Dissertations / Theses on the topic 'Muscular'

Embora as causas de DTM tenham sido muito estudadas e discutidas na literatura atual, a associação entre a dor muscular e sua temperatura não está totalmente clara. Para esta investigação, 40 pacientes com dor muscular foram encaminhados da clínica odontológica e foram examinados. Um total de 31 pacientes foram diagnosticados com dor miofascial no musculo masseter pelo RDC e foram incluídos neste estudo. O musculo masseter no lado com dor foi anestesiado e foi comparado ao lado oposto ao longo do tempo. Na análise estatística de comparação, foi encontrada associação entre o aumento de temperatura e a diminuição da dor relatada. Possíveis fatores de confusão, como tempo da dor crônica, idade, índice de massa corpórea, pontos de incapacidade, ICD, pior dor sentida nos últimos meses e dor media nos últimos meses foram levados em consideração e foram estatisticamente analisados e o único fator que mostrou estatisticamente correlação com a diminuição da dor foi o fator tempo. Conclusão: existe uma correlação negativa entre o aumento de temperatura e a diminuição da dor.
Although, TMD causes have been widely studied in the last years, the association between muscle pain and temperature remains unclear. For this investigation, 40 muscle pain patients were referred from dental clinic and were examined. A total of 31 patients were diagnosed with masseter myofascial pain by RDC criteria and were included in this study. Masseter muscle was blocked in the pain side and was compared among the time to opposite side. In the matching statistics association analysis, it was found association between temperature increase and related pain decrease. Possible confounders (time of chronic pain, age, Body Mass Index, ICD, incapacity points, worst pain in the last six months, average pain in last six month) were took in consideration and only time since the pain started seems to be related to decrease in pain. Conclusion: there is a negative association between muscle pain and muscle temperature.

Orientador: Alberto Chiquet Junior
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
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Resumo: As pesquisas na área de reabilitação ( Departamento de Engenharia Biomédica -F.E.E. ) têm focalizado o desenvolvimento de sistemas, via estimulação elétrica neuromuscular ( E.E.N.M.), para viabilizar a locomoção de pacientes portadores de lesão medular. Uma limitação da E.E.N.M. é a fadiga muscular, que é manifestada quando um músculo diminui a força esperada ou requisitada durante a marcha. O propósito deste estudo foi examinar a possibilidade de estimular os sistemas de controle do músculo do quadríceps femoral através da E.E.N.M., em pacientes com lesão medular, a fim de aumentar a resistência à fadiga muscular. Foram investigadas, através do programa experimental, duas técnicas: E.E.N.M. com um canal de estimulação ( programa inicial) e E.E.N.M. multicanal sequencial (programa alternativo). Os parâmetros de estimulação aplicados foram: frequência de 25Hz com uma largura de pulso de 300us. e ciclo de trabalho de 33%. O efeito dos programas experimentais foram determinados pelos registros periódicos dos tempos das sessões ( ambos os programas) e número de contrações das sessões (programa inicial)... Observação: O resumo, na íntegra, poderá ser visulaizado no texto completo da tese digital
Abstract: Research in the area of rehabilitation (Biomedical Engineering Department - F.E.E.) has focused on the development of systems by neuromuscular electrical stimulation (N.M.E.S.), to allow it possible the locomotion of spinal cord patients. A limitation of N.M.E.S. is muscle fatigue which shows up when a muscle reduces the expected or required strength during gait. The goal of this study was to examine the possibility of stimulating the quadriceps muscle control systems by N.M.E.S. in patients with spinal cord injury with the purpose of increasing resistance to muscle fatigue. We investigated two techniques in the experimental programme : N.M.E.S. with one stimulation channel ( initial programme ) and N.M.E.S. with sequential multichannel ( altemative programme ). Stimulation parameters used : frequency of 25 Hz with a pulse duration of 300us. and duty cycle of 33%. The effect of the experimental programmes were detennined by the periodic recording of time sessions ( both programmes ) and contraction numbers of sessions ( initial programme)... Note: The complete abstract is available with the full electronic digital thesis or dissertations
Mestrado
Mestre em Engenharia Elétrica

As distrofias musculares são doenças genéticas causadas por mutações em diferentes genes caracterizadas por degeneração muscular, prejuízos locomotores e, geralmente, morte precoce. Dentre elas, a de Duchenne, causada por mutações no gene que codifica para a proteína distrofina, é a mais comum e grave, tendo os camundongos MDX como modelo experimental mais utilizado. O objetivo do presente estudo foi testar quatro abordagens terapêuticas potencias neste modelo animal, divididas em dois experimentos: 1. treinamento físico voluntário em roda de atividade e/ou drogas agonistas das proteínas AMPK e PPAR em dias alternados (AICAR: 100 mg.Kg-1.dia-1, ip; GW 1516: 5 mg.Kg-1.dia-1, gavagem); 2. células-tronco estromais humanas provenientes de lipoaspiração (um milhão a cada injeção intravenosa; uma injeção a cada 10 dias nos dois primeiros meses de tratamento e injeções mensais nos quatro meses subsequentes) e/ou suplementação com os aminoácidos alanina e glutamina (10 mg.kg-1.dia-1, injeção diária intraperitoneal). Em relação ao primeiro experimento, o principal achado foi que os animais submetidos ao treinamento físico associado às drogas apresentaram índices de função muscular superiores aos outros grupos. Já em relação ao segundo grupo de análises, foi observado que os animais submetidos à terapia celular apresentaram tempo de vida significativamente maior quando comparados aos animais não tratados e aos tratados com ambas as terapias. Tais resultados, nunca demonstrados previamente pela literatura científica, podem contribuir para o entendimento da fisiopatologia das distrofias musculares e para o avanço de potenciais abordagens terapêuticas.
Muscular dystrophies are genetic diseases caused by mutations in different genes. They are characterized by muscle degeneration, motor prejudices and, generally, early death. Among them, Duchenne muscular dystrophy (DMD) is the most common and severe form and it is caused by mutations in the dystrophin gene. The most widely used animal model of DMD is the MDX mouse. The aim of this study was to test four potential therapeutic approaches assigned in two experiments: 1. voluntary exercise training in activity road and/or AMPK and PPAR agonists drugs every other day in MDX mice (AICAR: 100 mg.Kg-1.day-1, IP; GW 1516: 5 mg.Kg-1.day-1, gavage); 2. Intravenous injection of stromal stem cells from human adipose tissue (106 cells every 10 days in the first two months and monthly injections in the following four months) and/or alanine and glutamine amino acids supplementation (10 mg.Kg-1.day-1, daily IP injections). In the first experiment we demonstrated that mdx mice submitted to exercise training associated to drugs presented improved muscle function when compared to the other groups. In the second experiment, on the other hand, it was observed that the animals submitted to cell therapy presented increased survival when compared to non injected animals and animals treated with both approaches. These results, here demonstrated for the first time, can contribute to understand the physiopathology of muscular dystrophies and may give insights for future therapeutic approaches

La myopathie centronucléaire autosomique dominante (MCN-AD) est une maladie congénitale rare liée à des mutations principalement retrouvées dans le gène dynamine-2. La majorité des patients atteints de MCN-AD présente une évolution lentement progressive, avec une perte de masse et de force musculaire. A ce jour, aucune thérapie n’est disponible pour la MCN-AD. Des interventions thérapeutiques visant à limiter la progression et la sévérité de l’atteinte musculaire ainsi qu’à améliorer la qualité de vie des patients, sont donc nécessaires. Nous faisons l’hypothèse qu’une hypertrophie induite par l’invalidation de la myostatine (mstn), régulateur négatif majeur de la masse musculaire, pourrait être bénéfique pour la souris modèle de cette pathologie (KI-Dnm2R465W/+), permettant notamment le maintien de la masse et de la force musculaire. Nous avons généré un modèle doublement muté résultant du croisement de souris KI-Dnm2R465W/+ myopathe avec des souris KO-mstn hypermusclées. Notre étude démontre que l'inactivation du gène mstn permet une amélioration de la masse et du volume musculaire, limite la perte de force et de motricité. Nos données suggèrent également que cette amélioration est majoritairement due à une diminution du niveau d’expression de certains acteurs impliqués dans le système catabolique ubiquitine-protéasome. De plus, nous montrons une accélèration de la diminution de la fréquence des anomalies histologiques caractéristiques de la myopathie chez les souris KI-Dnm2R465W/+. Nous proposons que ces anomalies pourraient être dues à une altération de la structure et/ou de la fonction mitochondriale
Autosomal dominant centronuclear myopathy (AD-CNM) is a rare congenital muscle disease caused by mutations predominantly found in the dynamin 2 gene (DNM2). The clinical features generally reported are progressive muscle atrophy and weakness. To date, no treatment is available. The mouse model for AD-CNM harboring a mutation of the dynamin-2 gene (KI-Dnm2R465W/+) reproduces some of the human clinical features, notably muscle atrophy and weakness. Mstn, is a master negative regulator of skeletal muscle mass. We hypothesized that inactivation of mstn could limit muscle atrophy and weakness reported in the AD-CNM mouse model (KI-dnm2R465W/+). To test this hypothesis, we intercrossed KI-Dnm2R465W/+ mice with mice inactivated for mstn (KO-mstn) to generate a double mutated lineage (KIKO). The present study demonstrates that mstn gene inactivation allows for an improvement of muscle weight and volume, prevents muscle weakness and motor skill alterations. Our data also reveal that inactivation of mstn essentially downregulates some actors implicated in the catabolic ubiquitin-proteasome system. Furthermore, we show that inactivation of mstn decreases the frequency of of histological abnormalities characteristical in KI mice. We hypothesize that these abnormalities could be due to an alteration of mitochondrial function and network. The perspective to this work is to verify this hypothesis in the mouse model, which will contribute to a better understanding of the physiopathological mechanisms and can open new insight in the therapeutical approach to AD-CNM

