full Text Available The paper addresses the epidemiologic data of the death of pigs during the period of 2002 to 2009 following the ingestion of botulinum neurotoxin type C. This neurotoxin was present in food residues originating from restaurant and hotel kitchens, stored in barrels without shelter from the sun and administered in a collective trough without prior thermal treatment. Animals which died at different ages showed clinical signs of botulism characterized by flaccid paralysis, weight loss, anorexia, weakness, lack of coordination, locomotion difficulties with the evolution of lateral recumbency with involuntary urination and defecation. No alterations were observed at postmortem and histological examination. The bioassay with serum neutralization in mice was carried out on samples of intestinal contents from pigs affected and revealed the presence of large quantities of botulinum toxin type C.

[Acute laryngeal dyspnea in the patient with botulism cured in 2001 year in ENT Department Hospital in Kalisz].

Science.gov (United States)

Bartnik, Władysław; Szewczyk, M; Bartnik-Krystalska, A

2004-01-01

The authors presented symptoms of botulism, diagnostics and treatment. In this case there was a necessity of urgent tracheotomy. The authors had good results because of early treatment with serum antibotulism A+B+C and symptomatic treatment. Decannulation was only after 45 days because the paralytic symptoms declined very slowly.

Avian botulism type E in waterbirds of Lake Michigan, 2010–2013

Science.gov (United States)

Chipault, Jennifer G.; White, C. LeAnn; Blehert, David S.; Jennings, Susan K.; Strom, Sean M.

2015-01-01

During 2010 to 2013, waterbird mortality surveillance programs used a shared protocol for shoreline walking surveys performed June to November at three areas in northern Lake Michigan. In 2010 and 2012, 1244 total carcasses (0.8 dead bird/km walked) and 2399 total carcasses (1.2 dead birds/km walked), respectively, were detected. Fewer carcasses were detected in 2011 (353 total carcasses, 0.2 dead bird/km walked) and 2013 (451 total carcasses, 0.3 dead bird/km walked). During 3 years, peak detection of carcasses occurred in October and involved primarily migratory diving and fish-eating birds, including long-tailed ducks (Clangula hyemalis; 2010), common loons (Gavia immer; 2012), and red-breasted mergansers (Mergus serrator; 2013). In 2011, peak detection of carcasses occurred in August and consisted primarily of summer residents such as gulls (Larus spp.) and double-crested cormorants (Phalacrocorax auritus). A subset of fresh carcasses was collected throughout each year of the study and tested for botulinum neurotoxin type E (BoNT/E). Sixty-one percent of carcasses (57/94) and 10 of 11 species collected throughout the sampling season tested positive for BoNT/E, suggesting avian botulism type E was a major cause of death for both resident and migratory birds in Lake Michigan. The variety of avian species affected by botulism type E throughout the summer and fall during all 4 years of coordinated surveillance also suggests multiple routes for bird exposure to BoNT/E in Lake Michigan.

A large outbreak of bovine botulism possibly linked to a massive contamination of grass silage by type D/C Clostridium botulinum spores on a farm with dairy and poultry operations.

Science.gov (United States)

Relun, A; Dorso, L; Douart, A; Chartier, C; Guatteo, R; Mazuet, C; Popoff, M R; Assié, S

2017-12-01

Type D bovine botulism outbreaks associated with poultry litter are increasingly reported in European countries, but the circumstances of exposure to Clostridium botulinum toxins remain unclear. In spring 2015, a large type D/C bovine botulism outbreak affected a farm with dairy and poultry operations. Epidemiological and laboratory investigations strongly suggest that the outbreak was caused by feeding cattle with insufficiently acidified grass silage that was contaminated by type D/C C. botulinum spores. The source of the spores remains unclear, but could have been a stack of poultry litter stored in the grass silage pasture before harvesting. The presence of putrefied poultry carcasses mixed in with the litter is relatively unlikely considering the careful daily removal of poultry carcasses. These findings reinforce the importance of proper ensiling of feed materials and highlight the need for safe disposal of poultry litter, even in the case of good management of poultry deadstock, in order to prevent bovine botulism.

Emergence of suspected type D botulism in ruminants in England and Wales (2001-2009), associated with exposure to broiler litter.

NARCIS (Netherlands)

Payne, J.H.; Hogg, R.A.; Otter, A.; Roest, H.I.J.; Livesey, C.T.

2011-01-01

Scanning surveillance by the Veterinary Laboratories Agency revealed the emergence of suspected botulism in ruminants in 2003, presented as flaccid paralysis. From 2003 to 2009, 168 cattle and 19 sheep incidents were recorded, with mortality between 5 and 80 per cent. All sheep incidents and 95 per

Toxicoinfectious botulism in commercial caponized chickens

Science.gov (United States)

Trampel, D.W.; Smith, Susan; Rocke, Tonie E.

2005-01-01

During the summer of 2003, two flocks of commercial broiler chickens experienced unusually high death losses following caponizing at 3 wk of age and again between 8 and 14 wk of age. In September, fifteen 11-wk-old live capons were submitted to the Iowa State University Veterinary Diagnostic Laboratory for assistance. In both flocks, the second episode of elevated mortality was associated with incoordination, flaccid paralysis of leg, wing, and neck muscles, a recumbent body posture characterized by neck extension, and diarrhea. No macroscopic or microscopic lesions were detected in affected chickens. Hearts containing clotted blood and ceca were submitted to the National Wildlife Health Center in Madison, WI. Type C botulinum toxin was identified in heart blood and ceca by mouse bioassay tests. Enzyme-linked immunosorbent assay tests on heart blood samples were also positive for type C botulinum toxin. Clostridium botulinum was isolated from the ceca and genes encoding type C botulinum toxin were detected in cecal contents by a polymerase chain reaction test. Chickens are less susceptible to botulism as they age, and this disease has not previously been documented in broilers as old as 14 wk of age. Wound contamination by spores of C. botulinum may have contributed to the unusually high death losses following caponizing.

Lobotomies and Botulism Bombs: Beckett's Trilogy and the Cold War.

Science.gov (United States)

Piette, Adam

2016-06-01

The article argues that Beckett's Trilogy stages the effects of a lobotomy operation on a potentially politically subversive writer, and that the consequences of the operation can be traced in both the retreat of the narrator(s) of the Trilogy into the mind and into comatose mental states and in the detail of the operation itself, based on the 'icepick' lobotomies performed by neurologist Walter Freeman in the late 1940s and early 1950s. To write about extreme psychiatric situations in the post-war period is necessarily to invoke the political uses of psychosurgery with which this article engages. The article goes on to consider the figure of the brain-damaged mind as a Cold War trope in the references to botulism and the motif of the penetrated skull in The Unnamable.

Barbiturate ingestion in three adult captive tigers (Panthera tigris and concomitant fatal botulism of one : clinical communication

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J. H. Williams

2011-05-01

Full Text Available Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay

Análise retrospectiva das alterações da dinâmica facial após aplicações seriadas de toxina botulínica tipo A

OpenAIRE

Rodrigo Pinto Gimenez

2007-01-01

INTRODUÇÃO: A presença de rugas na face devido à hipercinese muscular é comum nas regiões frontal, glabelar e peri-orbitárias. São descritos diversos métodos para o tratamento das rugas de expressão, como a dermoabrasão, a ablação a laser, o laser não ablativo, preenchimentos, cirurgia e aplicações de toxina botulínica. O tratamento das rugas da face com toxina botulínica tipo A é método consagrado, porém são pouco definidos os efeitos a longo prazo. Este estudo retrospectivo teve como objeti...

Management of Animal Botulism Outbreaks: From Clinical Suspicion to Practical Countermeasures to Prevent or Minimize Outbreaks

DEFF Research Database (Denmark)

Anniballi, Fabrizio; Fiore, Alfonsina; Löfström, Charlotta

2013-01-01

and economic concern because of its high mortality rate. Moreover, meat or other products from affected animals entering the food chain may result in a public health problem. To this end, early diagnosis is crucial to define and apply appropriate veterinary public health measures. Clinical diagnosis is based...... outbreaks. In this article we outline all phases of management of animal botulism outbreaks occurring in wet wild birds, poultry, cattle, horses, and fur farm animals....

Botulism outbreaks in natural environments — an update

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Mari eEspelund

2014-06-01

Full Text Available Clostridium botulinum comprises a diverse group of botulinum toxin-producing anaerobic rod-shaped spore-forming bacteria that are ubiquitously distributed in soils and aquatic sediments. Decomposition of plants, algae and animals creates anaerobic environments that facilitate growth of C. botulinum, which may then enter into food webs leading to intoxication of animals. Via saprophytic utilization of nutrients, the bacteria rapidly sporulate, creating a reservoir of highly robust spores. In the present review, we focus on the occurrence of C. botulinum in non-clinical environments, and examine factors influencing growth and environmental factors associated with botulism outbreaks. We also outline cases involving specific environments and their biota. In wetlands, it has been found that some C. botulinum strains can associate with toxin-unaffected organisms—including algae, plants, and invertebrates—in which the bacteria appear to germinate and stay in the vegetative form for longer periods of time. We suggest the need for future investigations to resolve issues related to the environments in which C. botulinum spores may accumulate and germinate, and where the vegetative forms may multiply.

Emergence of suspected type D botulism in ruminants in England and Wales (2001 to 2009), associated with exposure to broiler litter.

Science.gov (United States)

Payne, J H; Hogg, R A; Otter, A; Roest, H I J; Livesey, C T

2011-06-18

Scanning surveillance by the Veterinary Laboratories Agency revealed the emergence of suspected botulism in ruminants in 2003, presented as flaccid paralysis. From 2003 to 2009, 168 cattle and 19 sheep incidents were recorded, with mortality between 5 and 80 per cent. All sheep incidents and 95 per cent of cattle incidents had proximity to broiler litter. From July 2006, the gut contents collected from 74 affected cattle and 10 affected sheep were tested for Clostridium botulinum toxins using mice bioassays and for organisms by culture. Type D toxin was identified in 32 per cent of cattle and 18 per cent of sheep samples. C botulinum type D organisms were identified in 40 per cent of cattle and 30 per cent of sheep samples, but broth from one sample reacted with C and D antisera. Type C botulism has previously been reported more commonly than type D in the UK and has been associated with the use of poultry litter as fertiliser, bedding or feed. The almost exclusive association with C botulinum type D toxins or organisms in the gut contents in this survey suggests a change in the source or epidemiology of botulism in the UK. The source of C botulinum type D was uncertain. Broilers may carry C botulinum type D in their gut flora subclinically. The emergence of a new type D strain, or changes in broiler husbandry and nutrition, medication and other enteric infections may have affected colonisation with C botulinum. Further investigation of poultry and farm environments for sources of type D awaits the development of tests for C botulinum toxins that do not require the use of mice.

Bibliography of references to avian botulism: Update

Science.gov (United States)

Wilson, Sonoma S.; Locke, Louis N.

1982-01-01

This bibliography, first compiled in 1970 (Allen and Wilson 1977) and published in 1977 in response to many requests for information on avian botulism, has been updated to include the literature published through 1980.In general, only articles dealing primarily with the avian disease are included, as opposed to those concerned with the various aspects of the biology of Clostridium botulinum, either type C or E. A few exceptions, such as Bengtson's report of the first isolation and description of the type C organism, are included for their historical interest. Progress reports and other administrative documents not available for distribution on request are excluded, as are most textbook accounts, which are generally summaries of work published elsewhere.This bibliography was a cooperative effort by the National Wildlife Health Laboratory, U.S. Fish and Wildlife Service, and the U.S. National Park Service. The National Park Service provided partial funding for the work through Contract No. 89100-0491.Although the authors attempted to list every important reference, they make no claim to complete coverage of the published literature. The authors will be grateful to users of the bibliography who call attention to errors or omissions.Wayne I. Jensen (Retired)Milton Friend, Director, National Wildlife Health Laboratory

Botulism in the ICU: Nursing care plan.

Science.gov (United States)

Zariquiey-Esteva, G; Galeote-Cózar, D; Santa-Candela, P; Castanera-Duro, A

Botulism is a rare disease in Europe, caused by the bacterium Clostridium botulinum, notifiable, non-transmissible person-to-person and potentially fatal (between 5 and 10%) if not treated quickly. The favourable opinion of the Clinical Research Ethics Committee was obtained. We present the nursing care plan of a 49-year-old man with a diagnosis of bacterial intoxication caused by Clostridium botulinum, secondary to ingestion of beans in poor condition, who was admitted to the ICU for a total of 35 days. Holistic nursing evaluation during the first 24hours, with prioritisation of the systems that were deteriorating fastest: neurological and respiratory. Nine diagnoses were prioritised according to the NANDA taxonomy: Risk for allergy response, Ineffective breathing pattern, impaired oral mucous membrane, Impaired physical mobility, Risk for disuse syndrome, Risk for dysfunctional gastrointestinal motility, Impaired urinary elimination, Risk for acute confusion and Risk for caregiver role strain. The nursing care plan, standardised and organised with the NANDA taxonomy and prioritised with the outcome-present state-test (OPT) model, guaranteed the best care based on evidence, as the NOC scores improvement demonstrated. It was impossible to compare the nursing intervention with other case reports. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

Neuronal Functions Associated with Endo- and Exocytotic Events-cum-Molecular Trafficking May Be Cell Maturation-Dependent: Lessons Learned from Studies on Botulism

Science.gov (United States)

2011-01-01

Clostridium botulinum type A progenitor toxins . Infect Immun 64:1589–1594 Li L, Singh BR (1999) Structure -function relationship of clostridial...experimental design and demonstration of the validity of the targeted neurologic therapeutic delivery approach based on recombinant botulinum toxin ...Endocytosis Exocytosis Molecular trafficking Cell maturation Botulism Targeted therapeutic Background Botulinum neurotoxins (BoNTs) are produced by

Treatment of cervical dystonia with botulinum toxin in a patient with myasthenia gravis Tratamento de distonia cervical com toxina botulínica em uma paciente com miastenia gravis

Directory of Open Access Journals (Sweden)

MARCIA RUBIA R. GONÇALVES

1999-09-01

Full Text Available We report the case of a 49-year-old woman who has the rare combination of myasthenia gravis and cervical dystonia. She was treated with botulinum toxin type A with good response and no evidence of deterioration of the myasthenic symptoms. We therefore conclude that it is possible to use botulinum toxin in the presence of defective neuromuscular transmission.Relatamos o caso de uma mulher de 49 anos com rara combinação de miastenia gravis e distonia cervical tratada com toxina botulínica tipo A, apresentando boa resposta e nenhuma evidência de piora do quadro miastênico. A partir dessas observações concluimos que é possível o uso de toxina botulínica na presença de doença da transmissão neuromuscular.

Toxina botulínica e fisioterapia em crianças com paralisia cerebral espástica: revisão bibliográfica

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Milena Silva Teles

Full Text Available INTRODUÇÃO: A paralisia cerebral (PC é definida como uma condição neurológica não progressiva originada em razão de uma lesão no encéfalo imaturo que compromete os movimentos e a postura. A espasticidade está presente em 75% dos casos. Essa patologia tem incidência na população de aproximadamente 2 em cada 1.000 nascidos vivos e pode chegar a até 7 por 1.000 em países em desenvolvimento. O objetivo do estudo foi realizar uma revisão bibliográfica por meio da seleção e análise criteriosa de artigos científicos que relatem os efeitos da aplicação da toxina botulínica tipo A associada à fisioterapia em crianças com paralisia cerebral espástica. MATERIAIS E MÉTODOS: Foi realizada uma revisão bibliográfica nas bases de dados eletrônicas MEDLINE, LILACS e SciELO, no período de 1997 a 2009. Os descritores utilizados foram: "paralisia cerebral" e "espasticidade muscular", combinados com "toxina botulínica tipo A" e "fisioterapia". RESULTADOS: Somando-se todos os bancos de dados, um total de 50 artigos que continham os desfechos de interesse dessa revisão foram encontrados, no entanto, alguns artigos aparecem em mais de uma busca e em duplicidade de idioma. Então, 23 artigos foram utilizados neste estudo. DISCUSSÃO: Vários estudos demonstram que, para maior efetividade da toxina botulínica tipo A, esta deve ser associada a um programa fisioterapêutico que sempre deve considerar as etapas do desenvolvimento motor da criança. CONSIDERAÇÕES FINAIS: De acordo com a revisão bibliográfica apresentada, a TBA associada à fisioterapia para o controle da espasticidade se mostra bastante eficaz. Contudo, novas pesquisas acerca deste assunto são necessárias.

Botulismo tipo C em ganso ocorrido em Minas Gerais, Brasil Type C botulism in a goose at Minas Gerais, Brazil

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Francisco Carlos Faria Lobato

2008-08-01

Full Text Available Botulismo é uma intoxicação causada pela ingestão das toxinas produzidas pelo Clostridium botulinum, que acomete mamíferos e aves, caracterizando-se por um quadro de paralisia flácida. Neste trabalho, é descrito um caso de botulismo em ganso, ocorrido no município de Santa Luzia, região metropolitana de Belo Horizonte, no Estado de Minas Gerais. Ao exame clínico, o animal apresentava-se com um quadro de paralisia flácida dos músculos do pescoço, das pernas e asas, além de apresentar ainda desprendimento de penas. A necropsia não revelou lesões significativas. Foi colhido o soro do animal e submetido ao teste de soroneutralização em camundongo, que identificou a toxina de C. botulinum tipo C.Botulism is an intoxication caused by the ingestion of toxins produced by Clostridium botulinum, that affects mammals and birds, characterized by a flaceid paralysis. This report describes a case of botulism in a goose in Santa Luzia, Minas Gerais State, Brazil. Clinical examinations showed dropping feathers and flaccid paralysis involving the muscles of the wings, legs and neck. post-mortem examination showed no significant gross or macroscopic lesions C. botulinum type C toxin was demonstrated in the serum of the affected animal through serum neutralization test in mice.

Botulismo em bovinos de corte e leite alimentados com cama de frango Botulism in beef and dairy cattle fed with poultry litter

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Iveraldo S. Dutra

2005-06-01

Full Text Available Surtos de botulismo causados pelos tipos C e D da toxina botulínica são freqüentes no país, estando originalmente associados à osteofagia e à ingestão de alimentos e água contaminados. No presente trabalho são descritos os aspectos epidemiológicos, clínico-patológicos e laboratoriais de sete surtos da intoxicação em bovinos de corte e leite alimentados com cama de frango, ocorridos nos estados de São Paulo e Minas Gerais entre 1989 e 2000. Cinco surtos ocorreram em rebanhos de corte confinados ou criados extensivamente e suplementados com o subproduto, e dois em propriedades leiteiras. De um total de 1.535 animais alimentados regularmente com a cama de frango, 455 (29,64% morreram em um período que variou de 2 a 4 semanas. A morbidade nos sete surtos estudados variou de 3,47 a 100%, da mesma forma que a mortalidade. Em uma das propriedades a letalidade foi de 60,52%, e em todos os outros surtos ela foi acima de 88,43%; em três propriedades o coeficiente foi de 100%. Os sinais clínicos de paralisia progressiva, dificuldade na locomoção, decúbito e estado mental aparentemente normal, diminuição do tônus da musculatura da língua e cauda, sialorréia e dificuldade respiratória caracterizaram o quadro clínico. À necropsia de 30 animais não foi observada qualquer alteração macroscópica digna de nota. A presença de esporos de Clostridium botulinum foi detectada em amostras de cama de frango colhidas nas sete propriedades. Nas amostras de fígado, líquido ruminal e intestinal, provenientes dos 30 animais necropsiados, foi possível detectar toxinas botulínicas tipos C (5 ou D (9, ou classificada como pertencente ao complexo CD (1, em pelos menos um dos materiais provenientes de 15 animais, confirmando assim o diagnóstico clínico-patológico e epidemiológico de botulismo.Outbreaks of botulism caused by type C and D of the botulinum toxin are frequent in Brazil, and are associated with bone chewing and ingestion of

Hemimasticatory spasm treated with botulinum toxin: case report Espasmo hemimastigatório tratado com toxina botulínica: relato de caso

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Hélio A.G. Teive

2002-06-01

Full Text Available We describe a female patient with hemimasticatory spasm, a rare movement disorder due to dysfunction of the motor trigeminal nerve of unknown origin. This patient had an excellent response to botulinum toxin therapy.Relatamos o caso de paciente feminina com espasmo hemimastigatório, distúrbio do movimento raro decorrente de disfunção da porção motora do nervo trigeminal, de etiologia desconhecida. A paciente teve excelente resposta clínica ao tratamento com toxina botulínica.

Toxina botulínica en parálisis cerebral infantil: resultados en 27 sujetos a lo largo de un año

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Sanchez-Carpintero, R. (Rocío); Narbona, J. (Juan)

1997-01-01

Introducción y objetivos. Resultados positivos en el tratamiento de la parálisis cerebral infantil espástica con toxina botulínica, en estudios anglosajones de los últimos años, nos han llevado a iniciar este trabajo, cuyo objetivo es mostrar nuestra experiencia con la toxina en el tratamiento de esta enfermedad, establecer sus indicaciones, analizar los resultados obtenidos y plantear posibles aplicaciones futuras. Material y métodos. Incluimos 10 pacientes hemipléficos y 17 dipl...

Distonia laríngea: relato de caso e tratamento com toxina botulínica Laryngeal dystonia: case report and treatment with botulinum toxin

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Victor José Barbosa Santos

2006-06-01

Full Text Available Distonia laríngea, ou disfonia espasmódica, é caracterizada por contrações involuntárias e inapropriadas da musculatura responsável pela fonação, sendo a do tipo adutora a mais comum. Caracteriza-se por quebras fonatórias, sendo seu diagnóstico confirmado por videolaringoestroboscopia. O tratamento de escolha é feito com a aplicação direta de toxina botulínica nos músculos responsáveis pelo movimento incoordenado. O objetivo desse trabalho é relatar o caso de uma paciente com diagnóstico de distonia laríngea do tipo adutora, tratada com toxina botulínica e discutir as vantagens e observações descritas na literatura a respeito desse tratamento.Laryngeal dystonia or spasmodic dysphonia is characterized by involuntary and innapropiate spasms of vocal muscles, having the adductor type as the most common one. It is chacterized by strain-strangled voice with pitch breaks. Diagnosis is made by means of videolaryngostroboscopic exam. The treatment of choice is done with botulinum toxin directly injected in the muscles responsible for the mismatched movement. The aim of this study is to report on an adductor- type dysphonia patient and to discuss the advantages and observations about this treatment reported in the literature.

Evaluation of coproexamination as a diagnostic test for avian botulism

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Jensen, Wayne I.

1981-01-01

Fecal extracts and blood sera from 113 ducks showing clinical signs of botulism were examined for Clostridium botulinum type C toxin by means of the mouse toxicity test to evaluate coproexamination as a diagnostic procedure, as compared with demonstration of toxin in serum. When death of test mice unprotected with type specific antitoxin (while protected controls survived) was the criterion, 78.8% of the sera and 5.3% of the fecal extracts were positive. When characteristic signs of intoxication in the unprotected mice was included as evidence of toxin in the specimens, these percentages increased to 86.7 and 6.2, respectively.Fecal specimens were collected hourly for the first 6 h after peroral dosing of eight mallards (Anas platyrhynchos) with 1.0 LD50, of type C toxin and at 24, 48, and 72 h from birds surviving that long. From 2 to 4 toxin-positive specimens were passed by all eight ducks during the first 6 h, five specimens were positive at 24 h, and three were positive at 48 h. Only three specimens were collected at 72 h, all of which were negative. These findings suggest that attempts to detect toxin in the feces of wild ducks might have been more successful had the birds been captured earlier in the course of the disease.

Characterization of Clostridium Baratii Type F Strains Responsible for an Outbreak of Botulism Linked to Beef Meat Consumption in France.

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Mazuet, Christelle; Legeay, Christine; Sautereau, Jean; Bouchier, Christiane; Criscuolo, Alexis; Bouvet, Philippe; Trehard, Hélène; Jourdan Da Silva, Nathalie; Popoff, Michel

2017-02-01

A second botulism outbreak due to Clostridium baratii occurred in France in August 2015 and included three patients who had their meal in a restaurant the same day. We report the characterization of C. baratii isolates including whole genome sequencing (WGS). Four C. baratii isolates collected in August 2015 from the outbreak 2 were analysed for toxin production and typing as well as for genetic characterization. WGS was done using using the NEBNext Ultra DNA Library Prep kit for Illumina (New England Biolabs) and sequenced on MiSeq machine (Illumina) in paired-end reads of 250 bases. The phylogenetic tree was generated based on the UPGMA method with genetic distances computed by using the Kimura two-parameter model. Evolutionary analyses were conducted in Bionumerics (V.6.6 Applied Maths). Three C. baratii isolates for patient's stools and one isolate from meat produced botulinum neurotoxin (BoNT) type F and retained a bont/F7 gene in OrfX cluster. All isolates were identical according to the WGS. However, phylogeny of the core genome showed that the four C. baratii strains were distantly related to that of the previous C. baratii outbreak in France in 2014 and from the other C. baratii strains reported in databanks. The fact that the strains isolated from the patients and meat samples were genetically identical supports that the meat used for the Bolognese sauce was responsible for this second botulism outbreak in France. These isolates were unrelated to that from the first C. baratii outbreak in France in 2014 indicating a distinct source of contamination. WGS provided robust determination of genetic relatedness and information regarding BoNT typing and toxin gene locus genomic localization.

Uso de toxina botulínica paravertebral para detener la progresión de escoliosis en pollos pinealectomizados: la columna vertebral como sistema de tensegridad

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Álvaro González-Miranda

Full Text Available Antecedentes y Objetivos. La escoliosis idiopática infantil no tiene un tratamiento satisfactorio que permita reducir la importante morbilidad y mortalidad asociada a los casos más severos y progresivos de la enfermedad. El desarrollo de procedimientos que puedan ralentizar la progresión de la enfermedad durante el desarrollo del niño puede influir favorablemente en el crecimiento y retrasar el tratamiento definitivo de la deformidad al momento de la madurez músculoesquelética. Presentamos un estudio sobre la influencia de la toxina botulínica en el desarrollo de deformidad en un modelo animal de escoliosis progresiva. Material y método. Utilizamos 52 pollos Broiler hembra, en los que se practicó pinealectomía para producir escoliosis. Comparamos la evolución de la deformidad entre un grupo control y un grupo intervención asignado a recibir toxina botulínica paravertebral en la concavidad de la curva, bajo control electromiográfico. Realizamos estudios radiográficos y anatomopatológicos de los animales para evaluar los resultados. El grado de escoliosis se midió utilizando el método del ángulo de Cobb. Resultados. Cinco animales no sobrevivieron al estudio (1 en el grupo control y 4 en el de intervención. En el grupo control observamos una deformidad media de 32.9º (n= 25 y en el grupo intervención de 18.8º (n=22, encontrando diferencias estadísticamente significativas (p < 0.05. Por tanto, la aplicación de toxina botulínica en la concavidad de la deformidad de pollos pinealectomizados frena la progresión de escoliosis. Conclusiones. La consideración de la columna vertebral y sus tejidos blandos asociados como una estructura de tensegridad puede explicar el fenómeno mediante el desequilibrio generado entre los componentes de tensión (músculos y ligamentos y compresión (vértebras que conforman el sistema. Estos resultados justifican nuevos estudios en investigación clínica para explorar una nueva alternativa

Diplopia após injeção de toxina botulínica tipo A para rejuvenescimento facial

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Márcia Melo de Oliveira Rassi

2012-06-01

Full Text Available Relato de 4 casos de pacientes encaminhadas ao serviço de Ortóptica deste Hospital, que apresentaram diplopia após a injeção de toxina botulínica tipo A para rejuvenescimento facial. Nas medidas de ângulo do estrabismo em posições diagnósticas todas apresentaram microestrabismo paralítico, sendo duas por déficit da função do músculo oblíquo inferior e duas por déficit de função de músculo reto lateral. Baseados nos casos descritos, aconselha-se aos profissionais que fazem uso desta toxina para fins de rejuvenescimento facial que estejam atentos para a diplopia como efeito colateral.

Correção de estrabismo paralítico por injeção de toxina botulínica Management of paralytic strabismus by injection of botulinum toxin

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Raquel Wattiez

2000-02-01

Full Text Available Objetivo: Avaliar a ação da toxina botulínica em paralisias adquiridas de VI e III nervos. Pacientes e métodos: Foram tratados com toxina botulínica 15 pacientes, com diagnóstico de paralisia de VI e III nervos, aguda ou crônica. Foram estudados de forma prospectiva, durante os meses de agosto de 1998 a maio de 1999. O estudo incluiu, além da avaliação do estrabismo, avaliação oftalmológica completa. Os pacientes foram acompanhados por um período de 2 a 7 meses após a última aplicação. Resultados: Onze pacientes (73% apresentaram paralisias do VI nervo e 4 pacientes (27%, paralisias de III nervo. Seis casos foram agudos (40% e 9 casos (60%, crônicos. Cinco dos 6 casos agudos (83% conseguiram controlar o desvio com a toxina botulínica como único tratamento e obter fusão. Dos 9 casos crônicos, 2 casos (22% corrigiram o desvio só com a toxina, os outros 7, além da aplicação, foram submetidos à cirurgia, dos quais 4 casos (46% foram corrigidos e os outros 3 casos (32% não. Conclusão: Concluímos que nos casos em que houve força muscular residual, após a paralisia, e bom potencial de fusão, a toxina botulínica foi o melhor tratamento, pois foi possível controlar o desvio e obter fusão, sem cirurgia.Purpose: To evaluate the treatment by injection of botulinum toxin in acquired sixth and third nerve palsies. Methods: Fifteen patients were treated with botulinum toxin. They were studied prospectively during nine months, between August, 1998 and May, 1999. In addition to the strabismus examination, a complete ophthalmological evaluation was performed. The patients were followed for 2 to 7 months after the last injection or surgical procedure. Results: Eleven patients (73% presented with sixth nerve palsy and four (27% with third nerve palsy. Six cases were acute (40% and 9 cases (60% were chronic. Five acute cases (83% obtained ocular alignment and controlled the deviation with toxin. Two of nine chronic cases (22

O uso da toxina botulínica no tratamento da distonia laríngea (disfonia espasmódica: estudo preliminar com doze pacientes Use of botulinum toxin in the treatment of laryngeal dystonia (spasmodic dysphonia: preliminary study of twelve patients

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Hélio A. G. Teive

2001-03-01

Full Text Available A distonia laríngea (disfonia espasmódica é distúrbio do movimento caracterizado por contrações involuntárias da musculatura laríngea envolvida no processo de vocalização. A utilização da toxina botulínica no tratamento da distonia laríngea trouxe consideráveis benefícios clínicos. Descrevemos os resultados preliminares do uso terapêutico da toxina botulínica no tratamento da distonia laríngea em 12 pacientes. Após investigação clínica, os pacientes foram submetidos a videolaringoestroboscopia para confirmação diagnóstica e as injeções de toxina botulínica foram realizadas através de punção da membrana cricotireóidea em direção ao músculo tireoaritenóideo, com uso de eletromiografia. A maioria dos pacientes submetidos ao tratamento com toxina botulínica apresentou melhora significativa da distonia laríngea (83% dos casos, com duração média do efeito de quatro meses, sem efeitos colaterais significativos.Laryngeal dystonia (spasmodic dysphonia is a movement disorder characterized by involuntary contractions of laryngeal muscles involved with vocalization. The introduction of botulinum toxin in the treatment of laryngeal dystonia had a major clinical impact due to the striking improvement of symptoms. We report the preliminary results of therapeutical use of botulinum toxin in the treatment of twelve patients with laryngeal dystonia. After an extensive clinical evaluation, the patients underwent a videostroboscopic exam for diagnostic confirmation. Botulinum toxin was injected in the cricothyreoid membrane, directed towards the thyreoaritenoid muscle, with the aid of eletromyography needles. Most of patients who underwent botulinum toxin injection had a significant improvement of their symptoms (83%, with effects lasting for four months in average and without important side effects.

