Excessive muscle tone or stiffness secondary to stroke frequently involves the ankle plantarflexors and has been associated with decreased mobility and reduced function. Although becoming more common in clinical practice, the effectiveness of botulinum toxin A (BTX-A) injected in the ankle plantarflexors on gait biomechanics is not well established. The primary objective of this study was to describe the kinematic and kinetic changes that occur during walking following BTX-A treatment of the hypertonic ankle plantarflexors. As well, the study explored whether there were clinical characteristics uniquely associated with subjects that exhibited biomechanical improvement. The study was a single group, open label trial with repeated measures, including multiple baseline and three post-intervention time points. Seven chronic hemiparetic stroke subjects with ankle hypertonicity were included in the study. Full lower limb bilateral gait analysis provided joint kinematic and kinetic information throughout stance. As well, clinical measures of ankle range of motion and spasticity were assessed pre and post treatment. Data were analyzed using paired samples t-tests and repeated measures ANOVA with Least Significant Difference adjustment for post-hoc analysis as necessary (significance level p≤0.05). Of the kinematic variables, significant improvements in peak dorsiflexion and plantarflexion and the ankle angle at initial contact were found 10 weeks post-injection relative to baseline. No significant kinetic changes were detected, however 2 subjects showed improved positive work at the ankle post-injection and 5 subjects demonstrated increased positive work at the hip post-treatment. Although subjects were classified as “responders” or “non-responders” based on clinical improvement observed 2 weeks post-injection, there was no observable association between those who responded clinically and those who demonstrated improved gait. The major findings suggest that BTX-A injection results in tone reduction and in some cases improves the biomechanical efficiency of gait. In cases where kinetic variables remained unchanged following treatment, perhaps the increased tone was not the limiting factor of reduced function. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2007-08-30 09:41:03.24

Thesis (Ph. D.)--University of Nevada, Reno, 2007. / "May, 2007." Includes bibliographical references. Online version available on the World Wide Web.

Thesis (M.S.)--University of Wisconsin--Madison, 1966. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

This study has brought an overview of botulinum toxin and its influence on the human muscles, especially on spastic muscles. In the practical part is resumed experience with botulinum toxin A therapy in children with cerebral palsy. There were observed two groups. Group A (n=9) was measured before and after therapy. Patients in group B (n=24) filled out a table of the global spasticity scale, which they returned by mail. All the patients improved after the treatment. Powered by TCPDF (www.tcpdf.org)

While the poisonous effects of botulinum neurotoxin (BoNT) have been recognized since antiquity, the overall actions and mechanisms of effects of BoNT have been elucidated primarily over the past several decades. The general utility of BoNT is described in the paper, but the focus is mainly on the approaches towards negating the toxic effects of BoNT, and on the projection of an engineered BoNT molecule serving as a Trojan Horse to deliver a therapeutic load for treatment of a host of medical disorders. The BoNT molecule is configured with a binding domain, a zinc-dependent protease with specificity primarily for vesicular proteins, and a translocation domain for delivery of the metalloprotease into the cytoplasm. The anti-toxin approaches for BoNT include the use of vaccines, antibodies, block of BoNT binding or translocation, inhibition of metalloprotease activity, impeded translocation of the protease/catalytic domain, and inhibition of the downstream Src signaling pathway. Projections of BoNT as a therapeutic include its targeting to non-cholinergic nerves, also targeting to non-neuronal cells for treatment of hypersecretory disorders (e.g., cystic fibrosis), and treatment of hormonal disorders (e.g., acromegaly). Still in the exploratory phase, there is the expectation of major advances in BoNT neuroprotective strategies and burgeoning utility of engineered BoNTs as therapeutics.

No description available.

No description available.

Fish products under vacuum (VAC) and/or modified atmosphere packaging (MAP) conditions can have a significantly extended shelf life. Prevention of toxin production by Clostridium botulinum is essential for processors of VAC and MAP refrigerated fishery products. The objective of this study was to determine if C. botulinum toxin development precedes microbiological spoilage and sensory rejection in fully cooked breaded and battered Alaskan Pollock or raw aquacultured flounder fillets. Aquacultured summer flounder (Paralichthys dentatus) fillets and fully cooked breaded and battered Alaskan pollock (Theragra chalcogramma) were either aerobically packed (Oxygen Transmission Rate (OTR) of 3,000 cc/m2/24h@70°F for flounder and 6,000 cc/m2/24h@70°F for Pollock), vacuum packed or MAP packaged in a 100% CO₂ atmosphere (OTR of 7.3 cc/m2/24h@70°F). Flounder fillets were stored at either 4 or 10°C while pollock portions were stored at 8 and 12°C. Based on the time to spoilage (counts >107 CFU/g), additional samples were inoculated with five strains of nonproteolytic C. botulinum and analyzed qualitatively for botulinum toxin using a mouse bioassay. For flounder at 4°C, toxin formation did not occur after 35 days in aerobically packed fillets. Vacuum packed and 100% CO2 fillets produced toxin before spoilage at days 20 and 25, respectively. In the aerobic packages at 10°C, toxin production occurred after spoilage at day 8, but before spoilage in the vacuum and 100% CO₂ packages at day 9. Sensory evaluation of toxic vacuum and 100% CO₂ packages at 4°C revealed toxin production proceeded spoilage and absolute sensory rejection. However, at 10°C toxin production was evident only after absolute sensory rejection and microbiological spoilage for aerobically packed fillets. Vacuum packages and 100% CO₂ packages were toxic during spoilage but before absolute sensory rejection. Toxin was not present in the aerobically and 100% CO₂ packed pollock samples at 8°C and the 100% CO2 packed samples at 12°C after 35 days. Aerobically packed portions stored at 12°C first produced toxin at day 25; toxicity occurred after absolute sensory rejection and before spoilage. The vacuum packed portions first formed toxin at day 25 for 8 and 12°C storage before spoilage and absolute sensory rejection. / Ph. D.

