A progressão da distrofia muscular de Duchenne (DMD) resulta no surgimento de múltiplas e variadas sinergias para compensar a fraqueza muscular e para lidar com as demandas de tarefas funcionais, como por exemplo, a marcha. Alguns instrumentos de avaliação funcional para pessoas com DMD permite a análise subjetiva (descrição) e objetiva (escore) sem levar em consideração os movimentos compensatórios. Por esta razão, os médicos e os fisioterapeutas enfrentam dificuldades na avaliação clínica e tomada de decisão. Este estudo teve como objetivo elaborar o domínio marcha da Escala de Avaliação Funcional para DMD / Functional Evaluation Scale (FES-DMD-D4), testar sua confiabilidade intraexaminador e interexaminadores e sua relação com a idade, escala Vignos e tempo de desempenho da marcha. Uma amostra de 120 vídeos da marcha de 30 crianças com DMD foi analisada. Os movimentos detectados foram classificados considerando suas características cinesiológicos e padrões de compensações. FES-DMD-D4 foi criada e submetida à avaliação de 10 especialistas. Após a incorporação das sugestões propostas, a escala foi utilizada no total da amostra para avaliação por três examinadores. Foi calculada a confiabilidade intraexaminador e interexaminadores utilizando ICC. As relações entre o FES-DMD-D4 e a idade, a escala Vignos e o tempo de desempenho foram testadas com teste de correlação de Spearman (p < 0,05). A FES-DMD-D4 foi composta por três fases, e 14 itens. Coeficientes de correlação intraclasse variaram de aceitável (0,79) a excelente (0,98). A pontuação total da FES-DMD-D4 correlacionou-se com a idade e o tempo de desempenho, mas não com a escala Vignos / The progression of Duchenne Muscular Dystrophy (DMD) results in the emergence of multiple and varied synergies to compensate muscle weakness and to deal with the demands of functional tasks, such as gait. Few functional evaluation instruments for people with DMD allows for subjective analysis (description) and objective (score) without taking into account the compensatory movements. For this reason, clinicians and physiotherapists face difficulties in clinical assessment and decision-making. This study aimed to elaborate the gait domain of the Functional Evaluation Scale for DMD, gait domain (FES-DMD-D4) and to test its reliability intraexaminer and interexaminers and its relationship with age, Vignos score and timed motor performance. A sample of 120 gait videos of 30 children with DMD was analyzed. The detected movements were classified, considering the kinesiological characteristics of the compensation movements. FES-DMD-D4 was created and submitted to the review of 10 experts. After the incorporation of the suggestions proposed by the experts, the scale was used to analyse a total sample by 3 examiners. The reliability intraexaminer and interexaminers was calculated using ICC. The relationships between FES-DMD-D4 and age, Vignos score and timed motor performance was tested with Spearman correlation test (p < 0.05). The FES-DMD-D4 was composed of 3 phases, and 14 items. Intraclass correlation coefficients ranged from acceptable (0.79) to excellent (0.98). The scores on FES-DMD-D4 correlated to age and timed motor performance, but not to Vignos score

Exquisite is defined as carefully selected or sought out. I believe myself to be a selected soul placed in a body of circumstance. My work is self-explorative and telling of those circumstances in hopes of evoking empathy. Our bodies function and exist on many different levels. What I understand as normal for most differs vastly from what is normal for me. I aim to offer my perspective on the world, establish understanding, and blur the lines of normalcy.

No description available.

