The muscle force determines the energy costs of locomotion and the loading of the musculoskeletal system. As the body size increases, the muscle force increases too. The observed less joint flexion in larger individuals could be a moderating mechanism to reduce muscle force when walking. To date, there is a lack of knowledge about the effect of body size and joint angles on muscle force. The aim of this study was to investigate how body size affects muscle force in the stance phase of walking and whether larger individuals can effectively compensate for the increase in muscle force through postural changes. We acquired kinematic, kinetic and electromyographic data for 19 men during normal walking and carrying additional 20 % of body weight. We estimated muscle force using the method of musculoskeletal modeling. We emploeyd the multiple linear regression to asses independent effect of body mass, lower limb length, biiliac breadth and joint flexion angle on total (iF) and maximum (maxF) lower limb muscle force. The body mass had a great positive effect on the gluteus medius muscle force (maxF and iF) but did not affect the iliopsoas muscle force (maxF and iF) nor the vasti muscles force (iF). The lower limb length had a positive effect on the gluteus maximus muscle force (maxF) and a negative effect...

Introdução: A doença pulmonar obstrutiva crônica (DPOC) apresenta repercussões sistêmicas que contribuem negativamente para a evolução da doença e aumentam a mortalidade nestes indivíduos. O nível de atividade física e a força muscular periférica têm sido evidenciados como fatores de morbi-mortalidade em pacientes com DPOC, entretanto os fenótipos previamente descritos na literatura não incluem estes fatores como determinante dos fenótipos. Objetivo: Identificar fenótipos em indivíduos com DPOC considerando o nível de atividade física, a composição corporal e a disfunção muscular esquelética. Casuísticas e Métodos: Foram avaliados 190 indivíduos em relação à função pulmonar (espirometria), ao controle clínico da DPOC (CCQ), aos fatores de saúde relacionados à qualidade de vida (CRQ), ao nível de atividade física na vida diária (acelerômetro - Actigraph GT3X), à força dos músculos esqueléticos (isometria máxima) e à composição corporal (biompedância). Após 3, 6, 9 e 12 meses destas avaliações, os indivíduos foram questionados quanto à ocorrência de exacerbações e hospitalizações. Para a identificação dos fenótipos foi realizada análise de agrupamento de cluster. As comparações entre os fenótipos identificados foram realizadas por meio do teste de one-way ANOVA seguido do pos teste de Tukey para dados paramétricos e do teste de Kruskal-Wallis seguido do teste de Dunn para dados não paramétricos. A normalidade dos dados foi avaliada por meio do teste de Kolmogorov-Smirnov. Para comparação das variáveis categóricas foi utilizado o teste de qui-quadrado. O nível de significância foi ajustado para 5%. Resultados: Foram identificados 3 fenótipos (clusteres) distintos de acordo com a idade, atividade física, composição corporal, força muscular, qualidade de vida e controle clínico. O fenótipo 1 englobou indivíduos mais jovens, com pior controle clínico e maior número de comorbidades, os indivíduos deste grupo apresentaram maior frequência de exacerbação comparados aos fenótipos 2 e 3. Os indivíduos do fenótipo 3 apresentaram menores valores de atividade física, maior tempo em comportamento sedentário e maior frequência de hospitalização nos indivíduos que exacerbaram. Conclusão: O presente estudo demonstrou a existência de diferentes fenótipos em pacientes com DPOC em relação à atividade física. Estes resultados são relevantes para o manejo clínico de indivíduos com DPOC e para a escolha de estratégias para aumentar o nível de atividade física destes pacientes / Rationale: The chronic obstructive pulmonary disease (COPD) has systemic repercussions that contribute negatively to the evolution of the disease and increase mortality in these individuals. The level of physical activity and peripheral muscle strength have been evidenced as morbidity and mortality factors in individuals with COPD, however the phenotypes previously described in the literature do not include these factors as determinant of the phenotypes. Objective: To identify phenotypes in individuals with COPD according to their levels of physical activity in daily life, body composition and skeletal muscle force. Methods: We evaluated 190 individuals in relation to pulmonary function (spirometry), clinical control of COPD (CCQ), health factors related to quality of life (CRQ), physical activity in daily life (Actigraph GT3X), skeletal muscle force (maximal isometry) and body composition (bioimpedance). After 3, 6, 9 and 12 months of these evaluations, subjects were questioned about the occurrence of exacerbations and hospitalizations. Participants were classified using hierarchical cluster analysis. The comparisons between the identified phenotypes were performed using the ANOVA one-way test followed by Tukey\'s post test for parametric data and the Kruskal-Wallis test followed by the Dunn test for non-parametric data. The normality of the data was evaluated using the Kolmogorov-Smirnov test. The chi-square test was used to compare the categorical variables. The level of significance was adjusted to 5%. Results: Three distinct phenotypes (clusters) were identified according to age, physical activity, body composition, muscle strength, quality of life and clinical control. The individuals in phenotype 1 were younger, with worse clinical control, with more comorbidities and with higher frequency of exacerbation compared to phenotypes 2 and 3. Subjects of phenotype 3 had lower values of physical activity, sedentary status and greater frequency of hospitalization after exacerbations. Conclusions: The present study demonstrated the existence of different phenotypes in patients with COPD according to physical activity. These results are relevant for the clinical management of individuals with COPD and for the choice of strategies to increase the level of physical activity of these patients