Botulinum toxin for treatment of cocontractions related to obstetrical brachial plexopathy Toxina botulínica para tratamento das co-contrações relacionadas à plexopatia braquial obstétrica

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Carlos O. Heise

2005-09-01

Full Text Available Botulinum toxin type A was recently introduced for treatment of biceps - triceps muscle cocontraction, which compromises elbow function in children with obstetrical brachial plexopathy. This is our preliminary experience with this new approach. Eight children were treated with 2 - 3 U/kg of botulinum toxin injected in the triceps (4 patients and biceps (4 patients muscle, divided in 2 or 3 sites. All patients submitted to triceps injections showed a long-lasting improvement of active elbow flexion and none required new injections, after a follow-up of 3 to 18 months. Three of the patients submitted to biceps injections showed some improvement of elbow extension, but none developed anti-gravitational strength for elbow extension and the effect lasted only three to five months. One patient showed no response to triceps injections. Our data suggest that botulinum toxin can be useful in some children that have persistent disability secondary to obstetrical brachial plexopathy.A toxina botulínica do tipo A foi introduzida recentemente para o tratamento das co-contrações entre os músculos biceps e triceps, que comprometem a função do cotovelo nas crianças com plexopatia braquial obstétrica. Apresentamos nossa experiência preliminar com esta abordagem. Oito crianças foram tratadas com 2 - 3 U/kg de toxina botulínica injetada nos músculos triceps (4 pacientes e biceps (4 pacientes, divididas em 2 ou 3 sítios. Todos os pacientes submetidos a injeções no triceps apresentaram melhora persistente da flexão do cotovelo e nenhum precisou de novas aplicações após seguimento de 3 a 18 meses. Três pacientes submetidos a aplicações no biceps apresentaram melhora na extensão do cotovelo, mas nenhum adquiriu força antigravitacional e o efeito durou apenas 3 a 5 meses. Um paciente não respondeu às injeções. Nossos dados sugerem que a toxina botulínica pode ser útil no tratamento de algumas crianças com seqüelas de plexopatia braquial

Reabilitação funcional e analgesia com uso de toxina botulínica A na síndrome dolorosa regional complexa tipo I do membro superior: relato de casos Rehabilitación funcional y analgesia con uso de toxina botulínica A en el síndrome doloroso regional compleja tipo I del miembro superior: relato de casos Functional rehabilitation and analgesia with botulinum toxin A in upper limb complex regional pain syndrome type I: case reports

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Gabriela Rocha Lauretti

2005-04-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Freqüentemente, soma-se ao quadro de alodínia e hiperalgesia em pacientes portadores de Síndrome Dolorosa Regional Complexa (SDRC tipo I a incapacidade funcional do segmento acometido. Relatam-se dois casos de SDRC em que a aplicação de toxina botulínica-A como fármaco coadjuvante contribuiu na recuperação funcional motora do membro acometido. RELATO DOS CASOS: Duas pacientes portadoras de SDRC tipo I foram inicialmente avaliadas para controle da dor no membro superior direito. Ambas apresentavam incapacidade para abrir a mão e dor pela escala analógica numérica (EAN de 10 em repouso ou quando a mão ou os dedos eram passivamente manipulados. Iniciou-se seqüência de 5 bloqueios, do gânglio estrelado ipsilateral a intervalos semanais, com clonidina e lidocaína. Simultaneamente, durante a realização do terceiro bloqueio do gânglio estrelado, foram administrados 75 UI de toxina botulínica-A nos músculos flexores das falanges e da articulação do punho. Uma semana após a aplicação da toxina botulínica-A, as pacientes apresentavam relaxamento das falanges e punho, relatavam facilidade para execução da fisioterapia passiva e a dor classificada foi como 2 (EAN à manipulação passiva. Ao término da realização da seqüência de bloqueios do gânglio estrelado, as pacientes foram submetidas a 3 sessões semanais de administração por via venosa regional de clonidina, lidocaína e parecoxib. Após 8 meses de avaliação, as pacientes apresentaram 70% e 80% de recuperação motora e funcional do membro acometido. CONCLUSÕES: A aplicação por via muscular de toxina botulínica A resultou em melhora da movimentação do membro acometido, analgesia auxiliando na sua recuperação funcional.JUSTIFICATIVA Y OBJETIVOS: Frecuentemente, se suman al cuadro de alodínia e hiperalgesia en pacientes portadores de Síndrome Doloroso Regional Complejo (SDRC tipo I la incapacidad funcional del segmento

Avaliação do filme lacrimal de pacientes com distonia facial durante tratamento com toxina botulínica tipo A Lacrimal film evaluation of patients with facial dystonia during botulinum toxin type A treatment

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Patricia Grativol Costa

2006-06-01

Full Text Available OBJETIVO: Determinar o efeito da toxina botulínica no filme lacrimal em pacientes com distonia facial. MÉTODOS: Foram incluídos 24 pacientes portadores de blefaroespasmo essencial e espasmo hemifacial que receberam aplicação de toxina botulínica tipo A que foram submetidos à propedêutica do filme lacrimal previamente à aplicação e após, com 7 e 30 dias. RESULTADOS: Houve diminuição das queixas de olho seco trinta dias após a aplicação, entretanto, o tempo de ruptura do filme lacrimal e o teste de Schirmer não demonstraram variação significativa entre os períodos pré-tratamento e 1 mês da aplicação. Em relação ao teste de coloração com rosa bengala, todos os olhos que coraram no pré-tratamento, melhoraram na última avaliação. CONCLUSÃO: A injeção de toxina botulínica pode aliviar as queixas de olho seco nos pacientes com distonia facial pela provável ação de inibição do orbicular na sua função de bomba lacrimal.PURPOSE: To determine the effect of botulinum toxin injection in the eyelid on lacrimal film in patients with facial dystonia. METHODS: Twenty-four patients with essential blepharospasm and hemifacial spasm were submitted to botulinum toxin injection and lacrimal film tests were performed before the application and after seven and thirty days. RESULTS: There was improvement in symptoms of dry eye and rose bengal test, however, the breakup time and Schirmer's test did not show significant variation between pretreatment and after 1 month of follow-up. CONCLUSION: The dry eye symptoms in patients with facial dystonia may be attenuated by botulinum toxin due to its possible inhibitory effect on the orbicular muscle leading to a decrease in lacrimal pump.

Efectividad del tratamiento conservador y/o toxina botulínica en la displasia de cadera en parálisis cerebral infantil espástica. Revisión sistemática

OpenAIRE

Busto Ruiz, Elena

2014-01-01

Objetivo: Estudiar la efectividad del tratamiento conservador y/o toxina botulínica tipo A en la prevención o tratamiento de la displasia o dislocación de la cadera en PCI espástica. Material y métodos: Se realizó una búsqueda bibliográfica en las bases de datos de Pubmed, Web of Science (WOS), PEDro y Cochrane Library. Las palabras clave utilizadas fueron hip dysplasia, hip dislocation, hip subluxation, cerebral palsy, treatment, management, child. Se incluyeron todo tipo d...

Foodborne botulinum type E intoxication associated with dried bean curd: first case report in Taiwan.

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Lai, Lung-Shiang; Wang, Yi-Mei; Lin, Chin-Hsien

2011-06-01

Botulism type E intoxication is a rare condition among human botulism. We aim to describe a first case of botulism type E intoxication in Taiwan. We report a 36-year-old young man with foodborne botulism type E associated with commercially vacuum packaged dried bean curd. He developed bilateral ptosis, diplopia and dysphagia 4 days after taking the dried bean curd. Electrophysiologic findings demonstrated waxing responses to 3 Hz repetitive nerve stimulation and decreased compound muscle action potentials on peripheral nerve conduction study. A bioassay for botulism in mice demonstrated that the patient had botulism caused by type E botulinum toxin. Antibodeis to C. botulinum type E were identified from his serum, confirming the diagnosis. This is the first known case of foodborne type E botulism in Taiwan. The potential source of this foodborne botulism should consider contaminated food made of soy beans.

Benefícios da aplicação de toxina botulínica associada à fonoterapia em pacientes disfágicos graves Benefits of botulinum toxin associated to swallowing therapy in patients with severe dysphagia

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Fernanda Teixeira Menezes; Katia Alonso Rodrigues; Isabella Christina de Oliveira Neto; Brasília Maria Chiari; Dayse Manrique; Maria Inês Rebelo Gonçalves

2012-01-01

Estudo de casos para caracterizar os benefícios da aplicação de toxina botulínica em glândulas salivares, associada à fonoterapia em pacientes disfágicos graves. Foram analisados cinco prontuários de pacientes neurológicos, em uso exclusivo de via alternativa de alimentação, com idades entre 17 e 70 anos, sendo quatro do gênero masculino e um do gênero feminino. Do total, quatro pacientes eram traqueostomizados. Foi considerado como critério de inclusão apresentar disfagia grave, com manifest...

Toxina botulínica no tratamento da dor Toxina botulínica en el tratamiento del dolor Botulinum toxin in pain treatment

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Orlando Carlos Gomes Colhado

2009-06-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: A toxina botulínica (TxB, uma das mais potentes toxinas bacterianas conhecidas, tem reconhecidamente ação terapêutica eficaz no tratamento de algumas síndromes dolorosas. Entretanto, algumas de suas indicações ainda estão em fase de comprovação com relação a sua eficácia. O objetivo deste estudo foi revisar o histórico, propriedades farmacológicas e aplicações clinicas da TxB, quando empregada no tratamento de dores de diferentes origens. CONTEÚDO: A TxB é o produto da fermentação do Clostridium Botulinum, uma bactéria anaeróbia Gram-positiva. Comercialmente, as TxB existem nas formas A e B, agentes biológicos obtidos laboratorialmente. A TxB, uma neurotoxina que possui alta afinidade pelas sinapses colinérgicas, ocasiona bloqueio na liberação de acetilcolina pelo terminal nervoso, sem alterar a condução neural de sinais elétricos ou síntese e armazenamento de acetilcolina. Comprovadamente, a TxB pode enfraquecer seletivamente a musculatura dolorosa, interrompendo o ciclo espasmo-dor. Com relação à dor, varias publicações têm demonstrado a eficácia e segurança da TxB-A no tratamento da cefaleia tipo tensão, migrânea, dor lombar crônica e dor miofascial. CONCLUSÕES: A TxB-A é segura e bem tolerada em desordens dolorosas crônicas, onde regimes de farmacoterapia podem sabidamente provocar efeitos colaterais. Outra vantagem é a redução do uso de analgésicos e o tempo de ação de 3 a 4 meses por dose. Entretanto pesquisas futuras serão necessárias para se estabelecer a eficácia da TxB-A em desordens dolorosas crônicas e seu exato mecanismo no alivio da dor, bem como seu potencial em tratamentos multifatoriais.JUSTIFICATIVA Y OBJETIVOS: La toxina botulínica (TxB, una de las más potentes toxinas bacterianas de que se tiene conocimiento, posee una reconocida acción terapéutica eficaz en el tratamiento de algunos síndromes dolorosos. Sin embargo, algunas de sus

[Intoxication of botulinum toxin].

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Chudzicka, Aleksandra

2015-09-01

Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. © 2015 MEDPRESS.

OCORRÊNCIA DE BOTULISMO EM BOVINOS CONFINADOS NO RIO GRANDE DO SUL

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Franciele Maboni

2010-12-01

Full Text Available Botulism is the intoxication caused by a neurotoxin produced by the Clostridium botulinum, distinguished by flacid or complete skeletal musculature paralysis. This study reports a botulism outbrake in feedlot bovine, fed with corn silage. Samples of the liver, and of the intestinal and ruminal content from one of the bovine that presented typical clinical state for botulism, as well as a portion of corn silage were sent for bacterial analysis. In the laboratory, bioassay and serum neutralization were performed on rats, confirming the suspect for type C botulism. This report intends to warn veterinaries and breeders, which practice herd feedlot, because this procedure increases botulism susceptibility, and it is mainly related to the type and quality of the food ingested.

Uso de toxina botulínica para tratamiento de la hipertrofía del músculo masetero Use of botulinum toxin for treatment of hypetrophy of the masseter muscle

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F. González Magaña

2012-09-01

Full Text Available Definimos la hipertrofia del músculo masetero como el crecimiento excesivo de la masa muscular de dicho músculo, de presentación subclínica y de etiología multifactorial. Presenta una incidencia entre los 20 a 40 años sin predilección de sexo. Desde que en 1880 Legg la describiera por primera vez, se han intentado múltiples tratamientos, desde los médicos hasta los quirúrgicos, siendo el tratamiento con toxina botulínica el de mayor aceptación en la actualidad. El objetivo del presente artículo es realizar una revisión bibliográfica y proveer una herramienta para el médico que se enfrente a la hipertrofia del músculo masetero, además de presentar un caso clínico unilateral y la técnica empleada para su tratamiento. Como método diagnóstico en el paciente empleamos TAC de cráneo y macizo facial con cortes finos a 1 mm, así como de la región maseterina y aplicamos toxina botulínica de acuerdo a la zona de seguridad propuesta por Nam-Ho Kim y en base a los puntos anatómicos que indica el mismo protocolo, a dosis de 50 U en intervalos de 3 meses. Empleamos también TAC postoperatorio como medio de evaluación del resultado. Los tratamientos médicos con toxina botulínica son variables en sus dosis, aplicaciones y técnicas, así como en los diferentes productos disponibles en el mercado. En nuestro caso, el resultado fue clínicamente satisfactorio, cubriendo en su totalidad las expectativas del paciente. Proponemos que la protocolización del paciente, las dosis adecuadas, el tiempo entre aplicaciones y los sitios anatómicos correctos de inyección, llevan a la corrección de la hipertrofia del músculo masetero.Masseter muscle hypertrophy is an overgrowth of muscle mass with subclinical presentation and multifactorial etiology, with an incidence between 20 to 40 years and without sex predilection. In 1880 Legg describes this pathology for the first time and since then have been reported and attempted to formally

Linden flower (Tilia spp. as potential vehicle of Clostridium botulinum spores in the transmission of infant botulism El té de tilo como vehículo potencial de esporas de Clostridium botulinum en la transmisión del botulismo infantil

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M. I. Bianco

2009-12-01

Full Text Available Infant botulism is an intestinal toxemia caused principally by Clostridium botulinum. Since the infection occurs in the intestinal tract, numerous food products have been investigated for the presence of C. botulinum and its neurotoxins. In many countries, people use linden flower (Tilia spp tea as a household remedy and give it to infants as a sedative. Therefore, to help provide a clear picture of this disease transmission, we investigated the presence of botulinum spores in linden flowers. In this study, we analyzed 100 samples of unwrapped linden flowers and 100 samples of linden flowers in tea bags to determine the prevalence and spore-load of C. botulinum. Results were analyzed by the Fisher test. We detected a prevalence of 3% of botulinum spores in the unwrapped linden flowers analyzed and a spore load of 30 spores per 100 grams. None of the industrialized linden flowers analyzed were contaminated with botulinum spores. C. botulinum type A was identified in two samples and type B in one sample. Linden flowers must be considered a potential vehicle of C. botulinum, and the ingestion of linden flower tea can represent a risk factor for infant botulism.El botulismo del lactante es una toxiinfección causada, principalmente, por Clostridium botulinum. Debido a que esta infección ocurre en el tracto intestinal, la presencia de esta bacteria y sus neurotoxinas ha sido investigada en numerosos alimentos. En muchos países se utiliza el té de tilo (Tilia spp. como sedante natural, el que se administra incluso a los lactantes. A fin de contribuir al esclarecimiento de la transmisión de esta enfermedad, se investigó la prevalencia y la carga de esporas botulínicas en esta hierba. Se analizaron 100 muestras de tilo comercializado a granel y 100 muestras de tilo industralizado en “saquitos”. Los resultados de prevalencia fueron analizados por el test de Fisher y la carga de esporas por la técnica del número más probable. Se halló una

Wound Botulism in Injection Drug Users: Time to Antitoxin Correlates with Intensive Care Unit Length of Stay

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Offerman, Steven R

2009-11-01

Full Text Available Objectives: We sought to identify factors associated with need for mechanical ventilation (MV, length of intensive care unit (ICU stay, length of hospital stay, and poor outcome in injection drug users (IDUs with wound botulism (WB.Methods: This is a retrospective review of WB patients admitted between 1991-2005. IDUs were included if they had symptoms of WB and diagnostic confirmation. Primary outcome variables were the need for MV, length of ICU stay, length of hospital stay, hospital-related complications, and death.Results: Twenty-nine patients met inclusion criteria. Twenty-two (76% admitted to heroin use only and seven (24% admitted to heroin and methamphetamine use. Chief complaints on initial presentation included visual changes, 13 (45%; weakness, nine (31%; and difficulty swallowing, seven (24%. Skin wounds were documented in 22 (76%. Twenty-one (72% patients underwent mechanical ventilation (MV. Antitoxin (AT was administered to 26 (90% patients but only two received antitoxin in the emergency department (ED. The time from ED presentation to AT administration was associated with increased length of ICU stay (Regression coefficient = 2.5; 95% CI 0.45, 4.5. The time from ED presentation to wound drainage was also associated with increased length of ICU stay (Regression coefficient = 13.7; 95% CI = 2.3, 25.2. There was no relationship between time to antibiotic administration and length of ICU stay.Conclusion: MV and prolonged ICU stays are common in patients identified with WB. Early AT administration and wound drainage are recommended as these measures may decrease ICU length of stay.[West J Emerg Med. 2009;10(4:251-256.

Comparação entre os métodos de injeção de toxina botulínica em músculo ocular externo com o uso do eletromiógrafo e com o uso da pinça de Mendonça Electromyograph assistance and Mendonça's forceps - a comparison between two methods of botulinum toxin A injection into the extraocular muscle

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Tomás Fernando Scalamandré Mendonça

2005-04-01

Full Text Available OBJETIVO: Comparar dois métodos de aplicação de toxina botulínica A (TBA em músculo ocular externo: com auxílio de eletromiógrafo (EMG e com a pinça de Mendonça. MÉTODOS: Foram analisados no Departamento de Oftalmologia da UNIFESP 29 pacientes que apresentavam estrabismo e baixa acuidade visual em um olho. Foram divididos em dois grupos: grupo I - 17 pacientes que receberam a toxina botulínica A por meio de injeção com auxílio da pinça de Mendonça e grupo II - 12 pacientes que receberam a toxina botulínica A por injeção guiada pelo eletromiógrafo. Os pacientes dos dois grupos foram avaliados no 7º e no 14º dia após aplicação. Compararam-se os resultados dos dois grupos neste período de tempo. Os testes de correlação de Friedman e Mann-Whitney foram usados para análise estatística. RESULTADOS: Houve diferença estatística entre as médias de desvio pré-aplicação e em pelo menos um período (7º ou 14º dia após aplicação, tanto no grupo dos pacientes em que foi utilizada a pinça, quanto no grupo de pacientes em que foi utilizado o eletromiógrafo. Não houve diferença estatística dos desvios pré-aplicação e pós-aplicação entre os dois grupos. CONCLUSÃO: Os dois métodos de aplicação da toxina botulínica A são equivalentes e portanto, o uso da pinça de Mendonça pode ser método alternativo ao uso do eletromiógrafo, para guiar a injeção de toxina botulínica A.PURPOSE: To compare two methods of botulinum toxin A (BTA injection into the extraocular muscle (EOM: the electromyographically (EMG guided injection and the injection using Mendonça's forceps. METHODS: Twenty-nine (29 patients with strabismus and low visual acuity in one eye were examined at the Department of Ophthalmology of UNIFESP. They were divided into 2 groups - group I with 17 patients receiving the botulinum toxin A injection using Mendonça's forceps, and group II with 12 patients receiving the toxin with electromyographical

Aplicación de la toxina botulínica A para el tratamiento del síndrome de Frey Application of botulinum toxin A for the treatment of Frey’s Syndrome

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J. Mareque Bueno

2008-10-01

Full Text Available El síndrome Aurículo-temporal también conocido como sudoración gustativa o síndrome de Frey, es una entidad caracterizada por sudoración y enrojecimiento de la piel del territorio inervado por el nervio aurículo-temporal durante las comidas. El síndrome de Frey es probablemente una secuela inevitable en la cirugía de la glándula parótida. Una vez que se presenta se perpetua durante toda la vida si no se realiza tratamiento. Realizando el test de Minor tras cirugía sobre la glándula parótida ha sido publicado que el 100% son positivos, y que el 50% son sintomáticos percibiendo la sudoración durante las comidas, y alrededor de un 15% consideran sus síntomas graves. En el siguiente articulo presentamos los resultados de nuestro estudio que consistió en la inyección intradérmica de toxina botulínica A a nuestros pacientes con síndrome de Frey y el seguimiento. Los resultados han sido desaparición de los síntomas durante un periodo medio de 16 meses con cierta variabilidad individual. Con estos resultados podría considerarse la inyección de toxina botulínica A como ténica de elección para el síndrome de Frey ya establecido.The auriculotemporal syndrome, also known as gustatory sweating or Frey’s syndrome, is a condition characterized by sweating and flushing of the cutaneous territory innervated by the auriculotemporal nerve while eating. Frey’s syndrome is probably an inevitable sequela of parotid gland surgery. Once it appears, it persists for the rest of the patient’s life if not treated. It has been reported that performance on the Minor test after parotid gland surgery is 100% positive and 50% of patients are symptomatic, experiencing sweating during meals. About 15% consider their symptoms serious. In this article we present the results of our study of the treatment of Frey’s syndrome by intradermal injection of botulinum toxin A and the follow-up of the patients. The patients’ symptoms disappeared during

A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food

Science.gov (United States)

Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...

Multiplex real-time PCR SYBR Green for detection and typing of group III Clostridium botulinum.

Science.gov (United States)

Anniballi, Fabrizio; Auricchio, Bruna; Delibato, Elisabetta; Antonacci, Monia; De Medici, Dario; Fenicia, Lucia

2012-01-27

Clostridium botulinum type C and type D belonging to the group III organisms, are mainly responsible for animal botulism outbreaks. Clinical signs alone are often insufficient to make a diagnosis of botulism and a laboratory confirmation is required. Laboratory confirmation can be performed by demonstrating the presence of botulinum neurotoxins in serum, gastrointestinal contents, liver, wound of sick or dead animals, or by demonstrating the presence of C. botulinum in gastrointestinal contents, liver, and wound. Demonstration of spores in gastrointestinal contents or tissue of animals with clinical signs indicative of botulism reinforces the clinical diagnosis. With the aim of detecting and typing C. botulinum group III organisms, a multiplex real-time PCR SYBR Green was developed and in-house validated. Selectivity, limit of detection, relative accuracy, relative specificity, relative sensitivity, and repeatability of the method were investigated. The multiplex real-time PCR SYBR green used showed a 100% selectivity, 100% relative accuracy, 100% relative specificity, 100% relative sensitivity and a limit of detection of 277 and 580 DNA copies for C. botulinum type C and C. botulinum type D, respectively. The method reported here represents a suitable tool for laboratory diagnosis of type C and D botulism and for testing a large number of samples collected during the animal botulism surveillance and prevention activities. Copyright © 2011 Elsevier B.V. All rights reserved.

Botulism

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... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations ...

Botulism

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... vegetables, cured pork and ham, smoked or raw fish, and honey or corn syrup, baked potatoes cooked ... infection. In adults, symptoms may include: Abdominal cramps Breathing difficulty that may lead to respiratory failure Difficulty ...

Botulism

Science.gov (United States)

... seafood. However, the disease has also occurred from chili peppers, foil-wrapped baked potatoes and oil infused ... people who inject black tar heroin. Are there benefits to botulinum toxin? You might wonder how something ...

Análise vocal em pacientes com disfonia espasmódica nos momentos pré e pós tratamento com toxina Botulínica A Vocal analysis in patients with spasmodic dysphonia before and after treatment with Botulinum toxin A

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Ana Cristina Côrtes Gama

2012-10-01

Full Text Available OBJETIVO: avaliar de forma objetiva e subjetiva a voz de pacientes com disfonia espasmódica nos momentos pré e pós aplicação de toxina botulínica A. MÉTODO: as emissões vocais de onze pacientes do sexo feminino foram registradas antes e após (15 dias o tratamento. As amostras vocais foram analisadas por duas fonoaudiólogas com experiência em voz por meio da análise perceptivo-auditiva (escala GRBASI e da análise espectrográfica. RESULTADOS: na análise perceptivo-auditiva com vogal sustentada os parâmetros que alteraram após o tratamento foram o grau de severidade, tensão e instabilidade, enquanto na fala encadeada foram o grau de severidade e a tensão. Na análise espectrográfica ocorreu melhora do traçado após o tratamento sem significância estatística entre os parâmetros. CONCLUSÃO: ocorreu melhora significante dos aspectos perceptivo-auditivos após o tratamento e, portanto, as injeções de toxina botulínica A mostraram-se eficazes no tratamento da disfonia espasmódica no grupo estudado.PURPOSE: to analyze in an objective and subjective manner the voice of patients with spasmodic dysphonia in the moments before and after botulinum toxin A. METHOD: the vocal emissions of eleven women patients were recorded before and after (15 days treatment. The vocal samples were analyzed by two experienced speech therapists through the perceptual analysis (GRBASI scale and spectrographic analysis. RESULTS: in the perceptual analysis with subtended vowel, the altered parameters were degree of severity, strain and instability, while in connected speech only degree of severity and strain changed after treatment. In the perceptual analysis with sustained vowel, the parameters that have changed, were the degree of severity, strain and instability, while in connected speech only degree of severity and strain changed after treatment. The spectrographic analysis was improved after treatment with no statistical significance found among

Comparação entre cirurgia e aplicações unilaterais e bilaterais de toxina botulínica para o tratamento dos estrabismos Comparison between surgery and unilateral and bilateral injections of botulinum toxin to treat strabismus

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Maria de Lourdes M. M. Villas Boas

2001-10-01

Full Text Available Objetivo: Comparar a eficácia de 3 formas de tratamento para estrabismos de pequeno e médio ângulos: cirurgia, aplicações unilaterais e bilaterais de toxina botulínica. Métodos: Foram estudados 97 pacientes, divididos em três grupos. No grupo I foi feito um estudo prospectivo no qual 44 pacientes receberam injeção unilateral da toxina botulínica tipo A; no grupo II, 24 pacientes receberam injeção bilateral da toxina, e no grupo III foi feito estudo retrospectivo de 29 pacientes previamente operados de estrabismo. A eficácia dos tratamentos foi estudada segundo o percentual de correção do desvio ocular e segundo o índice de sucesso terapêutico, definido como um desvio residual de até 10 DP (dioptrias prismáticas. Resultados: Os percentuais de correção dos desvios horizontais, para longe, no 3º mês, foram: grupo I = 50,9%; grupo II = 55,8% e grupo III = 77,0%. Para perto, foram: 48,6%, 49,2% e 72,8%, respectivamente. Os índices de sucesso terapêutico foram: grupo I = 57,1%; grupo II = 68,4% e grupo III = 72,4%. Conclusão: Concluiu-se não ter havido diferença estatisticamente significativa entre os percentuais de correção do desvio ocular e o índice de sucesso terapêutico entre os três grupos estudados.Purpose: To compare the efficacy of three types of treatment for strabismus: surgery, unilateral and bilateral botulinum toxin injections. Methods: To compose groups I and II, a prospective study was carried out observing the pretreatment measurement of the deviation, repeated after 7, 30 and 90 days after the injection. To compose group III, a retrospective study was carried out. Results: The percentage of horizontal deviation correction for distance, in 3 months, was: group I = 50.9%; group II = 55.8%, and group III = 77.0%; for near, 48.6%, 49.2% and 72.8% respectively.The therapeutic success rate, defined as residual deviation of 10 PD (prism diopter or less, was: group I = 57.1%; group II = 68.4% and group III

Avaliação de um programa de aplicação de toxina botulínica tipo A em crianças do Vale do Jequitinhonha com paralisia cerebral

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Grazielle Fernandes da Silva

2013-07-01

Full Text Available O objetivo do estudo foi avaliar os efeitos de um programa público de aplicação de toxina botulínica tipo A (TBA na espasticidade muscular, amplitude de movimento, qualidade da marcha, independência funcional e qualidade de vida de crianças e adolescentes com paralisia cerebral (PC. Foi realizado um estudo quase experimental que avaliou os efeitos do emprego da TBA, aplicada três vezes, com intervalos de três meses, em 14 crianças com PC. Estas foram avaliadas através da Escala Modificada de Ashworth, Goniometria Manual, Physician Rating Scale, Inventário de Avaliação Pediátrica de Incapacidade (PEDI e Questionário do Cuidador da Criança (QCC. Foi observada redução da espasticidade, aumento da amplitude de movimento, melhora das habilidades funcionais de autocuidado e mobilidade do PEDI e das áreas de cuidado pessoal, conforto e interação/comunicação do QCC. O programa de aplicação de TBA em crianças e adolescentes com PC, realizado em um núcleo de reabilitação público do Vale do Jequitinhonha, foi efetivo para a população beneficiada.

Science, practice, and human errors in controlling Clostridium botulinum in heat-preserved food in hermetic containers.

Science.gov (United States)

Pflug, Irving J

2010-05-01

The incidence of botulism in canned food in the last century is reviewed along with the background science; a few conclusions are reached based on analysis of published data. There are two primary aspects to botulism control: the design of an adequate process and the delivery of the adequate process to containers of food. The probability that the designed process will not be adequate to control Clostridium botulinum is very small, probably less than 1.0 x 10(-6), based on containers of food, whereas the failure of the operator of the processing equipment to deliver the specified process to containers of food may be of the order of 1 in 40, to 1 in 100, based on processing units (retort loads). In the commercial food canning industry, failure to deliver the process will probably be of the order of 1.0 x 10(-4) to 1.0 x 10(-6) when U.S. Food and Drug Administration (FDA) regulations are followed. Botulism incidents have occurred in food canning plants that have not followed the FDA regulations. It is possible but very rare to have botulism result from postprocessing contamination. It may thus be concluded that botulism incidents in canned food are primarily the result of human failure in the delivery of the designed or specified process to containers of food that, in turn, result in the survival, outgrowth, and toxin production of C. botulinum spores. Therefore, efforts in C. botulinum control should be concentrated on reducing human errors in the delivery of the specified process to containers of food.

Glebe House Nursing Home, Kilternan Care Centre, Glebe Road, Kilternan, Dublin 18.

LENUS (Irish Health Repository)

Ward, M

2009-01-08

In November and December 2008, six cases of suspect wound botulism were reported in heroin injecting drug users, all residents in Dublin, Ireland. Patients were aged between 23-42 years of age; four cases were male; one patient died shortly after admission. The patients presented to four different hospitals across the city. Botulism in injecting drug users in Ireland was last reported in 2002.

Denmark: Botulism in an infant or infant botulism?

DEFF Research Database (Denmark)

Pærregaard, A; Angen, Øystein; Lisby, M

2008-01-01

with preformed neurotoxin could not be excluded. The food history revealed consumption of a commercially produced banana/peach puree which was suspected as a possible source, and based on a precautionary principle this product was recalled. The case description illustrates a risk-management dilemma between...

Medical Surveillance Monthly Report. Volume 21, Number 6

Science.gov (United States)

2014-06-01

2000 through 31 December 2012. AFRESS was queried for ICD-9 codes correspond- ing to amebiasis, botulism, brucellosis, Campylobacter infection, cholera ...Typhoid fever 8 5 1 . 2 Listeriosis 4 1 1 1 1 Cholera 3 3 . . . Vibrio parahaemolyticus 3 2 . 1 . Trichinosis 3 1 1 1 . Botulism 2 . 2 . . Cyclospora...at clinics and hospitals near the U.S.– Mexico border from 25 November 2013 through 16 January 2014. Infl uenza cases were individ- uals who had

Botulinum neurotoxin vaccines: Past history and recent developments.

