La mitochondrie est de plus en plus reconnue pour sa contribution à la dégénerescence musculaire. Les dysfonctions mitochondriales, en plus de causer une défaillance énergétique, contribuent à la signalisation apoptotique, stimule la production de ROS et peuvent induire une surcharge calcique. Ces caractéristiques sont tous reliées à certains types de myopathies. Cette thèse met en lumières comment certaines dysfonctions mitochondriales peuvent intervenir dans la pathogenèse de diverses myopathies. Nous démontrons que les dysfonctions mitochondriales sont impliqués dans l’atrophie dû à la perte d’innervation. Par contre, la désensabilisation de l’ouverture du pore mitochondrial de transition de perméabilité, via ablation génétique de cyclophiline-D, ne prévient ni la signalisation apoptotique mitochondrial ni l’atrophie. Nous avons aussi observé des dysfonctions mitochondriales dans le muscle atteint de dystrophie musculaire de Duchenne qui furent améliorés suite à une transfection de PGC1-α, laquelle résulta aussi en une amélioration de la pathologie. Finalement, nous démontrons que le recyclage de mitochondrie par les voies de mitophagies et de contrôles de la qualité impliquant Parkin et possiblement d’autres voies de signalisation inconnues sont cruciales au recouvrement cardiaqe lors d’un choc septique. / Mitochondria are increasingly being recognized for their role in contributing in cellular damage. Mitochondrial dysfunctions, in addition to causing energy failure, contribute to apoptotic signaling, stimulate ROS production and calcium overload. These are all features of various types of myopathies. This thesis sheds light on how mitochondrial dyfunctions may contribute to the pathogenesis in certain myopathies that have been found to show mitochondrial abnormalities. Specifically, we found that although mitochondrial dysfunctions are involved in denervation-associated atrophy, desensitizing mitochondrial permeability transition pore opening through genetic ablation of CyclophilinD does not prevent mitochondrial apoptotic signaling nor atrophy in this model of chronic inactivity. We also observed mitochondrial dysfunctions in the Duchenne dystrophic muscle that were improved after PGC1-α transfection, which also resulted in an amelioration of the disease presentation. Finally, we found that mitochondrial recycling, led by Parkin and alternate mitophagy pathways a crucial component of cardiac recovery in sepsis.

No description available.

Sixteen outbreaks of Senna occidentalis (coffee senna) occurring in cattle from the state of Rio Grande do Sul, Brazil, were reviewed. The great majority (75%) of the outbreaks occurred in adult cattle at pasture during the autumn and winter months with 50% occurring in May, evidencing a striking seasonality. Mortality rates varied from 4.2% to 55.2% and cattle died 2 days up to 2 weeks after showing clinical signs that included dry feces (occasionally diarrhea), muscle weakness, reluctance to move, tachypnea, instability of the hind limbs with dragging of the toes, tremors in muscles of the thighs, neck, and head, ear dropping, sternal recumbency, lateral recumbency and death. Myoglobinuria characterized by a dark red or black discolored urine was a consistent finding in cattle affected at pasture but not in those poisoned by ration contaminated with coffee senna beans. Creatine phosphokinase serum activity was markedly elevated. Main gross changes observed in 23 necropsies involved skeletal muscles of the hind limbs. These changes consisted of varying degrees of paleness of muscle groups. Subepicardial and subendocardial hemorrhages were present in the hearts of all affected cattle. Histologically a segmental degenerative myopathy of striated muscles was present in every case and had a multifocal polyphasic or monophasic character. Myocardial (3/23), hepatic (3/13), renal (3/10), and splenic (1/6) microscopic lesions were observed occasionally. Myocardial lesions were mild and consisted of vacuolation of cardiomyocytes or focal fibrosis. Hepatic changes consisted of diffuse hepatocellular vacuolation, cytosegrosomes within hepatocytes, and individual hepatocellular necrosis. Kidneys have vacuolar degeneration of tubular epithelium associated with acidophilic casts (proteinosis) within tubular lumina. In the spleen there was marked necrosis of lymphocytes of the white pulp. No histological changes were found in the brains of 13 affected cattle. The data of this study suggest that coffee senna poisoning is an important cause of death in cattle in southern Brazil. The epidemiological, clinical and pathological features described in the study shoud be useful for diagnosing the condition in the