The purpose of this study was to determine the effects of storage temperature and film oxygen transmission rate (OTR) on toxin development by Clostridium botulinum in refrigerated raw vacuum packaged croaker fillets, and to determine if toxin development precedes microbiological and/or organoleptic spoilage. Raw croaker fillets were vacuum packaged in oxygen-permeable films (OTR of 10,000 cc/m2/24hr or 3,000 cc/m2/24hr) and stored at either 4ºC or 10ºC. Type 83F, 17 Type B, Beluga, Minnesota, and Alaska nonproteolytic strains of C. botulinum were used to inoculate fish prior to vacuum packaging. At both temperatures, microbial spoilage preceded toxin production in fillets vacuum packaged in both film types. At 4ºC microbial spoilage occurred after approximately 7 days for fillets vacuum packaged in the 10,000 cc/m2/24hr OTR film and after 8 days for fillets vacuum packaged in the 3,000 cc/m2/24hr OTR film. However, toxin was not detected until day 8. At 10ºC microbial spoilage occurred after approximately 3 days for fillets vacuum packaged in the 10,000 cc/m2/24hr OTR film, while toxin production occurred on day 5. For fillets vacuum packaged in the 3,000 cc/m2/24hr OTR film microbial spoilage occurred after 4 days. However toxin production did not occur until day 6. In contrast, at both temperatures toxin production preceded or coincided with organoleptic spoilage in fillets vacuum packaged in both film types. At 4ºC organoleptic spoilage occurred after 10 days for fillets packaged in the 10,000 cc/m2/24hr OTR film and after 9 days in the 3,000 cc/m2/24hr OTR film, while toxin production occurred on day 8. At 10ºC organoleptic spoilage occurred after 6 days for fillets packaged in the 10,000 cc/m2/24hr OTR film, and toxin was detected on day 5. For fillets packaged in the 3,000 cc/m2/24hr OTR film and stored at 10ºC, organoleptic spoilage occurred after 6 days, while toxin production occurred on day 6. Although toxin production preceded or coincided with organoleptic spoilage in both film types, this may have been because samples were presented on ice, which could have masked potential odors. This study shows that there are not significant differences between these film types when it comes to microbial and organoleptic spoilage. Therefore lower OTR films, such as 3,000 cc/m2/24hr film, may be used to vacuum package Atlantic croaker. / Master of Science in Life Sciences