Science.gov (United States)

Rusnak, Janice M; Smith, Leonard A

2009-12-01

Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

Environmental conditions synchronize waterbird mortality events in the Great Lakes

Science.gov (United States)

Prince, Karine; Chipault, Jennifer G.; White, C. LeAnn; Zuckerberg, Benjamin

2018-01-01

Since the 1960s, periodic outbreaks of avian botulism type E have contributed to large-scale die-offs of thousands of waterbirds throughout the Great Lakes of the United States. In recent years, these events have become more common and widespread. Occurring during the summer and autumn months, the prevalence of these die-offs varies across years and is often associated with years of warmer lake temperatures and lower water levels. Little information exists on how environmental conditions mediate the spatial and temporal characteristics of mortality events.In 2010, a citizen science programme, Avian Monitoring for Botulism Lakeshore Events (AMBLE), was launched to enhance surveillance efforts and detect the appearance of beached waterbird carcasses associated with avian botulism type E outbreaks in northern Lake Michigan. Using these data, our goal was to quantify the within-year characteristics of mortality events for multiple species, and to test whether the synchrony of these events corresponded to fluctuations in two environmental factors suspected to be important in the spread of avian botulism: water temperature and the prevalence of green macroalgae.During two separate events of mass waterbird mortality, we found that the detection of bird carcasses was spatially synchronized at scales of c. 40 km. Notably, the extent of this spatial synchrony in avian mortality matched that of fluctuations in lake surface water temperatures and the prevalence of green macroalgae.Synthesis and applications. Our findings are suggestive of a synchronizing effect where warmer lake temperatures and the appearance of macroalgae mediate the characteristics of avian mortality. In future years, rising lake temperatures and a higher propensity of algal masses could lead to increases in the magnitude and synchronization of avian mortality due to botulism. We advocate that citizen-based monitoring efforts are critical for identifying the potential environmental conditions associated

Shaping our future: animal health in a global trading environment

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More Simon J

2007-09-01

Full Text Available Abstract In this study, the clinical findings and results of haematological and biochemical analyses of 26 cattle with botulism were evaluated. The most important clinical signs in the affected cattle included: decreased appetite, ataxia, difficulty to rise, loss of tongue tone, salivation and bradycardia. A definitive diagnosis of botulism was based on demonstration of the preformed toxin in ruminal and intestinal contents and feed materials including poultry litter, by mouse inoculation test. This study is the first confirmation, by direct toxin isolation, of Clostridium botulinum type C and Clostridium botulinum type D in cattle, in Turkey.

Eficácia do resfriamento da pele no alívio da dor desencadeada pela injeção de toxina botulínica tipo A nas distonias faciais Skin cooling efficacy on pain relief in periocular injections with botulinum toxin A in facial dystonias

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Paula Barros Bandeira de Mello Monteiro

2012-12-01

Full Text Available OBJETIVO: Avaliar a eficácia do resfriamento da pele com gelo no alívio da dor desencadeada pela injeção de toxina botulínica tipo A na região periocular em pacientes portadores de distonia facial. MÉTODOS: Neste estudo prospectivo, 13 pacientes receberam injeção de toxina botulínica tipo A em região glabelar (m. prócero e periocular (m. orbicular para tratamento de distonia facial. Antes das aplicações, um lado da região glabelar foi resfriado com gelo durante 5 minutos, enquanto no outro lado foi aplicada pomada Epitezan®, funcionando como placebo. A aplicação foi feita primeiramente no lado resfriado. Após a aplicação em cada um dos lados os pacientes foram instruídos a dar uma nota para a dor desencadeada pela injeção, em uma escala de 0 a 10 onde 0 era ausência de dor e 10 a dor mais intensa. RESULTADOS: A média das notas dadas pelos pacientes à dor desencadeada pela injeção no lado onde foi aplicado placebo foi 3,92 ± 3,28. No local onde foi aplicado gelo a média das notas foi de 2,92 ± 2,18 (p PURPOSE: To evaluate the efficacy of skin cooling with ice on pain relief in periocular injection with botulinum toxin type A in patients with facial dystonias. METHODS: In this prospective study, 13 patients received botulinum toxin type A injection in glabela (procerus m. and periocular region (orbicular m. for facial dystonias treatment. Before the injections, one side of the glabela was submitted to a 5-minute cooling period, while the opposite side had Epitezan® cream applied, as a placebo. The application was done at the cooled side first. After the application on each side the patients were instructed to rate the pain associated with the injection on a scale from 0 to 10, with 0 indicating no pain and 10 the worst pain. RESULTS: The average pain score on the side where cold was applied was 3,92 ± 3,28, while on the control side the average pain score was 2,92 ± 2,18 (p < 0,0166. CONCLUSION: In this study

Botulinum Neurotoxin Detection Methods for Public Health Response and Surveillance

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Nagarajan Thirunavukkarasu

2018-06-01

Full Text Available Botulism outbreak due to consumption of food contaminated with botulinum neurotoxins (BoNTs is a public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns due to the potential for high mortality and morbidity. Rapid and reliable detection methods are necessary to support clinical diagnosis and surveillance for identifying the source of contamination, performing epidemiological analysis of the outbreak, preventing and responding to botulism outbreaks. This review considers the applicability of various BoNT detection methods and examines their fitness-for-purpose in safeguarding the public health and security goals.

Avian disease at the Salton Sea

Science.gov (United States)

Friend, M.

2002-01-01

A review of existing records and the scientific literature was conducted for occurrences of avian diseases affecting free-ranging avifauna within the Salton Sea ecosystem. The period for evaluation was 1907 through 1999. Records of the U.S. Department of Agriculture, Bureau of Biological Survey and the scientific literature were the data sources for the period of 1907a??1939. The narrative reports of the U.S. Fish and Wildlife Service's Sonny Bono National Wildlife Refuge Complex and the epizootic database of the U.S. Geological Survey's National Wildlife Health Center were the primary data sources for the remainder of the evaluation. The pattern of avian disease at the Salton Sea has changed greatly over time. Relative to past decades, there was a greater frequency of major outbreaks of avian disease at the Salton Sea during the 1990s than in previous decades, a greater variety of disease agents causing epizootics, and apparent chronic increases in the attrition of birds from disease. Avian mortality was high for about a decade beginning during the mid-1920s, diminished substantially by the 1940s and was at low to moderate levels until the 1990s when it reached the highest levels reported. Avian botulism (Clostridium botulinum type C) was the only major cause of avian disease until 1979 when the first major epizootic of avian cholera (Pasteurella multocidia) was documented. Waterfowl and shorebirds were the primary species affected by avian botulism. A broader spectrum of species have been killed by avian cholera but waterfowl have suffered the greatest losses. Avian cholera reappeared in 1983 and has joined avian botulism as a recurring cause of avian mortality. In 1989, avian salmonellosis (Salmonella typhimurium) was first diagnosed as a major cause of avian disease within the Salton Sea ecosystem and has since reappeared several times, primarily among cattle egrets (Bubulcus ibis). The largest loss from a single epizootic occurred in 1992, when an estimated

Weakness

Science.gov (United States)

... by a slipped disk in the spine) Stroke MUSCLE DISEASES Becker muscular dystrophy Dermatomyositis Muscular dystrophy (Duchenne) Myotonic dystrophy POISONING Botulism Poisoning ( insecticides , nerve gas) ...

Benefícios da aplicação de toxina botulínica associada à fonoterapia em pacientes disfágicos graves Benefits of botulinum toxin associated to swallowing therapy in patients with severe dysphagia

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Fernanda Teixeira Menezes

2012-06-01

Full Text Available Estudo de casos para caracterizar os benefícios da aplicação de toxina botulínica em glândulas salivares, associada à fonoterapia em pacientes disfágicos graves. Foram analisados cinco prontuários de pacientes neurológicos, em uso exclusivo de via alternativa de alimentação, com idades entre 17 e 70 anos, sendo quatro do gênero masculino e um do gênero feminino. Do total, quatro pacientes eram traqueostomizados. Foi considerado como critério de inclusão apresentar disfagia grave, com manifestações clínicas de escape extra oral e/ou acúmulo de saliva em cavidade oral e aspiração traqueal maciça de saliva, com limitação da fonoterapia. Quanto à avaliação clínica da deglutição, foram coletados dados pré e pós-fonoterapia associada à aplicação de toxina botulínica, quanto aos seguintes aspectos: mobilidade e força das estruturas orofaríngeas (lábios, língua, bochechas, elevação laríngea, grau da disfagia, uso de via alternativa de alimentação e traqueostomia. Quanto aos resultados pós- fonoterapia foi observado, em quatro pacientes, melhora da mobilidade e força de lábios, língua, bochechas e laringe. Quatro pacientes apresentaram deglutição funcional e um teve modificação do grau de gravidade da disfagia. Desta forma, a maioria foi capaz de receber dieta exclusiva por via oral e apenas um permaneceu com dieta mista, ou seja, gastrostomia e dieta via oral na consistência pastosa. Todos os pacientes traqueostomizados tiveram a cânula de traqueostomia removida. O estudo mostrou que o tratamento descrito acima contribui para a reabilitação da deglutição, reintrodução de alimentos por via oral e retirada da cânula de traqueostomia.Case report with the aim to characterize the benefits of botulinum toxin injection into salivary glands in association with swallowing therapy in patients with severe dysphagia. The medical records of five neurological patients (four male and one female, aged

Rugas glabelares: estudo piloto dos padrões de contração

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Ada Regina Trindade de Almeida

2010-03-01

Full Text Available Introdução: A atividade muscular nd glabela Provocação rugas perpendiculares à Direção decontração dos Músculos, hoje tratadas Pela toxina botulínica.Variações interpessoais nd forma de contração local, São exibidas Durante a Animação facial. Apesar dos Inúmeros artigos publicados Sobre o tema, Os padrões de contração glabelar Ainda Não Foram estudados adequadamente e Classificados. Objetivo: Identificar e classificar Os padrões de contração glabelar encontrados Na população Que recebe Tratamento cosmético toxina botulínica com.Métodos: Análise retrospectiva de Fotografías de 30 pacientes receberam toxina botulínica n Que glabelares Tratamento de rugas. De acordo com De hum Predominância de Movimentosde Depressão, Aproximação OU Elevação da glabela, Os padrões de contração Foram identificados e Classificados.Resultados: Cinco Padrões identificados foram: 1 "U", 2 "V", 3 "Omega", 4 "Setas convergentes" e 5 "Omega" invertido. A Classificação OS permitiu identificar Músculos Mais Importantes em CADA Padrão de contração.Discussão CONCLUSÃO /: Existem Diferenças interpessoais nd Animação facial. A Classificação das rugas glabelares Permite, Tratamento Mais INDIVIDUALIZADO com acurado e toxina botulínica Uma. recebem doses Mais Músculos recrutados Maiores OU Maior numero de Pontos de Aplicação. Os Menos requisitados poupados São OU recebem doses menores, permitindo resultados eficazes Mais e Naturais.

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum.

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Carter, Andrew T; Paul, Catherine J; Mason, David R; Twine, Susan M; Alston, Mark J; Logan, Susan M; Austin, John W; Peck, Michael W

2009-03-19

Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic C. botulinum and the closely related C. sporogenes tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to C. sporogenes), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI. Proteolytic C. botulinum has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic C. botulinum, and is suitable for clinical and forensic investigations of botulism outbreaks.

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum

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Twine Susan M

2009-03-01

Full Text Available Abstract Background Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Results Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic C. botulinum and the closely related C. sporogenes tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to C. sporogenes, and the flagellar glycosylation island (FGI. These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5 has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI. Conclusion Proteolytic C. botulinum has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic C. botulinum, and is suitable for clinical and forensic investigations of botulism

Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.

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Luciana A F Gil

Full Text Available Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB, a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH3 developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH3 developed a protective immune response against both BoNT/C (5 IU/mL and BoNT/D (10 IU/mL, as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle.

Atypical tetanus in a completely immunized 14-year-old boy.

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König, Kai; Ringe, Hannelore; Dorner, Brigitte G; Diers, Alexander; Uhlenberg, Birgit; Müller, Dominik; Varnholt, Verena; Gaedicke, Gerhard

2007-11-01

We report the uncommon clinical course of tetanus in a completely immunized 14-year-old boy. His initial symptoms, which included a flaccid paralysis, supported a diagnosis of botulism. Preliminary mouse-test results with combined botulinum antitoxins A, B, and E, obtained from tetanus-immunized horses, backed this diagnosis. The change in his clinical course from paralysis to rigor and the negative, more specific, botulinum mouse test with isolated botulinum antitoxins A, B, and E, obtained from nonvaccinated rabbits, disproved the diagnosis of botulism. Tetanus was suspected despite complete vaccination. The final results of a positive mouse test performed with isolated tetanus antitoxin confirmed the diagnosis. Adequate treatment was begun, and the boy recovered completely.

Utilización de la toxina botulínica para mejorar la funcionalidad y la expresión del labio en parálisis facial de larga evolución Use of botulinum toxin to improve the functionality and expression of the lip in long-term facial palsy

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C. Gómez Martín

2010-06-01

Full Text Available La parálisis de la rama marginal del nervio facial en el contexto de una parálisis facial de larga evolución, produce una deformidad estética y funcional que puede ser mejorada con la inyección de toxina botulínica. Utilizamos esta técnica en 2 pacientes consiguiendo unos resultados casi inmediatos en lo que se refiere a la apertura bucal, a la expresión y a la continencia oral. Indicamos esta técnica en pacientes de edad avanzada, con múltiples operaciones previas y que aceptan este procedimiento no invasivo para mejorar su autoestima y su calidad de vida.Paralysis of the marginal branch of the facial nerve in the context of a long-term facial paralysis, produces an aesthetic and functional deformity that can be improved with botulinum toxin injection. We use this technique in 2 patients who achieved almost immediate results in terms of oral opening, oral expression and continence. Botulinum toxin injection can be used in elderly patients with multiple previous operations who accept this non-invasive procedure, improving their selfesteem and their quality of life.

Botulinum toxin type A in refractory chronic migraine: an open-label trial Toxina botulínica tipo A no tratamento da enxaqueca refratária: um estudo aberto

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Carla Menezes

2007-09-01

Full Text Available Botulinum toxin type A (BT-A has been described as an important strategy to various types of pain such as cervical dystonia, myofascial pain syndrome and headache. Although BT-A efficacy has not been proven in tension type headache, its use in migraine continues controversial. In this open trial, we evaluated the efficacy of BT-A in refractory migraine. BT-A was injected in patients diagnosed with migraine who had previously used three classes of prophylactic drugs by at least one year with no response. The most important improvement was observed within 30 days, but pain intensity and frequency of headache had been decreased until the end of three months of follow up. Side effects of BT-A were mild and self limited. We conclude that BT-A seems to be a safe and effective treatment to refractory migraine patients.Toxina botulínica tipo A (TB-A tem sido descrita como importante estratégia para diversos tipos de dor como cefaléia e dores relacionadas a distonia cervical ou síndrome miofascial. Embora a eficácia da TB-A não tenha sido demonstrada na cefaléia do tipo tensional, seu uso na enxaqueca continua controverso. Nesse estudo avaliamos a eficácia da TB-A na enxaqueca refratária. TB-A foi injetada em pacientes com enxaqueca que fizeram tratamento prévio com no mínimo três classes de medicamentos profiláticos, sem resultados satisfatórios. A melhora mais significativa dos pacientes foi observada após 30 dias de aplicação de TB-A, enquanto intensidade da dor e freqüência de cefaléia continuaram reduzidas até o final de três meses de seguimento. Os efeitos colaterais observados após a aplicação de TB-A foram moderados e auto-limitados. Os nossos dados mostram que TB-A parece ser um tratamento seguro e eficaz para pacientes com enxaqueca refratária.

Disease: H00339 [KEGG MEDICUS

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Full Text Available 9 (2006) ... PMID:12503947 (description) ... AUTHORS ... Robinson RF, Nahata MC ... TITLE ... Management of botulism. ... JOURNAL ... Ann Pharmacother 37:127-31 (2003) DOI:10.1345/aph.1C034

Toxina botulínica no blefaroespasmo, no espasmo hemifacial e na distonia cervical: resultados em 33 pacientes Botulinum toxin in blepharospasm, hemifacial spasm and cervical dystonia: results in 33 patients

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Sérgio Ap. Novis

1995-09-01

Full Text Available Avaliamos os resultados terapêuticos obtidos com o emprego de toxina botulínica do tipo A em 33 pacientes com distonia (12 com blefaroespamo; 10 com espasmo hemifacial e 11 com torcicolo espasmódico. Utilizamos uma escala de pontuação de gravidade antes de cada aplicação, sendo reavaliados duas semanas após, seguindo a mesma escala. Entre os com blefaroespasmo, oito eram mulheres e quatro homens; a média de idade foi 57,7 anos; a média do tempo de doença de quatro anos; três tinham história similar na família; nove eram essenciais e três fizeram uso de neurolépticos (distonia tardia. A dose média empregada ficou em 51,3 U, com a duração média do efeito benéfico de 2,8 meses. Do total de 22 aplicações (injeções e reinjeções, 14 (63,7% tiveram resultado ótimo, 5 (22,7% bom e três (13,6% nulo. Naqueles com espasmo hemifacial, oito eram mulheres e dois homens; a média de idade foi 52,6 anos; a média do tempo de doença 7,4 anos; oito eram essenciais e dois pós-páralíticos. A dose média empregada ficou em 32 U. Do total de 15 aplicações, todos (100% tiveram resultado ótimo, com a duração média do efeito benéfico de 3,4 meses. Nos pacientes com distonia cervical, oito eram homens e três mulheres; a média de idade foi 44,2 anos; a média do tempo de doença 12,2 anos; seis eram essenciais, três fizeram uso de neuroléptico e dois tinham história familiar. A dose média empregada ficou em 238,6 U, com a duração média do efeito benéfico de 4,7 meses. Do total de 20 aplicações, 18 (90% tiveram resultado bom, 1 (5% regular e 1 (5% nulo. Ptose palpebral, paresia facial e disfagia foram os efeitos colaterais mais encontrados. Concluímos que a toxina botulínica revelou-se eficaz no tratamento destas condições.The effects of botulinum toxin type A were studied in 33 patients with dystonia (12 blepharospasms, 10 hemifacial spasms and 11 spasmodic torticollis. A rate scale was used to evaluate the severity

History of Bioterrorism: Botulism

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Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

Science.gov (United States)

Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

2013-03-19

Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

In-Vivo Neutralization of Botulinum Neurotoxin Serotype E Using Rabbit Polyclonal Antibody Developed against BoNT/E Light Chain.

Science.gov (United States)

Rani, Sarita; Ponmariappan, S; Sharma, Arti; Kamboj, D V; Jain, A K

2017-01-01

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. Hence there is an urgent need to develop therapeutic intervention for prevention and cure of botulism within short period. BoNT antiserum injection is still the effective treatment. In the present study, the recombinant light chain of BoNT/E was successfully purified in soluble form. The purified rBoNT/E LC was used for the generation of polyclonal antibody in rabbit. In order to find out the neutralizing capacity of generated antisera, rabbit antiserum was incubated with 20 LD50 of botulinum neurotoxin type E for 1 hour at 37°C and then injected intraperitoneally (IP) into mice. Further in another set of experiments antiserum was administered in different ways that included administration of - antiserum and BoNT/E toxin simultaneously without preincubation, one after another at the same and different time points for its therapeutic ability. To find out cross neutralization capacity, rBoNT/E LC antiserum was pre-incubated with 5 LD50 of BoNT/A, BoNT/B, BoNT/F and then injected (IP) into mice. In all the cases mice were observed continuously for 96 hours. The results clearly indicate that developed polyclonal rabbit antiserum showed serotype specific neutralization of BoNT/E toxin only but not of BoNT/A, BoNT/B and BoNT/F. The developed antibodies will be used for preventive and therapeutic intervention of type 'E' botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efeitos adversos associados à aplicação de toxina botulínica na face: revisão sistemática com meta-análise Adverse effects associated with facial application of botulinum toxin: a systematic review with meta-analysis

Directory of Open Access Journals (Sweden)

Roberta Melissa Benetti Zagui

2008-12-01

Full Text Available OBJETIVO: Verificar a ocorrência dos efeitos adversos relacionados ao uso da toxina botulínica na face, por meio de revisão sistemática, usando meta-análise. MÉTODOS: Foi realizada pesquisa eletrônica de artigos publicados no MEDLINE e Cochrane Library até setembro de 2007. A ocorrência dos efeitos adversos foi verificada pela freqüência relativa para os relatos de casos e do risco relativo para os estudos randomizados. A heterogeneidade foi avaliada pelo teste Q e pelo índice I². Foi utilizado o teste de significância de Egger para identificar viés de publicação e a análise de sensibilidade para verificar o efeito dos viéses de publicação. RESULTADOS: Oito estudos randomizados e treze relatos de casos preencheram os critérios de inclusão. Na revisão sistemática dos relatos de casos, 1.003 pacientes foram estudados, dos quais 182 (18,14% apresentaram efeitos adversos. O efeito adverso mais freqüente foi a ptose palpebral ocorrendo em 34 (3,39% pacientes dos relatos de casos. Na meta-análise dos estudos randomizados, o risco relativo global para os efeitos adversos como cefaléia, ptose palpebral, reação local e infecção foi 1,07, 3,25, 0,99 e 0,94, respectivamente. Para todas as comparações, o valor de P foi maior que 0,05. CONCLUSÃO: O efeito adverso mais freqüente e que apresentou o maior risco relativo relacionado ao uso da toxina botulínica na face foi a ptose palpebral. A padronização dos efeitos adversos relatados é necessária a fim de melhor estabelecer as características dos mesmos.PURPOSE: To estimate the occurrence of adverse effects associated with the use of botulinum toxin by performing a systematic review and meta-analysis. METHODS: A systematic literature search of MEDLINE and Cochrane Library was conducted until September 2007. The occurrence of the adverse effects was estimated of the relative frequency for case report and of the relative risk for randomized trials. Heterogeneity was

Investigation of Clostridium botulinum group III's mobilome content.

Science.gov (United States)

Woudstra, Cédric; Le Maréchal, Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie-Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B; Lobato, Francisco C F; Silva, Rodrigo O S; Dorner, Martin B; Fach, Patrick

2018-02-01

Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C. botulinum group III were developed with the objective to better characterize C. botulinum group III strains. The investigation of 110 C. botulinum group III strains and 519 naturally contaminated samples collected during botulism outbreaks in Europe showed alpha-toxin and C2-I/C2-II markers to be systematically associated with type C/D bont-positive samples, which may indicate an important role of these elements in the pathogenicity mechanisms. On the contrary, bont type D/C strains and the related positive samples appeared to contain almost none of the markers tested. Interestingly, 31 bont-negative samples collected on farms after a botulism outbreak revealed to be positive for some of the genetic mobile elements tested. This suggests loss of the bont phage, either in farm environment after the outbreak or during laboratory handling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxina botulínica tipo A tópica con iontoforesis para el tratamiento de la hiperhidrosis axilar: Efecto y persistencia Topic type A botulinum toxin with iontophoresis in the treatment of armpit hyperhidrosis: effect and persistency

Directory of Open Access Journals (Sweden)

J.F. Silva-Gavarrete

2011-09-01

Full Text Available La sobreproducción de sudor se denomina hiperhidrosis (HH y frecuentemente conlleva en el ser humano tanto problemas dermatológicos como de índole social. En la actualidad, existen múltiples tratamientos para controlar la HH axilar, siendo entre ellos el uso de la terapia con Toxina Botulínica tipo A (TXB-A uno de los más efectivos, con la limitante de que la toxina tiene que ser inyectada mediante múltiples punciones en la axila, por lo que tiende a ser un tratamiento rechazado por los pacientes. La iontoforesis es un método que utiliza corriente galvánica y se emplea de forma clínica para la introducción transdermal de medicamentos. Realizamos un ensayo clínico simple ciego sobre 10 pacientes a los que se les aplicó gel inerte mezclado con Toxina Botulínica tipo A (TXB-A de la marca Dysport® mediante una sesión de iontoforesis en una axila al tiempo que en la otra axila se les aplicó la TXB-A de forma tradicional, inyectada. Los resultados fueron evaluados con el Minor Test (Test Yodo-almidón comparativamente en ambas axilas y en cada paciente a los 10 días, 2 meses y 5 meses de la aplicación. Empleamos el mismo número de unidades y la misma dilución de TXB-A tanto para la administrada vía tópica, como para la inyectada. Los resultados presentaron una disminución de la HH axilar en ambas axilas durante todo el estudio, siendo la forma inyectada la que más altos porcentajes de efecto presentó. En general un 74.67% de disminución de la secreción sudoral para la forma tópica con iontoforesis y un 90.33% para la forma inyectada. En cuanto a la duración del efecto, ambas aplicaciones tuvieron resultados estadísticamente significativos para la persistencia del efecto a los 5 meses. Por lo tanto, en base al presente trabajo, concluimos que la TXBA aplicada tópicamente mediante iontoforesis mejora la HH axilar y además presenta una persistencia del efecto de un mínimo de 5 meses.The overproduction of sweat by the

U.S. CWMD Coordination

Science.gov (United States)

2012-12-11

coordination. For example, it conducted joint vehicle inspection training for Pakistani Customs and Border Guard personnel at a US- Mexico border...biological material, including such hazards as: anthrax, botulism, cholera , Ebola virus hemorrhagic fever, E. coli, Plague, and smallpox 79

Botulisme hos spaedbørn

DEFF Research Database (Denmark)

Hoffmann, Thomas; Mølbak, Kåre; Paerregaard, Anders

2010-01-01

Infant botulism is a rare disease that affects infants below the age of 12 months following absorption of neurotoxins produced by ingested Clostridium botulinum spores. The clinical manifestations are caused by symmetrical cranial nerve palsies followed by descending, symmetric flaccid paralysis...

Clostridium botulinum group I strain genotyping by 15-locus multilocus variable-number tandem-repeat analysis

NARCIS (Netherlands)

Fillo, S.; Giordani, F.; Anniballi, F.; Gorgé, O.; Ramisse, V.; Vergnaud, G.; Riehm, J.M.; Scholz, H.C.; Splettstoesser, W.D.; Kieboom, J.; Olsen, J.-S.; Fenicia, L.; Lista, F.

2011-01-01

Clostridium botulinum is a taxonomic designation that encompasses a broad variety of spore-forming, Gram-positive bacteria producing the botulinum neurotoxin (BoNT). C. botulinum is the etiologic agent of botulism, a rare but severe neuroparalytic disease. Fine-resolution genetic characterization of

Consumers’ perception and knowledge of food safety: results of questionnaires accessible on IZSalimenTO website

Directory of Open Access Journals (Sweden)

Amaranta Traversa

2015-04-01

Full Text Available The present survey was undertaken to investigate consumers’ knowledge of the main foodborne agents and dietary regimen during pregnancy. Data were collected using monthly questionnaires available on IZSalimenTO website between March 2013 and January 2014. Hepatitis A virus questionnaire: 20 respondents (77% recognized berries as foodstuff linked to the outbreak of hepatitis A. The majority correctly indicated as precautionary advice to boil berries before consumption. Botulism questionnaire: 29 respondents (62% indicated pesto as food involved in botulism alert in July 2013. The risk of infant botulism in infant less than 1 year old due to honey consumption is known by 24 respondents (51%. Main foodborne disease questionnaire: the risk of infection by Salmonella after the consumption of foods made with raw eggs is known by the majority (94%; N=17 as well as the treatments to be applied in order to make fresh fish safe from parasites (76%. Pregnancy questionnaire: 20 respondents (74% believed that washing vegetables and fruits with sodium bicarbonate or chlorate solution is able to inactivate Toxoplasma; only 4 (15% reported both raw meat and vegetables washed with sodium bicarbonate as food at risk. Results indicate that all consumers should be trained on behaviour and dietary regimen to be adopted in pregnancy and in infant <1 year old. The website may be considered as a useful tool to assess consumers’ knowledge: both the news section and the contents published may be a source of information and education for consumers on food safety.

Investigation of Clostridium botulinum group III's mobilome content

NARCIS (Netherlands)

Woudstra, Cédric; Maréchal, Le Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B.; Lobato, Francisco C.F.; Silva, Rodrigo O.S.; Dorner, Martin B.; Fach, Patrick

2018-01-01

Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of

Prevention and Treament of Botulism

Science.gov (United States)

2014-01-01

potent, and an additional series of molecular dynamics and docking simulations was performed using the existing crystal structures of the BoNT/A...4822 53. Byrne MP, Titball RW, Holley J, Smith LA (2000) Fermentation , purification and efficacy of a recombinant vaccine candidate against botulinum...up of the fermentation and purification of the recombinant heavy chain fragment C of botulinum neurotoxin serotype F, expressed in Pichia pastoris

Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies.

Science.gov (United States)

Šilhár, Peter; Silvaggi, Nicholas R; Pellett, Sabine; Čapková, Kateřina; Johnson, Eric A; Allen, Karen N; Janda, Kim D

2013-03-01

Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a series of hydroxamates derived from 1-adamantylacetohydroxamic acid (3a) were prepared. From this group of compounds, an improved potency of about 17-fold was observed for two derivatives. Detailed mechanistic studies on these structures revealed a competitive inhibition model, with a K(i)=27 nM, which makes these compounds some of the most potent small molecule, non-peptidic BoNT/A LC inhibitors reported to date. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera

Science.gov (United States)

The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...

Neurotoxin gene profiling of Clostridium botulinum types C and D gathered from different countries within Europe

NARCIS (Netherlands)

Woudstra, C.; Skarin, A.; Anniballi, F.; Fenicia, F.; Bano, L.; Drigo, I.; Koene, M.G.J.; Bäyon-Auboyer, M.H.; Buffereau, J.P.; Medici, D.; Fach, P.

2012-01-01

Clostridium botulinum types C and D, as well as their mosaic variants C-D and D-C, are associated with avian and mammalian botulism. This study reports on the development of low-density macroarrays based on the GeneDisc cycler platform (Pall-GeneDisc Technologies) applied to the simultaneous

Inhibiting oral intoxication of botulinum neurotoxin A by carbohydrate receptor mimics

Science.gov (United States)

Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes of BoNT intoxication, where BoNT assembles with several auxiliary proteins to surviv...

Identification of novel linear megaplasmids carrying a ß-lactamase gene in neurotoxigenic Clostridium butyricum type E strains.

Directory of Open Access Journals (Sweden)

Giovanna Franciosa

Full Text Available Since the first isolation of type E botulinum toxin-producing Clostridium butyricum from two infant botulism cases in Italy in 1984, this peculiar microorganism has been implicated in different forms of botulism worldwide. By applying particular pulsed-field gel electrophoresis run conditions, we were able to show for the first time that ten neurotoxigenic C. butyricum type E strains originated from Italy and China have linear megaplasmids in their genomes. At least four different megaplasmid sizes were identified among the ten neurotoxigenic C. butyricum type E strains. Each isolate displayed a single sized megaplasmid that was shown to possess a linear structure by ATP-dependent exonuclease digestion. Some of the neurotoxigenic C. butyricum type E strains possessed additional smaller circular plasmids. In order to investigate the genetic content of the newly identified megaplasmids, selected gene probes were designed and used in Southern hybridization experiments. Our results revealed that the type E botulinum neurotoxin gene was chromosome-located in all neurotoxigenic C. butyricum type E strains. Similar results were obtained with the 16S rRNA, the tetracycline tet(P and the lincomycin resistance protein lmrB gene probes. A specific mobA gene probe only hybridized to the smaller plasmids of the Italian C. butyricum type E strains. Of note, a ß-lactamase gene probe hybridized to the megaplasmids of eight neurotoxigenic C. butyricum type E strains, of which seven from clinical sources and the remaining one from a food implicated in foodborne botulism, whereas this ß-lactam antibiotic resistance gene was absent form the megaplasmids of the two soil strains examined. The widespread occurrence among C. butyricum type E strains associated to human disease of linear megaplasmids harboring an antibiotic resistance gene strongly suggests that the megaplasmids could have played an important role in the emergence of C. butyricum type E as a human

Effects of botulinum toxin on strength-duration properties.

Science.gov (United States)

Yerdelen, Deniz; Koc, Filiz; Sarica, Yakup

2007-10-01

Axonal excitability studies have been used in several diseases to investigate the underlying pathophysiology. The threshold tracking technique was developed to measure noninvasively several indices of axonal excitability, such as strength-duration properties. This study investigated the possible effects of botulinum toxin on strength-duration time constant (SDTC) in patients with the symptoms and signs of botulism. The clinical and electrophysiological findings of 13 patients who were admitted to the authors' clinic with botulism signs and symptoms were evaluated in a 5-day period after exposure to the toxin prospectively. After routine diagnostic electroneuromyographic examinations and electromyogram with repetitive nerve stimulation at 20-50 Hz, SDTC was studied. The results were compared with 13 age- and sex-matched healthy volunteers. The SDTCs were 381 +/- 60 micros and 471 +/- 84 micros in patients and controls, respectively. There was a statistical difference between the two groups (p = .003, Mann Whitney U test). These findings suggest a possible effect of botulinum toxin, known to be effective at neuromuscular junction, on Na(+)/K(+) pump activity, and Na(+) or K(+) conductance.

Mass Spectrometric Identification and Differentiation of Botulinum Neurotoxins through Toxin Proteomics.

Science.gov (United States)

Kalb, Suzanne R; Barr, John R

2013-08-01

Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.