field. / Dezesseis surtos de intoxicação por Senna occidentalis (fedegoso) em bovinos do Rio Grande do sul foram revisados. A grande maioria dos surtos (75%) ocorreu em bovinos adultos em pastoreio durante o outono e inverno com 50% dos surtos ocorrendo em maio, evidenciando uma notável sazonalidade. Os coeficientes de mortalidade variaram de 4,2% a 55,2% e os bovinos morriam dois dias a duas semanas após mostrarem sinais clínicos que incluíam fezes ressecadas (ocasionalmente diarreia), fraqueza muscular, relutância em mover-se, taquipneia, instabilidade dos membros pélvicos com arrastamento das pinças, tremores nos músculos das coxas, pescoço e cabeça; orelhas caídas, decúbito esternal, decúbito lateral e morte. Mioglobinúria, caracterizada por urina vermelho-escura ou preta foi regularmente encontrada em bovinos afetados em pastoreio, mas não naqueles que se intoxicaram ingerindo ração contaminada com as sementes da planta. A atividade sérica da creatina fosfocinase estava acentuadamente elevada. As principais alterações macroscópicas observadas em 23 necropsias envolviam os músculos esqueléticos dos membros pélvicos. Essas alterações consistiam de graus variáveis de palidez em grupos musculares. Hemorragias subepicárdicas e subendocárdicas ocorreram nos corações de todos os bovinos afetados. Histologicamente, miopatia degenerativa dos músculos estriados esteve presente em todos os casos e tinha um caráter multifocal monofásico ou polifásico. Lesões microscópicas no miocárdio (3/23), fígado (3/13), rim (3/10) e baço (1/6) foram ocasionalmente observadas. As lesões miocárdicas eram discretas e consistiam de vacuolização dos cardiomiócitos ou fibrose focal. As lesões hepatocelulares consistiam de vacuolização difusa, formação de citossegrossomos e necrose individual. Nos rins havia degeneração vacuolar do epitélio tubular associada a cilindros eosinofílicos (proteinose) na luz tubular. No baço havia marcada necrose de linfócitos da polpa branca. Nenhuma alteração foi encontrada ao exame histológico do encéfalo de 13 bovinos afetados. Os dados deste estudo sugerem que a intoxicação por fedegoso é uma importante causa de morte em bovinos do sul do Brasil. Os aspectos epidemiológicos, clínicos e patológicos descritos neste estudo deverão ser úteis no diagnóstico a campo desta intoxicação.

Nesse trabalho foi desenvolvida uma plataforma para o condicionamento, digitalização, visualização e gravação de sinais de eletromiografia (EMG). Posteriormente a aquisição, a análise pode ser realizada através de técnicas de processamento de sinais. A plataforma consiste em dois módulos que adquirem sinais de EMG através de eletrodos de superfície, limitam a faixa de frequências de interesse, filtram interferências da rede elétrica e digitalizam os sinais pelo conversor analógico-digital do microcontrolador dos módulos. Deste modo, os dados são enviados para o computador pela interface USB na especificação HID, sendo apresentados em tempo real na forma gráfica e armazenados em arquivo. Como recursos de processamento foram implementadas as operações de módulo do sinal, a determinação do valor eficaz (RMS), a análise de Fourier, filtro digital (IIR) e filtro adaptativo. Foram realizados testes iniciais de avaliação da plataforma com sinais de membros inferiores e superiores para fins de comparação de lateralidade de sinais de EMG. A plataforma aberta destina-se a atividades didáticas e a pesquisa acadêmica, permitindo acrescentar outros métodos de processamento que o pesquisador tenha interesse em avaliar ou outras análises que se façam necessárias. / In this work, a platform to the conditioning, digitizing, visualization and recording of the EMG signals was developed. After the acquisition, the analysis can be done by signal processing techniques. The platform consists of two modules witch acquire electromyography (EMG) signals by surface electrodes, limit the interest frequency band, filter the power grid interference and digitalize the signals by the analogue-to- digital converter of the modules microcontroller. Thereby, the data are sent to the computer by the USB interface by the HID specification, displayed in real-time in graphical form and stored in files. As processing resources was implemented the operations of signal absolute value, the determination of effective value (RMS), Fourier analysis, digital filter (IIR) and the adaptive filter. Platform initial tests were performed with signal of lower and upper limbs with the aim to compare the EMG signal laterality. The open platform is intended to educational activities and academic research, allowing the addition of other processing methods that the researcher want to evaluate or other required analysis.