In children, joint hypermobility (typified by structural instability of joints) manifests clinically as neuro-muscular and musculo-skeletal conditions and conditions associated with development and organization of control of posture and gait (Finkelstein, 1916; Jahss, 1919; Sobel, 1926; Larsson, Mudholkar, Baum and Srivastava, 1995; Murray and Woo, 2001; Hakim and Grahame, 2003; Adib, Davies, Grahame, Woo and Murray, 2005:). The process of control of the relative proportions of joint mobility and stability, whilst maintaining equilibrium in standing posture and gait, is dependent upon the complex interrelationship between skeletal, muscular and neurological function (Massion, 1998; Gurfinkel, Ivanenko, Levik and Babakova, 1995; Shumway-Cook and Woollacott, 1995). The efficiency of this relies upon the integrity of neuro-muscular and musculo-skeletal components (ligaments, muscles, nerves), and the Central Nervous System’s capacity to interpret, process and integrate sensory information from visual, vestibular and proprioceptive sources (Crotts, Thompson, Nahom, Ryan and Newton, 1996; Riemann, Guskiewicz and Shields, 1999; Schmitz and Arnold, 1998) and development and incorporation of this into a representational scheme (postural reference frame) of body orientation with respect to internal and external environments (Gurfinkel et al., 1995; Roll and Roll, 1988). Sensory information from the base of support (feet) makes significant contribution to the development of reference frameworks (Kavounoudias, Roll and Roll, 1998). Problems with the structure and/ or function of any one, or combination of these components or systems, may result in partial loss of equilibrium and, therefore ineffectiveness or significant reduction in the capacity to interact with the environment, which may result in disability and/ or injury (Crotts et al., 1996; Rozzi, Lephart, Sterner and Kuligowski, 1999b). Whilst literature focusing upon clinical associations between joint hypermobility and conditions requiring therapeutic intervention has been abundant (Crego and Ford, 1952; Powell and Cantab, 1983; Dockery, in Jay, 1999; Grahame, 1971; Childs, 1986; Barton, Bird, Lindsay, Newton and Wright, 1995a; Rozzi, et al., 1999b; Kerr, Macmillan, Uttley and Luqmani, 2000; Grahame, 2001), there has been a deficit in controlled studies in which the neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility have been quantified and considered within the context of organization of postural control in standing balance and gait. This was the aim of this project, undertaken as three studies. The major study (Study One) compared the fundamental neuro-muscular and musculo-skeletal characteristics of 15 children with joint hypermobility, and 15 age (8 and 9 years), gender, height and weight matched non-hypermobile controls. Significant differences were identified between previously undiagnosed hypermobile (n=15) and non-hypermobile children (n=15) in passive joint ranges of motion of the lower limbs and lumbar spine, muscle tone of the lower leg and foot, barefoot CoP displacement and in parameters of barefoot gait. Clinically relevant differences were also noted in barefoot single leg balance time. There were no differences between groups in isometric muscle strength in ankle dorsiflexion, knee flexion or extension. The second comparative study investigated foot morphology in non-weight bearing and weight bearing load conditions of the same children with and without joint hypermobility using three dimensional images (plaster casts) of their feet. The preliminary phase of this study evaluated the casting technique against direct measures of foot length, forefoot width, RCSP and forefoot to rearfoot angle. Results indicated accurate representation of elementary foot morphology within the plaster images. The comparative study examined the between and within group differences in measures of foot length and width, and in measures above the support surface (heel inclination angle, forefoot to rearfoot angle, normalized arch height, height of the widest point of the heel) in the two load conditions. Results of measures from plaster images identified that hypermobile children have different barefoot weight bearing foot morphology above the support surface than non-hypermobile children, despite no differences in measures of foot length or width. Based upon the differences in components of control of posture and gait in the hypermobile group, identified in Study One and Study Two, the final study (Study Three), using the same subjects, tested the immediate effect of specifically designed custom-made foot orthoses upon balance and gait of hypermobile children. The design of the orthoses was evaluated against the direct measures and the measures from plaster images of the feet. This ascertained the differences in morphology of the modified casts used to mould the orthoses and the original image of the foot. The orthoses were fitted into standardized running shoes. The effect of the shoe alone was tested upon the non-hypermobile children as the non-therapeutic equivalent condition. Immediate improvement in balance was noted in single leg stance and CoP displacement in the hypermobile group together with significant immediate improvement in the percentage of gait phases and in the percentage of the gait cycle at which maximum plantar flexion of the ankle occurred in gait. The neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility are different from those of non-hypermobile children. The Beighton, Solomon and Soskolne (1973) screening criteria successfully classified joint hypermobility in children. As a result of this study joint hypermobility has been identified as a variable which must be controlled in studies of foot morphology and function in children. The outcomes of this study provide a basis upon which to further explore the association between joint hypermobility and neuro-muscular and musculo-skeletal conditions, and, have relevance for the physical education of children with joint hypermobility, for footwear and orthotic design processes, and, in particular, for clinical identification and treatment of children with joint hypermobility.

In children, joint hypermobility (typified by structural instability of joints) manifests clinically as neuro-muscular and musculo-skeletal conditions and conditions associated with development and organization of control of posture and gait (Finkelstein, 1916; Jahss, 1919; Sobel, 1926; Larsson, Mudholkar, Baum and Srivastava, 1995; Murray and Woo, 2001; Hakim and Grahame, 2003; Adib, Davies, Grahame, Woo and Murray, 2005:). The process of control of the relative proportions of joint mobility and stability, whilst maintaining equilibrium in standing posture and gait, is dependent upon the complex interrelationship between skeletal, muscular and neurological function (Massion, 1998; Gurfinkel, Ivanenko, Levik and Babakova, 1995; Shumway-Cook and Woollacott, 1995). The efficiency of this relies upon the integrity of neuro-muscular and musculo-skeletal components (ligaments, muscles, nerves), and the Central Nervous System’s capacity to interpret, process and integrate sensory information from visual, vestibular and proprioceptive sources (Crotts, Thompson, Nahom, Ryan and Newton, 1996; Riemann, Guskiewicz and Shields, 1999; Schmitz and Arnold, 1998) and development and incorporation of this into a representational scheme (postural reference frame) of body orientation with respect to internal and external environments (Gurfinkel et al., 1995; Roll and Roll, 1988). Sensory information from the base of support (feet) makes significant contribution to the development of reference frameworks (Kavounoudias, Roll and Roll, 1998). Problems with the structure and/ or function of any one, or combination of these components or systems, may result in partial loss of equilibrium and, therefore ineffectiveness or significant reduction in the capacity to interact with the environment, which may result in disability and/ or injury (Crotts et al., 1996; Rozzi, Lephart, Sterner and Kuligowski, 1999b). Whilst literature focusing upon clinical associations between joint hypermobility and conditions requiring therapeutic intervention has been abundant (Crego and Ford, 1952; Powell and Cantab, 1983; Dockery, in Jay, 1999; Grahame, 1971; Childs, 1986; Barton, Bird, Lindsay, Newton and Wright, 1995a; Rozzi, et al., 1999b; Kerr, Macmillan, Uttley and Luqmani, 2000; Grahame, 2001), there has been a deficit in controlled studies in which the neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility have been quantified and considered within the context of organization of postural control in standing balance and gait. This was the aim of this project, undertaken as three studies. The major study (Study One) compared the fundamental neuro-muscular and musculo-skeletal characteristics of 15 children with joint hypermobility, and 15 age (8 and 9 years), gender, height and weight matched non-hypermobile controls. Significant differences were identified between previously undiagnosed hypermobile (n=15) and non-hypermobile children (n=15) in passive joint ranges of motion of the lower limbs and lumbar spine, muscle tone of the lower leg and foot, barefoot CoP displacement and in parameters of barefoot gait. Clinically relevant differences were also noted in barefoot single leg balance time. There were no differences between groups in isometric muscle strength in ankle dorsiflexion, knee flexion or extension. The second comparative study investigated foot morphology in non-weight bearing and weight bearing load conditions of the same children with and without joint hypermobility using three dimensional images (plaster casts) of their feet. The preliminary phase of this study evaluated the casting technique against direct measures of foot length, forefoot width, RCSP and forefoot to rearfoot angle. Results indicated accurate representation of elementary foot morphology within the plaster images. The comparative study examined the between and within group differences in measures of foot length and width, and in measures above the support surface (heel inclination angle, forefoot to rearfoot angle, normalized arch height, height of the widest point of the heel) in the two load conditions. Results of measures from plaster images identified that hypermobile children have different barefoot weight bearing foot morphology above the support surface than non-hypermobile children, despite no differences in measures of foot length or width. Based upon the differences in components of control of posture and gait in the hypermobile group, identified in Study One and Study Two, the final study (Study Three), using the same subjects, tested the immediate effect of specifically designed custom-made foot orthoses upon balance and gait of hypermobile children. The design of the orthoses was evaluated against the direct measures and the measures from plaster images of the feet. This ascertained the differences in morphology of the modified casts used to mould the orthoses and the original image of the foot. The orthoses were fitted into standardized running shoes. The effect of the shoe alone was tested upon the non-hypermobile children as the non-therapeutic equivalent condition. Immediate improvement in balance was noted in single leg stance and CoP displacement in the hypermobile group together with significant immediate improvement in the percentage of gait phases and in the percentage of the gait cycle at which maximum plantar flexion of the ankle occurred in gait. The neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility are different from those of non-hypermobile children. The Beighton, Solomon and Soskolne (1973) screening criteria successfully classified joint hypermobility in children. As a result of this study joint hypermobility has been identified as a variable which must be controlled in studies of foot morphology and function in children. The outcomes of this study provide a basis upon which to further explore the association between joint hypermobility and neuro-muscular and musculo-skeletal conditions, and, have relevance for the physical education of children with joint hypermobility, for footwear and orthotic design processes, and, in particular, for clinical identification and treatment of children with joint hypermobility.