The knee joint plays an essential role in the human musculoskeletal system. It has evolved to withstand extreme loading conditions, while providing almost frictionless joint movement. However, its performance may be disrupted by disease, anatomical deformities, soft tissue imbalance or injury. Knee disorders are often puzzling, and accurate diagnosis may be challenging. Current evaluation approach is usually limited to a detailed interview with the patient, careful physical examination and radiographic imaging. The X-ray screening may reveal bone degeneration, but does not carry sufficient information of the soft tissue conditions. More advanced imaging tools such as MRI or CT are available, but expensive, time consuming and can be used only under static conditions. Moreover, due to limited resolution the radiographic techniques cannot reveal early stage arthritis. The arthroscopy is often the only reliable option, however due to its semi-invasive nature, it cannot be considered as a practical diagnostic tool. Therefore, the motivation for this work was to combine three scientific methods to provide a comprehensive, non-invasive evaluation tool bringing insight into the in vivo, dynamic conditions of the knee joint and articular cartilage degeneration. Electromyography and inverse dynamics were employed to independently determine the forces present in several muscles spanning the knee joint. Though both methods have certain limitations, the current work demonstrates how the use of these two methods concurrently enhances the biomechanical analysis of the knee joint conditions, especially the performance of the extensor mechanism. The kinetic analysis was performed for 12 TKA, 4 healthy individuals in advanced age and 4 young subjects. Several differences in the knee biomechanics were found between the three groups, identifying age-related and post-operative decrease in the extensor mechanism efficiency, explaining the increased effort of performing everyday activities experienced by the elderly and TKA subjects. The concept of using accelerometers to assess the cartilage degeneration has been proven based on a group of 23 subjects with non-symptomatic knees and 52 patients suffering from knee arthritis. Very high success (96.2%) of pattern classification obtained in this work clearly demonstrates that vibroarthrography is a promising, non-invasive and low-cost technique offering screening capabilities.

Metabolic bone disease is a frequent complication of Crohn’s disease (CD) with the pathogenesis of reduced bone mass in CD reported to include body weight, disease severity, disease treatments and surgery, physical activity and nutritional status. To date, there have been no studies to examine the prevalence of osteopenia and osteoporosis in an Australian CD population. Similarly, the roles of disease state and treatment, lifestyle factors and the role of body composition in the development of bone loss in CD have not been examined in an Australian CD cohort to date. This thesis has sought, for the first time, to determine the prevalence and severity of bone loss in an Australian CD population and to examine the relationship between various clinical, genetic, lifestyle and treatment variables. The role of body composition in bone loss was assessed by close examination of the muscle-bone relationship by dual-energy X-ray absorptiometry (DXA) and the local muscle-bone unit by peripheral quantitative computed tomography (pQCT) so that informed targeted treatment strategies may be implemented. Study 1 assessed the prevalence of bone loss and both molecular and clinical risk factors for bone loss in a large Crohn’s disease population. Bone mineral density (BMD) data were combined with clinical information and correlated with single nucleotide polymorphisms within the TNF-α, interleukin-10, and NOD2/CARD15 genes. Study 2 examined the independent effects of body composition and muscle strength on regional and whole body BMD in a cohort of CD patients to determine their relative importance to bone strength in this population. Study 3 used pQCT for the first time in a CD population to assess the functional muscle-bone unit in order to determine if the high prevalence of low bone mass reported in CD patients is mediated by altered body composition, in particular muscle mass and strength. Study 1 revealed 45% of CD patients had previously been diagnosed with osteopenia and 18% with osteoporosis. Both the TNF-α “GT” haplotype and the -857 “CC” genotype showed strong associations with bone mineral density overall (p=0.003 and p=0.002, respectively). Body mass index (p=0.01) and previous bowel resection in females (p=0.03) were predictive of a higher spine bone density, whilst body mass index (p=0.003) and the effect of years since first bowel resection (p=0.02) remained independent predictors of proximal femur bone mineral density. When bone mineral density was