Nesse trabalho foi desenvolvida uma plataforma para o condicionamento, digitalização, visualização e gravação de sinais de eletromiografia (EMG). Posteriormente a aquisição, a análise pode ser realizada através de técnicas de processamento de sinais. A plataforma consiste em dois módulos que adquirem sinais de EMG através de eletrodos de superfície, limitam a faixa de frequências de interesse, filtram interferências da rede elétrica e digitalizam os sinais pelo conversor analógico-digital do microcontrolador dos módulos. Deste modo, os dados são enviados para o computador pela interface USB na especificação HID, sendo apresentados em tempo real na forma gráfica e armazenados em arquivo. Como recursos de processamento foram implementadas as operações de módulo do sinal, a determinação do valor eficaz (RMS), a análise de Fourier, filtro digital (IIR) e filtro adaptativo. Foram realizados testes iniciais de avaliação da plataforma com sinais de membros inferiores e superiores para fins de comparação de lateralidade de sinais de EMG. A plataforma aberta destina-se a atividades didáticas e a pesquisa acadêmica, permitindo acrescentar outros métodos de processamento que o pesquisador tenha interesse em avaliar ou outras análises que se façam necessárias. / In this work, a platform to the conditioning, digitizing, visualization and recording of the EMG signals was developed. After the acquisition, the analysis can be done by signal processing techniques. The platform consists of two modules witch acquire electromyography (EMG) signals by surface electrodes, limit the interest frequency band, filter the power grid interference and digitalize the signals by the analogue-to- digital converter of the modules microcontroller. Thereby, the data are sent to the computer by the USB interface by the HID specification, displayed in real-time in graphical form and stored in files. As processing resources was implemented the operations of signal absolute value, the determination of effective value (RMS), Fourier analysis, digital filter (IIR) and the adaptive filter. Platform initial tests were performed with signal of lower and upper limbs with the aim to compare the EMG signal laterality. The open platform is intended to educational activities and academic research, allowing the addition of other processing methods that the researcher want to evaluate or other required analysis.

Thesis Across the Line of the World: On Poetics of Being on the Road in the Central and East European Novel of the second half of the Twentieth Century dissert on the phenomen of vagabondism in a given space and time. Analysis of eight texts (Albahari, Bachmannová, Bernhard, Bondy, Chwin, Miłosz, Müllerová, Sebald, Velikić) through the concept of smooth and striated space (Gilles Deleuze, Félix Guattari), and Milan Balaban's exegesis on the Biblical Exodus shows four basic principals of this rather intensive than extensive vagabondism: nothingness, sense for smoothness, melancholy and fragmentarization. Central and East European Novel Vagabondism Smooth and striated space (Gilles Deleuze, Félix Guattari) Exodus (Milan Balabán) Melancholy Nothingness Sense for smoothness Fragmentarization

Les dystrpohies musculaires sont des maladies génétiques rares qui se caractérisent par une dégénérescence musculaire progressive. la Dystrophie Musculaire de Duchenne (DMD) qui est la plus sévère d'entre elles est due à des mutations dans le gène de la dystrophine. Les mécanismes cellulaires impliqués dans le processus de dégénérescence des muscles restent peu compris et aucun traitement efficace n'existe à ce jour. Notre équipe a développé un modèle de la DMD chez le nématode C. elegans qui présente une dégénérescence musculaire progressive. Pendant ma thèse, j'ai caractérisé le processus de dégénérescence musculaire chez ce modèle par microscopie électronique. J'ai également contribué à une étude du rôle des mitochondries dans la dégénérescence musculaire dystrophine-dépendante chez le nématode. Par ailleurs, j'ai étudié l'effet de suppresseurs pharmacologique et génétiques de la dégénérescence musculaire dystrophine-dépendante. Enfin, j'ai pu mettre en évidence que la force exercée par le muscle influence le taux de dégénérescence musculaire. L'ensemble des résultats obtenus au cours de ma thèse, suggèrent que la perte de fonctions de la dystrophine affecte chez le nématode l'intégrité du sarcolemme et des structures d'ancrage des sarcomères et déclenche ainsi une cascade