Ziel der vorliegenden Arbeit war es, einen Beitrag zur Aufklärung der Ätiologie der Graskrankheit mit Hilfe der DGGE, besonders im Hinblick auf in vitro unkultivierbare Bakterien der Darmflora zu leisten. Es sollte ebenfalls geprüft werden, ob die DGGE die Diagnose der Graskrankheit erleichtern kann. Weiterhin sollte der Einfluß von C. botulinum auf die Erkrankung durch den Nachweis von Toxin, Bakterien und Antikörpern untersucht werden. Es standen zur Untersuchung Proben des Colons, Caecums und Kotes von erkrankten Pferden und Kontrolltieren, Kotproben von klinisch gesunden Pferden, die aus denselben Beständen wie die erkrankten Tiere stammen sowie Serum aller drei Gruppen zur Verfügung. Wegen der hohen individuellen Variabilität der Darmflora war kein eindeutiges Merkmal der Graskrankheit im Profil der mikrobiellen Gemeinschaft des Darmes oder Kotes nachweisbar. Allerdings ließ sich anhand der Clusteranalyse ein Abgrenzung der Flora des Caecums und besonders des Colons der erkrankten und gesunden Tiere erkennen. Für eine Diagnose der Graskrankheit am lebenden Tier anhand der Kotflora ist die DGGE jedoch wegen ihrer geringen Aussagekraft und methodischen Probleme nicht geeignet. Der Verdacht, dass C. botulinum an der Ätiologie der Graskrankheit beteiligt ist, konnte durch die Ergebnisse im Tierversuch und ELISA weiter untermauert werden.

Botulinum toxin (BTX) is used in various fields of medicine, including the treatment of hyperhidrosis and cervical dystonia. Botox®, Dysport®, Xeomin® and NeuroBloc® are commercially available BTX products, which are formulated differently and their dosing units are unique. Dosage and concentration of the prepared solution for injection varies considerably among studies comparing the products. Improved guidelines on concentration and dosing when changing from one product to another are warranted. This would ensure the use of the lowest effective doses for good effect, minimal risk of antibody formation and side-effects as well as reduced costs. The aim of the present work was to find the most appropriate BTX concentration for each of the four products to achieve the highest sweat reducing effect and to investigate dose conversion ratios between Botox and Dysport in the treatment of cervical dystonia when the products are diluted to the same concentration, 100 U/ml. Paper I and II clearly confirm that it is crucial to consider the BTX concentration in a treatment regimen, especially when changing between different products. The optimal concentration to reduce sweating varies among the products and was found to be 25 U/ml for Botox and Xeomin, approximately 100 U/ml for Dysport and 50 U/ml for NeuroBloc. However, for NeuroBloc the optimal concentration might be even lower. In Paper III, which is a retrospective study using casebook notes from 75 patients with cervical dystonia, it was found that the most appropriate dose conversion ratio to use when switching from Botox to Dysport was 1:1.7. In Paper IV, Botox and Dysport were prospectively compared in a double-blind, randomized clinical trial in two different dose conversion ratios (1:3 and 1:1.7) when diluted to the same concentration (100 U/ml). No statistically significant difference was seen between Botox (1:3) and Dysport nor between Botox (1:1.7) and Dysport four weeks after treatment. Some of the secondary outcome observations, however, did indicate that the ratio 1:3 resulted in suboptimal efficacy of Botox but this must be further validated in a larger patient material.

Thesis (M.S.)--Brigham Young University. Dept of Physiology and Developmental Biology, 2007. / Includes bibliographical references (p. 41-44).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1966. / Typescript. Vita. Includes bibliographical references.

No description available.