assessed in Study 2, the prevalence of osteopenia and osteoporosis was 32% and 17%, respectively, with osteopenia more common at the hip and osteoporosis more common at the spine. In multiple regression analyses, appendicular muscle mass was an independent predictor of whole body and regional BMD while lean mass was an independent predictor at the hip. Neither grip strength nor fat mass were independently associated with BMD. Of the components of body composition, muscle mass was strongly associated with regional and whole body bone mineral density. When the muscle-bone unit was assessed using pQCT in Study 3 to further examine this relationship, CD patients demonstrated lower tibial shaft mass, tibial shaft cortical cross-sectional area, and proximal tibia bone mineral density than similarly aged healthy controls. CD subjects also had significantly lower areal bone mineral density by DXA than controls at the total body (P=0.038) and hip (P=0.019). There were no significant differences between groups for any of the muscle-bone indices assessed, such as bone mineral content/muscle cross-sectional area and bone cross sectional area / muscle strength. Together, these studies have demonstrated a high prevalence of metabolic bone disease in an Australian CD population. We were able to identify a novel protective association between a TNF-α haplotype and bone mineral density and also confirmed the importance of body mass index and intestinal resection on bone loss in this population. Furthermore, these studies indicated that lean mass, and more specifically muscle mass, was a significant independent predictor of regional and whole body BMD. Consequently, maintaining or increasing muscle mass in this patient population may have a positive effect on BMD and prevent the development of osteopenia and osteoporosis. Although only modest differences were found between CD patients and controls for areal BMD by DXA and some bone parameters by pQCT, there were no differences in indices of the muscle-bone unit. These results suggest that bone strength is adequate for muscle size and strength in our sample of male CD patients with well-controlled disease, inferring that no specific intervention is required to correct expected deficiencies in this relationship. Instead, an exercise training program introduced to this patient cohort should aim to maintain or increase bone mass through weight-bearing exercises as well as encourage the maintenance or increase in muscle mass.

La drépanocytose est la maladie génétique la plus répandue au monde. Elle est caractérisée par la synthèse d’une hémoglobine anormale S (HbS) et associée à une altération des processus de distribution d’oxygène. Bien que ces anomalies puissent impacter le muscle strié squelettique, ce tissu n’a que très rarement été étudié. L’objectif de ce travail de thèse était de décrire les réponses fonctionnelles et énergétiques du muscle à l’exercice aigu, à l’ischémie – reperfusion et à l’entraînement en endurance dans un modèle de souris drépanocytaires, et d’identifier les mécanismes responsables des échanges de protons entre le muscle et le sang.Des souris drépanocytaires sédentaires et entraînées ont été soumises à des protocoles standardisés de repos – stimulation – récupération et repos – ischémie – reperfusion pendant lesquels la force et le métabolisme énergétique (par spectroscopie de résonance magnétique du phosphore 31) étaient mesurés. Des souris hétérozygotes pour le transporteur de monocarboxylate 1 (MCT1) ont également été soumises au protocole de stimulation. Des analyses in vitro du métabolisme énergétique et des mécanismes de régulation du pH ont également été réalisées.Ce travail a permis de démontrer que les réponses fonctionnelles et énergétiques à l’exercice musculaire et l’ischémie - reperfusion étaient affectées par la présence d’HbS et que l’entraînement en endurance permettait d’améliorer une partie de ces anomalies. Nous avons également observé que MCT1 était responsable de l’entrée des protons dans la cellule au repos, mais peu actif pendant l’exercice. / Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is characterized by the synthesis of an abnormal hemoglobin S (HbS) and associated with impairments in oxygen delivery processes. If these abnormalities could impact skeletal muscle, this tissue has been rarely investigated. The aim of this thesis was to investigate muscular function and energetics in response to acute exercise, ischemia – reperfusion and endurance training in a mouse model of SCD, as well as identify the mechanisms involved in proton exchanges between muscle and blood.Sedentary and trained SCD mice were submitted to protocols of rest – stimulation – recovery and rest – ischemia – reperfusion during which muscular force and energetics (by magnetic resonance spectroscopy of phosphorus 31) were measured. Monocarboxylate transporter 1 (MCT1) haploinsufficient mice were also submitted to the stimulation protocol. Several muscles were sampled and permitted to analyze in vitro enzyme activities, content of proteins involved in pH regulation and some markers of oxidative stress.This thesis demonstrated that muscular function and energetics were impaired in SCD mice in response to both exercise and ischemia – reperfusion and that endurance training could alleviate some of these abnormalities, particularly acting on oxidative processes. We have also observed that MCT1 is involved in proton uptake by myocytes at rest, but its action is less important during exercise.