Le botulisme est une maladie nerveuse, commune à l’homme et aux animaux, due à l’action de la toxine botulique produite par Clostridium botulinum. Il existe 8 types de toxines dénommées A à H. Les bactéries capables de produire cette toxine se différencient en six groupe sur la base de leurs caractéristiques phénotypiques et biologiques. Les souches de C. botulinum responsables du botulisme humain appartiennent aux groupes I et II selon qu’elles soient protéolytiques ou non. Elles produisent les toxines A, B, E et F, ainsi que le nouveau type H récemment découvert. C. butyricum et C. baratii sont également capables de produire les toxines botuliques de type F et E et appartiennent au groupe V et VI. C. argentinense appartient au groupe IV et est capable de synthétiser la toxine de type G. Elle a été soupçonnée d’être impliquée dans des cas de botulisme infantile en Argentine. Les souches de C. botulinum responsables du botulisme animal appartiennent au groupe III (C. novyi sensu lato) et produisent les toxines C, D et leurs formes mosaïques C/D et D/C. La toxine botulique est le poison le plus puissant connu à ce jour. La dose létale nécessaire pour tuer une personne en bonne santé par intoxication alimentaire est de 70 µg seulement. C’est pourquoi cette toxine a fait l’objet d’études particulièrement approfondies, notamment celles impliquées dans des cas de botulisme humain. Elle peut également être utilisée pour le traitement de certaine pathologie ou la chirurgie esthétique (Botox). Malheureusement, elle peut également être utilisée à mauvais escient, en tant qu’arme de guerre ou à des fins de bioterrorisme. C’est pourquoi l’emploi de la toxine botulique ou de sa bactérie productrice fait l’objet d’une législation particulièrement stricte. Mon projet de doctorat s’est organisé autour de plusieurs projets de recherche visant à développer des méthodes de détection et de typage de du germe et de sa toxine (projets Européens BIOTRACER et AniBioThreat ; projets NRBC-bio ; LNR botulisme aviaire en France). Lors de mes recherches j’ai concentré mon travail sur le développement de méthodes capable de suivre et remonter à la source d’une contamination, qu’elle soit délibérée, accidentelle ou naturelle. Afin d’y parvenir j’ai investigué les gènes des flagellines de C. botulinum groupe I à III, responsables du botulisme humain et animal. L’analyse des gènes flaA et flaB a mis en évidence 5 groupes majeurs et 15 sous-groupes, certain étant spécifiques de régions géographiques. FlaB s’est montré spécifique de C. botulinum type E. Les gènes flagellines fliC, spécifiques à C. botulinum du groupe III, se divisent 5 groupes, avec fliC-I et fliC-IV associés aux types mosaïques C/D et D/C. J’ai étudié la prévalence des souches productrices de toxine de type mosaïques chez les volailles et les bovins. Les résultats montrent que les types C/D et D/C sont majoritaires en Europe. Enfin, j’ai séquencé 17 génomes provenant de souches responsables de botulisme animal en France (14 types C/D et 3 types D/C). Leur analyse montre que ces souches sont très proche génétiquement, entre elles et avec les souches Européennes. Grâce à ces données j’ai mis en évidence un large contenu extra chromosomique dans les souches C/D, qui peut être utilisé pour créer une carte d’identité génétique. D’autre part, l’étude des séquences Crisps à des fins de typage ne s’est pas avérée suffisamment résolutive, du fait de système Crispr-Cas déficient chez les souches C/D. Enfin, un très haut degré de discrimination a été atteint par typage SNP, qui a permis de distinguer jusqu’à l’origine de chaque souche. L’ensemble de ces résultats est développé dans le présent manuscrit / Clostridium botulinum is the etiologic agent of botulism, a deadly paralytic disease that can affects both human and animals. Different bacteria, producing neurotoxins type A to H, are responsible for the disease. They are separated into different groups (I to VI) on the basis of their phenotypical and biological characteristics. Human botulism is mainly due to Groups I and II producing neurotoxins A, B, E and F, with type H recently discovered. Also C. butyricum and C. baratii species (Groups V and VI), producing toxins type F and E respectively, are scarcely reported. C. argentinense Group IV, producing toxin type G, which has been suspected to be associated with infant botulism in Argentina. Animal botulism is mainly due to Group III, which is constituted by C. novyi sensu lato species. They produce toxin types C, D and their mosaic variants. Botulinum neurotoxins are the most powerful toxin known to date with as little as 70 µg enough to kill a person by food poisoning. Therefore, it received a great deal of attention. Botulinum neurotoxins have been deeply studied, especially human related toxins compared to animal. The toxins found to be useful for medical or cosmetic (Botox) treatments, but it was also used as a biological warfare agent, and for bioterrorism. Its extreme potency is equal to its dangerousness. Therefore, governments show concerns of its potential misuse as a bioterrorism weapon; research programs are funded to study and raise awareness about both the toxins and the producing organisms. My PhD work was structured by the different projects I was involved in, which were related to C. botulinum detection and typing, like BIOTRACER and AniBioThreat European projects, the French national CBRN program, or the NRL for avian botulism. The main transversal objective I followed lead me to develop new methods to trace back the origin of C. botulinum contamination, in case of a deliberate, accidental or naturally occurring botulism outbreak. I investigated flagellin genes as potential genetic targets for typing C. botulinum Group I-II and III, responsible for human and animal botulism respectively. Flagellin genes flaA and flaB showed the investigated C. botulinum Group I and II strains to cluster into 5 major groups and up to 15 subgroups, some being specific for certain geographical areas, and flaB being specific to C. botulinum type E. Flagellin fliC gene investigated in C. botulinum Group III showed to cluster into five groups, with fliC-I and fliC-IV associated to type C/D and D/C respectively, being not discriminative enough to differentiate highly genetically related strains. I also studied the prevalence of mosaic toxin genes in C. botulinum Group III in animal botulism, mainly in poultry and bovine. The results brought out the mosaic toxin types C/D and D/C to be predominant in the samples investigated throughout Europe. Finally, I explored the full genome sequences of 14 types C/D and 3 types D/C C. botulinum Group III strains, mainly originating from French avian and bovine botulism outbreaks. Analyses of their genome sequences showed them to be closely related to other European strains from Group III. While studying their genetic content, I was able to point out that the extrachromosomal elements of strains type C/D could be used to generate a genetic ID card. Investigation of Crispr typing method showed to be irrelevant for type C/D, due to a deficient Crispr-Cas mechanism, but deserve more investigation for type D/C. The highest level of discrimination was achieved while using SNP core phylogeny, which allowed distinguishing up to the strain level. Here are the results I’m going to develop in this manuscript