Objetivo: Construir Escala de Avaliação Funcional do Sentar e Levantar do Solo para Portadores de DMD (EAF-2) e testar sua confiabilidade intra e interexaminadores. Método: A construção da escala ocorreu em etapas: 1. Análise do movimento de sentar e levantar do solo em crianças saudáveis. 2. Análise do movimento de sentar e levantar do solo em crianças com DMD. 3. Elaboração da primeira versão da escala e do manual de instrução. 4. Avaliação por peritos e reajustes gerando a versão final. 5. Análise de confiabilidade inter e intraexaminador e correlação com a Escala de Vignos, idade e tempo de execução da atividade. Resultados: A escala abrange três fases para o sentar e cinco para o levantar, cada fase contendo itens que devem ser avaliados e pontuados. O escore pode variar de 0 a 10 para o sentar e de 0 a 15 para o levantar. Foi demonstrado muito boa repetibilidade da medida do sentar e levantar (ICC = 0,89 e 084, respectivamente) e excelente reprodutibilidade (ICC = 0,93 e 0,92, respectivamente). O Coeficiente Kappa para as 8 fases na análise interexaminadores variou de 0,77 a 1,00 (confiabilidade excelente para 5 fases e substancial para 3 fases), e na análise intra-examinador variou de 0,80 a 1,00 (confiabilidade excelente para 6 fases e substancial para 2 fases). Encontrou-se boa correlação entre as variáveis idade x Escala de Vignos (r= 0,58) e levantar x Escala de Vignos (r= 0,56), enquanto que nas variáveis restantes a correlação foi baixa.Conclusão: A EAF-2 é um instrumento de avaliação confiável que permite avaliar a atividade de sentar e levantar em portadores de DMD de forma detalhada e operacionalizada.
Objective: Construct the Scale of Functional Evaluation of Sit-and-Stand from the Ground for Patients with DMD (EAF-2) and to test its reliability intra and interexaminer. Method: The construction of the scale occurred in stages: 1. Analysis of the movement to sit and stand from the ground in healthy children. 2. Analysis of the movement to sit and stand from the ground in children with DMD. 3. Elaboration of the first version of the scale and the manual of instruction. 4. Evaluation by experts and readjustments generating the final version. 5. Analysis of Reliability inter and intra-examiner and correlation with the Vignos Scale, age and time length for the execution of the activity. Results: The scale comprehends three phases for the sitting and five for the standing, each phase with items that must be evaluated and scored. The score may vary from 0 to 10 for the sitting and from 0 to 15 for the standing. A very good repeatability of the measure of sitting as well as of standing was demonstrated (ICC = 0,89 and 084, respectively) and excellent reproducibility (ICC = 0,93 and 0,92, respectively). The Kappa Coefficient for the 8 phases in the interexaminer analysis varied from 0,77 to 1,00 (excellent reliability for 5 phases and substantial for 3 phases), and in the intra-examiner analysis varied from 0,80 to 1,00 (excellent reliability for 6 phases and substantial for 2 phases). Good correlation was found between the variable age x Vignos Scale (r= 0,58) and to stand x Vignos Scale (r= 0,56), whereas in the remaining variable the correlation was low. Conclusion: The EAF-2 is a trustful instrument of evaluation that allows to evaluate the activity of sitting and standing in people with DMD in a detailed and operationalized way.

En la presente Tesis Doctoral se muestra el estudio de la proteína Ankyrin repeat and kinase domain containing 1 (ANKK1) en el linaje miogénico durante el desarrollo y en la edad adulta. El gen ANKK1 ha sido ampliamente relacionado con trastornos neuropsiquiátricos y endofenotipos dopaminérgicos en el cerebro. Sin embargo, la función de su proteína es todavía desconocida. La localización del gen ANKK1 en un clúster genómico conservado a lo largo de la evolución que podría estar implicado en neurogénesis, y la expresión de su proteína en progenitores neurales y su relación con el ciclo celular, han relacionado este gen con el neurodesarrollo. ANKK1 pertenece a la familia Receptor-Interacting Proteins (RIP), cuyos miembros participan en la diferenciación de diversos tejidos, incluyendo el muscular. La observación de ANKK1 en miotúbulos embrionarios murinos nos llevó a plantearnos la hipótesis de la posible participación de esta proteína en el origen, el desarrollo y la regeneración muscular. Nuestros resultados muestran que ANKK1 es una proteína que participa en la biología muscular. Se localiza en precursores miogénicos durante el desarrollo embrionario murino y en las células satélite del músculo adulto. Además, los estudios in vitro utilizando mioblastos murinos y humanos muestran un patrón específico de la dinámica de sus isoformas: las isoformas ANKK1 quinasa (ANKK1-k) y ANKK1 completa (ANKK1-fl) se expresan en mioblastos y células satélite (SCs) quiescentes, mientras que sólo ANKK1-fl está presente en miotúbulos y SCs activadas. El transporte núcleo-citoplasmático de ANKK1 en mioblastos durante la diferenciación temprana se bloquea mediante la adición de leptomicina B, lo que indica que su salida del núcleo está mediada por exportinas. En el músculo adulto ANKK1 se expresa en las fibras de contracción rápida tipo II de metabolismo glicolítico. La activación de la vía glicolítica en mioblastos murinos incrementa la expresión de Ankk1. Todo ello confirma la relación entre la expresión de ANKK1 y el metabolismo glicolítico y explica la localización específica de la proteína en fibras musculares de contracción rápida. También se ha investigado la localización de ANKK1 en músculos de pacientes con diferentes distrofias musculares. Los mioblastos de pacientes con Distrofia Muscular de Duchenne (DMD) presentan una expresión alterada de ANKK1. La disminución de ANKK1 nuclear en estos mioblastos se asocia con un estadio celular más indiferenciado, definido por el incremento de expresión de PAX7. Paralelamente, en biopsias procedentes de pacientes con diferentes distrofias musculares, la expresión de ANKK1 se asocia con poblaciones celulares regenerativas, es decir, SCs y fibras regenerativas. En cuanto al estudio de su función, se ha investigado la participación de ANKK1 en el ciclo celular. La sobreexpresión de las variantes polimórficas de ANKK1 (A1-A2) en células HeLa incrementa la velocidad de progresión del ciclo celular, mientras que la sobreexpresión de la isoforma catalíticamente inactiva (K51R) la disminuye. En todos los casos, el porcentaje de células que alcanza la mitosis está reducido. Todo esto indica que la expresión de ANKK1 afecta tanto a la progresión del ciclo celular como al número de células que completan el ciclo. Finalmente, hemos estudiado la actividad quinasa de ANKK1. En las condiciones estudiadas, no se ha detectado esta actividad in vitro. Sin embargo, dado que es una RIP quinasa y su dominio quinasa es homólogo al resto de los miembros de la familia RIP, no podemos descartar que ANKK1 presente dicha actividad. En resumen, este Tesis Doctoral muestra por primera vez la participación de la proteína ANKK1 en la biología muscular desde el desarrollo embrionario hasta el músculo del adulto. Sin duda, ANKK1 es una proteína candidata a ser estudiada como biomarcador de enfermedad muscular.
The present Doctoral Thesis shows the study of the Ankyrin repeat and kinase domain containing 1 (ANKK1) protein in the myogenic lineage during development and in adulthood. The ANKK1 gene has been widely related to neuropsychiatric disorders and dopaminergic endophenotypes in the brain. However, the function of its protein is still unknown. The location of ANKK1 gene in a genomic cluster conserved throughout the evolution thay may be involved in neurogenesis, and the expression of its protein in neural progenitors and its relationship with the cell cycle, have linked ANKK1 gene to neurodevelopment. ANKK1 belongs to the Receptor-Interacting Proteins family (RIP), whose members participate in the differentiation of several tissues, including muscle tissue. The finding of the location of ANKK1 in murine embryonic myotubes led us to consider the hypothesis of the possible participation of this protein in muscles origin, development and regeneration. Our results show that ANKK1 is a protein that participates in muscle biology. It is located in myogenic precursors during murine embryonic development and in adult muscle satellite cells. In addition, in vitro studies using murine and human myoblasts show a specific pattern of the dynamics of its isoforms: the isoforms ANKK1 kinase (ANKK1-k) and ANKK1 full-length (ANKK1-fl) are expressed in myoblasts and quiescent satellite cells (SCs), whereas only ANKK1-fl is present in myotubes and activated SCs. The nuclear-cytoplasmic shuttle of ANKK1 in myoblasts during early differentiation is blocked by the addition of leptomycin B, which indicates that its exit from the nucleus is mediated by exportins. In the adult muscle ANKK1 is expressed in the Fast-Twitch muscle fibers type II with glycolytic metabolism. The activation of the glycolytic pathway in murine myoblasts increases Ankk1 expression. All this confirms the relationship between the expression of ANKK1 and the glycolytic metabolism and explains the specific location of the protein in Fast-twitch muscle fibers. The location of ANKK1 in the muscles of patients with different muscular dystrophies has also been investigated. The myoblasts of patients with Duchenne Muscular Dystrophy (DMD) present an altered expression of ANKK1. The decrease in nuclear ANKK1 in these myoblasts is associated with a more undifferentiated cell stage, defined by the increase in the expression of PAX7. In parallel, in biopsies from patients with different muscular dystrophies, the expression of ANKK1 is associated with regenerative cell populations, that is to say, SCs and regenerating fibers. Regarding the study of its function, we have investigated the participation of ANKK1 in the cell cycle. The overexpression of the polymorphic variants of ANKK1 (A1-A2) in HeLa cells increases the rate of progression of the cell cycle, while overexpression of the catalytically inactive isoform (K51R) decreases it. In all cases, the percentage of cells that reach mitosis is reduced. All this indicates that the expression of ANKK1 affects both the progression of the cell cycle and the number of cells that complete the cycle. Finally, we have studied the kinase activity of ANKK1. Under the conditions studied, this activity has not been detected in vitro. However, given that it is a RIP kinase and its kinase domain is homologous to the rest of the members of the RIP family, we cannot rule out that ANKK1 does not present this activity. In summary, this Doctoral Thesis shows for the first time the participation of the ANKK1 protein in muscle biology from embryonic development to adult muscle. Thus, we propose ANKK1 as a candidate protein to be studied as a biomarker of muscular disease.
En la present tesi doctoral es mostra l'estudi de la proteïna Ankyrin repeat and kinase domain containing 1 (ANKK1) en el llinatge miogènic durant el desenvolupament i en l'edat adulta. El gen ANKK1 ha estat àmpliament relacionat amb trastorns neuropsiquiàtrics i endofenotips dopaminèrgics en el cervell. No obstant això, la funció de la seua proteïna és encara desconeguda. La localització del gen ANKK1 en un clúster genòmic conservat al llarg de l'evolució que podria estar implicat en neurogènesi, i l'expressió de la seua proteïna en progenitors neurals i la seua relació amb el cicle cel¿lular, han relacionat aquest gen amb el neurodesenvolupament. ANKK1 pertany a la família Receptor-interacting Proteins (RIP), els membres de la qual participen en la diferenciació de diversos teixits incloent el muscular. L'observació d'ANKK1 en miotúbuls embrionaris murins ens va portar a plantejar-nos la hipòtesi de la possible participació d'aquesta proteïna en l'origen, el desenvolupament i la regeneració muscular. Els nostres resultats mostren que ANKK1 és una proteïna que participa en la biologia muscular. Es localitza en precursors miogènics durant el desenvolupament embrionari murí i en les cèl¿lules satèl¿lit del múscul adult. A més, els estudis in vitro utilitzant mioblasts murins i humans mostren un patró específic de la dinàmica de les seues isoformes: les isoformes ANKK1 quinasa (ANKK1-k) i ANKK1 completa (ANKK1-fl) s'expressen en mioblasts i cèl¿lules satèl¿lit (SCs) quiescents, mentre que només ANKK1-fl està present en miotúbuls i SCs activades. El transport nucli-citoplasmàtic d'ANKK1 a mioblasts durant la diferenciació primerenca es bloqueja mitjançant l'addició de leptomicina B, el que indica que la seua eixida del nucli està mediada per exportines. En el múscul adult ANKK1 s'expressa en les fibres de contracció ràpida tipus II de metabolisme glicolític. L'activació de la via glicolítica en mioblasts murins incrementa l'expressió d'Ankk1. Tot això confirma la relació entre l'expressió d'ANKK1 i el metabolisme glicolític i explica la localització específica de la proteïna en fibres musculars de contracció ràpida. També s'ha investigat la localització d'ANKK1 en músculs de pacients amb diferents distròfies musculars. Els mioblasts de pacients amb distròfia muscular de Duchenne (DMD) presenten una expressió alterada d'ANKK1. La disminució d'ANKK1 nuclear en aquests mioblasts s'associa amb un estadi cel¿lular més indiferenciat, definit per l'increment d'expressió de PAX7. Paral¿lelament, en biòpsies procedents de pacients amb diferents distròfies musculars, l'expressió d'ANKK1 s'associa amb poblacions cel¿lulars regeneratives, és a dir, SCs i fibres regeneratives. En quant a l'estudi de la seua funció, s'ha investigat la participació d'ANKK1 en el cicle cel¿lular. La sobreexpressió de les variants polimòrfiques d'ANKK1 (A1-A2) en cèl¿lules HeLa incrementa la velocitat de progressió del cicle cel¿lular, mentre que la sobreexpressió de la isoforma catalíticament inactiva (K51R) la disminueix. En tots els casos, el percentatge de cèl¿lules que arriba a la mitosi està reduït. Tot això indica que l'expressió d'ANKK1 afecta tant la progressió del cicle cel¿lular com al nombre de cèl¿lules que completen el cicle. Finalment, hem estudiat l'activitat quinasa d'ANKK1. En les condicions estudiades, no s'ha detectat aquesta activitat in vitro. No obstant això, atès que és una RIP quinasa i el seu domini quinasa és homòleg a la resta dels membres de la família RIP, no podem descartar que ANKK1 presente aquesta activitat. En resum, aquesta tesi doctoral mostra per primera vegada la participació de la proteïna ANKK1 en la biologia muscular des del desenvolupament embrionari fins al múscul de l'adult. Sens dubte, ANKK1 és una proteïna candidata a ser estudiada com a biomarcador de malaltia muscular.
Rubio Solsona, E. (2018). ESTUDIO DE LA PROTEÍNA ANKK1 EN LA FIBRA MUSCULAR: IMPLICACIONES EN DISTROFIAS MUSCULARES [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/100850
TESIS