76 FR 11783 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Science.gov (United States)

2011-03-03

... inhibited to avoid production of the deadly toxin that causes botulism. This is accomplished with good...(c)(1) and 108.35(c)(1) (21 CFR 108.25(c)(1) and 108.35(c)(1))). In addition to registering the plant... foods in hermetically sealed containers (Sec. Sec. 108.25(c)(2) and 108.35(c)(2)). Plant registration...

In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

Science.gov (United States)

Williamson, Judy L.; Rocke, Tonie E.; Aiken, Judd M.

1999-01-01

A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

Combined effects of irradiation and conventional methods of meat preservation on pathogenic bacteria

International Nuclear Information System (INIS)

Szczawinski, J.

1987-03-01

Experiments were carried out to determine the effect of irradiation (3 O 2 6 kGy) on the probability of outgrowth and toxin production by C. botulinum types A, B and E in inoculated cured pork during simulated temperature abuse. In addition, to determine whether lowering nitrite concentration and/or decrease in the risk of botulimum hazard could be achieved by combination of less curing salt, pasteurization and low dose irradiation of meat. The results demonstrated that increasing irradiation dose (0, 3, 6 kGy) systematically reduced spoilage and probability of toxin production by C. botulimum in pasteurized samples of cured meat at each level of added nitrite (0, 50, 100, 156 mg/kg). The level of nitrite presently used in some canned, pasteurized, cured meats (156 mg/kg) could be reduced to 100 mg/kg without increase of botulism hazard by irradiation with a dose of 3kGy. Decrease of botulism hazard and reduction of nitrite added into the meat could be achieved by combination of curing with 100mg/kg NaNO 2 , pasteurization and irradiation with a dose of 6kGy

Population estimates and monitoring guidelines for endangered Laysan Teal, Anas Laysanensis, at Midway Atoll: Pilot study results 2008-2010.

Science.gov (United States)

Reynolds, Michelle H.; Brinck, Kevin W.; Laniawe, Leona

2011-01-01

Accurate estimates of population size are often crucial to determining status and planning recovery of endangered species. The ability to detect trends in survival and population size over time enables conservation managers to make effective decisions for species and refuge management. During 2004–2007, the translocated population of endangered Laysan Teal (Anas laysanensis; also Laysan Duck) was fitted with radio transmitters providing known (―gold standard‖) measures of survival and reproduction. However, as the population grew, statistically rigorous monitoring protocols were needed that were less labor intensive than radio telemetry. A population die-off and alarmingly high number of carcasses (181) were recorded during a botulism epizootic in August–October 2008, which further reinforced the need for effective monitoring protocols since this endangered species is vulnerable to catastrophic population declines. In fall 2008, we initiated a pilot study using standardized surveys with uniquely marked birds to monitor abundance and estimate the population growth rate of the reintroduced Laysan Teal. Since few birds carried marks (leg bands) after the 2008 botulism die-off (only about 15% of the population), and standardized surveys were not yet implemented, the magnitude of the die-off on the population size was unknown.

National Imperative to Establish a Domestic Medical Intelligence Center

Science.gov (United States)

2007-09-01

Arboviral neuroinvasive and non-neuroinvasive diseases (such as Eastern and Western equine encephalitis) • Botulism • Brucellosis • Chancroid...Ancillary Services • Blood banks • Intensive care units o Burn unit o Cardiac care unit o Cardiac surgery unit o Neonatal unit o Neurology ...Microbiology o Urinalysis • Optometry • Pharmacy • X-ray • Physical therapy • Respiratory therapy 64 • Nutrition • Pathology • Toxicology

Bibliography of Technical Publications and Papers, October 1979 - September 1980

Science.gov (United States)

1980-11-01

technological procedures affecting quality of radappertized chicken rolls. Institute of Food Technolo- gists, New Orleans, LA, 9-11 June 1980. 93...temperature survey of ginger beef pot roast production at a Central Food Preparation Facility. J. Food Prot., 43(4): 292-294 (1980). 180. REESE, E. T...low-dose irradiated chicken skins. Interagency Botulism Research Coordinating Coummittee, Milford, CT, 8-9 October 1980. 207. CALLO, B. Protoplast

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

Science.gov (United States)

Kull, Skadi; Schulz, K Melanie; Weisemann, Jasmin; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P Wojtek; Nitsche, Andreas; Kalb, Suzanne R; Dorner, Martin B; Barr, John R; Rummel, Andreas; Dorner, Brigitte G

2015-01-01

Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might

Development of Targeted Therapeutic Agents for Botulism

National Research Council Canada - National Science Library

Dolly, Oliver

1998-01-01

.... Therefore, an ELISA was optimised and standardised for measuring their proteolysis of immobilised, bacterially-expressed SNAP-25, using purified IgGs reactive solely with full-length or BoNT/A-truncated SNAP-25...

A rare cause of acute flaccid paralysis: Human coronaviruses

OpenAIRE

Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir

2015-01-01

Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common ...

Modified, Packaged Tortillas Have Long Shelf Life

Science.gov (United States)

Bourland, Charles; Glaus-Late, Kimberly

1995-01-01

Tortillas made from modified recipe and sealed in low-pressure nitrogen in foil pouches in effort to increase their shelf life at room temperature. Preliminary tests show that shelf life of these tortillas at least five months; in contrast, commercial tortillas last only few days. Part of water in recipe replaced with glycerin. Particularly necessary to avoid Clostridium botulinum, which grows in anaerobic environments and produces deadly toxin that causes botulism.

Quality of life of children with cerebral palsy treated with botulinum toxin: are well-being measures appropriate? Qualidade de vida em crianças com paralisia cerebral tratadas com toxina botulínica: estas avaliações são adequadas?

Directory of Open Access Journals (Sweden)

Taísa R. Simões de Assis

2008-01-01

Full Text Available AIM: To analyze quality of life (QOL of children with cerebral palsy (CP treated with botulinum toxin type A (BTXA. METHOD: Two QOL evaluation tools, translated into Portuguese, were used: Pediatric Outcomes Data Collection Instrument (PODCI and Child's Caregiver Questionnaire (CCQ. Questionnaires were answered by caregivers on two occasions. Patients were divided into 3 groups: I - patients who had been previously treated with BTXA and who underwent a session of BTXA; II - patients who used BTXA for the first time; III - patients previously treated with BTXA but did not in this interval. RESULTS: Sixty-eight patients were evaluated. In group I (n=26 the functional ability had improvement for all types of CP (p=0.04, and tetraplegic increased interaction/communication (p=0.02. In group II (n=14 positioning improved (p=0.02. Group III (n=28 showed no change in QOL. CONCLUSIONS: PODCI and CCQ are able to capture outcome in children with CP.OBJETIVO: Analisar a qualidade de vida (QV de crianças com paralisia cerebral tratadas com toxina botulínica do tipo A (TBA. MÉTODO: Dois instrumentos de QV, adaptados para a língua portuguesa, foram utilizados: Instrumento para Avaliação de Resultados de Reabilitação em Pediatria (IARRP e Questionário do Cuidador da Criança (CQC, sendo respondidos pelos cuidadores. Os pacientes foram divididos em 3 grupos: I - já haviam utilizado TBA e foram submetidos à aplicação neste intervalo; II - utilizaram TBA pela primeira vez; III - utilizaram TBA previamente, mas não neste intervalo. RESULTADOS: Sessenta e oito pacientes foram avaliados, no grupo I (n=26 houve melhora da capacidade funcional em todos os tipos de PC (p=0.04, e tetraplégicos tiveram ganho também na interação/comunicação (p=0.02. No grupo II (n=14 houve melhora em posicionamento (p=0.02. Não foram observadas mudanças na QV do grupo III (n=28. CONCLUSÃO: IARRP e CQC são capazes de avaliar resultados em crianças com PC.

Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.

Science.gov (United States)

Kelch, W J; Kerr, L A; Pringle, J K; Rohrbach, B W; Whitlock, R H

2000-09-01

Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.

Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.

Science.gov (United States)

Yoneyama, Tohru; Miyata, Keita; Chikai, Tomoyuki; Mikami, Akifumi; Suzuki, Tomonori; Hasegawa, Kimiko; Ikeda, Toshihiko; Watanabe, Toshihiro; Ohyama, Tohru; Niwa, Koichi

2008-12-01

Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.

Botulismo tipo C em suínos alimentados com restos de restaurante

OpenAIRE

Raymundo, Djeison Lutier; Gomes, Danilo Carloto; Boabaid, Fabiana M.; Colodel, Edson Moleta; Schmitz, Milene; Corrêa, André Mendes Ribeiro; Dutra, Iveraldo dos Santos; Driemeier, David

2012-01-01

The paper addresses the epidemiologic data of the death of pigs during the period of 2002 to 2009 following the ingestion of botulinum neurotoxin type C. This neurotoxin was present in food residues originating from restaurant and hotel kitchens, stored in barrels without shelter from the sun and administered in a collective trough without prior thermal treatment. Animals which died at different ages showed clinical signs of botulism characterized by flaccid paralysis, weight loss, anorexia, ...

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

OpenAIRE

Yao, G; Lam, KH; Perry, K; Weisemann, J; Rummel, A; Jin, R

2017-01-01

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. 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 Bo...

Botulinum toxin in medicine and cosmetology – two hundred years’ history and new perspectives

OpenAIRE

Małgorzata Zbrojkiewicz; Agata Lebiedowska; Barbara Błońska-Fajfrowska Barbara Błońska-Fajfrowska

2018-01-01

It has been nearly 200 years since the discovery of the botulinum toxin and the strain responsible for its synthesis Clostridium botulinum. Over this period, the knowledge about botulism and the use of botulinum toxin in medicine has been significantly expanded. Currently, eight serotypes of botulinum toxin (A-H) are known and they differ from each other by molecular weight, antigenic structure, immunogenicity, receptors, localization of coding genes and by the duration of the therapeutic ...

Beltless Translocation Domain of Botulinum Neurotoxin A Embodies a Minimum Ion-conductive Channel*

OpenAIRE

Fischer, Audrey; Sambashivan, Shilpa; Brunger, Axel T.; Montal, Mauricio

2011-01-01

Botulinum neurotoxin, the causative agent of the paralytic disease botulism, is an endopeptidase composed of a catalytic domain (or light chain (LC)) and a heavy chain (HC) encompassing the translocation domain (TD) and receptor-binding domain. Upon receptor-mediated endocytosis, the LC and TD are proposed to undergo conformational changes in the acidic endocytic environment resulting in the formation of an LC protein-conducting TD channel. The mechanism of channel formation and the conformat...

Does botulinum toxin improve the function of the patient with spasticity after stroke? Toxina botulínica proporciona melhora funcional em pacientes com espasticidade secundária a acidente vascular cerebral?

Directory of Open Access Journals (Sweden)

Eduardo Cardoso

2007-09-01

Full Text Available Post-stroke spasticity is an important cause of disability in adults, due to muscle hyperactivity, which results in limb stiffness and muscle spasm. The prognosis for these patients depends on several features such as early management and adequate physical therapy to avoid muscle shortening, pain, and their consequences. Although several papers have shown that intramuscular injections of botulinum toxin type A (BT-A decreases spasticity in post-stroke patients, few authors have demonstrated functional improvement after this therapy. In order to assess if individualized BT-A injections improves upper limb function in post-stroke spastic patients, we prospectively followed 20 consecutive patients of 18 years of age or more with spastic hemiparesis secondary to stroke. Fulg-Meyer scale modified for upper limbs, measure of functional independence (MFI, Ashworth modified scale, and goniometry were applied in the beginning of the investigation and in the 16th and 32nd weeks. BT-A was applied at baseline and in the 16th week. All subjects were submitted to rehabilitation therapy. All patients showed improvement according to Ashworth modified scale and increase in the range of motion, which were sustained until the 32nd week (pEspasticidade secundária a acidente vascular cerebral (AVC é importante causa de incapacidade em adultos. O prognóstico para estes pacientes depende de vários fatores como tratamento precoce e terapia física adequada, evitando encurtamento muscular, dor e outras conseqüências. Vários estudos têm demonstrado que aplicacões intramusculares de toxina botulínica do tipo A (TxB-A reduzem a espasticidade após AVC, entretanto poucos autores observaram melhora funcional de membros superiores com esta terapêutica. Para determinar se aplicações individualizadas de TxB-A melhoram a função no membro superior espástico de pacientes com hemiparesia secundária a AVC, acompanhamos 20 pacientes com história de AVC entre 6 meses

A controlled evaluation of case clinical effect coding by poison center specialists for detection of WMD scenarios.

Science.gov (United States)

Beuhler, Michael C; Wittler, Mary A; Ford, Marsha; Dulaney, Anna R

2011-08-01

Many public health entities employ computer-based syndromic surveillance to monitor for aberrations including possible exposures to weapons of mass destruction (WMD). Often, this is done by screening signs and symptoms reported for cases against syndromic definitions. Poison centers (PCs) may offer significant contributions to public health surveillance because of their detailed clinical effect data field coding and real-time data entry. Because improper clinical effect coding may impede syndromic surveillance, it is important to assess this accuracy for PCs. An AAPCC-certified regional PC assessed the accuracy of clinical effect coding by specialists in poison information (SPIs) listening to audio recordings of standard cases. Eighteen different standardized cases were used, consisting of six cyanide, six botulism, and six control cases. Cases were scripted to simulate clinically relevant telephone conversations and converted to audio recordings. Ten SPIs were randomly selected from the center's staff to listen to and code case information from the recorded cases. Kappa scores and the percentage of correctly coding a present clinical effect were calculated for individual clinical effects summed over all test cases along with corresponding 95% confidence intervals. The rate of the case coding by the SPIs triggering the PC's automated botulism and cyanide alerts was also determined. The kappa scores and the percentage of correctly coding a present clinical effect varied depending on the specific clinical effect, with greater accuracy observed for the clinical effects of vomiting and agitation/irritability, and poor accuracy observed for the clinical effects of visual defect and anion gap increase. Lack of correct coding resulted in only 60 and 86% of the cases that met the botulism and cyanide surveillance definitions, respectively, triggering the corresponding alert. There was no difference observed in the percentage of coding a present clinical effect between

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

Directory of Open Access Journals (Sweden)

Skadi Kull

Full Text Available Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT. Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed

Computer-Assisted Communication Device for Botulinum-Intoxicated Patients

Science.gov (United States)

2008-01-01

development of small molecule therapeutics for botulinum neurotoxin and on the development of nerve agent pretreatments and therapies . He has published...Souayah, N., Karim, H., Kamin, S.S., McArdle, J. and Marcus, S. (2006) ‘Severe botulism after focal injection of botulinum toxin’, Neurology , Vol...67, pp.1855–1856. Tacket, C.O., Shandera, W.X., Mann, J.M., Hargrett, N.T. and Blake, P.A. (1984) ‘ Equine antitoxin use and other factors that

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

OpenAIRE

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-01-01

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 Bo...

SiMa Cells for a Serotype Specific and Sensitive Cell-Based Neutralization Test for Botulinum Toxin A and E.

Science.gov (United States)

Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea

2017-07-20

Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.

A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food

Directory of Open Access Journals (Sweden)

Larry H. Stanker

2013-11-01

Full Text Available Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT, produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D., ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule and readily detects toxin in those food samples tested.

A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food.

Science.gov (United States)

Stanker, Larry H; Scotcher, Miles C; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert

2013-11-18

Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD's) for individual antibodies ranging from 10 to 48 × 10-11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested.

Fuzzification of Botulism. | Imianvan | Journal of the Nigerian ...

African Journals Online (AJOL)

Journal of the Nigerian Association of Mathematical Physics. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 30 (2015) >. Log in or Register to get access to full text downloads.

DOES FOOD SAFETY CONFLICT WITH FOOD SECURITY? THE SAFE CONSUMPTION OF FOOD

OpenAIRE

Kinsey, Jean D.

2004-01-01

This paper concludes by saying no, food safety and security reinforce each other. It combines food safety and food security into the concept of "safe food consumption." Unsafe food consumption occurs when food contains known substances that lead to short or long term illness or death (botulism) and suspect substances that are believed to lead to delayed diseases (pesticides). It also occurs when hunger or over eating contribute to long-term illness and shorter life expectancy. The costs of il...

Role of Nitrite in Processed Meat Products and its Degradation during their Storage

OpenAIRE

ILIRJANA BOCI; ELDA ZIU; GENTJANA BARDHI

2014-01-01

This paper represents the analytical data of nitrite level obtained from the experimental work done on meat processed samples taken from a meat processing plant in Tirana. There has been a long debate and health concern about the nitrite content in meat products. Nitrite is added to e.g. sausages, and hams and other meat products to preserve these products and keep them free from dangerous bacteria. Among the aims are preventing botulism, a dangerous food poison. But also it’s important to us...

Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris.

Science.gov (United States)

Baghban, Roghayyeh; Gargari, Seyed Latif Mousavi; Rajabibazl, Masoumeh; Nazarian, Shahram; Bakherad, Hamid

2016-01-01

Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

New Insights into the genetic diversity of Clostridium botulinum Group III through extensive genome exploration

Directory of Open Access Journals (Sweden)

Cédric eWoudstra

2016-05-01

Full Text Available Animal botulism is caused by group III Clostridium botulinum strains producing type C and D toxins, or their chimeric forms C/D and D/C. Animal botulism is considered an emerging disease in Europe, notably in poultry production. Before our study, 14 genomes from different countries were available in the public database, but none were from France. In order to investigate the genetic relationship of French strains with different geographical areas and find new potential typing targets, 17 strains of C. botulinum group III were sequenced (16 from France and one from New Caledonia. Fourteen were type C/D strains isolated from chickens, ducks, guinea fowl and turkeys and three were type D/C strains isolated from cattle. The New Caledonian strain was a type D/C strain. Whole genome sequence analysis showed the French strains to be closely related to European strains from C. botulinum group III lineages Ia and Ib. The investigation of CRISPR sequences as genetic targets for differentiating strains in group III proved to be irrelevant for type C/D due to a deficient CRISPR/Cas mechanism, but not for type D/C. Conversely, the extrachromosomal elements of type C/D strains could be used to generate a genetic ID card. The highest level of discrimination was achieved with SNP core phylogeny, which allowed differentiation up to strain level and provide the most relevant information for genetic epidemiology studies and discrimination.

Espasmo hemifacial e impressão basilar associados a malformação de arnold-chiari relato de caso

Directory of Open Access Journals (Sweden)

Manoel Baldoino Leal Filho

1992-09-01

Full Text Available Os autores relatam o caso de uma paciente com espasmo hemifacial e impressão basilar associados a malformação de Arnold-Chiari. Com a descompressão cirúrgica da fossa posterior, empregada no tratamento da impressão basilar, houve melhora do quadro clínico e o espasmo hemifacial se reduziu quanto à frequência, duração e intensidade. É enfatizada a necessidade do tratamento etiológico do espasmo hemifacial, antes de se recorrer à toxina botulínica.

Produção e caracterização de quimeras recombinantes C e D de Clostridium botulinum

OpenAIRE

Gil, Luciana Aquini Fernandes

2012-01-01

O botulismo bovino é uma intoxicação letal causada pela ingestão da neurotoxina produzida pelo Clostridium botulinum principalmente dos tipos C e D que atua inibindo a liberação de acetilcolina na junção neuromuscular levando à morte por paralisia flácida, com grande importância econômica e sanitária, sendo uma das principais causas de morte em bovinos adultos no Brasil. O controle imunológico do botulismo bovino depende da presença de anticorpos neutralizantes contra as neurotoxinas botul...

Prospects for the Elimination of Clostridium Botulinum from Fish and Fishery Products by Irradiation

Energy Technology Data Exchange (ETDEWEB)

Hobbs, G. [Torry Research Station, Ministry of Technology, Aberdeen, Scotland (United Kingdom)

1968-07-15

The paper first discusses the occurrence of Clostridium botulinum in fish and fishery products and their resistance to irradiation, and then considers the different possible irradiation treatments such as radappertization, radurization and combined processes. For Great Britain it is suggested that sea- frozen fish should be thawed, filleted, packaged and irradiated at 0.3 Mrads. This irradiation treatment would give a sufficient extension of the market life. To eliminate the botulism hazard a temperature of less than 5 Degree-Sign C for storage and distribution is recommended. (author)

Food irradiation

International Nuclear Information System (INIS)

Hetherington, M.

1989-01-01

This popular-level article emphasizes that the ultimate health effects of irradiated food products are unknown. They may include vitamin loss, contamination of food by botulism bacteria, mutations in bacteria, increased production of aflatoxins, changes in food, carcinogenesis from unknown causes, presence of miscellaneous harmful chemicals, and the lack of a way of for a consumer to detect irradiated food. It is claimed that the nuclear industry is applying pressure on the Canadian government to relax labeling requirements on packages of irradiated food in order to find a market for its otherwise unnecessary products

Animal Botulism Outcomes in the AniBioThreat Project

DEFF Research Database (Denmark)

Woudstra, Cédric; Tevell Åberg, Annica; Skarin, Hanna

2013-01-01

and botulinum neurotoxins are considered potential weapons for bioterrorism and have been included in the Australia Group List of Biological Agents. In 2010 the European Commission (DG Justice, Freedom and Security) funded a 3-year project named AniBioThreat to improve the EU's capacity to counter animal...... new genetic information to better understand the diversity of these Clostridia and develop detection methods targeting both highly specific genetic markers of these Clostridia and the neurotoxins they are able to produce. Several European institutes participating in the AniBioThreat project...

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.

Science.gov (United States)

Schussler, Edith; Sobel, Jeremy; Hsu, Joy; Yu, Patricia; Meaney-Delman, Dana; Grammer, Leslie C; Nowak-Wegrzyn, Anna

2017-12-27

Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care. Published by Oxford

Bacterial spores as possible contaminants of biomedical materials and devices. [Bacillus anthracis, clostridium botulinum, C. perfringens, C. tetani

Energy Technology Data Exchange (ETDEWEB)

Grecz, N; Kang, T

1973-01-01

Destruction of spores on biomedical devices in drugs, and biologicals is essential for prevention of infection of patients with pathogenic sporeformers. Of particular concern are Clostridium tetani, C. perfringens, C. botulinum, Bacillus anthracis and other sporeforming pathogens. Spores are ubiquitous in nature and contamination of biomedical devices varies depending on manufacturing process, handling, raw materials and other variables. In the last 20 years the number of cases per year of specific notifiable diseases in the United States was as follows: tetanus, 120 to 500 cases, botulism, 7 to 47 cases, and anthrax, 2 to 10 cases. Gas gangrene is caused by a mixed flora consisting predominantly of sporeformers. C botulinum, which usually acts as saprophytic agent of food poisoning, may also initiate pathogenic processes; there are nine cases on record in the United States of botulism wound infections almost half of which ended in death. The spores of these organisms are distinguished by high radiation resistance and their erradication often requires severe radiation treatments. Representative bacterial spores in various suspending media show D/sub 10/ values (dose necessary to destroy 90 percent of a given population) ranging from approximately 0.1 to 0.4 Mrad. Some viruses show D/sub 10/ values up to greater than 1 Mrad. The D/sub 10/-values of spores vary depending on physical, chemical and biological factors. This variability is important in evaluation and selection of biological indicator organisms. Radiation sterilization of biomedical devices and biomedical materials must provide safety from infectious microorganisms including radiation resistant spores and viruses.

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Science.gov (United States)

Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

2015-01-01

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

Science.gov (United States)

Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Rugas glabelares: estudo piloto dos padrões de contração

OpenAIRE

Ada Regina Trindade de Almeida; Elisa Raquel Martins da Costa Marques; Bogdana Victoria Kadunc

2010-01-01

Introdução: A atividade muscular nd glabela Provocação rugas perpendiculares à Direção decontração dos Músculos, hoje tratadas Pela toxina botulínica.Variações interpessoais nd forma de contração local, São exibidas Durante a Animação facial. Apesar dos Inúmeros artigos publicados Sobre o tema, Os padrões de contração glabelar Ainda Não Foram estudados adequadamente e Classificados. Objetivo: Identificar e classificar Os padrões de contração glabelar encontrados Na população Que recebe Tratam...

Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay.

Science.gov (United States)

Williamson, Charles H D; Vazquez, Adam J; Hill, Karen; Smith, Theresa J; Nottingham, Roxanne; Stone, Nathan E; Sobek, Colin J; Cocking, Jill H; Fernández, Rafael A; Caballero, Patricia A; Leiser, Owen P; Keim, Paul; Sahl, Jason W

2017-09-15

Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Coding region sequences unique to each of the four species/subgroups were identified by in silico analyses of thousands of genome assemblies, and PCR primers were designed to amplify each marker. The resulting multiplex PCR assay correctly assigned 41 tested isolates to the appropriate species or subgroup. A separate PCR assay to determine the presence of the ntnh gene (a gene associated with the botulinum neurotoxin gene cluster) was developed and validated. The ntnh gene PCR assay provides information about the presence or absence of the botulinum neurotoxin gene cluster and the type of gene cluster present ( ha positive [ ha + ] or orfX + ). The increased availability of whole-genome sequence data and comparative genomic tools enabled the design of these assays, which provide valuable information for characterizing BoNT-producing clostridia. The PCR assays are rapid, inexpensive tests that can be applied to a variety of sample types to assign isolates to species/subgroups and to detect clostridia with botulinum neurotoxin gene ( bont ) clusters. IMPORTANCE Diverse clostridia produce the botulinum neurotoxin, one of the most potent known neurotoxins. In this study, a multiplex PCR assay was developed to differentiate clostridia that are most commonly isolated in connection with human botulism cases: C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Since Bo

Study of crotoxin on the induction of paralysis in extraocular muscle in animal model Estudo da crotoxina na indução de paralisia da musculatura extraocular em modelo animal

Directory of Open Access Journals (Sweden)

Geraldo de Barros Ribeiro

2012-10-01

crotoxina é a principal toxina do veneno da cobra cascavel sul-americana Crotalus durissus terrificus e causa bloqueio da neurotransmissão na junção neuromuscular. O objetivo deste estudo foi avaliar a ação e aplicabilidade da crotoxina na indução de paralisia da musculatura extrínseca ocular, e comparar seus efeitos com os da toxina botulínica do tipo A (TB-A. MÉTODOS: A crotoxina, com DL50 de 1,5 µg, foi aplicada no músculo reto superior direito de dez coelhos da raça neozelandesa, em concentrações que variaram de 0,015 µg a 150 µg. Em dois coelhos, utilizou-se 2 unidades de toxina botulínica do tipo A para análise comparativa. A avaliação da paralisia foi realizada através de eletromiografia seriada. Após a recuperação, que ocorreu em dois meses, seis coelhos foram sacrificados para estudo anátomopatológico. RESULTADOS: Os animais não apresentaram sinais de intoxicação sistêmica. Ptose palpebral transitória foi observada em quase todos os animais e permaneceu por até 14 dias. As toxinas causaram um bloqueio imediato da captação dos potenciais elétricos. A recuperação foi gradativa no período aproximado de um mês, observando-se sinais evidentes de regeneração no registro eletromiográfico. Os efeitos da crotoxina na paralização do músculo injetado foram proporcionais à concentração. A crotoxina, na concentração de 1,5 µg, induziu alterações semelhantes às da toxina botulínica do tipo A. Os achados anátomo-patológicos foram localizados somente na região em que se aplicou as toxinas, não havendo necrose de fibras musculares em nenhuma amostra analisada. As alterações causadas pela crotoxina também foram proporcionais à concentração utilizada e similares a toxina botulínica do tipo A na concentração de 1,5 µg. CONCLUSÃO: A crotoxina foi capaz de induzir paralisia transitória do músculo reto superior. Este efeito foi caracterizado pela redução na amplitude dos potenciais de ação e sinais inespec

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Directory of Open Access Journals (Sweden)

Siro Luvisetto

2015-09-01

Full Text Available Botulinum neurotoxin A (BoNT/A is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

Single-fiber electromyography analysis of botulinum toxin diffusion in patients with fatigue and pseudobotulism.

Science.gov (United States)

Ruet, Alexis; Durand, Marie Christine; Denys, Pierre; Lofaso, Frederic; Genet, François; Schnitzler, Alexis

2015-06-01

To characterize electromyographic abnormalities according to symptoms (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin injection. Retrospective, single-center study comparing single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis oculi (OO) muscles. Hospital. Four groups of adults treated for spasticity or neurologic bladder hyperactivity (N=55): control group (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness: n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20), and botulism group (from intensive care unit of the same hospital: n=3). Not applicable. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers were compared between groups. SFEMG was abnormal for 17.6% of control patients and 75% of patients in the pseudobotulism group. There were no differences between the control and fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers of the EDC muscle were significantly higher in the pseudobotulism group than in the fatigue and control groups. There were no differences between groups for the OO muscle. The SFEMG results in the botulism group were qualitatively similar to those of the pseudobotulism group. SFEMG of the EDC muscle confirmed diffusion of the toxin into muscles distant from the injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin type A were found away from the injection site in patients with fatigue but no motor weakness. Such fatigue may be related to other mechanisms. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Neurorehabilitación post toxina botulínica tipo A

OpenAIRE

Bugallo, Romina

2014-01-01

La espasticidad, como secuela neurológica, se comporta como una de las más importantes causas de invalidez en el adulto. El manejo de la espasticidad está dirigido por las necesidades de cada paciente en particular y sus metas funcionales. Determinados músculos espásticos pueden colaborar con una postura ventajosa funcionalmente, pero de forma inversa debe ser tratada cuando primen las desventajas, o sea, cuando existe interferencia en la función, posición, higiene y confort de...

Clinical and electrodiagnostic findings in cyhalothrine poisoning

Directory of Open Access Journals (Sweden)

Keivan Basiri

2016-01-01

Full Text Available Acute onset bulbar symptoms with respiratory failure and descending paralysis may occur in several neuromuscular disorders including variants of Guillain-Barre syndrome (GBS, diphtheria, botulism and toxins. We present a 51-year-old man who presented with complains of ptosis and dyspnea following pyrethroids spraying in an enclosed area for eradication of flea. Within 5-6 days of admission limb weakness, dysphagia, dysarthria, blurred vision, diplopia, tremor and respiratory distress added to previous symptoms. Temporal profile of events after exposure, development of similar symptoms in patient's son, electrodiagnostic findings and exclusion of other etiologies confirms intoxication etiology. We reviewed the literature and provide an extensive electrodiagnostic overview.

Sacroiliac Joint Interventions.

Science.gov (United States)

Soto Quijano, David A; Otero Loperena, Eduardo

2018-02-01

Sacroiliac joint (SIJ) pain is an important cause of lower back problems. Multiple SIJ injection techniques have been proposed over the years to help in the diagnosis and treatment of this condition. However, the SIJ innervation is complex and variable, and truly intra-articular injections are sometimes difficult to obtain. Different sacroiliac joint injections have shown to provide pain relief in patients suffering this ailment. Various techniques for intraarticular injections, sacral branch blocks and radiofrequency ablation, both fluoroscopy guided and ultrasound guided are discussed in this paper. Less common techniques like prolotherapy, platelet rich plasma injections and botulism toxin injections are also discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

PCR und ELISA - Alternativen zum Maustest für die Analyse des Botulismus-Neurotoxin-C1 Giftbildungspotentiales in Umweltproben? [PCR and ELISA - in vitro alternatives to the mouse-bioassay for assessing the botulinum-neurotoxin-C1 production potential in environmental samples?

Science.gov (United States)

Zechmeister, T.C.; Farnleitner, A.H.; Rocke, T.E.; Pittner, F.; Rosengarten, R.; Mach, R.L.; Herzig, A.; Kirschner, A.K.T.

2002-01-01

Botulism is one of the most important bird diseases world-wide and is caused by the intoxication with Botulinum-Neurotoxin-C1 (BoNt-C1), which is produced by toxigenic clostridia under appropriate conditions. Avian botulism leads regularly to large losses among the migrating bird populations breeding and resting at the saltwater pools of the Austrian national park Neusiedler See-Seewinkel. Despite of its ethical dubiousness and its high technical expense the mouse-bioassay is still used as the routine standard method for the detection of BoNt-C1. According to the 3R-concept, in vitro alternative methods for the qualitative detection of BoNt-C1 (immunostick-ELISA) and a corresponding BoNt-C1 gene fragment (nested-PCR) were established. In order to estimate the BoNt-C1 production potential the methods were tested with sediment samples from different saltwater pools subjected to cultivation conditions appropriate for in vitro BoNt-C1-production. With the mouse-bioassay, 52 out of 77 samples were found to have a positive toxin production potential. The immunostick-ELISA showed a similar sensitivity as the mouse-bioassay and exhibited a highly significant positive correlation (r=0.94; pELISA (r=0.09; p=0.46). Obviously, the PCR approach detected the BoNt-C1 gene fragment in some of the samples where no toxin expression has occurred. Thus it is suggested that the qualitative immunostick-ELISA represents a potential in vitro alternative to the mouse-bioassay for assessing the BoNt-C1 production potential in environmental samples. In contrast, qualitative BoNt-C1 gene fragment detection via PCR led to an overestimation of the actual toxin production potential.