nÃo hà / Background: Botulinum toxin type A (BTX-A), one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release and is a well-known treatment for poststroke spasticity, despite some variations among dose protocols. Spasticity is one of the factors that affect the functional rehabilitation process in stroke. Spasticity arises from the loss of myotatic reflex inhibition, resulting from upper motor neuron lesion. Equinus foot is common in lower limb spasticity after stroke worsening gait pattern and functional independence. The objective of this study is to evaluate the effects of BTX-A different doses on spastic foot in stroke patients in rehabilitation programme and on gait velocity and functional independence of these patients. Methods: This study was a randomized, prospective and double blind trial. Patients were recruited if they had diagnosis of stroke (ischemic or hemorrhagic) with a poststroke period of at least six months and hemiparesis with spastic equinus foot (Ashworth score 3 or 4 in a range from 0 to 5). Twenty-one hemiparetic stroke patients enrolled in a rehabilitation programme were divided into two groups. The first group (n=11) received BTX-A 300UI in spastic foot and the second group (n=10) received BTX-A 100UI. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for passive range of motion for ankle joint, Modified Ashworth Score, time walking 10 meters, clonus score and motor score of Functional Independence Measure (mFIM). Results: Higher dose group had significant improvement in range of motion on week 12 (p=0,021) and in Ashworth score on weeks 8 (p=0,012) and 12 (p < 0,0001) compared with lower dose group. There was slight improvement in clonus score in higher dose group on week 12 without statistical significance. Both groups had improvement in time walking 10 meters and mFIM without significant difference between them in the analyzed sample. There was no significant adverse effect. Conclusions: BTX-A is an important tool in poststroke rehabilitation for spasticity parameters improvement, but there was no significant difference between high and low doses of BTX-A for gait velocity neither for functional independence in the analyzed sample. Future studies with larger number of patients and evaluation of response to BTX-A reapplications are necessary to confirm these findings. / IntroduÃÃo: A toxina botulÃnica tipo A (TbA), uma das mais potentes toxinas biolÃgicas, age atravÃs do bloqueio da transmissÃo neuromuscular via inibiÃÃo da liberaÃÃo de acetilcolina e à um tratamento bem-estabelecido para espasticidade pÃs-AVE, apesar de variaÃÃes entre os protocolos de doses em diferentes centros. Espasticidade à um dos fatores que interferem no processo de reabilitaÃÃo funcional apÃs acidente vascular encefÃlico (AVE). Ela surge por causa da perda da inibiÃÃo do reflexo miotÃtico, resultante de lesÃo do neurÃnio motor superior. O pà equino à comum na espasticidade de membro inferior depois do AVE e sua instalaÃÃo piora o padrÃo de marcha e a independÃncia funcional. O objetivo desse estudo à avaliar os efeitos da TbA em diferentes doses sobre o pà espÃstico de pacientes com sequela de AVE inseridos em programa de reabilitaÃÃo e sobre a velocidade de marcha e independÃncia funcional desses pacientes. Metodologia: Este estudo foi realizado atravÃs de ensaio randomizado, prospectivo e duplo cego. Foram recrutados pacientes com diagnÃstico de AVE (isquÃmico ou hemorrÃgico) com perÃodo pÃs-AVE de pelo menos seis meses e hemiparesia com pà equino espÃstico (escore Ashworth 3 ou 4 em uma escala de 0 a 5). Vinte e um pacientes hemiparÃticos pÃs-AVE inseridos em programa de reabilitaÃÃo foram divididos em dois grupos. O primeiro grupo (n=11) recebeu aplicaÃÃo de 300UI de TbA no pà espÃstico e o segundo grupo (n=10) recebeu 100UI de TbA. Todos os pacientes foram avaliados no tempo zero e 2, 4, 8 e 12 semanas apÃs a injeÃÃo quanto aos seguintes parÃmetros: amplitude de movimento passivo da articulaÃÃo do tornozelo, escala de Ashworth modificada, tempo para andar 10 metros, escore clÃnus de aquileu e escore motor da Medida de IndependÃncia Funcional (MIFm). Resultados: O grupo 300UI TbA teve