Des études précédentes ont montré qu’une carence en vitamine E prédispose à la myopathie du poulet de chair. L’effet d’un ajout de vitamine E dans la diète commerciale sur la dégénérescence des fibres musculaires de la poitrine et de la cuisse a été étudié chez les poulets de chair. Des poulets mâles ROSS 308 (n = 1100) ont été assignés de façon aléatoire à deux traitements alimentaires (aliment commercial + 25 à 50 mg de vitamine E surajouté par kg vs aliment commercial + 0 mg de vitamine E supplémentaire). Les poulets ont été répartis sur 10 parquets (cinq répétitions par traitement). Le poids corporel et la consommation d’aliment ont été mesurés hebdomadairement. Aux jours j28, j35, j42 et j49, du sang a été prélevé pour mesurer le niveau de vitamine E et l’activité de la créatine kinase (CK). Les muscles Pectoralis superficialis et Adductor magnus ont été prélevés pour des analyses histologiques aux jours j28, j42 et j49; les fibres dégénérées ont été dénombrées sur chaque muscle prélevé. La concentration plasmatique de vitamine E était plus élevée dans le groupe supplémenté (P = 0.001). L’activité de la CK n’était pas différente dans les deux groupes (P = 0.20) mais très élevée, et n’était pas toujours en relation avec les dommages musculaires, à cause de grandes fluctuations de la CK entre les individus du même groupe. Le nombre de fibres endommagées était plus élevé dans le muscle Pectoralis superficialis (poitrine) que dans le muscle Adductor magnus (cuisse) dans les deux groupes; il y avait aussi moins de fibres dégénérées à j28 dans la poitrine des poulets qui ont reçus la diète supplémentée. Ces résultats suggèrent que l’ajout de vitamine E à la diète conventionnelle augmente le niveau de vitamine E dans le plasma et dans les tissus, diminue le nombre de fibres dégénérées dans la poitrine des jeunes poulets sans pour autant modifier la conversion alimentaire. La mesure de l’activité plasmatique de la CK ne saurait suffire à elle seule pour détecter précocement la myopathie nutritionnelle dans les élevages de poulets de chair. / Previous studies have shown that vitamin E deficiency could lead to nutritional myopathy in broiler chickens. Vitamin E was added to a conventional commercial diet to evaluate its effect on breast and thigh muscle fibers degeneration in broiler chickens. Male chickens ROSS 308 (n = 1100) were randomly assigned to two dietary treatments (a commercial diet with 25 to 50 mg of extra vitamin E per kg of commercial diet and a commercial diet without extra vitamin E). Chickens were randomly divided into 10 pens (five replicates per treatment). Body weight and feed intake were monitored weekly. At d28, d35, d42 and d49 blood from chickens were sampled and assayed for level of vitamin E and creatine kinase (CK) activity. Both Pectoralis superficialis and Adductor magnus muscles from chickens were sampled for histological examination at d28, d42 and d49, and degenerated fibers were numbered. Plasma levels of vitamin E were higher in the supplemented group (P = 0.001), whereas activity of CK was high in both groups, but not significantly different (P = 0.20) due to strong fluctuations in CK activities within groups of these fast growing chickens. Pectoralis superficialis muscle had more damaged fibers than adductor’s in both groups. There were less degenerated fibers in pectoral muscle from d28 chickens receiving the supplemented diet. These results suggested that adding vitamin E into conventional diet increases plasma vitamin E and decreases the number of degenerated muscle fibers within pectoral muscle of young chickens. Measuring the CK activity in plasma is not sufficient for early detection of nutritional myopathy in broiler chicken’s farms.

L’objectif central de cette thèse de Doctorat était d’investiguer les dysfonctions mitochondriales qui surviennent précocement au cours de la phase compensée du remodelage ventriculaire pathologique et qui pourraient jouer un rôle causal dans la progression vers l’insuffisance cardiaque. Nos travaux antérieurs, réalisés à l’aide d’un modèle de surcharge volumique chronique induite par une fistule aorto-cavale (ACF) chez le Rat WKHA, ont montré qu’au cours du remodelage ventriculaire, les mitochondries développaient une vulnérabilité à l’ouverture du pore de perméabilité transitionnelle (PTP : un élément clé de la signalisation de la mort cellulaire) [1]. Ceci était observable au stade compensé du remodelage en absence des dysfonctions mitochondriales majeures typiquement observées dans le cœur insuffisant. Ces résultats nous ont amenés à suggérer que la vulnérabilité à l’ouverture du PTP pourrait constituer un mécanisme précoce favorisant la progression de la cardiopathie. Dans l’étude 1 de cette thèse, nous avons tenté de tester cette hypothèse en induisant une ACF chez deux souches de rats affichant de très nettes différences au niveau de la propension à développer l’insuffisance cardiaque : les souches WKHA et Sprague Dawley (SD). Nos études in vitro sur organelles isolées et in situ sur l’organe entier ont permis de confirmer que, dans le cœur ACF, les mitochondries développent une vulnérabilité à l’ouverture du PTP et à l’activation de la voie mitochondriale de la mort cellulaire lorsqu’exposées à des stress pertinents à la pathologie (surcharge calcique, ischémie-reperfusion [I-R]). Cependant, bien que comparativement aux animaux WKHA, les animaux SD démontraient un remodelage ventriculaire plus rapide