Introdução: A doença pulmonar obstrutiva crônica (DPOC) apresenta repercussões sistêmicas que contribuem negativamente para a evolução da doença e aumentam a mortalidade nestes indivíduos. O nível de atividade física e a força muscular periférica têm sido evidenciados como fatores de morbi-mortalidade em pacientes com DPOC, entretanto os fenótipos previamente descritos na literatura não incluem estes fatores como determinante dos fenótipos. Objetivo: Identificar fenótipos em indivíduos com DPOC considerando o nível de atividade física, a composição corporal e a disfunção muscular esquelética. Casuísticas e Métodos: Foram avaliados 190 indivíduos em relação à função pulmonar (espirometria), ao controle clínico da DPOC (CCQ), aos fatores de saúde relacionados à qualidade de vida (CRQ), ao nível de atividade física na vida diária (acelerômetro - Actigraph GT3X), à força dos músculos esqueléticos (isometria máxima) e à composição corporal (biompedância). Após 3, 6, 9 e 12 meses destas avaliações, os indivíduos foram questionados quanto à ocorrência de exacerbações e hospitalizações. Para a identificação dos fenótipos foi realizada análise de agrupamento de cluster. As comparações entre os fenótipos identificados foram realizadas por meio do teste de one-way ANOVA seguido do pos teste de Tukey para dados paramétricos e do teste de Kruskal-Wallis seguido do teste de Dunn para dados não paramétricos. A normalidade dos dados foi avaliada por meio do teste de Kolmogorov-Smirnov. Para comparação das variáveis categóricas foi utilizado o teste de qui-quadrado. O nível de significância foi ajustado para 5%. Resultados: Foram identificados 3 fenótipos (clusteres) distintos de acordo com a idade, atividade física, composição corporal, força muscular, qualidade de vida e controle clínico. O fenótipo 1 englobou indivíduos mais jovens, com pior controle clínico e maior número de comorbidades, os indivíduos deste grupo apresentaram maior frequência de exacerbação comparados aos fenótipos 2 e 3. Os indivíduos do fenótipo 3 apresentaram menores valores de atividade física, maior tempo em comportamento sedentário e maior frequência de hospitalização nos indivíduos que exacerbaram. Conclusão: O presente estudo demonstrou a existência de diferentes fenótipos em pacientes com DPOC em relação à atividade física. Estes resultados são relevantes para o manejo clínico de indivíduos com DPOC e para a escolha de estratégias para aumentar o nível de atividade física destes pacientes / Rationale: The chronic obstructive pulmonary disease (COPD) has systemic repercussions that contribute negatively to the evolution of the disease and increase mortality in these individuals. The level of physical activity and peripheral muscle strength have been evidenced as morbidity and mortality factors in individuals with COPD, however the phenotypes previously described in the literature do not include these factors as determinant of the phenotypes. Objective: To identify phenotypes in individuals with COPD according to their levels of physical activity in daily life, body composition and skeletal muscle force. Methods: We evaluated 190 individuals in relation to pulmonary function (spirometry), clinical control of COPD (CCQ), health factors related to quality of life (CRQ), physical activity in daily life (Actigraph GT3X), skeletal muscle force (maximal isometry) and body composition (bioimpedance). After 3, 6, 9 and 12 months of these evaluations, subjects were questioned about the occurrence of exacerbations and hospitalizations. Participants were classified using hierarchical cluster analysis. The comparisons between the identified phenotypes were performed using the ANOVA one-way test followed by Tukey\'s post test for parametric data and the Kruskal-Wallis test followed by the Dunn test for non-parametric data. The normality of the data was evaluated using the Kolmogorov-Smirnov test. The chi-square test was used to compare the categorical variables. The level of significance was adjusted to 5%. Results: Three distinct phenotypes (clusters) were identified according to age, physical activity, body composition, muscle strength, quality of life and clinical control. The individuals in phenotype 1 were younger, with worse clinical control, with more comorbidities and with higher frequency of exacerbation compared to phenotypes 2 and 3. Subjects of phenotype 3 had lower values of physical activity, sedentary status and greater frequency of hospitalization after exacerbations. Conclusions: The present study demonstrated the existence of different phenotypes in patients with COPD according to physical activity. These results are relevant for the clinical management of individuals with COPD and for the choice of strategies to increase the level of physical activity of these patients