La asociación de divertículo de Zenker y acalasia

Directory of Open Access Journals (Sweden)

Juan David Martínez Marín

2008-01-01

Full Text Available Se presenta el caso de un paciente de 88 años, con disfagia y antecedentes de acalasia no tratada de veinte años de evolución y síntomas de disfagia oro faríngea. Los exámenes radiológicos y endoscópicos identificaron además de la acalasia un divertículo de Zenker. Se realizó terapia paliativa con inyección de toxina botulínica en el esfínter esofágico inferior, con mejoría de los síntomas. Se hace una revisión de la rara coexistencia de estas dos patologías.

Electrochemical Aptamer Scaffold Biosensors for Detection of Botulism and Ricin Proteins.

Science.gov (United States)

Daniel, Jessica; Fetter, Lisa; Jett, Susan; Rowland, Teisha J; Bonham, Andrew J

2017-01-01

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.

[Botulism: structure and function of botulinum toxin and its clinical application].

Science.gov (United States)

Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko

2012-08-01

Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.

Detection and Quantification of Biologically Active Botulinum Neurotoxin Serotypes A and B Using a Förster Resonance Energy Transfer-Based Quantum Dot Nanobiosensor

Energy Technology Data Exchange (ETDEWEB)

Wang, Yun [Center for Food; Fry, H. Christopher [Center for Nanoscale Materials, Argonne National Laboratory, 9700 S. Cass Avenue, Lemont, DuPage County, Illinois 60439, United States; Skinner, Guy E. [Center for Food; Schill, Kristin M. [Center for Food; Duncan, Timothy V. [Center for Food

2017-03-20

Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 mu g for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Forster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active forms of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U.S. from 2012 to 2015. Each peptide probe contains an enzymatic cleavage site specific to only one serotype. QDs were selected based on the spectral overlap with the quenchers. In the presence of the target BoNT serotype, the peptide probe is cleaved and the quenching of QD photoluminescence (PL) is reduced, giving a signal that is easily detected by a PL spectrophotometer. This sensor performance was evaluated with light chains of BoNT/A and BoNT/B (LcA and LcB), catalytic domains of the respective serotypes. LcA and LcB were detected in 3 h with limits of detection of 0.2 and 2 ng/mL, respectively. The specificity of the sensor was evaluated, and no cross-reactivity from nontarget serotypes was observed with 2 h of incubation. Because each serotype-specific peptide is conjugated to a QD with a unique emission wavelength, multiple biologically active BoNT serotypes could be detected in one PL spectrum. The sensor was also shown to be responsive to BoNT/A and BoNT/B holotoxins. Good performance of this sensor implies its potential application as a rapid screening method for biologically active BoNT/A and BoNT/B in the laboratory and in the field.

Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A.

Science.gov (United States)

Yalamanchili, Chinni; Manda, Vamshi K; Chittiboyina, Amar G; Guernieri, Rebecca L; Harrell, William A; Webb, Robert P; Smith, Leonard A; Khan, Ikhlas A

2017-02-02

Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest. Fifteen plants were selected from the book 'Diagnosis and treatment of diseases in Ayurveda' by Vaidya Bhagwan Dash and Lalitesh Kashyap, based on their frequency of use in the formulations used for the treatment of six diseases with neuromuscular symptoms similar to botulism. Phytochemicals from these plants were screened using in silico, and in vitro methods. Structures of 570 reported phytochemicals from 14 plants were docked inside six reported BoNT/A light chain crystal structures using ensemble docking module in Maestro (Schrödinger, LLE). From the docking scores and structural diversity, nine compounds including acoric acid 1, three flavonoids, three coumarins derivatives, one kava lactone were selected and screened using an in vitro HPLC-based protease assay. The bioassay results showed that several compounds possess BoNT/A LC inhibition of 50-60% when compared to positive controls NSC 84094 and CB7967495 (80-95%). Further testing of the active compounds identified from Ayurvedic literature and structure-activity studies of acoric acid 1 using more sensitive bioassays is under way. The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads. Copyright © 2016 Elsevier Ireland Ltd. All rights

Botulinum toxin for treating muscular temporomandibular disorders: a systematic review

Directory of Open Access Journals (Sweden)

Eduardo Machado

2012-12-01

Full Text Available OBJECTIVE: This study, through a systematic literature review, aims to analyze the effectiveness of Botulinum Toxin as a treatment for masticatory myofascial pain and muscles temporomandibular disorders (TMD. METHODS: Survey in research bases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, between the years of 1966 and April 2011, with focus in randomized or quasi-randomized controlled clinical trials, blind or double-blind. RESULTS: After applying the inclusion criteria, 4 articles comprised the final sample: 3 were double-blind randomized controlled clinical trials and 1 was single-blind randomized controlled clinical trial. CONCLUSIONS: According to the literature, there is lack of evidence about the real effectiveness of botulinum toxin in the treatment of masticatory myofascial pain and muscular TMD. Thus, further randomized controlled clinical trials, with representative samples and longer follow-up time, to assess the real effectiveness of the technique are needed.OBJETIVO: este trabalho, por meio de uma revisão sistemática da literatura, teve como objetivo analisar a efetividade da toxina botulínica como tratamento para dor miofascial mastigatória e disfunções temporomandibulares (DTM musculares. MÉTODOS: pesquisa nas bases de dados Medline, Cochrane, Embase, Pubmed, Lilacs e BBO, no período entre 1966 e abril de 2011, com enfoque em estudos clínicos controlados randomizados ou quase-randomizados, cegos ou duplo-cegos. RESULTADOS: após a aplicação dos critérios de inclusão, chegou-se a 4 artigos, sendo que 3 eram estudos clínicos controlados randomizados duplo-cego e 1 era estudo clínico controlado randomizado simples-cego. CONCLUSÕES: pela análise da literatura, verificou-se um número reduzido de evidências significativas sobre a real efetividade da toxina botulínica no tratamento da dor miofascial e de DTM musculares. Assim, são necessários novos estudos clínicos controlados randomizados, com amostras

Crystallization and preliminary X-ray analysis of a novel haemagglutinin component of the toxin complex of serotype C Clostridium botulinum.

Science.gov (United States)

Hayashi, Shintaro; Akiyama, Tomonori; Sagane, Yoshimasa; Miyashita, Shin-Ichiro; Watanabe, Toshihiro; Yajima, Shunsuke; Niwa, Koichi

2014-03-01

The botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kDa molecular weight (HA-33). The amino-acid sequence of the C-terminal half of HA-33 of the serotype C strain Yoichi (C-Yoichi) shares only 46% identity with those of the major serotype C strains. Additionally, C-Yoichi HA-33 exhibits a unique sugar-binding specificity. In the present work, C-Yoichi HA-33 was expressed in Escherichia coli and crystallized. Diffraction data were collected at a resolution of 2.2 Å. The crystals belonged to space group R3. The complete detailed protein structure will yield insight into how the unique HA-33 protein recognizes sugar moieties.

An Investigation of Immunogenicity of Chitosan-Based Botulinum Neurotoxin E Binding Domain Recombinant Candidate Vaccine via Mucosal Route

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Mohammad Javad Bagheripour

2017-01-01

Full Text Available Background and Objectives: Botulism syndrome is caused by serotypes A-G of neurotoxins of Clostridium genus. Neurotoxin binding domain is an appropriate vaccine candidate due to its immunogenic activity. In this study, the immunogenicity of chitosan-based botulinum neurotoxin E binding domain recombinant candidate vaccine was investigated via mucosal route of administration. Methods: In this experimental study, chitosan nanoparticles containing rBoNT/E protein were synthesized by ionic gelation method and were administered orally and intranasally to mice. After each administration, IgG antibody titer was measured by ELISA method. Finally, all groups were challenged with active botulinum neurotoxin type E. Data were analyzed using Duncan and repeated ANOVA tests. The significance level was considered as p0.05, even intranasal route reduced the immunogenicity.

Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome

DEFF Research Database (Denmark)

Rørbye, C; Petersen, Ina Sleimann; Nilas, Lisbeth

2000-01-01

Clostridium bacteria are anaerobic Gram positive spore-form-ing bacilli, known to cause distinct clinical syndromes such as botulism, tetanus, pseudomembranous colitis and myonecrosis. The natural habitats of Clostridium species are soil, water and the gastrointestinal tract of animals and humans....... In 5-10% of all women, Clostridium species are also found to be normal inhabitants in the microbial flora of the female genital tract. In case of a non-sexually transmitted genital tract infection, Clostridium species are isolated in 4-20%, and clostridium welchii seems to be the most common isolate....... Clostridium sordellii is rarely encountered in clinical specimens (1% of Clostridium species), but it has been described as a human pathogen with fatal potential. Two toxins, a lethal and a hemorrhagic (that antigenically and pathophysiologically appear similar to Clostridium difficile toxins B and A...

Feedtrough dirt as a source of Clostridium botulinum type C intoxication in a group of farm horses

Science.gov (United States)

Heath, Sebastian E.; Bell, Roxy J.; Chirino-Trejo, Manuel; Schuh, JoAnne C.L.; Harland, Richard J.

1990-01-01

Four horses from the same farm developed clinical signs of botulism during the winter months; three of these horses died. One horse survived an initial attack and recovered over a three-week period, but died during a second attack. The horse that survived took six weeks to recover. Clinical and postmortem examination ruled out other causes of disease. Confirmation of the diagnosis was made by isolation of Clostridium botulinum type C toxin from the dirt in the bottom of an oak feedtrough used by all horses, and from the colonic contents of one of the horses that died. To our knowledge, this is the second case of C. botulinum type C intoxication reported in horses in North America. In both cases, soil and sand near aquatic environments were identified as the source of toxin. PMID:17423488

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

Science.gov (United States)

Tehran, Domenico Azarnia; Pirazzini, Marco

2018-05-10

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

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Domenico Azarnia Tehran

2018-05-01

Full Text Available Botulinum neurotoxins (BoNTs, the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Avian botulism at a sugar beet processing plant in South Moravia (Czech Republic)

Czech Academy of Sciences Publication Activity Database

Hubálek, Zdeněk; Škorpíková, V.; Horal, D.

2005-01-01

Roč. 50, č. 10 (2005), s. 443-445 ISSN 0375-8427 Institutional research plan: CEZ:AV0Z60930519 Keywords : Clostridium botulinum * free-living birds Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 0.621, year: 2005 http://www.vri.cz/docs/vetmed/50-10-443.pdf

Análise estrutural da laringofaringe e suas implicações na miotomia do cricofaríngeo, na injeção de toxina botulínica e na dilatação por balão Laryngopharyngeal structural analysis and its morphofunctional correlation with cricopharyngeal myotomy, botulinum toxin injection and balloon dilation

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Milton Melciades Barbosa Costa

2003-06-01

Full Text Available RACIONAL: O músculo cricofaríngeo é de tipo estriado esquelético, por conseguinte, incapaz de manter contração continuada por longos períodos. Apesar disto, tem sido considerado como o responsável pela zona de alta pressão registrada manometricamente na transição faringoesofágica. Em razão desta crença, tem sido alvo de terapêuticas cruentas que visam, por ruptura de sua integridade, franquear a comunicação entre a faringe e o esôfago. OBJETIVO: Dar as bases anatômicas que definam os limites de participação do músculo cricofaríngeo na função da transição faringoesofágica; considerar alternativa morfofuncional para explicar a zona de alta pressão desta transição e as implicações das miotomias sobre ela, uso de toxina botulínica e das dilatações pneumáticas. MATERIAL E MÉTODOS: O total de 24 peças obtidas de cadáveres de adultos de ambos os sexos fixados em formaldeído a 10%, teve a laringofaringe estudada quanto as suas características morfológicas e relações. RESULTADOS: O músculo cricofaríngeo apresenta suas inserções ântero-laterais nas bordas póstero-laterais da cartilagem cricóide, configurando morfologia em meia calha ou de uma letra C que não permite, quando de sua contração, a geração de pressão com predomínio anterior e posterior, como a encontrada na transição faringoesofágica. Este tipo de distribuição pressórica tem sustentação na relação de pinça exercida, por um lado, pela rigidez oferecida pelos corpos vertebrais, por outro, pelo contorno posterior da cartilagem cricóide. CONCLUSÕES: A organização muscular da laringofaringe permite afiançar que a miotomia alargada da transição faringoesofágica, aquela que se estende além do fascículo transverso do cricofaríngeo, lesa musculatura ejetora e em área cuja a já maior dimensão luminar dispensaria a secção parietal. Miotomia que tome somente o fascículo transverso do cricofaríngeo poderá contribuir

Infectious disease morbidity in the US region bordering Mexico, 1990-1998.

Science.gov (United States)

Doyle, T J; Bryan, R T

2000-11-01

The United States and Mexico share an international boundary approximately 3000 km long. This border separates 2 nations with great differences in health status. The objective of this study was to assess morbidity due to infectious diseases in the US region bordering Mexico. The incidence between 1990 and 1998 of 22 nationally notifiable infectious diseases was compared between border and nonborder regions. Disease rates, reflected as rate ratios, were higher in the border region for botulism, brucellosis, diphtheria, hepatitis A, measles, mumps, rabies, rubella, salmonellosis, and shigellosis than in either of 2 nonborder comparison regions. These data indicate that incidence rates for a variety of infectious diseases of public health importance are significantly higher in the United States along the Mexican border than in nonborder regions. These results suggest that an inadequate public health infrastructure may contribute to excess morbidity due to infectious diseases in the border region.

Preliminary X-ray crystallographic study of the receptor-binding domain of the D/C mosaic neurotoxin from Clostridium botulinum

International Nuclear Information System (INIS)

Nuemket, Nipawan; Tanaka, Yoshikazu; Tsukamoto, Kentaro; Tsuji, Takao; Nakamura, Keiji; Kozaki, Shunji; Yao, Min; Tanaka, Isao

2010-01-01

To determine the binding mechanism of BoNT/OFD05 and its ganglioside receptors on neuronal cells, recombinant BoNT/OFD05 receptor-binding domain has been expressed, purified and crystallized. Botulinum toxin (BoNT) from Clostridium botulinum OFD05, isolated from bovine botulism, is a D/C mosaic-type BoNT. BoNTs possess binding, translocation and catalytic domains. The BoNT/OFD05 binding domain exhibits significant sequence identity to BoNT/C, which requires a single ganglioside as a binding receptor on neuronal cells, while BoNT/A and BoNT/B require two receptors for specific binding. To determine the binding mechanism of BoNT/OFD05 and its ganglioside receptors on neuronal cells, recombinant BoNT/OFD05 receptor-binding domain has been expressed, purified and crystallized. Native and SeMet-derivative crystals showed X-ray diffraction to 2.8 and 3.1 Å resolution, respectively. The crystals belonged to space group P2 1 2 1 2 1

Effect of irradiation in extending the storage life of boiled Chub mackerel (Rastrelliger spp.)

Energy Technology Data Exchange (ETDEWEB)

Loaharanu, P; Prompubesara, C; Songprasertchai, S; Kraisorn, K

1972-12-31

Effect of irradiation at doses of 0.1, 0.2, or 0.3 Mrad in extending the storage life of boiled Chub mackerel held at room temperature was described. Total aerobic count, trimethylamine nitrogen, and total volatile basic nitrogen contents were used and objective indices of quality in comparison with sensory evaluation of the product. Boiled fish irradiated at 0.1, 0.2, or 0.3 Mrad were found to be in good quality for 10, 15, and 17 days respectively, compared with 3 days for the unirradiated control. Trimethylamine nitrogen and total volatile basic nitrogen contents were found to be useful indices of quality, which showed fair correlation with sensory evaluation of the irradiated product. Total aerobic count showed little value as a quality index. Bacillus, Staphylococcus, and Micrococcus predominated in both unirradiated and irradiated boiled fish. The product was found to be free of faocal coliform. Safety of the irradiated boiled fish concerning botulism was discussed.

Acute muscular weakness in children

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Ricardo Pablo Javier Erazo Torricelli

Full Text Available ABSTRACT 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. Ophthalmoparesis, ptosis and bulbar signs are suggestive of myasthenia gravis or botulism. Distal weakness and hyporeflexia are clinical features of Guillain-Barré syndrome, the most frequent cause of acute muscle weakness. If all studies are normal, a psychogenic cause should be considered. Finding the etiology of acute muscle weakness is essential to execute treatment in a timely manner, improving the prognosis of affected children.

Prevalence of neurotoxic Clostridium botulinum type C in the gastrointestinal tracts of tilapis (Oreochromis mossambicus) in the Salton Sea

Science.gov (United States)

Nol, P.J.; Rocke, T.E.; Gross, K.; Yuill, Thomas M.

2004-01-01

Tilapia (Oreochromis mossambicus) have been implicated as the source of type C toxin in avian botulism outbreaks in pelicans (Pelecanus erythrorhynchos, Pelecanus occidentalis californicus) at the Salton Sea in southern California (USA). We collected sick, dead, and healthy fish from various sites throughout the Sea during the summers of 1999 through 2001 and tested them for the presence of Clostridium botulinum type C cells by polymerase chain reaction targeting the C1 neurotoxin gene. Four of 96 (4%), 57 of 664 (9%), and five of 355 (1%) tilapia tested were positive for C. botulinum type C toxin gene in 1999, 2000, and 2001, respectively. The total number of positive fish was significantly greater in 2000 than in 2001 (P<0.0001). No difference in numbers of positives was detected between sick and dead fish compared with live fish. In 2000, no significant relationships were revealed among the variables studied, such as location and date of collection.

Prevalence of neurotoxic Clostridium botulinum type C in the gastrointestinal tracts of tilapia (Oreochromis mossambicus) in the Salton Sea.

Science.gov (United States)

Nol, P; Rocke, T E; Gross, K; Yuill, T M

2004-07-01

Tilapia (Oreochromis mossambicus) have been implicated as the source of type C toxin in avian botulism outbreaks in pelicans (Pelecanus erythrorhynchos, Pelecanus occidentalis californicus) at the Salton Sea in southern California (USA). We collected sick, dead, and healthy fish from various sites throughout the Sea during the summers of 1999 through 2001 and tested them for the presence of Clostridium botulinum type C cells by polymerase chain reaction targeting the C(1) neurotoxin gene. Four of 96 (4%), 57 of 664 (9%), and five of 355 (1%) tilapia tested were positive for C. botulinum type C toxin gene in 1999, 2000, and 2001, respectively. The total number of positive fish was significantly greater in 2000 than in 2001 (P<0.0001). No difference in numbers of positives was detected between sick and dead fish compared with live fish. In 2000, no significant relationships were revealed among the variables studied, such as location and date of collection.

Uso de manometria computadorizada para estudo do espasmo do segmento faringoesofágico em pacientes com voz traqueoesofágica inadequada antes e após aplicação de toxina botulínica Computerized manometry use to evaluate spasm in pharyngoesophageal segment in patients with poor tracheoesophageal speech before and after treatment with botulinum toxin

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Carlos T. Chone

2009-04-01

Full Text Available Voz traqueoesofágica (VTE com prótese fonatória (PF é método eficaz e reproduzível na reabilitação vocal após laringectomia total (LT, impedida pelo espasmo do segmento faringoesofágico (SFE. A manometria computadorizada (MC é novo método objetivo e direto de avaliação do SFE. OBJETIVO: Análise objetiva do espasmo do SFE, com MC, antes e após aplicação de toxina botulínica (TB. DESENHO DO ESTUDO: Prospectivo clínico. MATERIAL E MÉTODOS: Análise de oito pacientes consecutivos submetidos à LT com VTE e PF, sem emissão vocal, com espasmo do SFE à videofluoroscopia, considerado padrão ouro para detecção de espasmo. Todos trataram o espasmo com injeção de 100 unidades de TB no SFE. Avaliação constituiu-se de videofluoroscopia e MC do SFE, antes e após aplicação de TB. RESULTADOS: Houve diminuição na pressão do SFE à MC, após injeção de TB em todos. A média de pressão do SFE à MC, nos oito pacientes, antes da aplicação de TB foi de 25.36 mmHg e após foi de 14.31 mmHg (p=0,004. Houve emissão vocal sem esforço e melhora do espasmo do SFE à videofluoroscopia após o uso da TB. CONCLUSÃO: Foi observada diminuição na pressão do SFE após injeção da TB à MC em todos os pacientes, com melhora do espasmo à videofluoroscopia.Tracheoesophageal voice (TEV with voice prosthesis (VP is an efficient and reproducible method used in vocal rehabilitation after total laryngectomy (TL, prevented by spasms in the pharyngoesophageal segment (PES. Computerized Manometry (CM is a new, direct and objective method used to assess the PES. AIM: to carry out an objective analysis of the PES, with CM, before and after the injection of botulinum toxin (BT. STUDY DESIGN: clinical-prospective. MATERIALS AND METHODS: analysis of eight patients consecutively submitted to TL with TEV and VP, without vocal emission, with PES spasms seen through videofluoroscopy, considered the gold standard for spasm detection. All had their

Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design.

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Yuan-Ping Pang

2009-11-01

Full Text Available Botulinum neurotoxin serotype A (BoNTA causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a K(i (app value of 3.8+/-0.8 microM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC(50 value of 100 microM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 A(2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750-1,500 A(2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a K(i value of 760+/-170 nM using synthesis-based computer-aided molecular design (SBCAMD. This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight

Preliminary characterization of digestive enzymes in freshwater mussels

Science.gov (United States)

Sauey, Blake W.; Amberg, Jon J.; Cooper, Scott T.; Grunwald, Sandra K.; Newton, Teresa J.; Haro, Roger J.

2015-01-01

Resource managers lack an effective chemical tool to control the invasive zebra mussel Dreissena polymorpha. Zebra mussels clog water intakes for hydroelectric companies, harm unionid mussel species, and are believed to be a reservoir of avian botulism. Little is known about the digestive physiology of zebra mussels and unionid mussels. The enzymatic profile of the digestive glands of zebra mussels and native threeridge (Amblema plicata) and plain pocketbook mussels (Lampsilis cardium) are characterized using a commercial enzyme kit, api ZYM, and validated the kit with reagent-grade enzymes. A linear correlation was shown for only one of nineteen enzymes, tested between the api ZYM kit and a specific enzyme kit. Thus, the api ZYM kit should only be used to make general comparisons of enzyme presence and to observe trends in enzyme activities. Enzymatic trends were seen in the unionid mussel species, but not in zebra mussels sampled 32 days apart from the same location. Enzymatic classes, based on substrate, showed different trends, with proteolytic and phospholytic enzymes having the most change in relative enzyme activity.

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A

Science.gov (United States)

Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan; Lam, Kwok-ho; Stern, Daniel; Bagramyan, Karine; Perry, Kay; Kalkum, Markus; Rummel, Andreas; Dong, Min; Jin, Rongsheng

2016-01-01

Botulinum neurotoxin serotype A1 (BoNT/A1) is one of the most dangerous potential bioterrorism agents, and exerts its action by invading motoneurons. It is also a licensed drug widely used for medical and cosmetic applications. Here we report a 2.0 Å resolution crystal structure of BoNT/A1 receptor-binding domain in complex with its neuronal receptor, the glycosylated human SV2C. We find that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2. This N-glycan—conserved in all SV2 isoforms across vertebrates—is essential for BoNT/A1 binding to neurons and its potent neurotoxicity. The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an anti-botulism drug. Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications to achieve highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors. PMID:27294781

Clostridium septicum Gas Gangrene in Colon Cancer: Importance of Early Diagnosis

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Sowmya Nanjappa

2015-01-01

Full Text Available The Clostridia species are responsible for some of the deadliest diseases including gas gangrene, tetanus, and botulism. Clostridium septicum is a rare subgroup known to cause atraumatic myonecrosis and is associated with colonic malignancy or immunosuppression. It is a Gram-positive, anaerobic, spore-forming bacillus found in the gastrointestinal tract and can lead to direct, spontaneous infections of the bowel and peritoneal cavity. The anaerobic glycolysis of the tumor produces an acidic, hypoxic environment favoring germination of clostridial spores. Tumor-induced mucosal ulceration allows for translocation of sporulated bacteria from the bowel into the bloodstream, leading to fulminant sepsis. C. septicum bacteremia can have a variable presentation and is associated with greater than 60% mortality rate. The majority of deaths occur within the first 24 hours if diagnosis and appropriate treatment measures are not promptly started. We report a case of abdominal myonecrosis in a patient with newly diagnosed colon cancer. The aim of this study is to stress the importance of maintaining a high suspicion of C. septicum infection in patients with underlying colonic malignancy.

Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occured before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

Comparison of toxin production by clostridium botulinum type E in irradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

Comparison of toxin production by clostridium botulinum type E in irradiated and unirradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

Outbreak of type C botulism in birds and mammals in the Emilia Romagna region, northern Italy.

Science.gov (United States)

Defilippo, Francesco; Luppi, Andrea; Maioli, Giulia; Marzi, Dario; Fontana, Maria Cristina; Paoli, Federica; Bonilauri, Paolo; Dottori, Michele; Merialdi, Giuseppe

2013-10-01

Over a 7-day period beginning 8 August 2011, a large number of wild birds of several species were found dead or with neurologic clinical signs along the shore of Crostolo stream, in the Emilia Romagna region, Italy. Twenty-eight Mallards (Anas platyrhynchos), two Hooded Crows (Corvus corone cornix), and three coypus (Myocastor coypus) were found moribund on the Crostolo stream bank, collected, and sent to Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Reggio Emilia Section. The cause of mortality was determined to be Clostridium botulinum type C toxin. The toxin was identified by a mouse bioassay for botulinum toxins and confirmed in bird sera and blowfly larvae (Lucilia caesar) collected from the stomachs of birds.

Tratamento farmacológico da gagueira: evidências e controvérsias Pharmacologic treatment of stuttering: evidences and controversies

Directory of Open Access Journals (Sweden)

Camila Vila-Nova

2006-01-01

Full Text Available OBJETIVO: Este artigo tem por objetivo analisar a situação do tratamento farmacológico da gagueira, mostrando a eficácia de diferentes abordagens baseadas em drogas psiquiátricas, além de evidenciar a utilização de outros fármacos no tratamento dessa enfermidade. MÉTODOS: Revisão de literatura em base de dados Medline, utilizando os termos stuttering treatment, disfluency, disfluency treatments, botulinum toxin and stuttering treatment, botulinum toxin and disfluency treatment. RESULTADOS: Foram encontrados estudos envolvendo as seguintes drogas: citalopram + clomipramina, paroxetina, olanzapina, citalopram + alprazolam, pimozida, risperidona, tiaprida, clomipramina e desipramina, levetiracetam, divalproato de sódio, clonidina e betanecol, além de ensaios clínicos com a utilização de toxina botulínica tipo A e anestésicos. Os estudos envolvendo citalopram + clomipramina, paroxetina, olanzapina, citalopram + alprazolam, risperidona, clomipramina e desipramina, levetiracetam, divalproato de sódio, lidocaína e toxina botulínica tipo A demonstraram resultados positivos. A maioria das pesquisas relativas ao tratamento farmacológico da gagueira se restringe a estudos de caso e ensaios clínicos com pequenas amostras. CONCLUSÃO: Não existem evidências suficientes que justifiquem a utilização de um tratamento específico para a gagueira. Os estudos apresentados indicam a necessidade da realização de mais ensaios clínicos duplo-cegos e controlados com placebo envolvendo amostras maiores.OBJECTIVE: This article analyzes the pharmacologic treatment of stuttering, assessing the effectiveness of different treatments using psychiatric drugs and further evidences of other drugs in the treatment of this disorder. METHODS: Search in Medline database, using the terms stuttering treatment, disfluency, disfluency treatments, botulinum toxin and stuttering treatment, botulinum toxin and disfluency treatment. RESULTS: Studies involving

An anatomical and clinical review of cricopharyngeal achalasia in the dog

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R.C. Elliott

2010-05-01

Full Text Available Cricopharyngeal achalasia is a rare cause of dysphagia in the dog. However it must be differentiated from other causes of dysphagia as it is treatable with surgery. It is a disruption of the cricopharyngeal phase of the oropharyngeal phase of deglutition. There appears to be an incoordination in the swallowing process between the relaxation of the rostral, middle pharyngeal muscles and the caudal pharyngeal muscles. It is seen as a primary condition in young animals presenting soon after weaning onto solid food. The dogs appear clinically healthy unless there is secondary aspiration pneumonia or emaciation. These dogs may present as respiratory emergencies and require intensive support and treatment prior to corrective surgery. The diagnosis is made on videofluoroscopy. The condition carries a good prognosis for cure with surgical myectomy of the cricopharyngeal muscle and the thyropharyngeal muscle, which make up the upper oesophageal sphincter. Temporary relief prior to surgery can be achieved by injection of the cricopharyngeal muscle with botulism toxin. Surgical treatment for dysphagia secondary to an underlying neurological, neuromuscular or pharyngeal weakness carries a guarded prognosis and will make aspiration pneumonia worse.

Recent advances in botulinum neurotoxin inhibitor development.

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Kiris, Erkan; Burnett, James C; Kane, Christopher D; Bavari, Sina

2014-01-01

Botulinum neurotoxins (BoNTs) are endopeptidases that target motor neurons and block acetylcholine neurotransmitter release. This action results in the muscle paralysis that defines the disease botulism. To date, there are no FDA-approved therapeutics to treat BoNT-mediated paralysis after intoxication of the motor neuron. Importantly, the rationale for pursuing treatments to counter these toxins is driven by their potential misuse. Current drug discovery efforts have mainly focused on small molecules, peptides, and peptidomimetics that can directly and competitively inhibit BoNT light chain proteolytic activity. Although this is a rational approach, direct inhibition of the Zn(2+) metalloprotease activity has been elusive as demonstrated by the dearth of candidates undergoing clinical evaluation. Therefore, broadening the scope of viable targets beyond that of active site protease inhibitors represents an additional strategy that could move the field closer to the clinic. Here we review the rationale, and discuss the outcomes of earlier approaches and highlight potential new targets for BoNT inhibition. These include BoNT uptake and processing inhibitors, enzymatic inhibitors, and modulators of neuronal processes associated with toxin clearance, neurotransmitter potentiation, and other pathways geared towards neuronal recovery and repair.

Botulinum neurotoxin: a marvel of protein design.

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Montal, Mauricio

2010-01-01

Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

Antibiotic, Pesticide, and Microbial Contaminants of Honey: Human Health Hazards

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Noori Al-Waili

2012-01-01

Full Text Available Agricultural contamination with pesticides and antibiotics is a challenging problem that needs to be fully addressed. Bee products, such as honey, are widely consumed as food and medicine and their contamination may carry serious health hazards. Honey and other bee products are polluted by pesticides, heavy metals, bacteria and radioactive materials. Pesticide residues cause genetic mutations and cellular degradation and presence of antibiotics might increase resistant human or animal's pathogens. Many cases of infant botulisms have been attributed to contaminated honey. Honey may be very toxic when produced from certain plants. Ingestion of honey without knowing its source and safety might be problematic. Honey should be labeled to explore its origin, composition, and clear statement that it is free from contaminants. Honey that is not subjected for analysis and sterilization should not be used in infants, and should not be applied to wounds or used for medicinal purposes. This article reviews the extent and health impact of honey contamination and stresses on the introduction of a strict monitoring system and validation of acceptable minimal concentrations of pollutants or identifying maximum residue limits for bee products, in particular, honey.

Gut content analysis of Lake Michigan waterbirds in years with avian botulism type E mortality, 2010–2012

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Essian, David A.; Chipault, Jennifer G.; Lafrancois, Brenda M.; Leonard, Jill B.K.