et prononcé et une progression précoce vers l’insuffisance cardiaque, aucune différence n’était observable entre les deux groupes au niveau des dysfonctions mitochondriales, suggérant quelles ne sont pas à l’origine de la progression plus rapide de la pathologie chez la souche SD, à tout le moins en réponse à la surcharge volumique. Nous avons par la suite déterminé, à l’aide des mêmes approches expérimentales, si cette vulnérabilité mitochondriale était observable dans une cardiopathie d’étiologie différente, plus spécifiquement celle qui est associée à la dystrophie musculaire de Duchenne (DMD), une maladie génétique causée par une mutation de la protéine dystrophine. Nos études menées (études 2-4) sur de jeunes souris mdx (le modèle murin de la DMD) exemptes de tout signe clinique de cardiopathie n’ont révélé aucune différence au niveau des fonctions mitochondriales de base. Cependant, tout comme dans le modèle d’ACF, les mitochondries dans le cœur de souris mdx étaient significativement plus vulnérables à l’ouverture du PTP lorsque soumises à une I-R (étude 2). Par ailleurs, nous avons démontré que l’administration aiguë de sildénafil aux souris mdx induisait une abolition de l’ouverture du PTP et de ses conséquences signalétiques, une diminution marquée du dommage tissulaire et une meilleure récupération fonctionnelle à la suite de l’I-R (étude 3). Nous avons ensuite testé chez la souris mdx l’administration aiguë de SS31, un peptide anti-oxydant ciblé aux mitochondries, cependant aucun effet protecteur n’a été observé, suggérant que le tamponnement des radicaux libres est d’une utilité limitée si les perturbations de l’homéostasie calcique typiques à cette pathologie ne sont pas traitées simultanément (étude 4). Globalement, les travaux effectués au cours de cette thèse démontrent que la vulnérabilité à l’ouverture du PTP constitue une dysfonction précoce et commune qui survient au cours de remodelages ventriculaires pathologiques d’étiologies différentes. Par ailleurs, ces travaux suggèrent des stratégies d’intervention pharmacologiques ciblant ce processus, dont l’efficacité pour la prévention de l’insuffisance cardiaque demande à être établie. / The central objective of this doctoral thesis was to investigate the mitochondrial dysfunction that occurs early during the compensated phase of pathological ventricular remodeling and which may play a causal role in the progression to heart failure. Our previous work using a model of chronic volume overload induced by aorto-caval fistula (ACF) in rats WKHA showed that during the ventricular remodeling, mitochondria developed a vulnerability to permeability transition pore opening (PTP: a key component of cell death signaling) [1]. This was observed at the stage of compensated remodeling in the absence of major mitochondrial dysfunction typically observed in the failing heart. These results led us to suggest that the vulnerability to PTP opening could be a mechanism facilitating the progression of the cardiomyopathy. In our first study of this thesis we have attempted to test this hypothesis by inducing ACF in two strains of rats displaying sharp differences in the propensity to develop heart failure: WKHA strains and Sprague Dawley (SD). Our studies in vitro on isolated organelles and in situ on the whole organ have confirmed that, in the ACF heart, mitochondria develop a vulnerability to PTP opening and activation of mitochondrial cell death when exposed to stresses relevant to the pathology (calcium overload, ischemia-reperfusion [I-R]). However, SD animals compared to WKHA showed a more rapid and pronounced ventricular remodeling and early progression to heart failure, no difference was found between the two groups in terms of mitochondrial dysfunction, suggesting that this is not behind the more rapid progression of the disease in the SD strain, at least in response to volume overload. We subsequently determined, using the same experimental approaches, if this vulnerability was observed in mitochondria of heart disease from other etiology more specifically that associated with Duchenne muscular dystrophy (DMD), a genetic disease caused by a mutation of the protein dystrophin. Our studies (studies 2-4) on young mdx mice (the mouse model of DMD) free of clinical signs of heart disease showed no difference in basal mitochondrial functions. However, as in the model of ACF, the mitochondria of mdx mice heart were significantly more vulnerable to PTP opening when subjected to I-R (study 2). Furthermore, we demonstrated that acute administration of sildenafil to mdx mice abolished the PTP opening and its signaling consequences, markedly reduced of tissue damage and improved functional recovery following I-R (Study 3). We then tested in mdx mice acute administration of SS31, an antioxidant peptide that targets and accumulates in mitochondria. However, no protective effect was observed, suggesting that the buffering of free radicals have a limited utility if the typical perturbations of the calcium homeostasis in this disease are not treated simultaneously (Study 4). Overall, the work done during this thesis show that the vulnerability to PTP opening is a common and early dysfunction that occurs during pathological ventricular remodeling of different etiologies. Moreover, these studies suggest pharmacological intervention strategies targeting this process, whose effectiveness in preventing heart failure needs to be established.