L'hémiparésie est une des déficiences fréquemment observée après un accident vasculaire cérébral (AVC). Elle s’accompagne d’une gestion anormale de la co-contraction musculaire et des déficits de production de force qui contribuent de manière significative à réduire la performance de la marche. Une réorganisation des stratégies musculaires est mise en place pour répondre aux contraintes de stabilité et de propulsion du centre de masse au cours de la marche. Cependant, la littérature reporte très peu de données sur les actions musculaires des membres, parétique et non-parétique, au cours de la marche. De plus, les patterns de co-contraction ont été évalués à partir des seules données EMG chez les patients post-AVC. Par ailleurs, les patients post-AVC présentent une fatigabilité plus importante que les individus sains. Alors que plusieurs facteurs sont impliqués dans la fatigue, le rôle de la co-contraction reste mal connu. L’objectif principal de ce travail était de caractériser les altérations des stratégies musculaires des membres inférieurs chez des patients hémiparétiques post-AVC au cours de la marche et lors de la fatigue induite par des contractions maximales volontaires concentriques isocinétiques. Ce travail introduit l'utilisation novatrice d'une modélisation neuromusculo-squelettique assistée par EMG pour estimer les forces musculaires générées autour des articulations du genou et de la cheville au cours de la marche chez des patients post-AVC. De plus, nous avons montré qu’une quantification de la co-contraction à partir des moments musculaires est préférable par rapport à des mesures EMG. Les résultats ont montré que les forces réduites développées par les fléchisseurs plantaires de la cheville et les extenseurs du genou du côté parétique seraient à l’origine des troubles de la marche hémiparétique. Les forces musculaires élevées produites par les quadriceps et les fléchisseurs du genou du côté nonparétique, ainsi que la force élevée générée par les fléchisseurs du genou du côté parétique, par rapport aux sujets sains, pendant la phase d’appui correspondrait à une réorganisation comportementale, permettant d’augmenter la stabilité et d’ajuster la propulsion du centre de masse. Cette réorganisation des patterns de coordination musculaire se manifeste également par des niveaux élevés de co-contraction (basée sur les moments musculaires) observés du côté parétique et non-parétique au cours de la marche. Il s’agit d’une stratégie d'adaptation permettant d’améliorer la stabilité articulaire. Cependant, la cocontraction plus élevée au cours de la marche peut contribuer à l’augmentation du coût énergétique chez les patients et entraîner une fatigue plus rapide. L’étude de la fatigue neuromusculaire chez les patients post-AVC a mis en évidence une fatigabilité moindre par rapport aux sujets sains en présence d’un niveau plus élevé de co-contraction (basée sur les données EMG). Le déclin de l’activité EMG agoniste lors de contractions concentriques répétées, s’est produit parallèlement à un déclin de l’activité EMG antagoniste diminuant la force d’opposition au mouvement et entraînant une moindre diminution du moment net. Ceci semble être un mécanisme potentiel par lequel la production du moment net est préservée chez les patients post-AVC qui sont intrinsèquement plus faibles. Les résultats de ce travail soulignent l’importance de développer des programmes de rééducation centrés sur le renforcement des fléchisseurs plantaires et des extenseurs du genou et sur la sélectivité du contrôle des mouvements tel que l’entraînement en puissance. / Hemiparesis is one of the most frequent deficits after stroke. It is accompanied by an abnormal muscle co-contraction pattern and an altered force production that significantly contribute to reduced gait performance. These alterations lead to a reorganization of muscle coordination patterns to ensure stability and adjust the propulsion of the center of mass during walking. However, less is known about muscle actions in the paretic and non-paretic lower limbs during walking. In addition, co-contraction patterns were evaluated from only EMG data in post-stroke patients. Furthermore, post-stroke patients manifest higher levels of fatigability than healthy individuals. While several factors are involved in fatigue, the role of co-contraction remains poorly understood. The main objective of this thesis was to characterize the alterations of the muscle strategies of the lower limbs in post-stroke hemiparetic patients during walking and during fatigue induced by isokinetic concentric maximal contractions. This thesis introduces the novel use of an EMG-driven modelling approach to measure muscle