d'événements intracellulaires conduisant in fin à la mort de la cellule musculaire. Ainsi mes travaux dethèse mettent en évidence de nouveau mécanismes cellulaires impliqués dans la dégénérescence musculaire et ouvrent de nouvelles perspectives pour le développement de thérapie visant à cibler les défauts primaires ou secondaires induits par la perte de fonction de la dystrophine / Muscle dystrophies are genetic diseases caraterized by progressive muscle degeneration. Duchenne Muscular Dystrophy (DMD) is the most severe and is due to a mutation in the gene coding the dystrophin protein. The cellular mechanisms implicated in the degenerating process arte not understood yet and there is still no efficient treatment to cure the disease. Our group decvelopped a DMD model in C. elegans that presents progressive muscle degeneration. During my PhD thesis, I characterized the process of muscle degeneration in this model by electron microscopy. I also contribued to an investigation of the role of mitochondira in dystophin-dependant muscle degeneration. I also studied the effect of pharmacological and genetic suppressors of muscle degeneration. Finally, I showed that the force developped by the worm to move influences the level of muscle degeneration. Altogether, the results I obtained during my PhD thesis, suggest that the loss of funciotnof the dystrophin protein affects the integrity of the muscle plasma membrane and the sarcomeres anchoring structures triggering a cascade of intracellular events leading to the muscle cell death in C. elegans. Therefore, my results highlight new cellular mechanisms implicated in the phenomenon of muscle degeneration and open new perspectives for the development of therapies targeting primary and secondary defects induced by the dystrophin loss of function.

Après un bref rappel des facteurs de risque cardiovasculaires et une revue du métabolisme des lipides, de la classification des dyslipidémies et de la pathophysiologie des xanthomes, sera abordée la dysbêtalipoprotéinémie (anciennement la dyslipidémie de type III). Cette dyslipidémie caractérisée par l’accumulation de particules de remnants, généralement secondaire à une apolipoprotéine E anormale, est hautement athérogène, tant au niveau vasculaire périphérique que coronarien. Jusqu’à présent, les plis palmaires orangés, définis comme étant une coloration jaune à orangée (parfois brunâtre) des plis palmaires ainsi que digitaux, ont été considérés pathognomoniques de cette dyslipidémie. Par l’étude d’une population caucasienne adulte du Saguenay –Lac Saint-Jean, nous avons pu démontrer une prévalence de 18,8% des plis palmaires orangés chez les patients atteints d’une dysbêtalipoprotéinémie. Également, cette étude a permis de mettre en lumière l’absence des critères de dysbêtalipoprotéinémie chez 10,7% des sujets présentant ce type de xanthome. Les données suggèrent que l’expression de plis palmaires orangés est associée à la présence d’une accumulation soutenue ou récurrente de remnants. L’accumulation de ces remnants est possible dans un large spectre de maladies lipidiques où il y a interférence dans l’hydrolyse ou la clairance des remnants, dont la dyslipidémie post-prandiale, la chylomicronémie, le déficit partiel en lipoprotéine lipase (LPL) et dans l’hypercholestérolémie familiale (HF) sévère, principalement chez les individus homozygotes. La recherche en clinique des plis palmaires orangés pourrait apporter des éléments complémentaires dans l’évaluation du risque cardiovasculaire en tant que marqueur d’une accumulation de remnants qui, pour leur part, ont été démontrés conférer un risque cardiovasculaire augmenté, tant en prévention primaire que secondaire. / After a brief review of cardiovascular risk factors and lipid metabolism, classification of dyslipidemias, the pathophysiology of xanthomas as well as dysbetalipoproteinemia will be discussed. This dyslipidemia which is characterized by the accumulation of remnants particules, generally secondary to an abnormal apolipoprotein E, is highly atherogenic, both at the peripheral vascular and coronary levels. The striated palmar xanthomas, defined as a yellow to orange (sometimes brownish) coloration of the palmar and digital folds, are considered pathognomonic of this formerly called type III dyslipidemia. By studying an adult Caucasian population from the Saguenay–Lac Saint-Jean region, we were able to demonstrate a prevalence of 18.8% of orange palmar folds in patients with