[Truncated abstract] The pro-inflammatory cytokine tumour necrosis factor (TNF) has a critical role in skeletal muscle atrophy. The catabolic effect of TNF is partially due to abrogation of the anabolic insulin-like growth factor 1 (IGF-1) signalling pathway. However, the precise signalling events that lead to the loss of myofibrillar protein following activation of TNF receptor are unknown. The over arching aim of the study is to determine the mechanisms of by which TNF induces atrophy in differentiated muscles cells. To achieve this aim a series of experiments were performed to: 1) investigate the molecular events that lead to TNF mediated myofibre atrophy, 2) determine to what extent c-Jun N-terminal Kinase (JNK) signalling plays a part in TNF induced myotube atrophy, and in TNF-mediated inhibition of IGF-1 induced hypertrophy, and 3) use inhibitors of JNK to block the catabolic effects of TNF. 1) To investigate the molecular events that lead to TNF mediated myofibre atrophy, the experiments were conducted using C2C12 mouse myotube cultures and primary myotube cultures derived from FVB mice, and transgenic mice which over-express Class 2 IGF-1 Ea in skeletal muscles (IGF:C2). The treatment of mature C2C12 and FVB primary myotubes (respectively at 7 and 4 days after fusion medium) with 10 ng/mL of TNF for 3 days resulted in statistically significant myotube atrophy (decreased mean width). The observed TNF-mediated atrophy has not previously been demonstrated in tissue cultured myotubes. In contrast, addition of IGF-1 (20 ng/ml) to 7 day C2C12 myotubes for 3 days resulted in significant hypertrophy. ... The most suitable inhibitor was TAT-TIJIP and was thus used in subsequent studies. Inhibition of JNK activity by TAT-TIJIP was confirmed indirectly by detecting nuclear translocation of c- Jun, which is a downstream target of phosphorylated JNK. Immunohistochemical analyses showed nuclear localisation and phosphorylation of c-Jun in TNF treated myotubes. Nuclear localisation and phosphorylation of c-Jun was not observed in cultures pre-treated with TAT-TIJIP before TNF treatment, nor in the untreated control myotubes. 3) The use of JNK inhibitors to block the catabolic effects of TNF was tested using C2C12 and primary myotube cultures. Pre-treatment of C2C12 and primary FVB myotubes with the JNK inhibitor TAT-TIJIP, 30 min before TNF administration (for 3 days) prevented myotube atrophy. The mean width of myotubes pre-treated with TATTIJIP prior to TNF treatment closely resembled that of the control myotubes. Administration of TNF in combination with TAT-TIJIP for 3 days to C2C12 myotubes prevented myotube atrophy and unexpectedly resulted in hypertrophy when compared to the mean widths of untreated and TAT-TIJIP treated myotubes. This trend was also demonstrated in the FVB primary cultures. These combined results strongly support the role of JNK in TNF-mediated atrophy. Preliminary studies were carried out in vivo using the mdx mouse model of muscular dystrophy, TAT-TIJIP was administered via intraperitoneal injection to the mice for 3 days at a dose of 10 mg/ml, however the results form this study are inconclusive. These novel observations are of considerable interest to the field of muscle wasting because they demonstrate for the first time TNF-mediated myotube atrophy, the role of JNK in situations of TNF induced muscle atrophy, and explore the use of JNK inhibitors to prevent muscle atrophy.