forces generated around the knee and ankle joints of the paretic and non-paretic lower limbs during gait in post-stroke patients. In addition, we have shown that quantification of co-contraction from muscle moments is preferable compared to EMG measurements. The results showed that the reduced forces exerted by the plantar-flexors and the knee-extensors on the paretic side, gives a possible explanation for hemiparetic gait abnormalities. Increased forces generated by the knee-flexor and knee-extensor muscles on the non-paretic side, as well as increased force generated by the knee flexors on the paretic side, compared to healthy subjects, during the stance phase would be a behavioral reorganization to better support body weight and properly adjust the forward center of mass. This reorganization of muscle coordination patterns is also reflected by the increased levels of co-contraction (based on muscle moments) observed on the paretic and non-paretic side during walking. This seems to be an adaptive, compensatory strategy to ensure postural stability. However, increased co-contraction during walking can contribute to an increased energy cost in patients and lead to a more rapid fatigue development. The study of neuromuscular fatigue in post-stroke patients showed less fatigability compared to healthy subjects, in the presence of a higher level of co-contraction (based on EMG data). Decreasing agonist EMG during repeated concetric contractions, occurred in parallel with decreasing antagonist EMG, reducing the relative opposing force and resulting in a less decline in net torque. This seems to be a potential mechanism by which net torque output is preserved in post-stroke patients who are inherently weaker. The results of these studies underline the importance of developing rehabilitation programs focused on the strengthening of plantar flexors and knee extensors and on the selectivity of movement control, such as power training.

No description available.

La dystrophie musculaire de Duchenne (DMD) touche un garçon sur 3500, contraint à l'usage du fauteuil roulant à l'âge de 10 ans, et entraîne le décès à une vingtaine d'années. Cette maladie demeure incurable, et les pistes thérapeutiques envisagées nécessitent d'être validées en amont, dans les modèles murins, puis au stade pré-clinique, dans les modèles canins.L'un d'eux, le chien GRMD (Golden Retriever Muscular Dystrophy), est le plus largement utilisé, et présente l'intérêt de partager, avec le patient qu'il modélise, de nombreuses similitudes génotypiques et phénotypiques. Les différentes fonctions touchées doivent donc pouvoir faire l'objet de mesures objectives et quantitatives, à l'aide d'outils dédiés. Par ailleurs, une problématique inhérente à l'utilisation de ce modèle est sa grande variabilité sur le plan phénotypique.L'objectif du travail mené ici a été de développer des outils d'évaluation du chien GRMD, afin de mieux connaître et maîtriser cette hétérogénéité clinique.La mesure de force de flexion du tarse a permis de démontrer que la force tétanique maximale pouvait être utilisée comme indice d'évaluation à différents stades de la maladie, sans que le déficit de force musculaire puisse être relié à l'atteinte motrice globale. De plus, la relaxation s'est avérée altérée chez les chiens GRMD, en corrélation avec leur atteinte motrice.La locomotion, évaluée par accélérométrie tri-dimensionnelle, a pu montrer des altérations multiples, mesurées par différentes variables. Certaines variables sont altérées de manière précoce, tandis que d'autres anomalies s'installent durant les premiers mois, traduisant l'aggravation de la fonction locomotrice.La dysfonction respiratoire, évaluée par spirométrie en respiration de Tidal, et cinématique diaphragmatique sur images radioscopiques, a également pu être objectivée par différents indices. Une moindre mobilité diaphragmatique, une rétraction caudale du diaphragme, et un effondrement du débit expiratoire en fin d'expiration, s'installent au cours des premiers mois.Afin de contrôler l'hétérogénéité clinique ainsi mesurée, une recherche de marqueurs prédictifs de l'évolution clinique a été menée. Différents indices histologiques et cliniques ont été évalués sur leur valeur pronostique à un stade précoce. La fréquence des cycles locomoteurs à 2 mois et le défaut de relaxation à 4 mois se sont avérés prédictifs de formes accélérées.Enfin, les différents outils mis en place ont été évalués dans le cadre du suivi d'animaux au cours d'un essai thérapeutique, qui a, de plus, permis de disposer d'une population de référence sous traitement immunosuppresseur. Une amélioration fonctionnelle des animaux traités a pu être démontrée par nombre des indices mesurés.Ces résultats démontrent que les outils