melhora significativa da amplitude de movimento na 12 semana (p=0,021) e da escala de Ashworth nas 8 (p=0,012) e 12 (p < 0,0001) semanas em comparaÃÃo ao grupo 100UI TbA. Houve tendÃncia à melhora do escore clÃnus na 12 semana no grupo 300UI TbA. Ambos os grupos apresentaram melhora durante o estudo no tempo para andar 10 metros e da MIFm sem diferenÃa significativa entre eles. NÃo foram observados efeitos adversos significativos no decorrer do estudo. ConclusÃes: TbA à uma importante ferramenta na reabilitaÃÃo pÃs-AVE para melhora dos parÃmetros de espasticidade, mas nÃo houve diferenÃa significativa entre dose alta e baixa de TbA para parÃmetros funcionais (velocidade de marcha e independÃncia funcional), na amostra analisada. Estudos futuros com um nÃmero maior de pacientes e avaliaÃÃo de resposta a reaplicaÃÃes de TbA sÃo necessÃrios para confirmaÃÃo desses achados.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Estuda atravÃs de ensaio duplo cego, controlado, randomizado o efeito da Toxina BotulÃnica do tipo A na profilaxia de crises de migrÃnea sem aura. A migrÃnea à um tipo comum de cefalÃia primÃria, benigna, episÃdica, e recorrente que se caracteriza por dor geralmente hemicrÃnica e pulsÃtil, e que à agravada pela atividade fÃsica. Existem outros sintomas associados como nÃuseas, fotofobia, fonofobia, ou irritabilidade. Na migrÃnea com aura podem tambÃm ocorrer alteraÃÃes neurolÃgicas motoras, sensitivas, ou visuais denominadas de aura. A migrÃnea, cuja fisiopatologia ainda nÃo à perfeitamente compreendida, seria o resultado de um processo patolÃgico complexo que envolveria o tronco cerebral e levaria à inflamaÃÃo local de vasos sangÃÃneos cranianos atravÃs da liberaÃÃo de neuropeptÃdeos vasoativos como SubstÃncia P (SP), Neurocinina A (NA), e PeptÃdio Relacionado ao Gene da Calcitonina (PRGC). Apesar das vÃrias opÃÃes terapÃuticas (analgÃsicos simples, antiinflamatÃrios hormonais e nÃo hormonais, triptanos, antipsicÃticos, derivados ergotamÃnicos, e opiÃides) para tratamento da crise ou para tratamento preventivo, somente cerca de um terÃo dos pacientes fica satisfeito com o tratamento. Foi observado que pacientes utilizando toxina botulÃnica para tratamento estÃtico de rugas da face ou distonias apresentavam uma reduÃÃo na quantidade de crises de migrÃnea. A toxina botulÃnica à uma potente neurotoxina produzida pela bactÃria Clostridium botulinum. A aÃÃo da toxina à impedir a liberaÃÃo de acetilcolina nos terminais nervosos. Ela tambÃm age inibindo a liberaÃÃo de neuropeptÃdeos vasoativos. O uso da toxina botulÃnica nos faria agir exatamente no cerne do processo fisiopatolÃgico da doenÃa. Com o objetivo de testar esse possÃvel efeito analgÃsico nos pacientes portadores de migrÃnea sem aura, realizou-se um estudo duplo-cego, controlado, e randomizado. Mediu-se o nÃvel de dor atravÃs de escalas para quantificar a intensidade e o nÃmero de dias com dor na semana antes e apÃs a injeÃÃo de Toxina BotulÃnica em mÃsculos da face. O grupo controle recebeu SF como placebo. Os pacientes foram seguidos durante trÃs meses. Ao final concluiu-se que nÃo houve diferenÃa estatÃstica na intensidade nem na freqÃÃncia da dor de cabeÃa nos pacientes que usaram a toxina botulÃnica em relaÃÃo aos que usaram placebo (SF) / A randomized, double-blind, placebo-controlled study of the use of botulinum toxin type A in the prophylactic treatment of Migraine is presented. Migraine is a common type of primary, benign, episodic headache. It is characterized by pain usually unilateral and throbbing. Other associated symptoms are nausea, sensitivity to light and sound, or irritability. The pain is usually worsened by physical activity. There are also motor, sensitive, or visual neurological alterations, denominated aura. The physiopathology of migraine is not still perfectly understood but it could involve liberation of vasoactive neuropeptides as Substance P, Neurokinine A, and Calcitonin gene-related peptide, promoting an inflammation. Migraine, then, would be the result of a complex process that would involve the brainstem and induce local inflammation of cranial blood vessels. In spite of the therapeutic options (analgesics, steroidal and non-steroidal anti-inflammatory, triptans, neuroleptics, ergot derivatives, and opioids) only about one third of patients is satisfied with the treatment. The preventive treatment is appropriate for those that have frequent crises. It was observed that the patients using botulinum toxin for aesthetic treatment of wrinkles of the face, or dystonia presented a reduction in the amount of migraine crises. The botulinum toxin is a potent neurotoxin produced by the bacterium Clostridium botulinum. The action of the toxin is to inhibit the acetylcholin liberation from the nerve terminal. It acts also inhibiting the liberation of vasoactive neuropeptides. Therefore, Botulinum Toxin would act exactly in the core of the physiopathologic process of the disease. With the objective of testing possible analgesic effects of botulinum toxin in migraine without aura bearers, we performed a double-blind, controlled, and randomized study. The pain level was measured by scales and by the amount, and number of days of pain in a week, before and after botulinum toxinâs injection in muscles of the face. The placebo group received saline injection. The patients were followed for three months. At the end it was concluded that there was not statistic difference in intensity nor in frequency of the headache of the patients that used botulinum toxin in relation to the people that used placebo (saline)

The neuroparalytic syndrome called botulism is caused by the neurotoxins produced by bacteria in the genus Clostridium. There are seven toxigenic types of C. botulinum (A to G) based on antigenically distinct toxins produced by different strains of the organism. Animal botulism is caused by C. botulinum type C and D neurotoxins and has a severe economic impact on cattle farming in South Africa and neighbouring countries. Current treatment regimes include the use of acetylcholine for symptomatic treatment, but this is unfortunately very seldom successful. All indications are that there is no cure for this disease and that effective control can only be achieved through development of efficacious vaccines. The botulinum vaccine currently in use in South Africa contains an adjuvanted toxoid form of the type C and o neurotoxins. However, this bivalent vaccine relies on problematic anaerobic cultivation of the Clostridium bacterium followed by isolation, purification and inactivation of the toxin by treatment with formalin. Apart from the fastidious growth requirements of this organism, it has been reported that the production of toxin by these cells declines rapidly and eventually ceases, following laboratory passaging of the bacterial cultures. In addition, improper inactivation of the toxins may also lead to the demise of animals following vaccination. Thus, there exists a great need for a safe, effective and inexpensive vaccine against botulism. To investigate the potential of types C and D botulinum neurotoxins as efficacious recombinant vaccine candidates against botulism, full-length copies of the genes were obtained by polymerase chain reaction (PCR) amplification from bacteriophage DNA isolated from Clostridium botulinum type C (Stockholm) and D (South Africa) cultures. The full-length genes were cloned and subsequently sequenced to verify their integrity. By making use of PCR-based site-directed mutagenesis procedures, three amino acid mutations were introduced in the zinc-binding motif of the respective neurotoxins. Mutation of this domain has previously been reported to successfully detoxify type C neurotoxin. The wild-type and mutant genes were subsequently expressed in insect cells using the BAC-to-BAC™ baculovirus system. Although, unique protein bands corresponding to the size of the neurotoxins could not be seen in Coomassie brilliant blue-stained gels, Western blot analysis indicated immunoreactive material for wild-type and mutant type C corresponding to the size of the type C toxin light chain. However, there was no conclusive evidence to support the successful expression of the full-length wild-type and mutant type D genes. / Dissertation (MSc (Microbiology))--University of Pretoria, 2006. / Microbiology and Plant Pathology / unrestricted