Le collagène XXII (COLXXII) a été décrit, en 2004, comme un marqueur des jonctions tissulaires chez la souris. En particulier, la jonction myotendineuse (JMT) est une matrice extracellulaire spécialisée qui assure une liaison structurale entre le muscle squelettique et le tendon et permet la transmission des forces de contraction au squelette. Mon projet de thèse a visé à caractériser le rôle de COLXXII in vivo; le modèle du poisson zèbre a été choisi. Chez le poisson zèbre, col22a1 code pour COLXXII dont l'expression débute dans tout le somite, puis, se restreint progressivement aux extrémités des fibres musculaires au niveau de la JMT, où est déposée la protéine. Utilisant la technique de morpholino-knockdown, nous avons montré que les morphants développent un phénotype dystrophique et que le COLXXII fait très probablement partie du complexe d'ancrage intégrine α7β1. Cependant, compte tenu de la durée d'efficacité réduite des morpholinos, notre étude était limitée. Utilisant la technologie CRISPR-Cas9, nous avons donc généré deux lignées invalidées pour col22a1. L'analyse ultra-structurale des poissons col22a1-/-, de la jeune larve à l'adulte, montre que les interdigitations du sarcolemme, caractéristiques de la JMT, sont pratiquement absentes chez les mutants (comme chez les morphants), pouvant impacter la transmission des forces et/ou l'attachement du muscle aux myoseptes (tendons). De façon intéressante, pour les deux lignées, la même proportion de larves présente un phénotype très sévère entrainant la mort vers 2 semaines post-fécondation (spf). Les autres larves, elles, survivent et ne montrent pas de phénotype global particulier. En revanche, une forte réduction des interdigitations de la JMT est constatée et dans de rares cas, après challenge des poissons, une rupture musculaire est observée. Une première approche de q- PCR par gène candidat a été réalisée et il semble possible que les différences phénotypiques soient liées à des évènements conjoints d'expressivité variable et de compensation génique. Enfin, utilisant un système original de test de nage à contre-courant par palier, j'ai montré que les poissons col22a1-/- âgés de 6 mois ont une capacité de nage très diminuée et consomment d'avantage d'O2 pendant l'effort comparés aux animaux sauvages. L'efficacité du système musculo-squelettique semble donc moindre en l'absence de collagène XXII. Nos résultats devraient permettre de considérer COL22A1 comme un gène candidat pour les cas de dystrophies musculaires dont la cause génétique est non élucidée / The myotendinous junction (MTJ) is a specialized extracellular matrix which allows the transmission of skeletal muscle forces to bones. My thesis project aimed at characterizing the in vivo role of COLXXII using the zebrafish as a model. The zebrafish col22a1 gene encodes COLXXII whose expression begins in the entire somite, and is then restricted gradually at the MTJ, where the protein is deposited. Morphants (Knockdown) develop a dystrophic phenotype and we have demonstrated that COLXXII is likely a member of the integrin a7ß1 anchoring complex. However, because morpholinos are efficient only few days after injection, our study was limited to early stages of zebrafish development. We thus generated two mutant lines (CRISPR-Cas9) invalidated for col22a1. The typical sarcolemmal interdigitations of the MTJ are almost absent in mutants, from larvae to adult (as in morphants), which could impact the force transmission and/or the muscle attachment to myosepta (tendons). In the two mutant lines, the same proportion of larvae displays a severe phenotype leading to fish death 14 days post-fertilization. On the contrary, other larvae survive without any obvious general phenotype. A first candidate genes approach was realized by qPCR and tends to show that the phenotypic differences may be due to both, variable expressivity and genetic compensation. Finally, I have shown that 6 months col22a1-/- fish show a highly decreased swimming capacity and consume more O2 during effort compared to wild type animals. Thus, we conclude that the musculoskeletal system efficiency seems altered in absence of COLXXII. Our results should allow considering COL22A1 as a candidate gene for muscular dystrophies with unclarified genetic cause.