dysbetalipoproteinemia. Also, this study allowed to shed light on the absence of criteria for dysbetalipoproteinemia in 10.7% of subjects with this type of xanthoma. These data suggest that the expression of striated palmar xanthomas is associated with the presence of a sustained or recurrent accumulation of remnants. The accumulation of these remnants is possible in a broad spectrum of lipid disorders where there is interference in the hydrolysis or clearance of the remnants, including postprandial dyslipidemia, chylomicronemia, partial lipoprotein lipase deficiency and familial hypercholesterolemia mainly in homozygotes. Clinical research of striated palmar xanthomas could provide additional information in the evaluation of cardiovascular risk as a marker of an accumulation of remnants which, for their part, have been shown to confer an increased cardiovascular risk, both in primary prevention and secondary.

But: Cette étude a pour but de comparer : a)la morphologie du plancher pelvien (PP), du col vésical et du sphincter urogénital strié (SUS) par IRM et b) la fonction du PP par palpation digitale (PERFECT scheme) chez les femmes âgées continentes ou avec incontinence urinaire à l’effort (IUE) et mixte (IUM). Méthode: Les femmes ont appris à contracter correctement leur PP et la fonction de leur PP a été évaluée. Une séance d’IRM dynamique 3T a suivi. Résultats: 66 femmes ont participé à l’étude. Les groupes étaient similaires en âge, IMC, nombre d’accouchements vaginaux et d’hystérectomie. La validité et la fidélité des différentes mesures anatomiques utilisées ont été confirmées au début de cette étude. Afin de contrôler l’effet potentiel de la taille du bassin sur les autres paramètres, les femmes ont été appariées par la longueur de leur inlet pelvien. Les femmes avec IUM ont un PP plus bas et un support des organes pelviens plus faible, selon leurs ligne M, angle LPC/Ligne H et hauteur de la jonction urétro-vésicale (UV). Les femmes avec IUE ont un PP similaire à celui des continentes, mais présentent plus d’ouverture du col vésical et un angle UV postérieur plus large au repos que les autres groupes. Il n’y a aucune différence de morphologie du SUS entre les groupes. De plus, selon les résultats du PERFECT scheme, les femmes avec IU ont une force du PP plus faible que les continentes. Les femmes avec IUM montrent aussi une faible élévation des muscles du PP à la contraction. Les femmes avec IUE ont, quant à elle, un problème de coordination à la toux. Conclusion: Les déficits causant l’IUE et l’IUM sont différents, mais supportent tous le rationnel des exercices du PP pour le traitement de l’IUE et l’IUM. Ces résultats supportent le besoin de traitements de rééducation spécifiques aux déficits de chacun des types d’IU. / Aims: The study’s aim was to compare: a) pelvic floor muscle (PFM), bladder neck and urethral sphincter morphologies using MRI and b) PFM function using digital palpation (PERFECT scheme) in continent women, women with stress (SUI) and mixed (MUI) urinary incontinence. Method: Women were taught how to perform PFM contractions correctly and their PFM function was assessed, then each woman completed a dynamic 3T MRI session. Results: 66 women participated in the study. Groups were similar for age, BMI, vaginal deliveries and hysterectomies. Validity and reliability of the different anatomical measures used has been confirmed at the beginning of the study. To control for the potential effect of pelvic size on study parameters, women were matched based on pelvic inlet length. MUI women seemed to have lower PFM resting position and pelvic organ support at rest, based on their M-Line, PCL/H-Line angle and urethrovesical (UV) junction height. However, SUI women seemed to have a PFM morphology similar to that of continent women, but presented a greater occurrence of bladder neck funnelling and a larger posterior UV angle. There were no differences in urethral sphincter morphology between the 3 groups. Functionally, as shown by the PERFECT scheme results, both UI groups had poorer PFM strength on MVC then continent women. The MUI group also showed poor PFM elevation on contraction. Conversely, women with SUI had a timing problem on cough. Conclusion: The deficits in women with SUI and MUI appear to be very different. Notwithstanding, they all support the rationale for PFM exercise treatment in older women with SUI and MUI. However, the findings suggest the need for rehabilitation treatments specificity for each UI type.