Orientador: José Paulo Cabral de Vasconcellos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T03:59:37Z (GMT). No. of bitstreams: 1 Teixeira_MyrianKatiaIser_M.pdf: 2342582 bytes, checksum: 2e51b6261b602fa9f018d1bd96ed680a (MD5) Previous issue date: 2015 / Resumo: Objetivo: Avaliar o efeito e a segurança da toxina botulínica tipo A quando aplicada na região do músculo elevador da pálpebra superior, para a indução de ptose palpebral protetora em gatos domésticos. Métodos: Neste estudo do tipo longitudinal, série de casos com intervenção, um total de 10 gatos foram submetidos à quimiodenervação do músculo elevador da pálpebra superior esquerdo, através da aplicação transpalpebral de 10 unidades de toxina botulínica do tipo A. Alterações sistêmicas, mobilidade ocular, função visual, pressão intraocular, o aparecimento, grau e duração da ptose foram avaliados antes da aplicação, diariamente, durante os sete primeiros dias e, posteriormente, nos dias 14, 21 e 28 após a aplicação. A mensuração da fenda palpebral foi realizada também no olho contralateral que funcionou como controle. Resultados: O início do efeito clínico foi observado entre os dias 1 e 4 após a aplicação; a ptose máxima foi observada entre o quinto e o sétimo dia e a duração média de ação da toxina foi de 21 dias. O tempo máximo para recuperação da ptose foi de 28 dias. A porcentagem média de redução da fenda palpebral foi de 39,66% (16,55% ¿ 59,64%). A análise qualitativa demonstrou que duas gatas (20%) apresentaram cobertura corneal maior que 50%, sete gatas (70%) obtiveram cobertura corneal entre 25 e 49% e uma gata (10%) mostrou cobertura corneal menor que 25%. Os valores da pressão intraocular permaneceram dentro dos limites de normalidade. A toxina botulínica não causou efeitos adversos nos gatos desse estudo. Conclusão: O uso de toxina botulínica tipo A no músculo elevador da pálpebra superior foi seguro e promoveu ptose palpebral temporária parcial nos gatos desse experimento / Abstract: Purpose: To evaluate the effect and safety and of botulinum toxin A for the induction of palpebral ptosis in felines. Methods: In this prospective interventional study, a total of 10 cats underwent transpalpebral chemodenervation of levator palpebral superioris with 10 units of botulinum toxin type A in the left eye. The systemic changes, ocular mobility, visual function, intraocular pressure, and the onset, degree and duration of ptosis were evaluated before application, on a daily basis during the first seven days and on days 14, 21 and 28 after application.The palpebral edge of the contralateral eye was also measured. Results: A clinical effect was observed beginning between the first and fourth days after botulinum toxin A administration. The extent of ptosis was maximal between the fifth and seventh days after administration, and ptosis was observed for a mean duration of 21 days. The maximum time for recovery of ptosis was 28 days. The palpebral edge was reduced by an average of 39.6% (16.55% - 59.64%). Qualitative analysis showed that two cats (20%) had greater than 50% coverage corneal, seven cats (70%) achieved corneal coverage between 25 and 49% and one cat (10%) showed corneal coverage less than 25%. Intraocular pressure values were within normal limits. Botulinum toxin did not cause undesirable effects. Conclusions: The use of botulinum toxin A in the levator palpebrae superioris muscle was safe and provided transient, partial palpebral ptosis in all of the studied cats / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas

Post-thoracotomy pain syndrome (PTPS) is a traumatic neuropathy that can affect as many as 50% of patients undergoing thoracotomy. Patients are often refractory to conservative management and may require multiple analgesics for adequate pain control. Botulinum toxin, derived from Clostridium botulinum, has many uses in treating conditions involving spasticity, dystonia, chronic migraine, and a variety of pain disorders including neuropathies. Botulinum toxin type A injections may provide an alternative or adjunct to improve symptom management in patients with PTPS.