Les processus de plasticité cérébrale entrainés par la perte visuelle restent un domaine méconnu dans le champ des neurosciences. La vision centrale et périphérique, le meilleur compromis évolutionniste entre une bonne résolution spatiale et un volume d’espace échantillonné maximal, sont traitées par des régions différentes du cerveau. Par conséquent, étudier et comprendre l’impact de la perte visuelle centrale ou périphérique dans ces régions constitue une étape cruciale dans l’étude du cerveau visuel. Afin d’étudier ces processus, nous avons utilisé deux modèles de perte visuelle sélective de la vision centrale (la dystrophie maculaire de Stargardt) et périphérique (la rétinopathie pigmentaire), et nous avons évalué l’impact à terme de ces deux types de désafférentation sur la structure et la connectivité fonctionnelle du cerveau. 1. Plasticité structurelle induite par la perte sélective de la vision centrale ou périphérique. Nous avons étudié l’épaisseur corticale (EpCo) et de l’entropie corticale (EnCo, marquer de complexité synaptique) du lobe occipital, région pour laquelle nous disposons d’une cartographie complète des régions cytoarchitectoniques. Nous avons constaté que la perte de la vision centrale induit un amincissement des régions appartenant au flux dorsal, tandis que la perte de la vision périphérique occasionne un amincissement du cortex visuel primaire (CVP), ainsi que des régions du flux ventral et dorsal. Ces effets étaient inattendus si on se rapporte au modèle canonique qui associe la vision centrale au flux ventral et la vision périphérique au flux dorsal. La normalité de l’EnCo dans ces régions, suggère que la complexité synaptique est préservée dans les réseaux neuronaux résiduels. Nous avons identifié des modifications de l’EnCo seulement en cas de perte de la vison centrale, où l’augmentation de l’EnCo dans des régions impliquées dans la reconnaissance des objets pourrait traduire une réponse adaptative à la perte de la haute résolution spatiale de cette partie du champ visuel. Cette augmentation de la complexité synaptique pourrait compenser une éventuelle perte neuronale et être responsable de la normalité de l’EpCo dans ces régions. 2. Plasticité de la connectivité fonctionnelle des régions du cortex visuel primaire recevant les projections de la partie centrale » et périphérique champ visuel Dans cette étude, nous avons exploré et comparé la connectivité fonctionnelle des régions afférentées et desafférentées du CVP de sujets souffrant de dystrophie maculaire de Stargardt et retinitis pigmentosa, avec les régions afféréntées correspondantes du CVP de sujets avec une vision normale. Cette étude a révélé une réorganisation fonctionnelle distincte du CVP afférenté et désafférenté. Ainsi, le CVP qui reçoit les afférences visuelles résiduelles présente une connectivité fonctionnelle accrue avec des régions voisines, probablement afin de favoriser le traitement de l’information visuelle, tandis que le CVP désafférenté augmente sa connectivité fonctionnelle avec des régions plus éloignées, vraisemblablement pour contribuer aux fonctions supérieures et à des processus de type top-down. L’analyse comparative des données morphologiques et fonctionnelles suggère une correspondance des régions amincies du cortex visuel associatif avec des régions qui montrent une diminution de la connectivité fonctionnelle avec le CVP périphérique, et des régions présentant une augmentation de la complexité synaptique avec des régions qui montrent une connectivité fonctionnelle accrue avec le CVP périphérique. Ces données suggèrent que la désafferentation sensorielle du CVP périphérique est plus propice au développement d’une réorganisation cérébrale. Synoptique : Ces travaux révèlent un aspect inattendu de la plasticité cérébrale induite une perte isolée de la vision centrale ou périphérique. La réorganisation s’avère plus complexe que le laisser présager le modèle canonique actuel, vraisemblablement trop simple. / Cerebral plasticity induced by visual loss represents a poorly understood field of neuroscience, with numerous questions that don’t yet have an answer. Central and peripheral vision, the evolutionary compromise between spatial resolution and the sampled space volume, are processed in distinct areas of the brain. Understanding the impact of vision loss in theses regions, is of utmost interest for the study of visual brain. Herein, in two models of retinal disorders affecting central and peripheral vision (namely Stargardt macular dystrophy and retinitis pigmentosa), we specifically investigated the effects of the central and peripheral visual loss on brain morphology and its functional connectivity. 