développés sont utilisables au cours d'essais pré-cliniques, et permettent, malgré l'hétérogénéité clinique qu'ils mesurent, de démontrer un bénéfice fonctionnel. Plus largement, ces données permettent d'optimiser l'utilisation pré-clinique du modèle GRMD. / Duchenne Muscular Dystrophy (DMD) affects one boy over 3500 at birth. The affected individuals are wheelchair-bound at about 10 years, and death occurs in the early twenties. DMD remains incurable, and therapeutic strategies need to be validated in murine models, and, subsequently, at the preclinical stage, in canine models.Among the existing canine models, the GRMD (Golden Retriever Muscular Dystrophy) dog is the most widely used. The strong genotypic and phenotypic similarities it shares with DMD patients make this model of great interest. The many affected functions must therefore be reliably measured using dedicated tools, providing objective and quantitative evaluation. Moreover, the wide phenotypic heterogeneity peculiar to this model may compromise its use in preclinical studies.The aim of the present work was to develop evaluation tools for the GRMD dog, in order to better know and handle this clinical variability.The measurement of the contraction force generated by tarsal flexion has shown that the maximal tetanic force could be used as an evaluation index, at different stages of the disease. However, no correlation with the global motor impairment could be found. Conversely, the relaxation has shown to be altered in GRMD dogs, and correlated with the motor impairment.The locomotion was evaluated using three-dimensional accelerometry. This method allowed the measurement of several variables, some of which being early impaired, and some others being altered in a more progressive fashion, reflecting the degradation of the locomotor function.The respiratory impairment has been evaluated by diaphragmatic kinematics using radioscopic acquisitions and by Tidal-breathing spirometry. The diaphragm was shown to be less mobile, and to be caudally displaced. The end-expiration flows were decreased. These abnormalities progressed during the first months.In order to better handle the clinical heterogeneity, some markers able to predict the clinical evolution were looked for. The prognostic value of many histological and clinical indexes at an early stage has been evaluated. The stride frequency at the age of 2 months, as well as the relaxation impairment at the age of 4 months succeeded in predicting severe accelerated forms.Finally, the developed tools have been tested in the context of a clinical follow-up during a therapeutic trial. This trial also aimed to provide a reference-group of GRMD dogs treated with immunosuppressive drugs. Several indexes have demonstrated a clinical improvement of the treated animals.These results show that the developed tools are useable during preclinical trials and allow to quantitatively highlight a functional improvement, despite the clinical heterogeneity. More widely, these data will lead to an optimization of the preclinical use of GRMD dogs.

O objetivo deste estudo foi analisar e comparar os efeitos de 12 semanas do treinamento de força (TF) com o treinamento de força com instabilidade (TFI) nos desfechos clínicos, na capacidade de produção de força muscular, nos mecanismos inibitórios espinhais e no volume total de treinamento (VTT) de indivíduos entre os estágios 2 e 3 da doença de Parkinson (DP). Para tanto, 39 indivíduos (testados e treinados no estado \"on\" da medicação) atenderam aos critérios de inclusão e foram randomizados em três grupos: grupo controle nenhum exercício (GC), grupo TF (GTF) e grupo TFI (GTFI). O GTF e o GTFI realizaram 12 semanas de TF orientado à hipertrofia, duas vezes por semana, em dias não consecutivos. Apenas o GTFI adicionou acessórios de instabilidade (e.g., BOSU®) ao TF que progrediram dos menos para os mais instáveis. Antes e após as 12 semanas foram avaliados os seguintes desfechos: a) clínicos - mobilidade (desfecho primário), sintomas motores, comprometimento cognitivo, medo de cair, equilíbrio, desempenho da marcha (distância, cadência e velocidade) em condições de dupla tarefa e qualidade de vida; b) capacidade de produção de força muscular - raiz quadrada média (RMS), mean spike frequency (MSF) e retardo eletromecânico (REM) dos músculos vasto lateral, vasto medial e gastrocnêmio medial; pico de torque, taxa de desenvolvimento de torque (TDT) e tempo de meio relaxamento (TMR) dos músculos extensores do joelho e flexores plantares; uma repetição máxima (1RM) dos membros inferiores e área de secção transversa do músculo quadríceps femoral (ASTQ) e; c) mecanismos inibitórios espinhais - inibições pré-sináptica e recíproca do músculo sóleus. O VTT foi