Orientador: Humberto Santo Neto
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Mestrado
Anatomia
Mestre em Biologia Celular e Estrutural

O tecido muscular tem uma alta capacidade de regeneração após lesão, que está diretamente ligada à presença de células satélites (SCs). Essas células são as principais células-tronco do músculo e também têm um papel fundamental no desenvolvimento muscular na embriogênese. Embora quiescente nos músculos adultos normais, as SCs podem ser ativadas por sinais específicos após lesão muscular. Em doenças caracterizadas por processo de degeneração crônica, como distrofias musculares, as SCs são constantemente ativadas, e esta condição pode levar à depleção do pool de SCs e consequente falha no processo regenerativo. Nós estudamos as SCs musculares nas linhagens distróficas murinas DMDmdx, Largemyd, DMDmdx/Largemyd, em comparação a camundongos normais, com o principal objetivo de avaliar o comportamento das SCs em músculos distróficos com diferentes graus de degeneração histopatológica. A expressão de genes e proteínas de fatores de transcrição relacionados a SCs foram estudadas no músculo, e os resultados foram comparados com as características histopatológicas de regeneração e degeneração e estado de proliferação de células musculares. Nossos resultados mostraram que o músculo distrófico mantém seu pool de células satélites, expressando PAX7, um importante fator muscular para autorrenovação do pool de SCs, em níveis semelhantes em todas as linhagens distróficas e controle normal. As células isoladas de músculo distrófico apresentaram uma maior proporção de células em proliferação, como observado pela análise dos marcadores de ciclo celular no músculo gastrocnêmio dissociado, com maior número de células na fase G2/M. A cascata de genes de regeneração é ativada no músculo distrófico, com altos níveis de expressão de fatores de regeneração muscular, como MYOD e Myogenin. O músculo distrófico mantém a capacidade de formar novas fibras, observada por um número significativo de fibras recém formadas, que expressam dMHC, em todas as linhagens analisadas. No entanto, essas novas fibras mostram características de maturação incompleta, como tamanho pequeno e pouca variação em seu calibre, que pode ser determinante para sua disfunção. A degeneração muscular é intensa apesar da regeneração, com infiltração significativa de tecido conjuntivo em camundongos distróficos. Em conclusão, nossos achados sugerem que os músculos distróficos, independentemente do grau de degeneração, mantêm o pool de células satélites com capacidade proliferativa e estão prontos para responder aos estímulos regenerativos. Por outro lado, a maturação dessas novas fibras é incompleta e não previne a degeneração do músculo
Muscle tissue has a high regeneration capacity after injury, which is directly linked to satellite cells (SCs). These cells are the main stem cells of the muscle and also have a key role in muscle development in embryogenesis. Although quiescent in normal adult muscles, SCs can be activated by specific signals upon muscle injury. In diseases characterized by chronic degeneration process, such as muscular dystrophies, the SCs are constantly activated, leading to depletion of the SC pool and consequent failure of the regenerative process. We studied muscle SCs in the mouse dystrophic strains DMDmdx, Largemyd, DMDmdx/Largemyd, comparing to wild-type mice, with the main objective to evaluate SCs behavior in dystrophic muscles with different degrees of histopathological degeneration. Gene and protein expression of transcription factors related to SCs were studied in the muscle, and the results were compared to regenerating and degenerating histopathologic pattern and proliferative state of muscle cells. Our results showed that the dystrophic muscle retains its satellite cells pool, expressing PAX7, an important muscle factor for self-renewal of the SCs pool, at similar levels in all dystrophic strains and wild-type. Dystrophic muscle single cells presented a higher proportion of proliferating cells, as observed by the analysis of cell cycle markers in dissociated gastrocnemius muscle, with a greater number of cells in the G2/M phase. The cascade of regeneration genes is activated in the dystrophic muscle, with high levels of expression of muscle regenerating factors, such as MYOD and Myogenin. Dystrophic muscle retains the ability to form new fibers, as observed by a significant number of new fibers expressing dMHC in all dystrophic strains. However, these new fibers show incomplete maturation characteristics, such as small size and no variation in fiber caliber, which could be determinant for its dysfunction. Muscle degeneration is intense in spite of regeneration, with significant more connective tissue infiltration in dystrophic mice than wild-typemice. In conclusion, our findings suggest that dystrophic muscles, independently of the degree of degeneration, retain the pool of satellite cells with proliferating capacity and ready to respond to regenerating stimuli. On the other hand, the maturation of these new fibers is incomplete and do not prevent the degeneration of the muscle

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A tilápia do Nilo (Oreochromis niloticus L.), amplamente utilizada na piscicultura brasileira, destaca-se por apresentar inúmeras qualidades para o mercado consumidor. Assim como ocorre com outras espécies de peixes, o desenvolvimento muscular das tilápias pode sofrer a influência de diversos fatores (extrínsecos e intrínsecos), podendo assim comprometer os custos de produção. Neste estudo, objetivamos avaliar a morfologia e a expressão de genes que controlam o crescimento muscular em tilápia do Nilo (Oreochromis niloticus) da linhagem GIFT cultivada em diferentes temperaturas. Noventa peixes (n=10) de uma população monosexo de machos revertidos, pesando aproximadamente 1,4 g, foram distribuídos aleatoriamente em seis caixas d’água de 0,5 m3 em sistema de recirculação d’água e cultivados em três diferentes temperaturas (22, 28 e 30° C) durante 7, 30 e 60 dias. Foram realizadas análises biométricas e morfológicas, bem como análises de expressão gênica dos fatores reguladores miogênicos (MyoD e Miogenina) e do fator de crescimento Miostatina. A análise de expressão gênica foi realizada através da técnica de Reação em Cadeia da Polimerase em Tempo Real após Transcrição Reversa (qRT-PCR). Os dados de peso(g) e comprimento padrão (cm) demonstraram que a temperatura pode influenciar o ganho de peso final, sendo que os animais cultivados a 22°C apresentaram menor peso a partir do 30º dia, quando comparado com os animais cultivados a 28 e 30°C. A análise morfométrica (distribuição do diâmetro médio das fibras), não apresentou diferenças significativas entre os animais nas temperaturas estudadas. Entretanto, os animais cultivados a 22 e 30°C apresentaram comportamento similar na distribuição do diâmetro médio das fibras. A análise de expressão gênica para a MyoD, apresentou os maiores... .
The Nile tilapia (Oreochromis niloticus L.), widely used in Brasilian aquaculture, stands out for its numerous qualities to the consumer market. As with other fish species, tilapia muscle development may be influenced by several factors (extrinsic and intrinsic) and, thus, it can lead to compromise production costs. This study aimed to evaluate the morphology and expression of genes that control muscle growth in Nile tilapia (Oreochromis niloticus) of GIFT strain grown at different temperatures. Ninety fish (n = 10) of a reverted males monosex population, weighing about 1.4 g were randomly divided into six water tanks of 0.5 m3 of water recirculation system and reared in three different temperatures (22, 28 and 30 ° C ) for 7, 30 and 60 days. It was performed biometric and morphological analysis, along with gene expression of myogenic regulatory factors (MyoD and myogenin) and growth factor myostatin analysis. The gene expression analysis was performed using the technique of Polymerase Chain Reaction Real-Time after Reverse Transcription (qRT-PCR). Weight (g) and standard length (cm) data showed that temperature can influence final weight gain, and the animals grown at 22 ° C had lower weight from the 30th day, when compared with animals reared at 28 and 30 ° C. The morphometric analysis (distribution of the fiber mean diameter), did not show significant differences among animals in the studied temperatures. However, animals reared at 22 and 30 ° C showed similar behavior in the distribution of the fiber mean diameter. The gene expression analysis for MyoD, showed the highest mRNA levels in animals grown at 22 ° C, when compared to animals reared at 28 and 30 ° C in almost all studied periods. The levels of mRNA for the myogenin were constant at all studied temperatures and periods. At seven days... (Complete abstract click electronic access below)

Resultats anteriors mostraven que rates amb obesitat nutricional ("dieta de cafeteria") tenien un perfil metabòlic d'estalvi de nitrogen, mentre que pel model d'obesitat genètica (Zucker (fa/fa)) es suggeria un malbaratament de nitrogen. Es mostra una reducció en la taxa de recanvi d'alanina per l'animal sencer en el model d'obesitat nutricional, i un increment en el model d'obesitat genètica. La fracció anabòlica de la taxa és la responsable d'aquestes alteracions, suggerint perturbacions en el metabolisme de proteïnes. S'estudiaren músculs individuals, escollits per a assolir un rang ampli de perfils fibril•lars. L'obesitat genètica causa una reducció del contingut en proteïna, principalment en els músculs lents i oxidatius, la qual cosa correlaciona amb un increment en l'activitat µ-calpaïna, congruent amb una taxa de degradació de proteïnes incrementada Per contra, a l'obesitat nutricional, s'observa un increment en el contingut de proteïnes, fonamentalment en els músculs ràpids i glicolítics que no es va poder associar a variacions en l'activitat del sistema calpaïna, congruent amb una taxa de síntesi de proteïnes incrementada

At every joint there is a redundant set of muscle activated during movement or loading of the system. Optimization techniques are needed to evaluate individual forces in every muscle. The objective in this thesis was to use static optimization techniques to calculate individual muscle forces in the human extremities.