1. Morphological plastic changes induced by central and peripheral visual loss. We explored the effects of visual loss on cortical thickness (CoTks) and cortical entropy (CoEn, marker of synaptic complexity) in the cytoarchytectonic regions of the occipital lobe. Central visual loss associated thinning in dorsal stream regions, while peripheral visual loss in early visual cortex (EVC) and regions belonging both to dorsal and ventral stream. Theses effects were unpredicted by the canonical view “central vision – ventral stream”, “peripheral vision – dorsal stream”. Normal CoEn in theses areas suggests that synaptic complexity is preserved in the remaining networks. Only central visual field loss presented CoEn alterations, namely an increase in areas involved in object recognition, that likely reflects a synaptic complexity enhancement in response to the loss of the high spatial resolution of central vision. The gain in synaptic complexity could mask neuronal loss due to deafferentation and may account for the CoTks normality. 2. Plastic changes in the functional connectivity of central and peripheral EVC. We explored and compared to normally afferented EVC, the functional connectivity of afferented and deafferented parts of EVC and found that central and peripheral visual loss induce different patterns of reorganization. Residually afferented early visual cortex reinforce local connections presumably to enhance the processing of altered visual input, while deafferented EVC strengthen long-range connections presumably to assist high-order functions. Combined structural and functional data indicate that areas with reduced CoTks superpose with several areas presenting reduced functional connectivity with the peripheral EVC and that areas with increased CoEn superpose with several areas presenting increased functional connectivity with afferented peripheral EVC. These data point that alterations of the sensory input to the peripheral field are more prone to induce plastic changes. Overview : Data in the current work provide an interesting perspective about the plasticity following central or peripheral visual field loss and show that it is more complex than the canonical model would have let to presume.

A progressão da distrofia muscular de Duchenne (DMD) resulta no surgimento de múltiplas e variadas sinergias para compensar a fraqueza muscular e para lidar com as demandas de tarefas funcionais, como por exemplo, a marcha. Alguns instrumentos de avaliação funcional para pessoas com DMD permite a análise subjetiva (descrição) e objetiva (escore) sem levar em consideração os movimentos compensatórios. Por esta razão, os médicos e os fisioterapeutas enfrentam dificuldades na avaliação clínica e tomada de decisão. Este estudo teve como objetivo elaborar o domínio marcha da Escala de Avaliação Funcional para DMD / Functional Evaluation Scale (FES-DMD-D4), testar sua confiabilidade intraexaminador e interexaminadores e sua relação com a idade, escala Vignos e tempo de desempenho da marcha. Uma amostra de 120 vídeos da marcha de 30 crianças com DMD foi analisada. Os movimentos detectados foram classificados considerando suas características cinesiológicos e padrões de compensações. FES-DMD-D4 foi criada e submetida à avaliação de 10 especialistas. Após a incorporação das sugestões propostas, a escala foi utilizada no total da amostra para avaliação por três examinadores. Foi calculada a confiabilidade intraexaminador e interexaminadores utilizando ICC. As relações entre o FES-DMD-D4 e a idade, a escala Vignos e o tempo de desempenho foram testadas com teste de correlação de Spearman (p < 0,05). A FES-DMD-D4 foi composta por três fases, e 14 itens. Coeficientes de correlação intraclasse variaram de aceitável (0,79) a excelente (0,98). A pontuação total da FES-DMD-D4 correlacionou-se com a idade e o tempo de desempenho, mas não com a escala Vignos / The progression of Duchenne Muscular Dystrophy (DMD) results in the emergence of multiple and varied synergies to compensate muscle weakness and to deal with the demands of functional tasks, such as gait. Few functional evaluation instruments for people with DMD allows for subjective analysis (description) and objective (score) without taking into account the compensatory movements. For this reason, clinicians and physiotherapists face difficulties in clinical assessment