2016-01-01

Waterbird die-offs caused by Clostridium botulinum neurotoxin type E (BoNT/E) have occurred sporadically in the Great Lakes since the late 1960s, with a recent pulse starting in the late 1990s. In recent die-offs, round gobies (Neogobius melanostomus) have been implicated as vectors for the transfer of BoNT/E to fish-eating birds due to the round goby invasion history and their importance as prey. Dreissenid mussels (Dreissena spp.) are also potentially involved in BoNT/E transmission to birds and round gobies. We examined gut contents of waterbirds collected in Lake Michigan during die-offs in 2010–2012, and the gut contents of culled, presumably BoNT/E-free double-crested cormorants (Phalacrocorax auritus). Round gobies were found in 86% of the BoNT/E-positive individuals, 84% of the BoNT/E-negative birds, and 94% of the BoNT/E-free cormorants examined. Double-crested cormorants, ring-billed gulls (Larus delewarensis), and common loons (Gavia immer) consumed larger-sized round gobies than horned and red-necked grebes (Podiceps auritus and Podiceps grisegena), white-winged scoters (Melanitta deglandi), and long-tailed ducks (Clangula hymealis). Other common prey included dreissenid mussels, terrestrial insects, and alewives (Alosa pseudoharengus). Our data emphasize the importance of round gobies and mussels in diets of Lake Michigan waterbirds and suggest they may play a role in the transfer of BoNT/E to waterbirds; however, round gobies and mussels were found in BoNT/E-positive, -negative, and -free individuals, suggesting that other factors, such as alternative trophic pathways for toxin transfer, bird migratory timing and feeding locations, prey behavior, and individual physiological differences across birds may affect the likelihood that a bird will succumb to BoNT/E intoxication.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

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Stéphanie Simon

2015-11-01

Full Text Available Botulinum neurotoxins (BoNTs cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G, of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples.

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Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B

2015-11-26

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A-G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as "category A" bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

The orphan germinant receptor protein GerXAO (but not GerX3b) is essential for L-alanine induced germination in Clostridium botulinum Group II.

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Brunt, Jason; Carter, Andrew T; Pye, Hannah V; Peck, Michael W

2018-05-04

Clostridium botulinum is an anaerobic spore forming bacterium that produces the potent botulinum neurotoxin that causes a severe and fatal neuro-paralytic disease of humans and animals (botulism). C. botulinum Group II is a psychrotrophic saccharolytic bacterium that forms spores of moderate heat resistance and is a particular hazard in minimally heated chilled foods. Spore germination is a fundamental process that allows the spore to transition to a vegetative cell and typically involves a germinant receptor (GR) that responds to environmental signals. Analysis of C. botulinum Group II genomes shows they contain a single GR cluster (gerX3b), and an additional single gerA subunit (gerXAO). Spores of C. botulinum Group II strain Eklund 17B germinated in response to the addition of L-alanine, but did not germinate following the addition of exogenous Ca 2+ -DPA. Insertional inactivation experiments in this strain unexpectedly revealed that the orphan GR GerXAO is essential for L-alanine stimulated germination. GerX3bA and GerX3bC affected the germination rate but were unable to induce germination in the absence of GerXAO. No role could be identified for GerX3bB. This is the first study to identify the functional germination receptor of C. botulinum Group II.

High-level expression, purification, crystallization and preliminary X-ray crystallographic studies of the receptor-binding domain of botulinum neurotoxin serotype D

International Nuclear Information System (INIS)

Zhang, Yanfeng; Gao, Xiaoli; Qin, Ling; Buchko, Garry W.; Robinson, Howard; Varnum, Susan M.

2010-01-01

The receptor-binding domain of botulinum neurotoxin serotype D was expressed in E. coli using a codon-optimized cDNA. The highly purified protein crystallized in space group P2 1 2 1 2 1 , with unit-cell parameters a = 60.8, b = 89.7, c = 93.9 Å, and the crystals diffracted to 1.65 Å resolution. Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and animals that are responsible for the deadly neuroparalytic disease botulism. Here, details of the expression and purification of the receptor-binding domain (HCR) of BoNT/D in Escherichia coli are presented. Using a codon-optimized cDNA, BoNT/D-HCR was expressed at a high level (150–200 mg per litre of culture) in the soluble fraction. Following a three-step purification protocol, very pure (>98%) BoNT/D-HCR was obtained. The recombinant BoNT/D-HCR was crystallized and the crystals diffracted to 1.65 Å resolution. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 60.8, b = 89.7, c = 93.9 Å. Preliminary crystallographic data analysis revealed the presence of one molecule in the asymmetric unit

Selection of RNA Aptamers Against Botulinum Neurotoxin Type A Light Chain Through a Non-Radioactive Approach.

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Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Cai, Shuowei

2016-09-01

Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive-based systematic evolution of ligands by exponential enrichment (SELEX) process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nanomolar range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting that they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that the 2'-fluorine-pyrimidine-modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for SELEX, by using regular nucleotide during SELEX, and 2'-fluorine-pyrimidine-modified nucleotide for final application to enhance their RNase-resistance.

Bacterial Signaling to the Nervous System through Toxins and Metabolites.

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Yang, Nicole J; Chiu, Isaac M

2017-03-10

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. Second, peripheral sensory neurons-olfactory chemosensory neurons and nociceptor sensory neurons-detect bacterial toxins, formyl peptides, and lipopolysaccharides through distinct molecular mechanisms to elicit smell and pain. Bacteria also damage the central nervous system through toxins that target the brain during infection. Finally, the gut microbiota produces molecules that act on enteric neurons to influence gastrointestinal motility, and metabolites that stimulate the "gut-brain axis" to alter neural circuits, autonomic function, and higher-order brain function and behavior. Furthering the mechanistic and molecular understanding of how bacteria affect the nervous system may uncover potential strategies for modulating neural function and treating neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mortality patterns in endangered Hawaiian geese (Nene; Branta sandvicensis)

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Work, Thierry M.; Dagenais, Julie; Rameyer, Robert; Breeden, Renee

2015-01-01

Understanding causes of death can aid management and recovery of endangered bird populations. Toward those ends, we systematically examined 300 carcasses of endangered Hawaiian Geese (Nene; Branta sandvicensis) from Hawaii, Maui, Molokai, and Kauai between 1992 and 2013. The most common cause of death was emaciation, followed by trauma (vehicular strikes and predation), and infectious/inflammatory diseases of which toxoplasmosis (infection with Toxoplasma gondii) predominated. Toxicoses were less common and were dominated by lead poisoning or botulism. For captive birds, inflammatory conditions predominated, whereas emaciation, trauma, and inflammation were common in free-ranging birds. Mortality patterns were similar for males and females. Trauma predominated for adults, whereas emaciation was more common for goslings. Causes of death varied among islands, with trauma dominating on Molokai, emaciation and inflammation on Kauai, emaciation on Hawaii, and inflammation and trauma on Maui. Understanding habitat or genetic-related factors that predispose Nene (particularly goslings) to emaciation might reduce the impact of this finding. In addition, trauma and infection with T. gondii are human-related problems that may be attenuated if effectively managed (e.g., road signs, enforcement of speed limits, feral cat [Felis catus] control). Such management actions might serve to enhance recovery of this endangered species.

Botulinum toxin: bioweapon & magic drug.

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Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

2010-11-01

Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

Challenges in searching for therapeutics against Botulinum Neurotoxins.

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Pirazzini, Marco; Rossetto, Ornella

2017-05-01

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. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

Microbiological food safety: a dilemma of developing societies.

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Akhtar, Saeed; Sarker, Mahfuzur R; Hossain, Ashfaque

2014-11-01

Current food safety issues are deleteriously reshaping the life style of the population in the developing world. Socioeconomic status of the population in poorer economies is one of the major determinants to delineate the availability of safe food to the vulnerable population. Assessment of the prevalence of foodborne illness in developing world is the most neglected area to control disease. Botulism, Shigellosis, Campylobacteriosis, Escherichia coli infection, Staphylococcus aureus infection, Salmonellosis, Listeriosis and Cholerae are extensively prevalent and pose a major threat to human health in underdeveloped communities. The existing food safety status of many African, South Asian, Central, and South American developing countries is distressing therefore; it seems much timely to highlight the areas for the improvement to ensure the supply of safe food to the population in these regions. Extensive literature search at PubMed, Science Direct and Medline was carried out during the current year to catch on relevant data from 1976 to date, using selective terms like food safety, South East Asia, Africa, Central and South America, and foodborne illness etc. Efforts were made to restrict the search to low income countries of these regions with reference to specific foodborne pathogens. This report briefly discusses the present food safety situation in these developing countries and associated consequences as prime issues, suggesting foodborne illness to be the most distressing threat for human health and economic growth.

Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B

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Luisa W. Cheng

2015-11-01

Full Text Available Botulinum neurotoxins (BoNT are some of nature’s most potent toxins. Due to potential food contamination, and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed a sensitive electrochemiluminescent (ECL immunoassay for BoNT/B, using monoclonal antibodies (mAbs MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B

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SWAMINATHAN, S.; ESWARAMOORTHY, S.

2001-01-01

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases[1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD(sub 50) for humans in the range of 0.1 - 1 ng kg(sup -1)[2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and(gamma)-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization[3

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

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SWAMINATHAN,S.; ESWARAMOORTHY,S.

2001-11-19

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].

Hemifacial spasm in a patient with neurofibromatosis and Arnold-Chiari malformation: a unique case association Espasmo hemifacial em paciente com neurofibromatose e malformação de Arnold-Chiari: uma associação rara

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Andre Carvalho Felício

2007-09-01

Full Text Available BACKGROUND: The association of hemifacial spasm (HFS, Chiari type I malformation (CIM and neurofibromatosis type 1 (NF1 has not been described yet. CASE REPORT: We report the case of a 31-year-old woman with NF1 who developed a right-sided HFS. On magnetic resonance imaging (MRI a CIM was seen without syringomyelia. The patient has been successfully treated with botulinum toxin type A injections for 5 years without major side effects. CONCLUSION:Clinical features of HFS, CMI and NF1 are highlighted together with their possible relationship. Also, therapeutic strategies are also discussed.INTRODUÇÃO: A associação entre espasmo hemifacial (EHF, malformação de Chiari tipo I (MCI e neurofibromatose tipo I (NFI ainda não foi descrita. RELATO DO CASO: Relatamos o caso de mulher com 31 anos com NFI que desenvolveu EHF à direita. Na ressonância magnética (RM foi observada MCI sem seringomielia associada. A paciente foi tratada com sucesso com toxina botulínica tipo A por 5 anos sem efeitos colaterais. CONCLUSÃO: Ressaltamos as características clínicas do EHF, MCI e NFI assim como uma possível relação entre elas. Além disto, discutimos também estratégias terapêuticas.

William Horner Andrews (1887-1953)- first professor of physiology at Onderstepoort.

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Verwoerd, D W; Andrews, W J H

2011-03-01

W H Andrews qualified as a veterinarian in London in 1908 and was recruited soon after, in 1909, by Sir Arnold Theiler to join the staff of the newly established veterinary laboratory at Onderstepoort. After initial studies on the treatment of trypanosomosis and on snake venoms he was deployed by Theiler in 1911 to start research on lamsiekte (botulism)at a field station on the farm Kaffraria near Christiana, where he met and married his wife Doris. After a stint as Captain in the SA Veterinary Corps during World War I he succeeded D T Mitchell as head of the Allerton Laboratory in 1918, where he excelled in research on toxic plants, inter alia identifying Matricaria nigellaefolia as the cause of staggers in cattle. When the Faculty of Veterinary Science was established in 1920 he was appointed as the first Professor of Physiology. After the graduation of the first class in 1924, and due to health problems, he returned to the UK, first to the Royal Veterinary College and then to the Weybridge Veterinary Laboratories of which he became Director in 1927. After his retirement in 1947 he returned to South Africa as a guest worker at Onderstepoort where he again became involved in teaching physiology when Prof. Quin unexpectedly died in 1950. Andrews died in Pretoria in 1953 and was buried in the Rebecca Street Cemetery.

The innovative therapeutic application of botulinum toxin type A in urology patients

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Chrysoula Belai

2016-06-01

Full Text Available In the history of medical science the use of botulinum toxin was impressive. In the early 18th century it was defined as the neurotoxin implicated in the deadly disease botulism. Today, despite the toxic action finds application in the treatment of various diseases in a wide range of Medicine. Its use in urology was revolutionary in the treatment of neurogenic bladder, refractory idiopathic detrusor overactivity and other painful syndromes. The purpose of this review was to describe the treatment option of intravesical injection of botulinum toxin, in diseases of the urinary tract. The review showed that after many test applications under the experimental studies, the botulinum toxin type A has already established itself as the new treatment of choice after failure of conservative drug dealing in patients with neuro-urological symptoms of lower urinary tract. Cases of application of botulinum toxin in Urology are related to overactive bladder, neurogenic or idiopathic etiology, as bladder pain syndrome and chronic pelvic pain syndrome. According to the guidelines of the European Union directives Urology, the intravesical botulinum toxin injections are the most effective, minimally invasive treatment which results in reducing neurogenic hyperactivity of detrusor. In conclusion, this is a safe, easy and effective method that can be applied by health professionals, helping improve patients’ quality of life with neuro-urological diseases.

Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

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Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

2013-01-01

Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

Beltless translocation domain of botulinum neurotoxin A embodies a minimum ion-conductive channel.

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Fischer, Audrey; Sambashivan, Shilpa; Brunger, Axel T; Montal, Mauricio

2012-01-13

Botulinum neurotoxin, the causative agent of the paralytic disease botulism, is an endopeptidase composed of a catalytic domain (or light chain (LC)) and a heavy chain (HC) encompassing the translocation domain (TD) and receptor-binding domain. Upon receptor-mediated endocytosis, the LC and TD are proposed to undergo conformational changes in the acidic endocytic environment resulting in the formation of an LC protein-conducting TD channel. The mechanism of channel formation and the conformational changes in the toxin upon acidification are important but less well understood aspects of botulinum neurotoxin intoxication. Here, we have identified a minimum channel-forming truncation of the TD, the "beltless" TD, that forms transmembrane channels with ion conduction properties similar to those of the full-length TD. At variance with the holotoxin and the HC, channel formation for both the TD and the beltless TD occurs independent of a transmembrane pH gradient. Furthermore, acidification in solution induces moderate secondary structure changes. The subtle nature of the conformational changes evoked by acidification on the TD suggests that, in the context of the holotoxin, larger structural rearrangements and LC unfolding occur preceding or concurrent to channel formation. This notion is consistent with the hypothesis that although each domain of the holotoxin functions individually, each domain serves as a chaperone for the others.

Investigations of a large scale eared grebe (Podiceps nigricollis) die-off at the Salton Sea, California in 1992

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Meteyer, C.U.; Audet, D.J.; Rocke, T.E.; Radke, W.; Creekmore, L.H.; Duncan, R.

2004-01-01

An estimated 150,000 Eared Grebes (Podiceps nigricollis) died at the Salton Sea between 16 December 1991 and 21 April 1992. This represented the largest documented mortality event of Eared Grebes at the time and approximately 6% of the North American population. During the die-off, grebes exhibited several uncharacteristic behaviors, such as congregating at freshwater tributaries, repeatedly gulping freshwater, preening excessively, moving onto land, and allowing close approach and/or capture. Avian cholera was diagnosed in Eared Grebes collected along the north and west shoreline of the Sea late in the die-off but not from the majority of the Eared Grebes dying along the south shore. Gross and histological examinations and diagnostic testing for viruses, bacteria, and parasites did not identify the cause of mortality in the majority of Eared Grebes examined from the south shore of the Sea. Liver concentrations of arsenic, chromium, DDE, mercury, selenium, and zinc were elevated in some Eared Grebes, but none of those contaminants exceeded known thresholds for independent lethality. Poisoning by heavy metals, organochlorine, organophosphorus, or carbamate pesticides, avian botulism, and salt were ruled out as the cause of mortality. Hypotheses for the die-off are interactive effects of contaminants, immunosuppression, a yet unidentified biotoxin or pathogen present in the Salton Sea, impairment of feather waterproofing leading to hypothermia, or a unique manifestation of avian cholera that evades laboratory detection.

Morphological and genetic characterization of group I Clostridium botulinum type B strain 111 and the transcriptional regulator spoIIID gene knockout mutant in sporulation.

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Hosomi, Koji; Kuwana, Ritsuko; Takamatsu, Hiromu; Kohda, Tomoko; Kozaki, Shunji; Mukamoto, Masafumi

2015-06-01

Clostridium botulinum is a heat-resistant spore-forming bacterium that causes the serious paralytic illness botulism. Heat-resistant spores may cause food sanitation hazards and sporulation plays a central role in the survival of C. botulinum. We observed morphological changes and investigated the role of the transcriptional regulator SpoIIID in the sporulation of C. botulinum type B strain 111 in order to elucidate the molecular mechanism in C. botulinum. C. botulinum type B formed heat-resistant spores through successive morphological changes corresponding to those of Bacillus subtilis, a spore-forming model organism. An analysis of the spoIIID gene knockout mutant revealed that the transcriptional regulator SpoIIID contributed to heat-resistant spore formation by C. botulinum type B and activated the transcription of the sigK gene later during sporulation. Transcription of the spoIIID gene, which differed from that in B. subtilis and Clostridium difficile, was observed in the sigE gene knockout mutant of C. botulinum type B. An analysis of the sigF gene knockout mutant showed that the sporulation-specific sigma factor SigF was essential for transcription of the spoIIID gene in C. botulinum type B. These results suggest that the regulation of sporulation in C. botulinum is not similar to that in B. subtilis and other clostridia. Copyright © 2015 Elsevier Ltd. All rights reserved.

BACTERIA CARRIED BY CHRYSOMYA MEGACEPHALA (FABRICIUS, 1794 (DIPTERA: CALLIPHORIDAE IN SINOP, MATO GROSSO, BRAZIL

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J. S. Carneiro

2014-07-01

Full Text Available Chrysomya megacephala (Diptera: Calliphoridae, popularly known as blowfly, has a great capacity for dispersion and, due to factors such as food abundance and favorable climate, it colonizes Brazil completely in a short time. These insects are important to the sectors of epidemiology, public health and forensics, especially due to carrying microorganisms such as bacteria, viruses, protozoa and helminthes, which are responsible for the spread of diseases such as dysentery, cholera, botulism, typhoid fever, brucellosis, polio, smallpox and tuberculosis. The objective of this study was to verify the diversity of bacteria carried by this species in the Federal University of Mato Grosso – Campus of Sinop during the month of January of 2012. The flies were collected using two traps baited with 100 g of fresh sardines on each and maintained in the field for 24 hours. Twenty specimens of C. megacephala were placed in Petri dishes, to walk for two minutes upon Nutrient Agar (NA. After establishment of the colonies, isolation of the bacteria on the NA medium and their multiplication in test tubes containing the same culture medium was performed, and later sent to identification by gas chromatography. The bacteria encountered were Aquaspirillum polymorphum; Burkholderia ambifaria; Burkholderia anthina; Burkholderia cepacia; Burkholderia cenocepacia; Burkholderia pyrrocinia; Burkholderia stabilis; Paenibacillus macerans; Virgibacillus pantothenticus, Bacillus subtilis e Photorhabdus luminescens luminescens, with the last two species considered of importance in the plant protection sector.

Small-molecule quinolinol inhibitor identified provides protection against BoNT/A in mice.

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Padma Singh

Full Text Available Botulinum neurotoxins (BoNTs, etiological agents of the life threatening neuroparalytic disease botulism, are the most toxic substances currently known. The potential for the use as bioweapon makes the development of small-molecule inhibitor against these deadly toxins is a top priority. Currently, there are no approved pharmacological treatments for BoNT intoxication. Although an effective vaccine/immunotherapy is available for immuno-prophylaxis but this cannot reverse the effects of toxin inside neurons. A small-molecule pharmacological intervention, especially one that would be effective against the light chain protease, would be highly desirable. Similarity search was carried out from ChemBridge and NSC libraries to the hit (7-(phenyl(8-quinolinylaminomethyl-8-quinolinol; NSC 84096 to mine its analogs. Several hits obtained were screened for in silico inhibition using AutoDock 4.1 and 19 new molecules selected based on binding energy and Ki. Among these, eleven quinolinol derivatives potently inhibited in vitro endopeptidase activity of botulinum neurotoxin type A light chain (rBoNT/A-LC on synaptosomes isolated from rat brain which simulate the in vivo system. Five of these inhibitor molecules exhibited IC(50 values ranging from 3.0 nM to 10.0 µM. NSC 84087 is the most potent inhibitor reported so far, found to be a promising lead for therapeutic development, as it exhibits no toxicity, and is able to protect animals from pre and post challenge of botulinum neurotoxin type A (BoNT/A.

Toxin production of non-proteolytic Cl. botulinum type B in radurized fish. Part of a coordinated programme on the wholesomeness of the process of food irradiation

International Nuclear Information System (INIS)

Suhadi, F.

1981-02-01

Toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in radurized raw fish and in radurized Pindang fish was investigated. In radurized Pindang fish samples, inoculation was done either before or after cooking. Radurization process with 2 and 3 kGy caused the extension of storage life of Rastrelliger sp., Euthynnus sp., and Scomberomorus sp. by factors of 2 and 2.5 at storage temperatures between 5 and 10 0 C. In general at 10.5 +- 0.3 0 C, no toxin was formed before the samples were spoiled both in irradiated and unirradiated samples. At 5.6 +- 0.5 0 C no toxin was formed until after the samples were spoiled. The earliest toxin formation in unirradiated Pindang samples stored at ambient temperature was detected after the samples were spoiled. In irradiated Pindang samples inoculated with C. botulinum spores after cooking and stored at ambient temperature the toxin formation was detected before the samples were spoiled. However, if the inoculation was done before the fish was processed into Pindang, the toxin was always detected after the samples were spoiled regardless of the irradiation dose, strain and inoculation level. As fish may be contaminated - if at all - with spores of C. botulinum in its raw state, processing of fish into Pindang and irradiation would not contribute to the health hazard concerning botulism even if the samples are stored at ambient temperature

Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization.

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Rasooly, Reuven; Do, Paula M

2010-12-08

Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). To study the heat stability of Clostridium botulinum neurotoxins, we needed to measure and compare the activity of botulinum neurotoxins, serotypes A and B, under various pasteurization conditions. Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. In this study, noninvasive methods were used to simultaneously detect and distinguish between active BoNT serotypes A and B in one reaction and sample. We developed an enzymatic activity assay employing internally quenched fluorogenic peptides corresponding to SNAP-25, for BoNT-A, and VAMP2, for BoNT-B, as an alternative method to the mouse bioassay. Because each peptide is labeled with different fluorophores, we were able to distinguish between these two toxins. We used this method to analyze the heat stability of BoNT-A and BoNT-B. This study reports that conventional milk pasteurization (63 °C, 30 min) inactivated BoNT serotype A; however, serotype B is heat-stable in milk and not inactivated by pasteurization. Using this activity assay, we also showed that the commonly used food processes such as acidity and pasteurization, which are known to inhibit C. botulinum growth and toxin production, are more effective in inactivating BoNT serotype A than serotype B when conventional pasteurization (63 °C, 30 min) is used.

Immuno-detection of cleaved SNAP-25 from differentiated mouse embryonic stem cells provides a sensitive assay for determination of botulinum A toxin and antitoxin potency.

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Yadirgi, G; Stickings, P; Rajagopal, S; Liu, Y; Sesardic, D

2017-12-01

Botulinum toxin type A is a causative agent of human botulism. Due to high toxicity and ease of production it is classified by the Centres for Disease Control and Prevention as a category A bioterrorism agent. The same serotype, BoNT/A, is also the most widely used in pharmaceutical preparations for treatment of a diverse range of neuromuscular disorders. Traditionally, animals are used to confirm the presence and activity of toxin and to establish neutralizing capabilities of countermeasures in toxin neutralization tests. Cell based assays for BoNT/A have been reported as the most viable alternative to animal models, since they are capable of reflecting all key steps (binding, translocation, internalization and cleavage of intracellular substrate) involved in toxin activity. In this paper we report preliminary development of a simple immunochemical method for specifically detecting BoNT/A cleaved intracellular substrate, SNAP-25, in cell lysates of neurons derived from mouse embryonic stem cells. The assay offers sensitivity of better than 0.1LD50/ml (3fM) which is not matched by other functional assays, including the mouse bioassay, and provides serotype specificity for quantitative detection of BoNT/A and anti-BoNT/A antitoxin. Subject to formal validation, the method described here could potentially be used as a substitute for the mouse bioassay to measure potency and consistency of therapeutic products. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The use of upconverting phosphors in point-of-care (POC) testing

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Tanke, Hans J.; Zuiderwijk, Michel; Wiesmeijer, Karien C.; Breedveld, Robert N.; Abrams, William R.; de Dood, Claudia J.; Tjon Kon Fat, Elisa M.; Corstjens, Paul L. A. M.

2014-03-01

Point-of-care (POC) testing is increasingly applied as a cost effective alternative to many diagnostic tests. Key in POC testing is to create sufficient assay sensitivity with relatively low cost reagents and equipment. For this purpose we have employed a unique reporter, upconverting phosphor (UCP) particles, in combination with lateral flow (LF) assays. UCPs, submicron ceramic particles doped with rare earth ions (lanthanides), convert infrared to visible light and do not suffer from autofluorescence which limits conventional fluorescence based assays. Low cost handheld readers and microfluidics were evaluated in various applications. Designed assays are well suited for applications outside diagnostic laboratories, in resource poor settings, and can even be used by patients at home. Using two distinctly different UCP-LF assay formats, we focussed on assays for infectious diseases based on the detection of pathogen-specific antibodies and/or antigens including nucleic acids to demonstrate active infection with HIV. Only minor adaptation of the standard UCP-LF assay format is needed to render the format suitable for applications involving low affinity capture antibodies (e.g. in the detection of neurotoxin, botulism), capture of small molecules (e.g. detection of melatonin, a key hormone in chronopharmacology) or the use of dry UCP reagents (e.g. detection of protein based fruit-ripening markers, of economic interest in agriculture). Finally, we anticipate on developments in healthcare (personalized medicine) by discussing the potential of one of the UCP-LF assay formats to measure serum trough levels of immunodrugs (e.g. infliximab or adalimumab) in patients treated for inflammatory bowel disease and rheumatoid arthritis.

Development and Application of a New Method for Specific and Sensitive Enumeration of Spores of Nonproteolytic Clostridium botulinum Types B, E, and F in Foods and Food Materials ▿

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Peck, Michael W.; Plowman, June; Aldus, Clare F.; Wyatt, Gary M.; Penaloza Izurieta, Walter; Stringer, Sandra C.; Barker, Gary C.

2010-01-01

The highly potent botulinum neurotoxins are responsible for botulism, a severe neuroparalytic disease. Strains of nonproteolytic Clostridium botulinum form neurotoxins of types B, E, and F and are the main hazard associated with minimally heated refrigerated foods. Recent developments in quantitative microbiological risk assessment (QMRA) and food safety objectives (FSO) have made food safety more quantitative and include, as inputs, probability distributions for the contamination of food materials and foods. A new method that combines a selective enrichment culture with multiplex PCR has been developed and validated to enumerate specifically the spores of nonproteolytic C. botulinum. Key features of this new method include the following: (i) it is specific for nonproteolytic C. botulinum (and does not detect proteolytic C. botulinum), (ii) the detection limit has been determined for each food tested (using carefully structured control samples), and (iii) a low detection limit has been achieved by the use of selective enrichment and large test samples. The method has been used to enumerate spores of nonproteolytic C. botulinum in 637 samples of 19 food materials included in pasta-based minimally heated refrigerated foods and in 7 complete foods. A total of 32 samples (5 egg pastas and 27 scallops) contained spores of nonproteolytic C. botulinum type B or F. The majority of samples contained <100 spores/kg, but one sample of scallops contained 444 spores/kg. Nonproteolytic C. botulinum type E was not detected. Importantly, for QMRA and FSO, the construction of probability distributions will enable the frequency of packs containing particular levels of contamination to be determined. PMID:20709854

Development and application of a new method for specific and sensitive enumeration of spores of nonproteolytic Clostridium botulinum types B, E, and F in foods and food materials.

Science.gov (United States)

Peck, Michael W; Plowman, June; Aldus, Clare F; Wyatt, Gary M; Izurieta, Walter Penaloza; Stringer, Sandra C; Barker, Gary C

2010-10-01

The highly potent botulinum neurotoxins are responsible for botulism, a severe neuroparalytic disease. Strains of nonproteolytic Clostridium botulinum form neurotoxins of types B, E, and F and are the main hazard associated with minimally heated refrigerated foods. Recent developments in quantitative microbiological risk assessment (QMRA) and food safety objectives (FSO) have made food safety more quantitative and include, as inputs, probability distributions for the contamination of food materials and foods. A new method that combines a selective enrichment culture with multiplex PCR has been developed and validated to enumerate specifically the spores of nonproteolytic C. botulinum. Key features of this new method include the following: (i) it is specific for nonproteolytic C. botulinum (and does not detect proteolytic C. botulinum), (ii) the detection limit has been determined for each food tested (using carefully structured control samples), and (iii) a low detection limit has been achieved by the use of selective enrichment and large test samples. The method has been used to enumerate spores of nonproteolytic C. botulinum in 637 samples of 19 food materials included in pasta-based minimally heated refrigerated foods and in 7 complete foods. A total of 32 samples (5 egg pastas and 27 scallops) contained spores of nonproteolytic C. botulinum type B or F. The majority of samples contained <100 spores/kg, but one sample of scallops contained 444 spores/kg. Nonproteolytic C. botulinum type E was not detected. Importantly, for QMRA and FSO, the construction of probability distributions will enable the frequency of packs containing particular levels of contamination to be determined.

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.

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Jin, Rongsheng; Rummel, Andreas; Binz, Thomas; Brunger, Axel T

2006-12-21

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the neuroparalytic syndrome of botulism. With a lethal dose of 1 ng kg(-1), they pose a biological hazard to humans and a serious potential bioweapon threat. BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery. The molecular details of the toxin-cell recognition have been elusive. Here we report the structure of a BoNT in complex with its protein receptor: the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution. On binding, a helix is induced in the luminal domain which binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice is adjacent to the non-overlapping ganglioside-binding site of BoNT/B. Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at both neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies of structure-based mutations indicate high specificity and affinity of the interaction, and high selectivity of BoNT/B among synaptotagmin I and II isoforms. Synergistic binding of both synaptotagmin and ganglioside imposes geometric restrictions on the initiation of BoNT/B translocation after endocytosis. Our results provide the basis for the rational development of preventive vaccines or inhibitors against these neurotoxins.

Detection of Clostridium botulinum in liquid manure and biogas plant wastes.

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Neuhaus, Jürgen; Schrödl, Wieland; Shehata, Awad A; Krüger, Monika

2015-09-01

Biogas plants have been considered as a source for possible amplification and distribution of pathogenic bacteria capable of causing severe infections in humans and animals. Manure and biogas wastes could be sources for spore-forming bacteria such as Clostridium botulinum. In the present study, 24 liquid manure and 84 biogas waste samples from dairies where the majority of the cows suffered from chronic botulism were investigated for the presence of botulinum neurotoxins (BoNT) and C. botulinum spores. The prevalence of BoNT/A, B, C, D, and E in biogas wastes was 16.6, 8.3, 10.7, 7.1, and 10.8 %, respectively, while in manure, the prevalence was 0.0, 0.0, 0.0, 8.3, and 4.1 %, respectively. After enrichment of samples in reinforced cultural medium, they were tested for C. botulinum BoNT/A, B, C, D, and E using ELISA (indirect C. botulinum detection). The prevalence of C. botulinum type A, B, C, D, and E samples in biogas wastes was 20.2, 15.5, 19, 10.7, and 34.8 %, respectively, while the prevalence in liquid manure was 0.0, 0.0, 0.0, 8.3, and 12.5 %, respectively. In conclusion, the occurrence of BoNT and C. botulinum spores in biogas waste of diseased animals indicates an increased and underestimated hygienic risk. Application of digestates from biogas fermentations as fertilizers could lead to an accumulation of long lifespan spores in the environment and could be a possible health hazard.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes

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Consuelo Garcia-Rodriguez

2018-03-01

Full Text Available Human botulism is most commonly caused by botulinum neurotoxin (BoNT serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS. A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD. By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633 is in pre-clinical development with an investigational new drug (IND application filing expected in 2018.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

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Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

2018-03-01

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

Difícil manejo do paciente com distonia segmentar respiratória The difficult management of patients with respiratory segmental dystonia

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Noemi Grigoletto De Biase

2007-04-01

Full Text Available A forma respiratória da distonia laríngea é rara, de difícil diagnóstico e provoca restrição respiratória de graus variados. O objetivo deste trabalho é apresentar um caso de distonia respiratória envolvendo laringe e faringe e sua evolução em relação à intensidade dos espasmos e seu controle. ESTUDO DE CASO: Paciente de 24 anos, sexo masculino, acompanhado por 5 anos: diagnóstico por nasofibroscopia e eletromiografia e tratamento com toxina botulínica conforme necessidade de controle dos sintomas. CONCLUSÃO: O difícil manejo se deve ao fato do desconhecimento da etiologia e a pouca opção de tratamento, bem como do envolvimento da função respiratória.Respiratory dystonia is a rare and difficult to diagnose disorder, that causes breathing restriction of various degrees. The objective of the study is to report the case of a patient with respiratory dystonia involving the larynx and the pharynx and its evolution concerning spasms intensity and control. CASE REPORT: A 24 year-old-man has been followed for 5 years. The diagnosis was made by means of nasofibroscopy and electromyography. Treatment was carried out with laryngeal and pharyngeal Botulin toxin injections, as it became necessary for symptoms control. CONCLUSION: The difficult management can be secondary to the lack of knowledge on the etiology and physiopathology of the impairment, and because of the limitations in the treatment of associated respiratory symptoms.

Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

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Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

2014-04-01

Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico.

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Rafful, Claudia; Wagner, Karla D; Werb, Dan; González-Zúñiga, Patricia E; Verdugo, Silvia; Rangel, Gudelia; Strathdee, Steffanie A

2015-11-01

Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27-3.53 and AOR: 2.65; 95% CI: 1.52-4.53 respectively]. Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance ('hit doctors') may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Creation of a virtual antidotes network between pharmacy departments of catalan hospitals

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Raquel Aguilar-Salmerón

2017-05-01

Full Text Available 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. It can be accessed through the platform: www.xarxaantidots.org. The application has an open area with overall information about the project and the option to ask toxicological questions of non-urgent nature. The private area is divided into four sections: 1 Antidotes: data of interest about the 15 antidotes included in the network and their recommended stock depending on the complexity of the hospital, 2 Antidote stock management: virtual formulary, 3 Loans: location of antidotes through the on-line map application Google Maps, and virtual loan request, and 4 Documentation: As of June, 2016, 40 public and private hospitals have joined the network, from all four provinces of Catalonia, which have accessed the private area 2 102 times, requested two loans of silibinin, one of hydroxocobalamin, three of antiophidic serum and three of botulism antitoxin. Thirteen toxicological consultations have been received.Conclusions: The implementation of this network improves the communication between centers that manage poisoned patients, adapts and standardizes the stock of antidotes in hospitals, speeds up loans if necessary, and improves the quality of care for poisoned patients.

Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1 and A5.

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Wang, Dongxia; Krilich, Joan; Pellett, Sabine; Baudys, Jakub; Tepp, William H; Barr, John R; Johnson, Eric A; Kalb, Suzanne R

2013-12-01

Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening disease botulism through the inhibition of neurotransmitter release by cleaving essential SNARE proteins. There are seven serologically distinctive types of BoNTs and many subtypes within a serotype have been identified. BoNT/A5 is a recently discovered subtype of type A botulinum neurotoxin which possesses a very high degree of sequence similarity and identity to the well-studied A1 subtype. In the present study, we examined the endopeptidase activity of these two BoNT/A subtypes and our results revealed significant differences in substrate binding and cleavage efficiency between subtype A5 and A1. Distinctive hydrolysis efficiency was observed between the two toxins during cleavage of the native substrate SNAP-25 versus a shortened peptide mimic. N-terminal truncation studies demonstrated that a key region of the SNAP-25, including the amino acid residues at 151 through 154 located in the remote binding region of the substrate, contributed to the differential catalytic properties between A1 and A5. Elevated binding affinity of the peptide substrate resulted from including these important residues and enhanced BoNT/A5's hydrolysis efficiency. In addition, mutations of these amino acid residues affect the proteolytic performance of the two toxins in different ways. This study provides a better understanding of the biological activity of these toxins, their performance characteristics in the Endopep-MS assay to detect BoNT in clinical samples and foods, and is useful for the development of peptide substrates. © 2013. Published by Elsevier B.V. All rights reserved.

Towards Better Understanding of the Pathogenesis of Neuronal Respiratory Network in Sudden Perinatal Death

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Riffat Mehboob

2017-07-01

Full Text Available Sudden perinatal death that includes the victims of sudden infant death syndrome, sudden intrauterine death syndrome, and stillbirth are heartbreaking events in the life of parents. Most of the studies about sudden perinatal death were reported from Italy, highlighting two main etiological factors: prone sleeping position and smoking. Other probable contributory factors are prematurity, male gender, lack of breastfeeding, respiratory tract infections, use of pacifiers, infant botulism, extensive use of pesticides and insecticides, etc. However, extensive studies across the world are required to establish the role of these factors in a different subset of populations. Previous studies confirmed the widely accepted hypothesis that neuropathology of the brainstem is one of the main cause of sudden perinatal death. This study is an effort to summarize the neuropathological evaluation of the brainstems and their association to sudden perinatal death. Brainstem nuclei in vulnerable infants undergo certain changes that may alter the sleep arousal cycle, cardiorespiratory control, and ultimately culminate in death. This review focuses on the roles of different brainstem nuclei, their pathologies, and the established facts in this regard in terms of it’s link to such deaths. This study will also help to understand the role of brainstem nuclei in controlling the cardiorespiratory cycles in sudden perinatal death and may provide a better understanding to resolve the mystery of these deaths in future. It is also found that a global initiative to deal with perinatal death is required to facilitate the diagnosis and prevention in developed and as well as developing countries.

On depleted uranium: gulf war and Balkan syndrome.

Science.gov (United States)

Duraković, A

2001-04-01

The complex clinical symptomatology of chronic illnesses, commonly described as Gulf War Syndrome, remains a poorly understood disease entity with diversified theories of its etiology and pathogenesis. Several causative factors have been postulated, with a particular emphasis on low level chemical warfare agents, oil fires, multiple vaccines, desert sand (Al-Eskan disease), botulism, Aspergillus flavus, Mycoplasma, aflatoxins, and others, contributing to the broad scope of clinical manifestations. Among several hundred thousand veterans deployed in the Operation Desert Storm, 15-20% have reported sick and about 25,000 died. Depleted uranium (DU), a low-level radioactive waste product of the enrichment of natural uranium with U-235 for the reactor fuel or nuclear weapons, has been considered a possible causative agent in the genesis of Gulf War Syndrome. It was used in the Gulf and Balkan wars as an armor-penetrating ammunition. In the operation Desert Storm, over 350 metric tons of DU was used, with an estimate of 3-6 million grams released in the atmosphere. Internal contamination with inhaled DU has been demonstrated by the elevated excretion of uranium isotopes in the urine of the exposed veterans 10 years after the Gulf war and causes concern because of its chemical and radiological toxicity and mutagenic and carcinogenic properties. Polarized views of different interest groups maintain an area of sustained controversy more in the environment of the public media than in the scientific community, partly for the reason of being less than sufficiently addressed by a meaningful objective interdisciplinary research.

Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

Energy Technology Data Exchange (ETDEWEB)

Nuemket, Nipawan [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Yoshikazu [Creative Research Institution ' Sousei,' Hokkaido University, Sapporo 001-0021 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tsukamoto, Kentaro; Tsuji, Takao [Department of Microbiology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192 (Japan); Nakamura, Keiji; Kozaki, Shunji [Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531 (Japan); Yao, Min [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Isao, E-mail: tanaka@castor.sci.hokudai.ac.jp [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan)

2011-07-29

Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinum neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.

Science.gov (United States)

Yao, Guorui; Lam, Kwok-Ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-03-08

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. Sequence analyses indicate that the receptor-binding domain (H C ) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the H C . Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-H C at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine.

Science.gov (United States)

Prathiviraj, R; Prisilla, A; Chellapandi, P

2016-06-01

Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages.

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

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Guorui Yao

2017-03-01

Full Text Available 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. Sequence analyses indicate that the receptor-binding domain (HC of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2 that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG and synaptic vesicle glycoprotein 2 (SV2. Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding

Energy Technology Data Exchange (ETDEWEB)

Yao, Guorui; Lam, Kwok-ho; Weisemann, Jasmin; Peng, Lisheng; Krez, Nadja; Perry, Kay; Shoemaker, Charles B.; Dong, Min; Rummel, Andreas; Jin, Rongsheng (BCH); (Cornell); (Tufts CTSI); (UCI); (MHH)

2017-08-07

Antibody treatment is currently the only available countermeasure for botulism, a fatal illness caused by flaccid paralysis of muscles due to botulinum neurotoxin (BoNT) intoxication. Among the seven major serotypes of BoNT/A-G, BoNT/A poses the most serious threat to humans because of its high potency and long duration of action. Prior to entering neurons and blocking neurotransmitter release, BoNT/A recognizes motoneurons via a dual-receptor binding process in which it engages both the neuron surface polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Previously, we identified a potent neutralizing antitoxin against BoNT/A1 termed ciA-C2, derived from a camelid heavy-chain-only antibody (VHH). In this study, we demonstrate that ciA-C2 prevents BoNT/A1 intoxication by inhibiting its binding to neuronal receptor SV2. Furthermore, we determined the crystal structure of ciA-C2 in complex with the receptor-binding domain of BoNT/A1 (HCA1) at 1.68 Å resolution. The structure revealed that ciA-C2 partially occupies the SV2-binding site on H_CA1, causing direct interference of HCA1 interaction with both the N-glycan and peptide-moiety of SV2. Interestingly, this neutralization mechanism is similar to that of a monoclonal antibody in clinical trials, despite that ciA-C2 is more than 10-times smaller. Taken together, these results enlighten our understanding of BoNT/A1 interactions with its neuronal receptor, and further demonstrate that inhibiting toxin binding to the host receptor is an efficient countermeasure strategy.

Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

Science.gov (United States)

Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

2006-11-17

The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

Prospects of eliminating pathogens by the process of food irradiation

International Nuclear Information System (INIS)

Kampelmacher, E.H.

1981-01-01

Food-borne diseases are an increasing health hazard throughout the world. Some of these diseases, such as salmonellosis, staphylo-entero-toxicosis, botulism, vibriosis and parasitic infections have always played an important role, whereas some other food-borne pathogens, such as Campylobacter, Vibrio parahaemolyticus and toxin-producing fungi have only been recognised in recent decades. Changing food-production methods, food processing and especially food habits, together with the enormous trade in foods and feeds from one part of the world to the other, are responsible for the increase of these diseases. To meet this situation, prevention and control of food-borne diseases, which involve large groups of persons and play a major socio-economic role in many parts of the world, are of utmost importance. In prevention and control programmes food irradiation can be applied successfully and may solve some of the food and feed contamination problems. The author summarizes to-day's most important food-borne diseases, the type of foods which are responsible for infections in man and animals, and the commodities in which low-dose food irradiation may be of great value in preventing these diseases. The advantages of irradiation versus the use of chemical additives and pesticides and with respect to the prevention of cross-contamination (which plays a very important role in initiating food-borne diseases) by pre-packaging, are emphasized. The required irradiaton doses to eliminate or reduce the number of pathogenic organisms which may be present in foods, the problem of radioresistance and the acceptability of irradiated food are discussed. Finally to-day's situation of irradiated foods with regard to legislation, consumers' information and economic feasibility is summarized. (author)

Genetic Diversity Among Botulinum Neurotoxin Producing Clostridial Strains

Energy Technology Data Exchange (ETDEWEB)

Hill, K K; Smith, T J; Helma, C H; Ticknor, L O; Foley, B T; Svennson, R T; Brown, J L; Johnson, E A; Smith, L A; Okinaka, R T; Jackson, P J; Marks, J D

2006-07-06

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and even death in humans and various other animal species. A collection of 174 C. botulinum strains were examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the16S rRNA sequences confirmed earlier reports of at least four distinct genomic backgrounds (Groups I-IV) each of which has independently acquired one or more BoNT serotypes through horizontal gene transfer. AFLP analysis provided higher resolution, and can be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from serotypes A, B and E in multiple strains confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes, and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven serotypes of BoNT were compared and show varying degrees of interrelatedness and recombination as has been previously noted for the NTNH gene which is linked to BoNT. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism.

Plasmidome interchange between Clostridium botulinum, Clostridium novyi and Clostridium haemolyticum converts strains of independent lineages into distinctly different pathogens.

Science.gov (United States)

Skarin, Hanna; Segerman, Bo

2014-01-01

Clostridium botulinum (group III), Clostridium novyi and Clostridium haemolyticum are well-known pathogens causing animal botulism, gas gangrene/black disease, and bacillary hemoglobinuria, respectively. A close genetic relationship exists between the species, which has resulted in the collective term C. novyi sensu lato. The pathogenic traits in these species, e.g., the botulinum neurotoxin and the novyi alpha toxin, are mainly linked to a large plasmidome consisting of plasmids and circular prophages. The plasmidome of C. novyi sensu lato has so far been poorly characterized. In this study we explored the genomic relationship of a wide range of strains of C. novyi sensu lato with a special focus on the dynamics of the plasmidome. Twenty-four genomes were sequenced from strains selected to represent as much as possible the genetic diversity in C. novyi sensu lato. Sixty-one plasmids were identified in these genomes and 28 of them were completed. The genomic comparisons revealed four separate lineages, which did not strictly correlate with the species designations. The plasmids were categorized into 13 different plasmid groups on the basis of their similarity and conservation of plasmid replication or partitioning genes. The plasmid groups, lineages and species were to a large extent entwined because plasmids and toxin genes had moved across the lineage boundaries. This dynamic process appears to be primarily driven by phages. We here present a comprehensive characterization of the complex species group C. novyi sensu lato, explaining the intermixed genetic properties. This study also provides examples how the reorganization of the botulinum toxin and the novyi alpha toxin genes within the plasmidome has affected the pathogenesis of the strains.

Production and characterisation of a neutralising chimeric antibody against botulinum neurotoxin A.

Directory of Open Access Journals (Sweden)

Julie Prigent

Full Text Available Botulinum neurotoxins, produced by Clostridium botulinum bacteria, are the causative agent of botulism. This disease only affects a few hundred people each year, thus ranking it among the orphan diseases. However, botulinum toxin type A (BoNT/A is the most potent toxin known to man. Due to their potency and ease of production, these toxins were classified by the Centers for Disease Control and Prevention (CDC as Category A biothreat agents. For several biothreat agents, like BoNT/A, passive immunotherapy remains the only possible effective treatment allowing in vivo neutralization, despite possible major side effects. Recently, several mouse monoclonal antibodies directed against a recombinant fragment of BoNT/A were produced in our laboratory and most efficiently neutralised the neurotoxin. In the present work, the most powerful one, TA12, was selected for chimerisation. The variable regions of this antibody were thus cloned and fused with the constant counterparts of human IgG1 (kappa light and gamma 1 heavy chains. Chimeric antibody production was evaluated in mammalian myeloma cells (SP2/0-Ag14 and insect cells (Sf9. After purifying the recombinant antibody by affinity chromatography, the biochemical properties of chimeric and mouse antibody were compared. Both have the same very low affinity constant (close to 10 pM and the chimeric antibody exhibited a similar capacity to its parent counterpart in neutralising the toxin in vivo. Its strong affinity and high neutralising potency make this chimeric antibody interesting for immunotherapy treatment in humans in cases of poisoning, particularly as there is a probable limitation of the immunological side effects observed with classical polyclonal antisera from heterologous species.

Plasmidome interchange between Clostridium botulinum, Clostridium novyi and Clostridium haemolyticum converts strains of independent lineages into distinctly different pathogens.

Directory of Open Access Journals (Sweden)

Hanna Skarin

Full Text Available Clostridium botulinum (group III, Clostridium novyi and Clostridium haemolyticum are well-known pathogens causing animal botulism, gas gangrene/black disease, and bacillary hemoglobinuria, respectively. A close genetic relationship exists between the species, which has resulted in the collective term C. novyi sensu lato. The pathogenic traits in these species, e.g., the botulinum neurotoxin and the novyi alpha toxin, are mainly linked to a large plasmidome consisting of plasmids and circular prophages. The plasmidome of C. novyi sensu lato has so far been poorly characterized. In this study we explored the genomic relationship of a wide range of strains of C. novyi sensu lato with a special focus on the dynamics of the plasmidome. Twenty-four genomes were sequenced from strains selected to represent as much as possible the genetic diversity in C. novyi sensu lato. Sixty-one plasmids were identified in these genomes and 28 of them were completed. The genomic comparisons revealed four separate lineages, which did not strictly correlate with the species designations. The plasmids were categorized into 13 different plasmid groups on the basis of their similarity and conservation of plasmid replication or partitioning genes. The plasmid groups, lineages and species were to a large extent entwined because plasmids and toxin genes had moved across the lineage boundaries. This dynamic process appears to be primarily driven by phages. We here present a comprehensive characterization of the complex species group C. novyi sensu lato, explaining the intermixed genetic properties. This study also provides examples how the reorganization of the botulinum toxin and the novyi alpha toxin genes within the plasmidome has affected the pathogenesis of the strains.

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

Energy Technology Data Exchange (ETDEWEB)

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng (Cornell); (Dusseldorf); (UCI)

2017-03-01

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. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures

Heat shock and prolonged heat stress attenuate neurotoxin and sporulation gene expression in group I Clostridium botulinum strain ATCC 3502.

Science.gov (United States)

Selby, Katja; Mascher, Gerald; Somervuo, Panu; Lindström, Miia; Korkeala, Hannu

2017-01-01

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. botulinum Group I strain ATCC 3502 was grown in continuous culture at 39°C and exposed to heat shock at 45°C, followed by prolonged heat stress at 45°C to allow adaptation of the culture to the high temperature. Growth in continuous culture was performed to exclude secondary growth phase effects or other environmental impacts on bacterial gene transcription. Changes in global gene expression profiles were studied using DNA microarray hybridization. During acute heat stress, Class I and III heat shock genes as well as members of the SOS regulon were activated. The neurotoxin gene botA and genes encoding the neurotoxin-associated proteins were suppressed throughout the study. Prolonged heat stress led to suppression of the sporulation machinery whereas genes related to chemotaxis and motility were activated. Induced expression of a large proportion of prophage genes was detected, suggesting an important role of acquired genes in the stress resistance of C. botulinum. Finally, changes in the expression of a large number of genes related to carbohydrate and amino acid metabolism indicated remodeling of the cellular metabolism.

Sôbre a patogenia da Grangrena gasona

Directory of Open Access Journals (Sweden)

Genésio Pacheco

1954-06-01

Full Text Available Since von Hibler gas grangrene has been considered a local infection with systemic symptoms. When we consider some of the symptoms of gas gangrene, those of the central nervous system are in evidence beeing similar to those observed in tetanus and botulism. It is likely therefore that gas gangrene intoxication and the disease caused by it are of neurotoxic nature. With Almeida Cardoso and Araujo Costa we were able to demonstrate lesions in the central nervous system of animals wich had been intoxicated during a short period of time as well in those with intoxication of longer duration. In acute intoxication, after intracreneal inoculation, severe alterations were seen within 20 to 30 minutes in the cells of the spinal cord, specially in motor cells and also in some cells of the posterior cord and spinal bulb. The changes consisted in chromatolysis and picnosis and were more marked in animals intoxicated with Clostridium histolyticum and Cl. perfringens toxines. Myelin sheet was unchanged. in delayed intoxication with greater and repeated dosis lesions of the central nervous system (brain, protuberance, medula ablongate and medula spinal were observed. They consisted in hyperemia, perivascular hemorrages in white and grey substances, oedema, accumulation of glia cells with enlarged and hyperchromatic nuclei, fragmentation of the myelin sheet and balooning degeneration of the described by Spielmeyer. Such changes were found in the swollen and hemorragic zones and were generally similar to those found in the acute type of Spielmeyer 9acute swelling and liquefation. Other changes found sometimes were agglutination of Nissl's bodies, sinous appearence of the dendritic endings, shruncken cells of Spielmeyer and neuronophagy around "ghost" cells. In short the changes...

Uso de toxina botulímica paravertebral para detener la progresión de escoliosis en pollos pinealectomizados: la columna vertebral como sistema de tensegridad

OpenAIRE

González Miranda, Álvaro

2016-01-01

La escoliosis idiopática infantil no tiene un tratamiento satisfactorio que permita reducir la importante morbilidad y mortalidad asociada a los casos más severos y progresivos de la enfermedad. Independientemente de su origen, se postula que las curvas de escoliosis presentan una debilidad estructural de partes blandas en el lado de la convexidad de la curva. Trabajos previos subrayan la capacidad de la pinealectomía en pollos de experimentación para producir escoliosis, como modelo de estud...

Ciguatera poisoning: a global issue with common management problems.

Science.gov (United States)

Ting, J Y; Brown, A F

2001-12-01

Ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food-borne illness related to contaminated fish consumption. As many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the Pacific Basin, Indian Ocean and Caribbean. Isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as Europe and North America. Increase in travel between temperate countries and endemic areas and importation of susceptible fish has led to its encroachment into regions of the world where ciguatera has previously been rarely encountered. In the developed world, ciguatera poses a public health threat due to delayed or missed diagnosis. Ciguatera is frequently encountered in Australia. Sporadic cases are often misdiagnosed or not medically attended to, leading to persistent or recurrent debilitating symptoms lasting months to years. Without treatment, distinctive neurologic symptoms persist, occasionally being mistaken for multiple sclerosis. Constitutional symptoms may be misdiagnosed as chronic fatigue syndrome. A common source outbreak is easier to recognize and therefore notify to public health organizations. We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu. All responded well to intravenous mannitol. This is in contrast to a fifth patient who developed symptoms suggestive of ciguatoxicity in the same week as the index cases but actually had staphylococcal endocarditis with bacteraemia. In addition to a lack of response to mannitol, clinical and laboratory indices of sepsis were present in this patient. Apart from ciguatera, acute gastroenteritis followed by neurological symptoms may be due to paralytic or neurotoxic shellfish poisoning, scombroid and pufferfish toxicity, botulism, enterovirus 71, toxidromes and

Genomic determinants of sporulation in Bacilli and Clostridia: towards the minimal set of sporulation-specific genes.

Science.gov (United States)

Galperin, Michael Y; Mekhedov, Sergei L; Puigbo, Pere; Smirnov, Sergey; Wolf, Yuri I; Rigden, Daniel J

2012-11-01

Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia and Negativicutes, include numerous members that are capable of producing heat-resistant endospores. Spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus subtilis, sporulation involves over 500 genes, many of which are conserved among other bacilli and clostridia. This work aimed to define the genomic requirements for sporulation through an analysis of the presence of sporulation genes in various firmicutes, including those with smaller genomes than B. subtilis. Cultivable spore-formers were found to have genomes larger than 2300 kb and encompass over 2150 protein-coding genes of which 60 are orthologues of genes that are apparently essential for sporulation in B. subtilis. Clostridial spore-formers lack, among others, spoIIB, sda, spoVID and safA genes and have non-orthologous displacements of spoIIQ and spoIVFA, suggesting substantial differences between bacilli and clostridia in the engulfment and spore coat formation steps. Many B. subtilis sporulation genes, particularly those encoding small acid-soluble spore proteins and spore coat proteins, were found only in the family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of sporulation genes, compiled in this work, confirm the presence of a common sporulation gene core, but also illuminate the diversity of the sporulation processes within various lineages. These profiles should help further experimental studies of uncharacterized widespread sporulation genes, which would ultimately allow delineation of the minimal set(s) of sporulation-specific genes in Bacilli and Clostridia. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Dysphagia associated with presumed pharyngeal dysfunction in 16 neonatal foals.

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Holcombe, S J; Hurcombe, S D; Barr, B S; Schott, H C

2012-02-01

Dysphagia due to pharyngeal dysfunction occurs in human neonates and is associated with prematurity and hypoxic episodes. This syndrome probably occurs in neonatal foals but has not been reported. The objectives of this study were to describe 1) a series of neonatal foals with dysphagia due to pharyngeal dysfunction; 2) the progression, treatment and resolution of the dysphagia; 3) the comorbidities; and 4) the prognosis for life and athleticism for affected foals. Records from 3 referral equine hospitals were reviewed from neonatal foals with dysphagia of pharyngeal origin. Inclusion criteria were a normal to strong suckle, dysphagia evidenced by milk at the nostrils after nursing the dam, and endoscopic examination of the airway. Foals with mechanical reasons for dysphagia, botulism or hyperkalaemic periodic paralysis were not included. Sixteen neonatal foals qualified for the study. Eight (50%) were premature and/or diagnosed with hypoxic ischaemic encephalopathy. Twelve (75%) had aspiration pneumonia. Fifteen foals were discharged alive from the hospital, nursing the mare with no evidence of dysphagia (n = 14), or mild dysphagia (n = 1), a mean +/- s.d. of 7 +/- 6 days (median = 6.3 days, range 0-22 days) after hospital admission. One foal was subjectedto euthanasia in hospital. Follow-up nformation was available for 14 animals. Thirteen of 16 (81%) were alive and included one yearling and 12 horses >2 years old. Seven of the 14 (50%) were racing, training or in work, and 6 horses were pets, breeding animals or had unknown athletic status. Two had laryngeal deficits. One foal was subjected to euthanasia within weeks of discharge from the hospital due to aspiration pneumonia. Dysphagia related to pharyngeal dysfunction occurs in equine neonates and can resolve, but may require days to weeks of supportive care. Prognosis for life is favourable and for athleticism fair.

Monitoring the Various Types of Clostridium botulinumin in Four Kinds of Food Stuffs Using Multiplex PCR

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Mohammad Vahid Sadeghi Sarvestani

2014-03-01

Full Text Available Background &Objective: Food poisoning (FP caused by C. botulinum is the most serious feature of FP inpeople consuming the contaminated foodstuffs (Canned meat, vegetarian foods, dairy products and seafood products. Botulism is basically detected by the identification of live bacteria and/or its toxins. Among various types of microorganisms (i.e. A, B, C1, C2, D, E, F, serotypes A, B, E and F are considered as the main human pathogens. The present study was aimed at investigating the possible roles of various foodstuffs to induce the food intoxication and also to compare the culture and molecular assays for identifying the microorganism.Materials &Methods: Three Lab techniques including biochemical, culture (enriched in TPGY and cooked meat medium and MPCR were used to detect C. botulinum in the samples. As the molecular based techniques have recently employed for the rapid and reliable identification of the bacteria and its toxins, the PCR assay, using three pairs of primers were designed and optimized to identify A, B and E strains in the contaminated specimens. The PCR was able to amplify 782, 205 and 389 bp genes specified for A, B and E types of the bacteria, respectively. Results: Total number of 290 specimens including fish, honey,"kashk"and"Dough" were tested, in which 5%, 4%, 2.5% and 1.25%, were found positive, respectively. Using selective culture of the specimens on the enriched samples, it was shown that just four samples were found positive.Conclusion: As a final conclusion, the molecular based techniques are recommended as a reliable tool to detect C. botulinum and, its toxins and spores in foodstuffs. Moreover, it is strongly advised to use it in food microbial Lab and also the epidemiological surveys.

Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management

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Chun, Chan Lan; Kahn, Chase I.; Borchert, Andrew J.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Peller, Julie R.; Pier, Christina; Lin, Guangyun; Johnson, Eric A.; Sadowsky, Michael J.

2015-01-01

The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophoraspp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011–2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed inCladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 100–104 MPN/g dried algae, which was much greater (up to 103 fold) than that found in sand or the water column, indicating thatCladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putativeC. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

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Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam

2015-11-15

The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins. Because of their extreme toxicity and history of weaponization, the BoNTs are regarded as potential biowarfare/bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than intensive care; therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was evaluated in a FRET assay for its ability to inhibit BoNT/A light chain (Balc). CPI was found to be highly potent, exhibiting a Ki of 12.3 nM with full-length Balc448 and 39.2 nM using a truncated crystallizable form of the light chain (Balc424). Cocrystallization studies revealed that in the Balc424-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn(2+) binding region involved in catalysis. This differs from linear peptide inhibitors described to date which block only the latter. Published by Elsevier Ltd.

Toxin formation by Clostridium botulinum type B in radurized fish

International Nuclear Information System (INIS)

Suhadi, F.; Thayib, S.S.

1981-01-01

The relation between maximum storage life and earliest toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in irradiated and unirradiated raw fish was determinated. The fish species used were Rastrelliger sp., Euthynnus sp. and Scomberomorus sp. Uninoculated fish samples held under the same treatment conditions were evaluated for the estimation of storage life by untrained panelist. The results showed that a storage temperature at or lower than 5.6 0 C is recommended in order to avoid botulism hazard caused by nonproteolytic type B. When the samples were inoculated with spores of proteolytic strains, no toxic samples were found during the storage life in all treatments with storage temperatures at or lower than 10.2 0 C. Toxin formation by proteolytic strains of C. botulinum type B in boiled (''Pindang'') chub mackerel (Rastrelliger sp.) under storage at ambient temperatures (27-31 0 C) was also determinated. The results showed that in the samples which were inoculated before the process of ''Pindang'', the earliest toxin formations were detected after the samples were spoiled regardless of the irradiation dose, strain and inoculum level; while in control unsalted samples, toxin was detected before or after the samples were spoiled, depending on the strain and inoculum level. Salt content in ordinary ''Pindang'' fish plays a major role both in extension of the storage life and the delay in toxin formation. When the samples were inoculated after the process of ''Pindang'', toxin was detected before or after the samples were spoiled, depending on the strain, salt content, irradiation dose and inoculum level. Irradiation does not prevent the toxin formation in ''Pindang'' fish if the samples are heavily contaminated with proteolytic strains of C. botulinum type B after cooking. (author)

Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

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Suzanne R. Kalb

2017-06-01

Full Text Available 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. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

Construction of a nontoxigenic Clostridium botulinum strain for food challenge studies.

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Bradshaw, Marite; Marshall, Kristin M; Heap, John T; Tepp, William H; Minton, Nigel P; Johnson, Eric A

2010-01-01

Clostridium botulinum produces the most poisonous natural toxin known and is a perennial concern to the food industry and to regulatory agencies due to the potential threat of food-borne botulism. To ensure the botulinal safety of foods, rigorous food challenge testing to validate food-processing conditions and food formulations has been routinely performed. Detection of the botulinum neurotoxin is performed by using a mouse bioassay and/or in vitro assays. There has been considerable interest by the food industry and regulatory agencies in minimizing or even replacing the use of animals in these challenge studies. In addition, due to stringent select-agent regulations, the testing of various foods using toxigenic C. botulinum strains requires facilities and personnel that are certified for work with this organism. For this purpose we propose to generate sets of nontoxigenic C. botulinum strains from proteolytic and nonproteolytic groups that differ from the wild-type strains only by their inability to produce botulinum neurotoxin. In this initial study we describe the generation of a nontoxigenic mutant of C. botulinum strain 62A using the ClosTron mutagenesis system by inserting a group II intron into the botulinum neurotoxin type A gene (bont/A). The mutant clones were nontoxigenic as determined by Western blots and mouse bioassays but showed physiological characteristics, including growth properties and sporulation, that were similar to those of the parent strain in laboratory media. Additional studies will be required to evaluate comparable characteristics in various food matrices. The availability of suitable nontoxigenic C. botulinum strains for food challenge studies will be beneficial for enhancing the botulinal safety of foods as well as increasing the biosafety of workers and may eliminate the use of laboratory animals.

Distonia laríngea respiratória

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Lebl Mariana Dantas Aumond

2003-01-01

Full Text Available A distonia laríngea respiratória (DLR é uma desordem rara caracterizada por espasmos da musculatura adutora das pregas vocais durante a fase inalatória da respiração, com manifestação clínica de dispnéia e estridor. O diagnóstico etiológico do estridor laríngeo, entretanto, nem sempre é fácil de ser realizado, principalmente em situações emergenciais, de forma que a DLR pode não ser diagnosticada, o que nos leva a supor ser mais freqüente do que usualmente é descrita. O diagnóstico da DRL requer primeiramente a realização de uma história médica e exames laringológico e neurológico apropriados, com ênfase na verificação da presença de características distônicas e na exclusão de outras etiologias causadoras de movimentos paradoxais de pregas vocais. Muitos tratamentos foram propostos para a DLR, mas nenhum deles apresentou resultados satisfatórios. O uso da Toxina Botulínica do tipo A (Botox® no músculo tireoaritenoídeo tem oferecido melhoras admiráveis, apesar dos poucos casos descritos. Apresentamos dois casos clínicos de pacientes com DLR tratados com Botox® que apresentavam o fechamento glótico inspiratório causado tanto pelos espasmos anômalos dos músculos tireoaritenoídeos, como pela movimentação paradoxal da epiglote. Dentro da classificação proposta por Koufman e Blabock para as distonias laríngeas, inserimos um novo subtipo de DLR caracterizado pela presença de paroxismos de adução de estruturas glóticas e supraglóticas durante a respiração.