But: Cette étude a pour but de comparer : a)la morphologie du plancher pelvien (PP), du col vésical et du sphincter urogénital strié (SUS) par IRM et b) la fonction du PP par palpation digitale (PERFECT scheme) chez les femmes âgées continentes ou avec incontinence urinaire à l’effort (IUE) et mixte (IUM). Méthode: Les femmes ont appris à contracter correctement leur PP et la fonction de leur PP a été évaluée. Une séance d’IRM dynamique 3T a suivi. Résultats: 66 femmes ont participé à l’étude. Les groupes étaient similaires en âge, IMC, nombre d’accouchements vaginaux et d’hystérectomie. La validité et la fidélité des différentes mesures anatomiques utilisées ont été confirmées au début de cette étude. Afin de contrôler l’effet potentiel de la taille du bassin sur les autres paramètres, les femmes ont été appariées par la longueur de leur inlet pelvien. Les femmes avec IUM ont un PP plus bas et un support des organes pelviens plus faible, selon leurs ligne M, angle LPC/Ligne H et hauteur de la jonction urétro-vésicale (UV). Les femmes avec IUE ont un PP similaire à celui des continentes, mais présentent plus d’ouverture du col vésical et un angle UV postérieur plus large au repos que les autres groupes. Il n’y a aucune différence de morphologie du SUS entre les groupes. De plus, selon les résultats du PERFECT scheme, les femmes avec IU ont une force du PP plus faible que les continentes. Les femmes avec IUM montrent aussi une faible élévation des muscles du PP à la contraction. Les femmes avec IUE ont, quant à elle, un problème de coordination à la toux. Conclusion: Les déficits causant l’IUE et l’IUM sont différents, mais supportent tous le rationnel des exercices du PP pour le traitement de l’IUE et l’IUM. Ces résultats supportent le besoin de traitements de rééducation spécifiques aux déficits de chacun des types d’IU. / Aims: The study’s aim was to compare: a) pelvic floor muscle (PFM), bladder neck and urethral sphincter morphologies using MRI and b) PFM function using digital palpation (PERFECT scheme) in continent women, women with stress (SUI) and mixed (MUI) urinary incontinence. Method: Women were taught how to perform PFM contractions correctly and their PFM function was assessed, then each woman completed a dynamic 3T MRI session. Results: 66 women participated in the study. Groups were similar for age, BMI, vaginal deliveries and hysterectomies. Validity and reliability of the different anatomical measures used has been confirmed at the beginning of the study. To control for the potential effect of pelvic size on study parameters, women were matched based on pelvic inlet length. MUI women seemed to have lower PFM resting position and pelvic organ support at rest, based on their M-Line, PCL/H-Line angle and urethrovesical (UV) junction height. However, SUI women seemed to have a PFM morphology similar to that of continent women, but presented a greater occurrence of bladder neck funnelling and a larger posterior UV angle. There were no differences in urethral sphincter morphology between the 3 groups. Functionally, as shown by the PERFECT scheme results, both UI groups had poorer PFM strength on MVC then continent women. The MUI group also showed poor PFM elevation on contraction. Conversely, women with SUI had a timing problem on cough. Conclusion: The deficits in women with SUI and MUI appear to be very different. Notwithstanding, they all support the rationale for PFM exercise treatment in older women with SUI and MUI. However, the findings suggest the need for rehabilitation treatments specificity for each UI type.