and decision-making. This study aimed to elaborate the gait domain of the Functional Evaluation Scale for DMD, gait domain (FES-DMD-D4) and to test its reliability intraexaminer and interexaminers and its relationship with age, Vignos score and timed motor performance. A sample of 120 gait videos of 30 children with DMD was analyzed. The detected movements were classified, considering the kinesiological characteristics of the compensation movements. FES-DMD-D4 was created and submitted to the review of 10 experts. After the incorporation of the suggestions proposed by the experts, the scale was used to analyse a total sample by 3 examiners. The reliability intraexaminer and interexaminers was calculated using ICC. The relationships between FES-DMD-D4 and age, Vignos score and timed motor performance was tested with Spearman correlation test (p < 0.05). The FES-DMD-D4 was composed of 3 phases, and 14 items. Intraclass correlation coefficients ranged from acceptable (0.79) to excellent (0.98). The scores on FES-DMD-D4 correlated to age and timed motor performance, but not to Vignos score

Orientadores: Maria Julia Marques, Humberto Santo Neto / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-10T12:44:34Z (GMT). No. of bitstreams: 1 Pertille_Adriana_D.pdf: 3109380 bytes, checksum: b99b5c31b8c138b7d403dd2de4f6629c (MD5) Previous issue date: 2008 / Resumo: A distrofia muscular de Duchenne (DMD) é caracterizada pela falta de distrofina, proteína estrutural do sarcolema que promove a sua estabilização. Em ausência de distrofina, ocorre aumento da permeabilidade ao cálcio e conseqüente mionecrose. Músculos como tibial anterior, sóleo, diafragma e esternomastóide sofrem ciclos de mionecrose e regeneração muscular. Por outro lado, os músculos extra-oculares (EO) não apresentam degeneração, sendo protegidos da falta da distrofina. A atividade das proteínas ligadas ao Ca++ pode ser um dos mecanismos envolvidos para explicar tal proteção. Nossos resultados revelaram aumento significativo do conteúdo da calmodulina (CaM) e quinase da cadeia leve de miosina (MLCK) no músculos EO mdx quando comparado ao controle. A quantidade da calpaína 1 dos músculos EO distróficos foi igual ao controle, confirmando a ausência do processo de degeneração muscular. Também verificamos se alterações no padrão de distribuição dos receptores de acetilcolina (ACh) e dos terminais nervosos, observadas em junções neuromusculares distróficas, são decorrentes da falta da distrofina ou da regeneração da fibra muscular. O padrão de distribuição dos receptores ACh nos músculos retos e oblíquos distróficos, não mostraram alteração quando comparados ao controle. No músculo retrator do bulbo mdx (parcialmente afetado pela distrofia) 56% dos receptores apresentaram padrão de distribuição alterado. Nossos resultados sugerem que a distrofina ou o complexo distrofina-glicoproteínas (CDG), não estão diretamente envolvidos na organização dos receptores nos músculos EO / Abstract: Duchenne muscular dystrophy (DMD) is characterized by the lack of dystrophin, structural protein that provides stability to the sarcolemma. In the absence of dystrophin, causes increased calcium permeability, leading to myonecrosis. Tibialis anterior, soleus, diaphragm and stermomastoid muscles undergoes myonecrosis and regeneration cycles. However, extraocular muscles (EO) do not show degeneration and are spared of the lack of dystrophin. We investigated whether this protection is related to an activated of calcium-binding proteins. Ours results showed significantly increased of calmodulin (CaM) and of the myosin light chain kinase (MLCK) in the mdx EO compared to control muscles. Calpain quantity in the dystrophic EO was equal of the control, confirmed the lack of the degeneration muscular processed. We also investigated whether changes in acetylcholine (Ach) receptor distribution at the neuromuscular junction and the nerve terminal, showed in the dystrophic neuromuscular junction, which could be correlated to the lack of dystrophy or the muscle fiber regeneration. Distribution ACh receptor in the dystrophic rectus and oblique exhibited no changes compared to control. In mdx retractor bulbi (partial affected by the dystrophy) 56% of the receptor exhibited distribution altered. Taken together, the results suggest the dystrophin or the dystrophin-glycoprotein complex does not influence the distribution of acetylcholine receptors at the neuromuscular junction of spared EO / Doutorado / Anatomia / Doutor em Biologia Celular e Estrutural