A cost function based on a performance criterion of the involved muscular forces was set to be minimized together with constraints on the muscle forces, restraining negative and excessive values. Load-sharing, load capacity and optimal forces of a system can be evaluated, based on a description of the muscle architectural properties, such as moment arm, physiological cross-sectional area, and peak isometric force.

The upper and lower extremities were modelled in two separate studies. The upper extremity was modelled as a two link-segment with fixed configurations. Load-sharing properties in a simplified model were analyzed. In a more complex model of the elbow and shoulder joint system of muscular forces, the overall total loading capacity was evaluated.

A lower limb model was then used and optimal forces during gait were evaluated. Gait analysis was performed with simultaneous electromyography (EMG). Gait kinematics and kinetics were used in the static optimization to evaluate of optimal individual muscle forces. EMG recordings measure muscle activation. The raw EMG data was processed and a linear envelope of the signal was used to view the activation profile. A method described as the EMG-to-force method which scales and transforms subject specific EMG data is used to compare the evaluated optimal forces.

Reasonably good correlation between calculated muscle forces from static optimization and EMG profiles was shown. Also, the possibility to view load-sharing properties of a musculoskeletal system demonstrate a promising complement to traditional motion analysis techniques. However, validation of the accurate muscular forces are needed but not possible.

Future work is focused on adding more accurate settings in the muscle architectural properties such as moment arms and physiological cross-sectional areas. Further perspectives with this mathematic modelling technique include analyzing pathological movement, such as cerebral palsy and rheumatoid arthritis where muscular weakness, pain and joint deformities are common. In these, better understanding of muscular action and function are needed for better treatment.

The muscular dystrophies, Duchenne muscular dystrophy being the most common type, are a group for which there is no apparent pathology to the spinal motor neurons concomitant to progressive muscular degeneration. After this fact was established during the nineteenth century through postmortem examination, Charcot divided muscular disease into the "Great Classes" of myopathy and neuropathy. Erb's study of the histopathology brought a further division between the two before death and therefore the muscle biopsy became a tool for differential diagnosis. He also discovered that the response of muscle in myopathy and neuropathy to the application of electric current differed. While the response of myopathic muscle was progressively diminishing and equally so to the application of either galvanic or alternating current, neuropathic muscle maintained its ability to contract upon the application of galvanic current during the course of the disease. As well as the animating power of the nervous system by way of the anterior nerves, its trophic effect upon the muscle was evident by loss of volume upon interruption of its influence. Even though the absence of a lesion involving the spinal motor neurons or descending motor tracts was a constant in muscular dystrophy, there remained some reluctance to accept myopathy as being independent of the nervous system. According to the maintenance of the contractile response to galvanic current in neuropathy Erb suggested that there was a nerve centre other than that of the anterior cornua of the spinal cord which supplied the trophic influence. When he found histological features which were typical of myopathy in poliomyelitis he was convinced that muscular dystrophy was the result of a trophic disturbance. However, this theory was not sustainable because there was no anatomical evidence for a special trophic centre. In 1970 McComas again proposed that a neurogenic phenomenon was responsible for the pathogenesis of the muscular dystrophies. It was the re-emergence of a neurogenic hypothesis for muscular dystrophy which was the purpose of my exercise. In order to answer the question as to why a trophic theory reappeared I followed the research and theory regarding muscular dystrophy over time. The powerful effect of the somatic innervation upon muscle metabolism as determined by cross innervation experiments during the 1960's, set the stage for the reassertion of a trophic disturbance in muscular dystrophy. In addition, the division between myopathy and neuropathy had become less.distinct by 1970 in terms of histology, serum enzymes and the intramuscular innervation. Histological features considered to by typical of myopathy were seen in the biopsies of Charcot-Marie-Tooth disease and Kugelberg-Welander spinal muscular atrophy. As well, abnormally elevated serum levels of creatine phosphokinase which was characteristic of muscular dystrophy, were measured in these neuropathies. Changes in the intramuscular innervation of myotonic dystrophy and the animal model for muscular dystrophy also brought into question the myopathicity of muscular dystrophy. By 1970 the types of muscular dystrophy had been classified according to clinical and genetic criteria and were thus known to be genetically distinct diseases. A unifying hypothesis is always desireable and therefore, mental deficiency according to clinical assessment in Duchenne and myotonic dystrophy, the latter being an "impure" dystrophy, were considered to be supportive of the neurogenic hypothesis. "Hypertrophic paraplegia of infancy of cerebral origin" was the original title of what became known as Duchenne dystrophy. The frequent occurrence of mental retardation was the foundation of the name but with knowledge concerning the profound influence of the nerve upon the metabolism of the muscle, the alleged cerebral defect in Duchenne dystrophy favoured the neuropathicity of dystrophy even more.
Medicine, Faculty of
Cellular and Physiological Sciences, Department of
Graduate

Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of conditions that usually present in the first months of life with weakness and hypotonia. Extramuscular manifestations are common and may include brain, skin and eye abnormalities. CMDs are relatively rare disorders and despite the major progress made over the last 2 decades in identifying, mapping and investigating these conditions, there remains a lot to be learned. Little is known about the relative frequency of the various forms of CMD in the UK population. Experience had shown that founder mutations are common in different ethnic populations and epidemiological studies performed in other countries are of limited value in this regard. Since 2001, the Dubowitz Neuromuscular Centre (DNC) has been the National Commissioning Group UK Centre for CMD. As such we are in the privileged position to have access to a large number of UK patients with CMD. I analysed a cohort of 214 CMD referrals to the DNC between 2001 and 2008 with a view to reporting the diagnostic outcome and the frequency of the various forms of CMD encountered in our patient population. The second part of the thesis is concerned with the dystroglycanopathies, a recently described group of CMDs associated with aberrant glycosylation of alpha dystroglycan. To date, 7 genes have been identified, some of which give rise to multiple dystroglycanopathy phenotypes. I studied the genotype-phenotype relationship in a large group of dystroglycanopathy patients, reporting new clinical phenotypes and establishing the mutation frequency in this group. I also report in detail the spectrum of MRI brain changes seen in 27 dystroglycanopathy patients. In summary, this work reports the diagnostic outcome in the largest cohort of UK CMD cases studied and refines the genotype-phenotype correlation in patients with dystroglycanopathies.

Introdução: As distrofias de cinturas representam um grupo de miopatias progressivas, geneticamente determinadas, envolvendo 16 formas de herança autossômica recessiva e oito dominantes, sendo as formas recessivas mais comuns, particularmente em crianças. Caracterizam-se por fraqueza muscular progressiva de predomínio proximal em cinturas escapular e pélvica, existindo desde formas graves de início na infância a formas leves de início em adultos. A biópsia muscular, com estudo histológico e imunoistoquímico, é fundamental para o diagnóstico, porém o exame molecular é o teste padrão ouro para o diagnóstico de certeza. Objetivos: Determinar a freqüência dos diferentes subtipos de distrofia de cinturas em crianças na nossa população, descrevendo os aspectos clínicos, histológicos e moleculares. Resultados: Fizeram parte deste estudo 39 crianças provenientes do ambulatório de doenças neuromusculares do HC-FMUSP, sendo a proporção entre o sexo feminino e masculino de 3:1. A idade de início da doença variou de dois a 13 anos, com média de 7,5 anos. Os sinais e sintomas na apresentação clínica incluíram: quedas frequentes (22 casos), dificuldades em subir escadas (13 casos), marcha digitigrada (2 casos) e dificuldades para se levantar do chão (2 casos). Os níveis de CK foram elevados em todos os pacientes, sendo maiores naqueles com diferlinopatia e algumas formas de sarcoglicanopatias. Dentre os 39 pacientes, 37 foram classificados como LGMD. Destes, 15 (40,5%) receberam o diagnóstico de sarcoglicanopatia (LGMD2C-F), cinco (13,5%) de disferlinopatia (LGMD2B), cinco (13,5%) de calpainopatia, dois (5,5%) de LGMD1B, dois (5,5%) de LGMD2I, um (2,5%) de caveolinopatia (LGMD1A), e em sete (19%) não foi possível identificar o subtipo específico. A biópsia muscular mostrou um padrão distrófico em todos os casos, sendo mais acentuado nas sarcoglicanopatias e na LGMD2I. A presença de inflamação foi incomum na LGMD2B, e a presença de fibras lobuladas foi um achado marcante na LGMD2A. Conclusões: O diagnóstico do subtipo específico de LGMD em crianças é um desafio. Este estudo em crianças brasileiras provenientes de um centro de doenças neuromusculares de um grande hospital da rede pública mostrou alta frequência de sarcoglicanopatias, seguida por LGMD2A e LGMD2B. Já a LGMD2I parece ser incomum no Brasil
Background: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic muscular dystrophies, involving 16 autosomal recessive subtypes and eight autosomal dominant subtypes. Autosomal recessive dystrophy is far more common than autosomal dominant dystrophy, particularly in children. The clinical course in this group is characterized by progressive proximal weakness, initially in pelvic and after in shoulder-girdle musculature, varying from very mild to severe degree. Significant overlap of clinical phenotypes, with genetic and clinical heterogeneity, constitutes the rule for this group of diseases. Muscle biopsies are useful for histopathologic and immunolabeling studies, and DNA analysis is the gold standard to establish the specific form of muscular dystrophy. Objectives: The aim of this study was to characterize the clinical, histological and molecular aspects in children with LGMD who attend a big public neuromuscular centre in our country to determine the frequency of different forms. Results: Thirty seven patients were classified as LGMD and included in this analysis. The study period extended from 2009-2012. The female to male ratio was 3:1. The age of onset ranged from two to 13 years, mean 7,5 years. Onset in the first decade was seen in 90%. The initial clinical signs included: frequent falls (22 cases), difficulty in climbing stairs (13 cases), walk on tip toes (2 cases), difficulty in rising from the floor (2 cases) and difficulty on walking (1 case). The serum CK levels were high in all cases. Among the 37 patients, 15 (40,5%) were classified as sarcoglycanopathies (LGMD2C-F), five (13,5%) as dysferlinopathy (LGMD2B), five (13,5%) as calpainopathy (LGMD2A). Mutations in LMNA gene (LGMD1B), FKRP gene (LGMDI) and caveolin gene (LGMD 1C) were identified in two (5,5%), two (5,5%) and one patient (2,5%), respectively. In seven of 37 cases (19%) it was impossible to determine specific diagnosis. Calf hypertrophy, scapular winging and scoliosis were the most characteristic signs in sarcoglycanopathies. In LGMD2I calf hypertrophy is also observed. Atrophy of posterior compartment of thighs is frequent in children with LGMD2B and could suggest the diagnosis. In LGMD2A winging of scapulae and contractures in Achilles tendons were important findings. Muscle biopsy showed a dystrophic pattern in all cases, more intense in sarcoglycanopathies and LGMD2I. Differently from adult\'s patients, inflammation changes in dysferlinopaties were uncommon. Lobuled fibers were characteristic changes in calpainopathies in children. Conclusions: A definitive diagnosis among various subtypes of LGMD in children is challenging. Our series was a large study on LGMD in Brazilian children and showed high frequency of sarcoglycanopathies followed by LGMD2A, LGMD2B, LGMD2I, LGMD1B and LGMD1C