avaliado durante o protocolo experimental para os exercícios agachamento, flexão plantar e leg-press. Do pré ao pós-treinamento, somente o GTFI melhorou todos os desfechos clínicos (P<0,05), os desfechos da capacidade de produção de força muscular (P<0,05) com exceção do TMR dos músculos extensores de joelho (P=0.068) e melhorou os desfechos dos mecanismos inibitórios espinhais (P<0,05). Houve diferenças significantes entre o GTFI e o GC no pós-treinamento para os seguintes desfechos: mobilidade, comprometimento cognitivo, equilíbrio, desempenho na marcha em condições de dupla tarefa (distância, cadência e velocidade), RMS de todos os músculos avaliados, MSF do músculo gastrocnêmio medial, pico de torque e TDT dos flexores plantares, pico de torque dos extensores de joelho, 1RM dos membros inferiores e inibições pré-sináptica e recíproca (P<0,05). Além disso, o GTFI apresentou melhores valores do que o GTF para os seguintes desfechos: desempenho na marcha em condições de dupla tarefa (distância e velocidade), RMS do músculo vasto medial, MSF do músculo gastrocnêmio medial, TDT dos flexores plantares e inibições pré-sináptica e recíproca (P<0,05). O GTFI apresentou um menor VTT comparado ao GTF (P<0,05). Por fim, nenhum efeito adverso foi observado. Em conclusão, somente o TFI melhorou os desfechos clínicos e foi mais efetivo do que o TF em promover adaptações neuromusculares mesmo com um menor VTT. Assim, o TFI é recomendado como uma inovadora intervenção terapêutica para minimizar os declínios na mobilidade e em um amplo espectro de deficiências, sem causar efeitos adversos em indivíduos com DP / The aim of this study was to analyze and to compare the effects of 12 weeks of strength training (ST) with strength training with instability (STI) on clinical outcomes, muscle-force-production capacity, spinal inhibitory mechanisms and the total training volume (TTV) of individuals between stages 2 and 3 of Parkinson\'s disease (PD). For this, 39 individuals (assessed and trained in the clinically defined \"on\" state) met the inclusion criteria and were randomized into three groups: non-exercising control group (CG), ST group (STG) and STI group (STIG). The STG and STIG performed 12 weeks hypertrophy-oriented ST, twice a week, on non-consecutive days. Only STIG added unstable devices (e.g., BOSU®) to ST that progressed from the less to the more unstable devices. Before and after 12 weeks were assessed the following outcomes: a) clinical - mobility (primary outcome), motor symptoms, cognitive impairment, fear of falling, balance, dual-task gait performance (distance, cadence, and, velocity), and quality of life; b) muscle-force-production capacity - root mean square (RMS), mean spike frequency (MSF), and electromechanical delay (EMD) of the vastus lateralis, vastus medialis, and gastrocnemius medialis; peak torque, rate of torque development (RTD) and half-relaxation time (HRT) of the knee-extensors and plantar flexors; one repetition maximum (1-RM) of the lower limbs and quadriceps cross sectional area (QCSA) and; c) spinal inhibitory mechanisms - presynaptic inhibition and reciprocal inhibition of the soleus muscle. The TTV for each lower limb exercise (half-squat, plantar flexion, and leg-press) was determined during the experimental protocol. From pre- to post-training, only the STIG improved all of the clinical outcomes (P <0.05), the muscle-force-production capacity outcomes (P <0.05) with exception of the HRT of the knee-extensors (P = 0.068) and, improved the spinal inhibitory mechanisms outcomes (P <0.05). There were differences between the STIG and the CG for the following outcomes: mobility, cognitive impairment, balance, dual-task gait performance (distance, cadence, and speed), RMS all of the muscles assessed, MSF of the gastrocnemius medialis, peak torque and RTD of the plantar flexor, peak torque of the knee-extensors, 1RM of the lower limbs, presynaptic inhibition, and reciprocal inhibition at post-training (P <0.05). Moreover, the STIG showed better values than the STG for the following outcomes: dual-task gait performance (distance and speed), RMS of the vastus medialis, MSF of the gastrocnemius medialis, RTD of the plantar flexors, presynaptic inhibition, and reciprocal inhibition at post-training (P <0.05). The STIG showed a lower TTV than the STG (P <0.05). Finally, no adverse effects were observed. In conclusion, only the STIG improved all of the clinical outcomes and it was more effective than the STG to promote neuromuscular adaptations even the STIG has had a lower TTV than the STG. Thus, STI is recommended as a novel therapeutic intervention to minimize declines in mobility and in a wide spectrum of impairments without causing adverse effects in individuals with PD