Causes of mortality in laying hens in different housing systems in 2001 to 2004

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Etterlin Pernille

2009-01-01

Full Text Available Abstract Background The husbandry systems for laying hens were changed in Sweden during the years 2001 – 2004, and an increase in the number of submissions for necropsy from laying hen farms was noted. Hence, this study was initiated to compare causes of mortality in different housing systems for commercial laying hens during this change. Methods Based on results from routine necropsies of 914 laying hens performed at the National Veterinary Institute (SVA in Uppsala, Sweden between 2001 and 2004, a retrospective study on the occurrence of diseases and cannibalism, i.e., pecking leading to mortality, in different housing systems was carried out. Using the number of disease outbreaks in caged flocks as the baseline, the expected number of flocks with a certain category of disease in the other housing systems was estimated having regard to the total number of birds in the population. Whether the actual number of flocks significantly exceeded the expected number was determined using a Poisson distribution for the variance of the baseline number, a continuity correction and the exact value for the Poisson distribution function in Excel 2000. Results Common causes of mortality in necropsied laying hens included colibacillosis, erysipelas, coccidiosis, red mite infestation, lymphoid leukosis and cannibalism. Less common diagnoses were Newcastle Disease, pasteurellosis and botulism. Considering the size of the populations in the different housing systems, a larger proportion of laying hens than expected was submitted for necropsy from litter-based systems and free range production compared to hens in cages (P P P Conclusion The results of the present study indicated that during 2001–2004 laying hens housed in litter-based housing systems, with or without access to outdoor areas, were at higher risk of infectious diseases and cannibalistic behaviour compared to laying hens in cages. Future research should focus on finding suitable prophylactic

A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

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Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng; Lou, Jianlong; Conrad, Fraser; Ho, Mengfei; Pires-Alves, Melissa; Wilson, Brenda A.; Stevens, Raymond C.; Marks, James D. (UIUC); (Scripps); (UCSF)

2010-08-13

Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody) antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.

Dermatologia clínico-cirúrgica: avaliação da mudança no perfil dos procedimentos de um serviço de residência médica no Paraná-BR

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Fabiane Mulinari-Brenner

2010-06-01

Full Text Available Introdução: Nas últimas quatro décadas a dermatologia transformou-se, de especialidade puramente clínica, em especialidade clinicocirúrgica. O dermatologista passou a realizar, além da diagnose e do tratamento clínico,o tratamento cirúrgico das afecções e neoplasias cutâneas,a correção de cicatrizes e procedimentos cutâneos necessários para melhora da aparência individual. Objetivo: Demonstrar a mudança do perfil das atividades do Serviço de Dermatologia do HC-UFPR no período estudado. Material e métodos: Foi realizada a revisão sistemática dos registros próprios do Ambulatório de Dermatologia, além dos dados fornecidos pelo Sistema de Estatística e Planejamento do HC-UFPR entre 2002 e 2007. Resultados: Houve aumento relativo de 16% no número de procedimentos cirúrgicos no período estudado, com aumento também de sua complexidade, passando o índice de exerese de lesões benignas em relação ao da exerese de tumores malignos de 2,25:1 em 2002 para 1,04:1 em 2007. Quanto aos procedimentos cosmiátricos, a realização de peelings ampliou-se 74% no período estudado. O preenchimento e aaplicação de toxina botulínica passaram de procedimentos esporádicos em 2002 para procedimentos de rotina, com 3,33 preenchimentos/mês e três aplicações toxina/mês. Conclusões: Os dados obtidos demonstram objetivamente a transformação das atividades do Serviço de Dermatologia do HC-UFPR, de principalmente clínicas, para clinicocirúrgicas, com aumento da complexidade dos procedimentos realizados no treinamento do residente de dermatologia, em concordância com a evolução da especialidade no Brasil e no mundo.

Lessons from the Tōhoku tsunami: A model for island avifauna conservation prioritization

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Reynolds, Michelle H.; Berkowitz, Paul; Klavitter, John; Courtot, Karen

2017-01-01

Earthquake-generated tsunamis threaten coastal areas and low-lying islands with sudden flooding. Although human hazards and infrastructure damage have been well documented for tsunamis in recent decades, the effects on wildlife communities rarely have been quantified. We describe a tsunami that hit the world's largest remaining tropical seabird rookery and estimate the effects of sudden flooding on 23 bird species nesting on Pacific islands more than 3,800 km from the epicenter. We used global positioning systems, tide gauge data, and satellite imagery to quantify characteristics of the Tōhoku earthquake-generated tsunami (11 March 2011) and its inundation extent across four Hawaiian Islands. We estimated short-term effects of sudden flooding to bird communities using spatially explicit data from Midway Atoll and Laysan Island, Hawai'i. We describe variation in species vulnerability based on breeding phenology, nesting habitat, and life history traits. The tsunami inundated 21%–100% of each island's area at Midway Atoll and Laysan Island. Procellariformes (albatrosses and petrels) chick and egg losses exceeded 258,500 at Midway Atoll while albatross chick losses at Laysan Island exceeded 21,400. The tsunami struck at night and during the peak of nesting for 14 colonial seabird species. Strongly philopatric Procellariformes were vulnerable to the tsunami. Nonmigratory, endemic, endangered Laysan Teal (Anas laysanensis) were sensitive to ecosystem effects such as habitat changes and carcass-initiated epizootics of avian botulism, and its populations declined approximately 40% on both atolls post-tsunami. Catastrophic flooding of Pacific islands occurs periodically not only from tsunamis, but also from storm surge and rainfall; with sea-level rise, the frequency of sudden flooding events will likely increase. As invasive predators occupy habitat on higher elevation Hawaiian Islands and globally important avian populations are concentrated on low-lying islands

Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons.

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Laura Restani

2012-12-01

Full Text Available The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neurotransmitters in the spinal cord, causing a spastic paralysis. In contrast, botulinum neurotoxins (BoNTs block acetylcholine release at the neuromuscular junction, therefore inducing a flaccid paralysis. Whilst overt experimental evidence supports the sorting of TeNT to the axonal retrograde transport pathway, recent findings challenge the established view that BoNT trafficking is restricted to the neuromuscular junction by highlighting central effects caused by these neurotoxins. These results suggest a more complex scenario whereby BoNTs also engage long-range trafficking mechanisms. However, the intracellular pathways underlying this process remain unclear. We sought to fill this gap by using primary motor neurons either in mass culture or differentiated in microfluidic devices to directly monitor the endocytosis and axonal transport of full length BoNT/A and BoNT/E and their recombinant binding fragments. We show that BoNT/A and BoNT/E are internalised by spinal cord motor neurons and undergo fast axonal retrograde transport. BoNT/A and BoNT/E are internalised in non-acidic axonal carriers that partially overlap with those containing TeNT, following a process that is largely independent of stimulated synaptic vesicle endo-exocytosis. Following intramuscular injection in vivo, BoNT/A and TeNT displayed central effects with a similar time course. Central actions paralleled the peripheral spastic paralysis for TeNT, but lagged behind the onset of flaccid paralysis for BoNT/A. These results suggest that the fast axonal retrograde transport compartment is composed of multifunctional trafficking organelles orchestrating the simultaneous transfer

Purification and characterization of a novel subtype a3 botulinum neurotoxin.

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Tepp, William H; Lin, Guangyun; Johnson, Eric A

2012-05-01

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2, and -/A5 have been purified, and their properties have been studied. BoNT/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1 antibodies, and thus, it may potentially replace BoNT/A1 for patients who have become refractive to treatment with BoNT/A1 due to antibody formation or other modes of resistance. Purification of BoNT/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain) and boost toxin production. BoNT/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse bioassay was 5.8 × 10(7) 50% lethal doses (LD(50))/mg. Neutralization of BoNT/A3 toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT/A3 and those that were injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins.

Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS Trial

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Nick Steen

2012-11-01

Full Text Available Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.

El estrabismo en el niño y anestesia Strabismus in the child and anesthesia

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Joaquín L. de la Lastra Rodríguez

2001-06-01

Full Text Available Se analiza el manejo anestésico de 41 niños tratados por estrabismo con anestesia general, administrada a 37 de ellos por vía endotraqueal para la corrección quirúrgica y a los 4 restantes por vía intravenosa para la inyección de toxina botulínica (TBX tipo A en microdosis intraocular. Se destacan aspectos importantes de interés anestesiológico como son las implicaciones clínicas que pudieran resultar del manejo anestésico, los cuidados especiales que requieren estos pacientes, la importancia de la evaluación preoperatoria que considere aspectos de interés especial y propios, etc. No hubo complicaciones transoperatorias. El vómito fue la complicación posoperatoria vista en 6 pacientes y sólo 1 sometido a tratamiento quirúrgico requirió además del mantenimiento de una hidratación intravenosa con la administración de una dosis de dimenhidrinato, antihistamínico de fuerte acción antiemética. Se presenta el manejo anestésico para la inyección intraocular de microdosis de TBX tipo A realizada con buenos resultados con Atropina, Diazepán y Clorhidrato de Ketamina por vía intravenosa.The anesthetic management of 41 children with strabismus treated with general anesthesia is analyzed. 37 of them were administered intratracheal anesthesia for surgical correction and the other 4 intravenous anesthesia for the injection of an intraocular microdose of botulinum toxin A (TBX. Important aspects of anesthesiologic interest as the clinical implications that may result from the anesthetic management, the special care required by these patients, the importance of the preoperative evaluation that takes into account aspects of special interest, of the authors' interest and others, are stressed . There were no transoperative complications. Vomiting was the postoperative complication observed in 6 patients and only one of those who underwent surgery required besides the maintenance of an intravenous hydration the administration of a dose

Notalgia parestésica: relato de caso

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José Otávio Alquezar Gozzano

2016-10-01

Full Text Available Introdução: Notalgia parestésica (NP é uma condição neurocutânea, caracterizada por crises pruriginosas, hiperpigmentação e neuropatia sensorial. Apesar de pouco descrita em literatura, a doença é mais frequente do que se imagina, sendo subdiagnosticada em muitos casos. NP pode afetar qualquer idade e sexo, mas acomete principalmente pessoas de média idade e mulheres. Sua etiologia inclui alterações degenerativas vertebrais, trauma vertebral e predisposição genética. NP envolve o trajeto anatômico dos nervos espinhais e está relacionada com o comprometimento de neuropeptídios, dando origem a marcapassos neurais ectópicos, responsáveis pela clínica da NP. O diagnóstico é clínico, a partir da identificação de máculas hiperpigmentadas unilaterais em zona escapular, sem eritema ou descamação, com piora ao estresse. Deve-se diferenciar de líquen simples, amiloidose macular e hanseníase. Na anatomopatologia observa-se acantose focal e queratinócitos necróticos; a derme papilar mostra depósito de substância amiloide. Com sintomas leves o tratamento medicamentoso nem sempre é necessário, se mais severa utiliza-se capsaicina tópica, gabapentina, oxicarba-mazepina, corticoides e toxina botulínica. Objetivo: Relatar caso de NP. Material e métodos: Paciente atendida ambulatorialmente com revisão de literatura. Relato de Caso: Feminina, 50 anos, com queixa de mancha em dorso há 2 anos; refere dor na coluna torácica. Ao exame: presença de mácula hipercrômica. Hipótese diagnóstica: NP. Foi prescrito corticoide tópico para alívio de sintomas. Conclusão: Por tratar-se de uma doença subdiagnosticada, o conhecimento médico da clínica de NP é fundamental para o diagnóstico precoce, permitindo a escolha do tratamento específico, o que melhora a evolução dos pacientes e evita o uso de fármacos ineficazes.

Acalasia de esôfago de causa desconhecida na infância Esophageal achalasia of unknown etiology in children

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Pedro M. Fernandez

2004-12-01

Full Text Available OBJETIVO: Os autores descrevem o caso de uma criança do sexo feminino, de 9 anos de idade, com acalasia de esôfago de causa indeterminada, tratada cirurgicamente. Discutem também os métodos empregados para diagnóstico e tratamento, além de realizarem uma revisão da literatura. DESCRIÇÃO: A acalasia do esôfago é uma doença rara em crianças, geralmente de origem indeterminada. Tem como principais sintomas regurgitação, vômitos de características esofágicas, disfagia e perda de peso. O diagnóstico é feito por esofagograma, endoscopia e, mais precisamente, por manometria esofágica. O tratamento de escolha é a cardiomiotomia a Heller, associada ou não a válvula anti-refluxo. A dilatação endoscópica por balão e a toxina botulínica têm sido descritas como alternativas terapêuticas. COMENTÁRIOS: A acalasia de esôfago é uma doença rara em crianças, e sua origem geralmente é indeterminada. O quadro clínico pode ser confundido com doença do refluxo gastroesofágico, podendo retardar seu diagnóstico. A cardiomiotomia a Heller, associada à confecção de válvula anti-refluxo, consiste na modalidade terapêutica de escolha.OBJECTIVE: To report a case of a 9-year-old female presented with esophageal achalasia and approached with surgery. The authors discuss the treatment and make a literature review on the topic. DESCRIPTION: Childhood esophageal achalasia is an unusual disease, often with unknown etiology. The main symptoms are esophageal vomits, dysphagia and weight loss. The diagnosis can be made by esophagogram and endoscopy, but the main examination is the esophageal manometry. Even though the surgical approach is a well-established therapy, some alternative treatments have been used, such as the endoscopy balloon dilatation and the use of botulinum toxin. COMMENTS: Esophageal achalasia is a rare disease in childhood, with unknown etiology. The presentation may be confused with gastroeshophageal reflux, sometimes

Qualidade de Vida em Voz: estudo na doença de Parkinson idiopática e na Disfonia Espasmódica Adutora Quality of life in voice: a study in Parkinson's disease and in adductor spasmodic dysphonia

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Bárbara Pereira Lopes

2012-01-01

Full Text Available OBJETIVO: avaliar o impacto causado pela alteração vocal na qualidade de vida (QV dos pacientes com doença de Parkinson (DP idiopática e com disfonia espasmódica adutora (DEA. MÉTODO: o estudo foi realizado com 56 indivíduos do sexo feminino, dos quais 28 compunham o grupo controle; 14, o grupo de DEA, no período anterior ao tratamento com toxina botulínica; e 14, o grupo de DP idiopática. Os participantes preencheram o questionário de Qualidade de Vida em Voz (QVV validado para o português brasileiro. Para verificar a diferença entre as médias dos grupos foi utilizado o método de análise de variância por postos de Kruskal-Wallis e o teste de Tamhane para comparações múltiplas, com significância PURPOSE: to evaluate the impact of voice disorders on quality of life of patients with idiopathic Parkinson's disease and with adductor spasmodic dysphonia. METHOD: the study consisted of 56 females, 28 in the control group; 14, the adductor spasmodic dysphonia group in the period prior to treatment with botulinum toxin; and 14, the group of idiopathic Parkinson's disease. The participants filled in the Voice-Related Quality of life (V-RQOL questionnaire validated for Brazilian Portuguese. To check the difference between averages of the groups it was used the method of analysis of variance by Kruskal-Wallis and Tamhane test for multiple comparisons, with significance <0.05. RESULTS: the average age of the groups were 66.18 for the control group, 67.21 for the Parkinson's disease group and 59.7 for the adductor spasmodic dysphonia group, with no statistical difference between the groups. In the V-RQOL protocol the mean domain social-emotional, physical functioning and total score were higher in the control group, followed by group of Parkinson's disease and, finally, the group of adductor spasmodic dysphonia with statistically significant difference between them. In addition, there was statistical difference for each pair of groups

Qualidade de Vida em Voz: estudo na doença de Parkinson idiopática e na disfonia espasmódica adutora Quality of life in voice: a study in Parkinson's disease and in adductor spasmodic dysphonia

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Bárbara Pereira Lopes

2013-04-01

Full Text Available OBJETIVO: avaliar o impacto causado pela alteração vocal na qualidade de vida (QV dos pacientes com doença de Parkinson (DP idiopática e com disfonia espasmódica adutora (DEA. MÉTODO: o estudo foi realizado com 56 indivíduos do sexo feminino, dos quais 28 compunham o grupo controle; 14, o grupo de DEA, no período anterior ao tratamento com toxina botulínica; e 14, o grupo de DP idiopática. Os participantes preencheram o questionário de Qualidade de Vida em Voz (QVV validado para o português brasileiro. Para verificar a diferença entre as médias dos grupos foi utilizado o método de análise de variância por postos de Kruskal-Wallis e o teste de Tamhane para comparações múltiplas, com significância PURPOSE: to evaluate the impact of voice disorders on quality of life of patients with idiopathic Parkinson's disease and with adductor spasmodic dysphonia. METHOD: the study consisted of 56 females, 28 in the control group; 14, the adductor spasmodic dysphonia group in the period prior to treatment with botulinum toxin; and 14, the group of idiopathic Parkinson's disease. The participants filled in the Voice-Related Quality of life (V-RQOL questionnaire validated for Brazilian Portuguese. To check the difference between averages of the groups it was used the method of analysis of variance by Kruskal-Wallis and Tamhane test for multiple comparisons, with significance <0.05. RESULTS: the average age of the groups were 66.18 for the control group, 67.21 for the Parkinson's disease group and 59.7 for the adductor spasmodic dysphonia group, with no statistical difference between the groups. In the V-RQOL protocol the mean domain social-emotional, physical functioning and total score were higher in the control group, followed by group of Parkinson's disease and, finally, the group of adductor spasmodic dysphonia with statistically significant difference between them. In addition, there was statistical difference for each pair of groups

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

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Graham Laura

2008-10-01

Full Text Available Abstract Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group or upper limb therapy alone (control group. Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT. Secondary outcomes include: spasticity (Modified Ashworth Scale; grip strength; dexterity (Nine Hole Peg Test; disability (Barthel Activities of Daily Living Index; quality of life (Stroke Impact Scale, Euroqol EQ-5D and attainment of patient-selected goals (Canadian Occupational Performance Measure. Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56. Trial registration ISRCTN78533119 EudraCT 2004-002427-40 CTA 17136/0230/001 Funding National Institute for Health Research, Health Technology Assessment Programme. Ipsen Ltd provide botulinum toxin type A (Dysport®.

Doenças do sistema nervoso de bovinos no semiárido nordestino Diseases of the nervous system of cattle in the semiarid of Northeastern Brazil

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Glauco J.N. Galiza

2010-03-01

pituitary abscesses, malignant catarrhal fever (6.3%, botulism (6.3%, congenital malformations (4.5%, trauma (4.5%, tuberculosis (2.7%, tetanus (2.7%, infection by bovine hervesvirus-5 (2.7%, non-suppurative encephalomyelitis (2.7%, intoxication by Prosopis juliflora (2.7%, congenital status spongiosus of unknown etiology (1.8%, and polioencephalomalacia (1.8%. Other diseases diagnosed only once (0.9% were cryptococcosis, listeriosis, thromboembolic encephalitis, lymphosarcoma, trypanosso-miasis, and babesiosis by Babesia bovis.

Aplicação de toxina botulínica tipo A para reduzir a saliva em pacientes com esclerose lateral amiotrófica Application of botulinum toxin to reduce the saliva in patients with amyotrophic lateral sclerosis

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Dayse Manrique

2005-10-01

Full Text Available OBJETIVO: Demonstrar o efeito da aplicação local Botox® em glândulas salivares de pacientes com diagnóstico de esclerose lateral amiotrófica (ELA, seguindo nosso protocolo institucional de tratamento da sialorréia de 2002. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Cinco pacientes com ELA avaliados na Clínica de Otorrinolaringologia da AACD (Associação de Assistência à Criança Deficiente foram submetidos à aplicação tópica de Botox® nas glândulas salivares e acompanhados por um ano. O protocolo consiste num questionário clínico sobre as habilidades de deglutir saliva e as repercussões na qualidade de vida. Os pacientes deveriam ter tratamento odontológico prévio, intolerância aos efeitos adversos dos anti-colinérgicos, e ausência de aplicação de. Botox® em outros sítios por pelo menos seis meses. A aplicação foi guiada por ultra-sonografia para as glândulas submandibulares e a dose administrada foi de 30U em um ponto, e 20U em cada glândula parótida distribuída em dois pontos, após anestesia tópica com prilocaína. RESULTADOS: Cinco pacientes com ELA, com idade entre 45 e 59 anos foram submetidos ao tratamento de redução de saliva pela aplicação de Botox® em glândulas salivares. Nós observamos que os sintomas de sialorréia melhoraram dramaticamente em quatro pacientes. Três pacientes permaneceram quatro meses sem queixas, com acentuada melhora na qualidade de vida. Nenhum paciente apresentou efeitos colaterais locais ou sistêmicos com a aplicação de Botox® em glândulas salivares. Nós observamos que os sintomas de sialorréia melhoraram dramaticamente em quatro pacientes. Três pacientes permaneceram quatro meses sem queixas, com acentuada melhora na qualidade de vida. Nenhum paciente apresentou efeitos colaterais locais ou sistêmicos com a aplicação de Botox® em glândulas salivares.AIM: To demonstrate the effect of local application of Botox® in patients with amyotrophic lateral sclerosis (ALS, following our 2002 institutional protocol of sialorrhea treatment. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Five patients with ALS assisted at Clinic of Otolaryngology of AACD (Associação de Assistência à Criança Deficiente. They were all submitted to local application of Botox® in salivary glands and followed up for a year. The protocol consisted of clinical questionnaire about the inability of swallowing saliva and its repercussions in quality of life. Patients were submitted to previous odontological treatment, had intolerance to the adverse effects of anti-cholinergic agents and had not used Botox® for at least six months. The application was guided by ultrasound and the doses were 30U in one point for submandibular gland, and 20U in two points for each parotid gland, after topic anesthetic with prilocaine. RESULTS: Five patients with ALS with sialorrhea, aged 45 to 59 years, were submitted to Botox® salivary glands application. We observed that the symptoms of sialorrhea changed dramatically in four patients. Three patients stayed almost four months without complaints with repercussion in quality of life. No patient presented local or systemic effects with local injection of Botox®.

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

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Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

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 is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium 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 and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

Tratamento médico e fonoaudiológico da disfonia espasmódica: uma revisão bibliográfica Medical treatment and speech therapy for spasmodic dysphonia: a literature review

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Eliana Maria Gradim Fabron

2013-01-01

Full Text Available A disfonia espasmódica (DE é um distúrbio vocal caracterizado por voz tensa-estrangulada, com quebras de sonoridade e que compromete a comunicação do indivíduo. O objetivo deste estudo é apresentar uma revisão bibliográfica dos tratamentos médico e fonoaudiológico proposto para a DE no período entre 2006 e 2010. Os tratamentos descritos foram: injeção de toxina botulínica (TB, miectomia, neurectomia, denervação e reinervação laríngea seletiva adutora, tireoplastia, miotermia tiroaritenóidea com radiofrequência, injeção de lidocaína, homeopatia e tratamento fonoaudiológico (fonoterapia. O uso de injeção de TB mostrou resultados que indicaram a satisfação dos pacientes tratados, embora alguns dos artigos apontassem a necessidade de reaplicação da toxina frequentemente, como desvantagem. Os procedimentos cirúrgicos foram considerados duradouros e indicados para os pacientes que não quiseram se submeter às aplicações de TB. Tais estudos, no entanto, apresentaram contingência de pacientes restrita e os resultados foram baseados, na maioria das investigações, no julgamento dos próprios pacientes sobre a sua qualidade vocal. Os tratamentos, com uso de lidocaína e homeopatia, mostraram resultados positivos em relação à qualidade vocal dos pacientes e foram sugeridos como uma opção, também, para aqueles que não gostariam de ser submetidos ao tratamento cirúrgico ou à aplicação de TB. Os poucos estudos que reportam fonoterapia assinalaram bons resultados quando a mesma foi associada à injeção de TB, mostrando a escassez de informações nesta área. Futuras pesquisas envolvendo a fonoterapia no tratamento da DE são necessárias.Spasmodic dysphonia (SD is a voice disorder characterized by a strained-strangled voice, with sound breaks and has implications in one's communication. The purpose of this study is to present a bibliographic review of the speech therapy and medical treatment suggested for SD

Current endoscopic techniques in the treatment of obesity Técnicas endoscópicas actuales en el tratamiento de la obesidad

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Eduardo Espinet-Coll

2012-02-01

últimos años han surgido y se han ido desarrollando nuevas estrategias y técnicas endoscópicas para el tratamiento de la obesidad. Propósito del estudio: en este artículo revisamos y analizamos el estado actual de estas técnicas y las características básicas diferenciales entre cada una de ellas: balones y prótesis, inyección de sustancias, sistemas de suturas, técnicas malabsortivas y otras actualmente en investigación. Métodos: se evalúa tanto la técnica endoscópica como sus principales indicaciones, resultados, tolerancias, complicaciones y efectos adversos observados, aportando nuestra experiencia personal y en relación con una revisión bibliográfica extensa. Resultados: comparativamente con la técnica más extendida del balón Bioenterics, el Spatz puede ofrecer mayor pérdida de peso pero con peor tolerancia y más complicaciones y el Heliosphere Bag consigue una pérdida parecida de peso pero con mayor dificultad técnica. Otros balones y prótesis (Ullorex, Semiestacionario, Silimed, Endogast requieren todavía mejorías técnicas y mayores estudios. La inyección de toxina botulínica, aunque segura, parece ofrecer una eficacia menor y más transitoria. Los sistemas de sutura (TOGa, gastroplastia vertical endoluminal y POSE parecen eficaces pero son técnicamente más laboriosos. Los procedimientos malabsortivos (Endobarrier, ValenTX son algo laboriosos pero eficaces, especialmente indicados en pacientes que asocien diabetes mellitus del adulto. Conclusiones: el desarrollo de nuevas técnicas endoscópicas y las mejorías en los diseños de las existentes condicionan un papel cada vez más importante del endoscopista en el tratamiento de la obesidad. Consideramos importante seleccionar la técnica endoscópica individualmente, en función de los resultados deseables (eficacia, tolerancia, seguridad, efectos adversos y riesgos y de la experiencia propia de cada centro. Creemos que estas técnicas deben aplicarse por endoscopistas espec

Dor torácica não-cardiogênica Non-cardiac chest pain

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Gerson Ricardo de Souza Domingues

2009-09-01

Full Text Available CONTEXTO: Dor torácica não-cardiogênica ou dor torácica funcional é síndrome clínica com elevada prevalência no mundo ocidental, podendo estar presente entre 15% a 30% dos pacientes com coronariografias normais. Tem importante impacto na qualidade de vida dos pacientes e associa-se com considerável aumento da utilização dos serviços de saúde. FONTES DE INFORMAÇÃO: Para esta revisão, foram utilizadas as seguintes bases de dados: Medline, the Cochrane Library, LILACS e livros nacionais. Das publicações dos últimos 5 anos foram selecionadas fontes relevantes como artigos originais, artigos de revisão, consensos, diretrizes e revisões sistemáticas de literatura com meta-análise. Publicações relevantes anteriores ao período de tempo analisado, foram também incluídas. RESULTADOS: Foram incluídas 44 publicações, sendo 28 artigos originais, 12 trabalhos de revisão, 2 diretrizes, 1 meta-análise e 1 consenso. CONCLUSÕES: A dor torácica não-cardiogênica abrange a investigação do trato digestório, do aparelho musculoesquelético, do aparelho respiratório e de distúrbios psicológicos. O objetivo do tratamento é o alívio ou eliminação do sintoma e deve estar voltado para o principal mecanismo gerador. A base do tratamento é medicamentosa, entretanto, pode ser necessária intervenção de natureza psicológica e, nos pacientes com acalásia a terapia endoscópica ou cirúrgica. Considerando-se que a maioria dos pacientes apresentarão causas relacionadas ao esôfago, sendo as principais, a doença do refluxo gastroesofágico e distúrbios motores, as principais medicações utilizadas no controle da dor torácica não-cardiogênica são os inibidores da bomba de prótons e os antidepressivos tricíclicos. Recentemente, novas modalidades diagnósticas e também formas de tratamento, tais como, a injeção por endoscopia de toxina botulínica no esôfago e a hipnose, estão em investigação e algumas poder

ACCEPTANCE OF GUARIROBA [Syagrus oleracea (Mart. Becc.] PALM HEART IN PRESERVES OF DIFFERENT ORGANIC ACIDS ACEITAÇÃO DO PALMITO DE GUARIROBA [Syagrus oleracea (Mart. Becc.] EM CONSERVAS SOB DIFERENTES ÁCIDOS ORGÂNICOS

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Nilson Gomes Jaime

2007-12-01

Full Text Available

The objective of this study was to evaluate the acceptation of guariroba [Syagrus oleracea (Mart. Becc.] palm heart preserved, acidified with organic the acids acetic, citric monohydrate, dl-lactic 85%, and dl-malic and L(+-tartaric. The 75 preserves of guariroba were processed, packed in glass bottles, immersed in brine acidified with different organic acids, in quantities sufficient to lower the pH of the mixture to about 4.3, projected for balance. The experiment was completely randomized, with five treatments and fifteen repetitions. Six glasses of palm hearts at random were used to determine the stabilizing pH of the preserves. Nine glasses were used to assess the acceptance of preserved guariroba and other physical and chemical analyses. The acceptance was evaluated through a tasting portion of approximately 50 g of the product, based on a hedonic scale of seven levels, applied to 500 not trained volunteers. All treatments have had acceptance exceeding 80% among judgers used to guariroba consumption, and over 65% among non-consumers. The treatment with malic acid (pH 3.50 obtained lower acceptance than those acidified with acetic (pH 4.01, citric (pH 3.67, lactic (pH 3.88, and tartaric acids (pH 3.43, which did not differ significantly among them. In such levels of pH, the costs of acidification with lactic acid, citric acid, and acetic acid were equivalent among them and lower than those processed with malic and tartaric acids.

KEY-WORD: Palmetto; canned heart-of-palm; botulism.

O objetivo deste trabalho foi avaliar a aceitação de palmito de guariroba [Syagrus oleracea (Mart. Becc.] em conserva, acidificada

Crotoxin in humans: analysis of the effects on extraocular and facial muscles Crotoxina em humanos: estudo da ação em músculos extraoculares e faciais

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Geraldo de Barros Ribeiro

2012-12-01

é-sináptico. O objetivo da pesquisa é avaliar a capacidade da crotoxina em induzir paralisia transitória de músculos extraoculares e faciais em seres humanos. MÉTODOS: As doses utilizadas de crotoxina foram de 2 a 5 unidades (U, sendo que cada unidade correspondia a uma DL-50. Na primeira etapa, aplicou-se 2U de crotoxina em músculos extraoculares de 3 indivíduos amauróticos, candidatos à evisceração. Na segunda etapa, realizaram-se 12 aplicações de crotoxina em músculos extraoculares de 9 indivíduos estrábicos e amblíopes. Na terceira e última etapa, utilizou-se a crotoxina para o tratamento do blefaroespasmo essencial em 3 indivíduos. RESULTADOS: Nenhum paciente demonstrou qualquer efeito sistêmico ou alteração da visão ou de qualquer estrutura ocular. O único efeito local adverso foi hiperemia conjuntival, que melhorou espontaneamente. Em 2 pacientes não houve alteração do desvio ocular após a aplicação de 2U de crotoxina. Observou-se em 8 das 12 aplicações, limitação do movimento ocular no campo de ação do músculo aplicado. A diminuição do desvio ocular com 2U crotoxina (9 aplicações foi em média de 15,7 dioptrias prismáticas (DP; na dosagem de 4U (2 aplicações foi em média de 37,5 DP e na única aplicação de 5U, obteve-se redução de 16 DP no desvio ocular. A alteração do alinhamento ocular manteve-se por 1 a 3 meses. Dois dos 3 pacientes portadores de blefaroespasmo apresentaram melhora dos espasmos hemifacias, os quais voltaram após 2 meses. CONCLUSÕES: Através dos resultados observados neste estudo, acreditamos que a crotoxina possa ser útil no tratamento do estrabismo e do blefaroespasmo. Novos estudos precisam ser realizados para confirmar a eficácia e a segurança da crotoxina como opção terapêutica para diversas áreas da medicina que atualmente utilizam a toxina botulínica.