Introdução: As distrofias musculares de cinturas (limb-girdle muscular dystrophies - LGMD) são causadas por mutações em uma grande variedade de genes que codificam proteínas musculares, podendo ser herdadas de forma autossômica dominante ou recessiva. O diagnóstico é feito tanto através de exame de biópsia muscular que mostra um padrão histológico distrófico ao lado de deficiência específica de proteínas musculares quanto por estudo genético. Em alguns subtipos de LGMD não é possível fazer o diagnóstico específico pela biópsia muscular, tais como na deficiência da calpaína-3 (CAPN3) e da proteína relacionada a fukutina (FKRP). Nestes casos, portanto, o exame molecular é de grande valor para a confirmação do diagnóstico. Objetivos: Analisar os genes CAPN3 e FKRP em pacientes com diagnóstico histológico de LGMD e verificar a expressão proteica da CAPN3 nesses pacientes, correlacionando com as mutações identificadas e com o quadro clínico e histológico dos mesmos. Resultados: Fizeram parte deste estudo 36 pacientes com LGMD provenientes do ambulatório de miopatias do HC-FMUSP em que a biópsia muscular não identificou deficiência de distrofina, disferlina, caveolina-3 e sarcoglicanas. Destes, nove (25%) foram diagnosticados com LGMD2A, seis (17%) com LGMD2I e em 21 (58%) não foi possível identificar o subtipo específico. Foram encontradas mutações patogênicas no gene CAPN3 em oito pacientes, sendo em homozigose em dois casos, heterozigose composta em cinco casos e em heterozigose em um caso. Em um caso o diagnóstico de LGMD2A foi realizado baseado apenas na análise da expressão da proteína CAPN3 no tecido muscular. Em seis pacientes foram identificadas mutações patogênicas no FKRP, sendo em homozigose em cinco casos e em heterozigose em um caso. A maioria dos pacientes com LGMD2I (cinco casos) apresentava a mutação c.826C > A. Foi observada ausência total ou parcial da expressão da CAPN3 em pacientes com LGMD2A. Conclusões: O presente estudo mostrou que mutações nos genes CAPN3 e FKRP são frequentes em pacientes com diagnóstico clínico e histológico de LGMD. A análise da expressão da CAPN3 se mostrou como uma importante ferramenta no diagnóstico da LGMD2A
Introduction: The Limb-Girdle Muscular Dystrophies (LGMD) are caused by mutations on a wide variety of genes that encode muscular proteins which can be inherited in dominant or recessive autosomal forms. The diagnosis is made either by genetic study or by muscle biopsy which shows a dystrophic histologic pattern with specific deficiency of muscular proteins. On some LGMD subtypes such as calpain-3 (CAPN3) and fukutin related protein (FKRP) deficiencies it is not possible to make a specific diagnosis by muscle biopsy. In these cases, the molecular exam is of great value to confirm the diagnosis. Objectives: Analyze the CAPN3 and FKRP genes in patients with histological diagnoses of LGMD, and verify the protein expression of CAPN3 on these patients correlating it with the identified mutations and their clinical and histological pattern. Results: Thirty-six patients with LGMD, where the muscular biopsy did not identify deficiency of dystrophin, dysferlin, caveolin-3 and sarcoglycans, from the Muscle Ambulatory of HC-FMUSP took part in this study. Of these, nine (25%) were diagnosed with LGMD2A, six (17%) with LGMD2I, and on 21 of them (58%), it was not possible to identify the specific subtype. Pathogenic mutations on CAPN3 were found in eight patients, being homozygous in two cases, compound heterozygous in five cases and heterozygous in one case. The diagnosis of LGMD2A in one patient was done based exclusively by CAPN3 protein analysis on the muscle tissue. Pathogenic mutations on FKRP were found in six patients, being homozygous in five cases and heterozygous in one case. Most of the patients with LGMD2I (five cases) presented the mutation c.826C > A. It was observed total or partial absence of the CAPN3 expression in patients with LGMD2A. Conclusions: The study showed that mutations on CAPN3 and FKRP are frequent in patients with clinical and histological diagnosis of LGMD. The CAPN3 expression analysis proved as an important tool in the LGMD2A diagnosis

Strength and flexibility training are widely used in various sports. However, studies about the effect of strength training using concentric action alone in the variables of flexibility capacity were not found in the literature. The aim of the present study was to analyze the effects of a 6 week strength training program using only concentric actions with or without the combined flexibility training of hamstring muscles in the variables maximal voluntary contraction (CVM), one repetition maximum (1RM), stiffness, energy, maximum range of motion (ADMmáx), maximum passive torque, subjective stretch tolerance (PSA) and integrated electromyographic activity (iEMG). Twenty-two male volunteers with a mean age of 23,0 ± 3,7 years, height of 176,5 ± 6,0 cm and a mass of 72,5 ± 10,0 kg participated of this study. Volunteers were randomly divided into concentric (n=12) and control (n=10) groups. The concentric group performed strength training for both lower limbs, while the right limb also performed a flexibility training (concentric_flex). The strength training consisted of 3 sets of 12 repetitions at 70% of 1RM, and at a frequency of 3 times per week. Flexibility training was performed twice a week, and in each section 4 sets of 20 second passive static stretch was performed. The control group did not perform any strength and flexibility training during the 6 weeks of this study. The results of the present study showed significant increase in the variables CVM and 1RM for the concentric. The concentric_flex group showed significant change in the variables CVM, 1RM, maximum ADM, maximum passive torque and PSA. All variables were unchanged in the control group. It can be concluded that strength training combined with flexibility training increases the variables of both capacities without other physical effects.
O treinamento das capacidades físicas força e flexibilidade é amplamente empregado em diversas modalidades esportivas. No entanto, estudos sobre o efeito do treinamento da força utilizando isoladamente a ação concêntrica sobre os parâmetros da flexibilidade não foram encontrados na literatura. O objetivo desse estudo foi analisar os efeitos de 6 semanas de treinamento da força utilizando isoladamente a ação concêntrica associada ou não ao treinamento da flexibilidade dos posteriores da coxa sobre os parâmetros contração voluntária máxima (CVM), teste de 1 repetição máxima (1RM), rigidez, energia, amplitude de movimento máxima (ADMmáx), torque passivo máximo, percepção subjetiva ao alongamento (PSA) e integral do sinal eletromiográfico (iEMG). A amostra foi composta de 22 voluntários do gênero masculino com média de idade de 23,0 ± 3,7 anos, estatura de 176,5 ± 6,0 cm e massa corporal de 72,5 ± 10,0 kg. Os voluntários foram aleatoriamente divididos nos grupos concêntrico (n=12) ou controle (n=10). O grupo concêntrico realizou treinamento da força utilizando a ação concêntrica em ambos os membros inferiores, enquanto somente o membro inferior direito executava o treinamento da flexibilidade (Concêntrico_flex). O treinamento da força consistiu de 3 séries de 12 repetições à 70% do teste de uma repetição máxima (1RM) com a freqüência de 3 vezes por semana. A flexibilidade foi treinada 2 vezes por semana sendo que em cada sessão eram realizadas 4 séries de alongamento passivo estático por uma duração de 20 segundos cada. O grupo controle não realizou nenhum treinamento durante o período do estudo. Os resultados deste estudo mostraram que não houve alteração para nenhum parâmetro para o grupo controle. o grupo concêntrico apresentou aumento significativo para os parâmetros CVM e o 1RM, enquanto o subgrupo concêntrico_flex apresentou aumento significativo dos parâmetros CVM, 1RM, ADM máxima, Torque passivo máximo, percepção subjetiva do alongamento (PSA). Podemos concluir que o treinamento simultâneo das capacidades força e flexibilidade gera melhora das duas capacidades sem interferência entre elas.

The purpose of this study is to develop a prediction equation for (performance variables) vertical jump, broad jump, 40-yard sprint time, and pro-agility shuttle time using body mass and 1-RM values of strength for bench press and back squat. Participants (n = 76) used in the study were members of the University of South Florida D-1 football team in fall of 2009. Squat/BM demonstrated the strongest relationship in both correlation and multiple regression data for every performance variable. Squat 1-RM and Squat/BP indicated a decreased relationship and negative impact on performance. Results indicate that with increased Squat/BM improvement for all performance variables can be achieved. In addition analysis divided the entire football team into three positions (AT, LN, and SK), and noted differences for 10 of the possible 12 mean comparisons of performance variables.

Orientador: Maeli Dal Pai
Resumo: A musculatura esquelética em peixes corresponde mais de 70% do peso corporal total desses animais e o desenvolvimento, crescimento e manutenção do fenótipo muscular envolvem o balanço dinâmico entre as vias de anabolismo e catabolismo muscular, sendo influenciado por diversos fatores, como a disponibilidade alimentar. Períodos com baixa ou nenhuma disponibilidade de alimento é frequentemente observado na natureza e talvez, por isso, garantem aos peixes uma alta capacidade adaptativa para enfrentar períodos de jejum prolongado. Com a realimentação e os níveis metabólicos restabelecidos, o animal pode apresentar um processo de crescimento acelerado, chamado crescimento compensatório. Existe um grande interesse da aquicultura nos processos de crescimento compensatório após jejum, uma vez que bem estabelecido pode gerar diminuição do custo com a alimentação e aumento dos níveis de produção. Uma ferramenta para o estudo do músculo de peixes durante períodos de jejum e realimentação é a proteômica. A proteômica permite identificar o conjunto de proteínas expressas por uma célula ou tecido em determinadas situações e modificações ambientais e possui a vantagem de caracterizar eventos pós-traducionais, algo impossibilitado pela genômica e transcriptoma. Dessa forma, nós testamos a hipótese de que juvenis de pacu (Piaractus mesopotamicus) submetidos a 30 dias de jejum e 30 e 60 dias de realimentação apresentam crescimento compensatório e alterações no perfil de expressão proteico da m... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The skeletal muscle in fish corresponds more than 70% of the total body weight and the development, growth and maintenance of the muscle phenotype involves the dynamic balance between muscle anabolism and catabolism pathways, being influenced by several factors, such as food availability. Periods with low or no food availability are often observed in nature and may therefore, ensure a high adaptive capacity in fish to deal with prolonged fasting periods. With refeeding and metabolic levels restored, the animal may exhibit accelerated growth, called compensatory growth. There is a great interest of aquaculture in the processes of fasting/refeeding, once well-established can generates decrease of the feeding costs and increase of the production levels. An important tool to analyze muscle fish during fasting/refeeding is Proteomics. The proteomics allows to identify a set of proteins expressed by a cell or tissue in some situations and environmental changes and has the advantage of characterizing post-translational events, something impossible to detect by genomic and transcriptome analysis. This way, we tested the hypothesis that juveniles pacu (Piaractus mesopotamicus) submitted to 30 days of fasting and 30 and 60 days of refeeding present compensatory growth and alterations in the protein expression profile of the skeletal muscle. For this, we used two animals groups: Control group (C) fed continuously for 90 days and experimental group (E), submitted to 30 days of fasting fo... (Complete abstract click electronic access below)
Doutor

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, 2005.
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O objetivo deste estudo foi analisar simultaneamente o comportamento de alguns músculos flexores e extensores do cotovelo durante fadiga isométrica do Bíceps Braquial. Foram coletados os EMG dos músculos Bíceps Braquial (BBL), Braquiorradial (BRD), Flexores Superficiais dos Dedos (FSD), Tríceps Braquial (TBL) e Extensores Comuns dos Dedos (ECD). Simultaneamente foram registradas a força de flexão do cotovelo e a força dos dígitos. Foram analisadas as evoluções dos seguintes parâmetros durante o exercício: Freqüência Mediana (FMN), do Ângulo de Queda da FMN (AQ-FMN), do valor do RMS e do Tempo de Resistência (TR). Participaram 12 voluntários do sexo masculino da faixa de 20 a 25 anos, não praticantes de atividade física. O protocolo experimental consistiu na flexão do membro não dominante com o antebraço em supinação e o punho em posição neutra, nos ângulos de 45º, 90º e 135º de flexão de cotovelo, com carga de 30% da Contração Voluntária Máxima (CVM), até a exaustão, em 3 dias diferentes separados por 48 horas. Os resultados mostraram uma intensa atuação do TBL, que apresentou para RMS e FMN, diferenças significativas quando comparado com os outros músculos estudados. Ao contrário do esperado, os músculos flexores apresentaram comportamentos similares entre si. O ECD, entretanto, apresentou comportamento inesperado, similar aos flexores. Foram discutidas as possíveis explicações para esses resultados. _______________________________________________________________________________ ABSTRACT
This study aimed to simultaneously analyze the behavior of some elbow flexors and extensors muscles during Bíceps Brachii isometric fatigue. Surface EMGs were recorded from long head of biceps brachii (BBL), braquiorradial (BRD), flexor digitorum superficialis (FDS), lateral head of triceps brachii (TBL) and extensor digitorum (ED). Force of flexion of the elbow and force of the digits were also recorded. The evolutions of the following parameters during exercise were analyzed: median frequency (FMN), angle of FMN fall, RMS value and resistance time (RT). The sample was composed of 12 male volunteers, aged 20-25 years, not doing physical activity. The experimental protocol consisted of an isometric flexion of the elbow of the not dominant member until exhaustion at 45º, 90º e 135º angles, with a 30% of the Maximum Voluntary Contraction (MVC) load. The forearm was kept in supine and the fist in neutral position. The results showed a sensible activity of the TBL, which exhibited for both RMS and FMN significant differences when compared to the other studied muscles. As expected, the flexor muscles presented similar behaviors between themselves. Otherwise, the ECD presented an unexpected behavior, much similar to the flexors. The possible explanations for these results had been argued.

El objetivo de este trabajo de tesis es el desarrollo de un dispositivo de electroestimulación muscular portátil, ligero y de bajo costo, que permita complementar el entrenamiento físico voluntario y tonifique las fibras musculares
Tesis

Orientador : Prof. Dr. André Luiz Felix Rodacki
Dissetação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia. Defesa: Curitiba, 29/09/2014
Inclui referências
Área de concentração : Fisiologia
Resumo: A prática esportiva de alta intensidade causa pequenas rupturas dos componentes músculo-tendíneos que são seguidos por processo inflamatórios marcados por elevada sensibilidade nos receptores da dor. A dor muscular tardia pós-exercício caracteriza-se por dor e desconforto muscular, a qual tem sido apontada como um dos fatores que pode reduzir a capacidade de produzir força e diminuir o desempenho atlético. A acupuntura tem sido proposta como uma forma efetiva para reduzir a dor e pode prover melhorias na sensibilidade muscular e restituir a capacidade muscular de produzir elevada força e desempenho. Assim, o presente estudo visou verificar o efeito da aplicação da acupuntura sobre a dor muscular de inicio tardio e a capacidade contrátil. Trinta participantes (12 homens e 18 mulheres; 26.3 ± 3.1 anos; 66.5 ± 12.6 kg e 1.70 ± 0.08 m) foram divididos aleatoriamente em três grupos: acupuntura (GA; n = 10), Sham (GS; n = 10) e controle (GC; n =10). Os grupos foram avaliados quanto a percepção da dor com o uso da escala visual analógica, limiar da dor por algometria. A ativação muscular foi quantificada por meio da RMS e frequência mediana. Finalmente, a força muscular isométrica foi determinada pelo pico de força isométrica. No grupo que recebeu acupuntura houve diminuição da percepção da dor através da escala visual analógica (p<0.05) e aumento no limiar da dor com o algômetro (p<0.05), no grupo placebo e controle essas alterações não foram encontradas. Em relação à ativação muscular, houve um decréscimo na RMS (p<0.05) e aumento da frequência mediana (p<0.05) para o grupo que recebeu acupuntura, o mesmo resultado não foi encontrado nos grupos placebo e controle. Não houve alteração na força muscular nos grupos acupuntura, placebo e controle (p>0.05) após intervenção com acupuntura. A acupuntura foi efetiva para diminuir a percepção da dor muscular tardia, proporcionou alterações eletromiográficas no músculo estudado, mas não otimizou a capacidade de contração muscular. Palavras Chaves: Acupuntura, Dor, Dor Muscular Tardia.
Abstract: Sports practice of high intensity cause small ruptures of the muscle-tendon components that are followed by inflammatory process marked by a enhance sensitivity to pain receptors. The delayed onset muscle soreness after exercise is characterized by muscle pain and discomfort, which has been identified as one of the factors that can reduce the ability to produce force and decrease athletic performance. The acupuncture has been proposed as an effective way to reduce pain and can provide improvements in muscle sensitivity and restoring the capacity to produce high muscle strength and performance. Thus, the present study aimed to verify the effect of the application of acupuncture on delayed onset muscle soreness and contractile capacity. Thirty participants (12 men and 18 women, 26.3 ± 3.1 years, 66.5 ± 12.6 kg and 1.70 ± 0:08 m) were randomly divided into three groups: acupuncture (GA, n = 10), placebo (GP, n = 10) and control (GC, n = 10). The groups were evaluated for the perception of pain using the visual analog scale, pain threshold by algometry. Muscle activation was quantified by the RMS and median frequency. Finally, the isometric muscular strength was determined by the peak isometric force. In the acupuncture group showed decreased perception of pain using a visual analog scale (p <0.05), and increase in pain threshold with the algometer (p <0:05), in the placebo and control these changes were not found. In relation to muscle activation, there was a decrease in the RMS (p <0.05), and increased median frequency (p <0.05) in the acupuncture group, the same result was not found in the placebo and control groups. Acupuncture was effective to decrease the perception of DOMS, provided electromyographic changes in the muscle studied, but did not optimize the ability of muscle contraction. Keywords: Acupuncture, Pain, delayed onset muscle soreness.

Orientador: Humberto Santo Neto
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A distrofia muscular de Duchenne (DMD) é uma miopatia ligada ao cromossomo X, provocada pela ausência de distrofina, uma proteína da membrana da fibra muscular esquelética, cuja função está relacionada à manutenção da estab11idade do sarcolema. A ausência de distrofina, abera a integridade estrutural do sarcolema fazendo com que a fibra muscular sofra necrose e posterior regeneração. Com o surgimento de uma linhagem de camundongos mutantes (mdx) cujas fibras musculares à semelhança dos pacientes humanos são deficientes em distrofina, diversos trabalhos vêm sendo desenvolvidos com estes animais. Até o início da senilidade, os camundongos não apresentam fraqueza muscular e não vão a óbito. Outra diferença fenotipica fundamenta} entre a DMD humana e a dos camundongos é o fato de que, nestes últimos, as fibras musculares mantém a capacidade de regeneração. É certo que a ausência de distrofina seja a responsável direta pela necrose das fibras musculares, entretanto, é possível que a perda da capacidade regenerativa esteja relacionada a outros fatores. Um desses fatores, fundamental no presente trabalho, refere-se às células satélites das fibras musculares precursoras dos mioMastos e que originam novas fibras musculares. Estudos in vitro com células satélites de pacientes com DMD, demonstram que elas perdem, com o avançar da idade, a capacidade de se dividir. Dessa forma o presente traba1ho procura demonstrar experimenta1mente a capacidade regenerativa das fibras do músculo tibial anterior através de uma série de injeções de doridrato de lidocaína 2%. Os animaís de ambos os grupos (Grupo A - mdx; Grupo B -Black 10) foram submetidos a 20 e 55 aplicações de cloridrato de lidocaína, induzindo-se ciclos de degeneração e regeneração das fibras musculares. Os músculos coletados foram incluídos em historresina e corados pelos métodos da Hematoxilina-Eosina e Picrosirius-hematoxilina (para análise de tecido conjuntivo). Após a quantificação das populações das fibras musculares, os resu1tados mostraram que ao final 55 aplicações, a população de fibras regeneradas nos animais mdx sofreu uma redução de 48% em relação ao grupo controle, sendo que, ao final de 20 aplicações a redução da população de fibras foi de 0.2%. Não foi constatado o desenvolvimento de fibrose, o que exclui a tese sustentada por a1guns pesquisadores, de que este fator 100... seria o responsáve{ pe{a redução da capacidade regenerativa das fibras. De acordo com nossos resultados, podemos concluir que a redução da capacidade regenerativa das fibras está diretamente ligada a exaustão da capacidade miogênica das células satélites, não se encontrando qualquer evidência de que a redução desta atividade esteja associada ao aparecimento de fibrose intersticial
Abstract: The Duchenne (Dl
Doutorado
Histologia
Doutor em Biologia Celular e Estrutural

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The respiratory muscles as the skeletal muscles, are sensitive to an appropriate program of physical training and they can be training with the goal of improve their force and endurance. The aim of the present study is to value the effects of the inspiratory muscles training (IMT) on muscle force and on lung function in asthmatic infants. It is an analytic, experimental and random study. It were valued 50 infants by random choose, in two groups: Experimental Group (EG) composed of 25 infants who did IMT in a program of help an education on asthma and a Control Group (CG), composed of 25 infants who were submit only to monthly medical consults and education on asthma. The IMT was implement by using the Threshold IMT with load of 40% of Inspire Maximum Pressure. The analysis of the results was made by using the Student t Test paired and non-paired and the Qui-Square Test with p ≤ 0,05. At the comparative analysis the variables muscle force and peak flow before and after intervention, was observed an increased of the Inspire Maximum Pressure on EG from -48,32 ± 5,706 to 109,92 ± 18,041 (p≤0,0001); Expire Maximum Pressure from 50,64 ± 6,55 to 82,04 ± 17,006 (p≤0,0001) and Peak flow from 173,6 ± 50,817 to 312 ± 54,848 (p≤0,0001). There was no significant increased at the variables Inspire Maximum Pressure and Expire Maximum Pressure on CG. There was a significant increased of the Peak flow at the CG from 188 ± 43,97 to 208,80 ± 44,283 (p≤0,0001). There was a significant increased at the variables gravity of the nocturnes symptoms, frequency of looking for emergency room and hospitalizations at the two groups (p≤0,0001). In the variable gravity of attack frequency only the EG had significant increased (p≤0,0001). Believe that the RMT can increase the mechanical efficiency at the respiratory muscles and at the lung function in asthmatic infants.
Os músculos respiratórios como os músculos esqueléticos, são sensíveis a um programa de treinamento físico adequado e podem ser treinados a fim de melhorarem sua força e endurance. O presente estudo tem como objetivo avaliar os efeitos do treinamento muscular inspiratório (TMI) com Threshold na força muscular e função pulmonar em crianças asmáticas. Trata-se de um estudo analítico, experimental e aleatório. Foram avaliadas 50 crianças alocadas aleatoriamente em dois grupos: Grupo Experimental (GE) composto de 25 crianças que realizaram TMI em um programa de assistência e educação em asma e um Grupo Controle (GC), composto de 25 crianças que foram submetidas apenas às consultas médicas mensais e educação em asma. O TMI foi realizado com o Threshold com a carga de 40% da pressão inspiratória máxima ( Pimáx). A análise dos resultados foi realizada através do Teste t de Student pareado e não pareado e Teste de χ2 (qui-quadrado) com p ≤ 0,05. Na análise comparativa das variáveis força muscular, pressão inspiratória máxima (Pimáx) e pressão expiratória máxima (Pemáx) e pico de fluxo expiratório (PFE) pré e pós intervenção, foi observado aumento da Pimáx. em GE de -48,32 ± 5,706 para -109,92 ± 18,041 (p ≤ 0,0001); Pemáx de 50,64 ± 6,55 para 82,04 ± 17,006(p ≤ 0,0001) e PFE de 173,6 ± 50,817 para 312 ± 54,848 (p ≤ 0,0001). Não houve aumento significativo das variáveis Pi máx e Pe máx. no GC. Houve aumento significativo do PFE no GC de 188 ± 43,97 para 208, 80 ± 44,283 (p ≤ 0,0001). Houve melhora significativa das variáveis de gravidade como sintomas noturnos, frequência de procura ao pronto-socorro e hospitalização nos dois grupos (p<0,001). Na variável de gravidade frequência de crises apenas GE apresentou melhora significativa (p<0,001). Acredita-se que o TMI proporcione uma melhora na eficiência mecânica nos músculos respiratórios e na no pico de fluxo expiratório das crianças asmáticas.

A fisioterapia motora vem sendo empregada como terapia de suporte para as distrofias musculares, porém, seu efeito no músculo distrófico e na função motora global precisa ser melhor compreendida para direcionar os tratamentos. Esta pesquisa objetiva elucidar o papel da fisioterapia motora na deposição de colágeno muscular, bem como em alguns parâmetros cinemáticos e dinâmicos da marcha do modelo Golden Retriever Muscular Dystrophy (GRMD). Fragmentos do músculo bíceps femoralis foram coletados por biópsia de cinco animais GRMD de mesma idade para análises por microscopia de luz e imuno-histoquímica. A marcha dos animais foi registrada por câmeras de vídeo e as Forças de Reação do Solo (FRS) nos sentidos vertical (Fy), craniocaudal (Fx) e mediolateral (Fz) coletadas utilizando uma plataforma de força Kistler AG (9287A/100Hz) com os valores normalizados pelo peso corporal. Dois animais (tratados: TD) participaram do protocolo de fisioterapia que consistiu de atividade de marcha com velocidade controlada em área de 288 metros, 3 vezes/semana durante 12 semanas. Os animais controles (CD) mantiveram sua rotina de atividades diárias. A coleta I foi considerada como tempo zero (t0) com n=5 e o tempo após a fisioterapia (t1) como coleta II. As análises estatísticas consideraram p<.01. Foi realizada Imuno-histoquímica anti-colágenos tipo I, III (Calbiochem®) e IV (Bioreagents®). As características histopatológicas foram observadas no t0. Os CD apresentaram fibras hipercontraídas no t1, não observadas nos TD. Os colágenos do tipo I e III foram os mais presentes e aumentados. No t1, feixes espessos de colágeno do tipo I foram observados no endomísio dos TD, comparado ao t0. Os animais GRMD apresentaram velocidade lenta de marcha no t0 (0.64 m.s-1) com diminuição da mesma no t1 para os TD (0.45 m.s-1). No t1, os TD apresentaram diminuição da ADM do quadril (p<.0001), bem como do ombro (p<.05). O joelho e carpo dos animais foram as articulações com maiores ADM durante a marcha. Houve aumento da força vertical (Fy) dos membros torácicos e pélvicos dos TD e CD no t1 comparada ao t0. Os CD mostraram aumento do tempo de suporte dos membros torácicos no t1. A força propulsiva (Fx-) dos animais GRMD estava diminuída no t0, não mostrando sofrer influência da fisioterapia. A força medial (Fz+) do membro torácico dos TD mostrou aumento no t1 quando comparada aos CD p<.0001). Os animais tratados apresentam diminuição da flexibilidade e menor regeneração do tecido muscular em comparação aos animais não tratados. Funcionalmente, a fraqueza muscular dos animais distróficos reflete em uma marcha lenta, com característica de sobrecarga e dificuldade de avançar com o corpo. Além destas características, os TD apresentam menor amplitude de movimento articular proximal quando comparado ao t0. A fisioterapia motora aplicada acelera as alterações morfológicas no músculo distrófico sem interferir na progressão das disfunções de marcha no modelo canino da distrofia muscular.
Physiotherapy has been widely used as support treatment for muscular dystrophies. Its effect on dystrophic muscle and global function should be better understood to guide treatments. This study aims to understand the role of motor physical therapy on muscular collagen deposition and some kinematics and dynamical parameters of gait of the Golden Retriever Muscular Dystrophy (GRMD) model. Five GRMD dogs with the same age had fragments of biceps femoralis collected by biopsy for light microscopy and Immunohistochemistry analysis. Gait of the dogs were video recording for kinematics analysis and Ground Reaction Forces (GRF) in vertical (Fy), craniocaudal (Fx) and mediolateral (Fz) direction were collect using a Force Plate Kistler AG (9287A/100Hz) and normalized for body weight. Two animals (therapy dogs: TD) underwent a protocol which consisted of velocity controlled walking activity in an area of 288 meters total length, 3 times/week per 12 weeks. Control dogs (CD) maintained their daily routine. Zero time (t0) is considered at collect I (n=5) and time after therapy (t1) - collect II. Statistical analysis considered p<.01. Immunohistochemistry anticollagen types I, III (Calbiochem®) and IV (Bioreagents®) were performed. Histopathology features were observed at t0. CD presented hypercontracted fibers that were not observed on TD at t1. Collagen types I and III were the most increased ones. At t1, thicker tracts of collagen type I were observed at the endomysium of TD compared to t0. GRMD dogs presented slow velocity of gait (0.64 m.s-1) at t0 and there were a decrease of this velocity of TD at t1 (0.45 m.s-1). Hip ROM was decrease at t1 (p<.0001), as well as the shoulder ROM (p<.05) for TD. Stifle and Carpal ROM presented the highest active ROM during gait of dystrophic dogs. Fy of thoracic and pelvic limbs at t1 of TD and CD was higher than t0. CD presented increase of support time of thoracic limbs at t1 (49 to 53%). Propulsive force (Fx-) of GRMD dogs were decrease at t0, with no effect of physical therapy. Medial force (Fz+) of TD thoracic limbs were higher at t1 when compared to CD (p<.0001). TD presents less muscular flexibility and regeneration when compared to CD. Functionally, the muscular weakness of dystrophic dogs reflects a gait with slow velocity, overloaded and difficulty to goes forward. Moreover, TD presented lower range of motion of the proximal joints when compared to t0. The applied motor physical therapy accelerates the morphological alterations on dystrophic muscle without stop the gait disorders of the canine model of Duchenne muscular dystrophy.

Introdução. Pacientes portadores de diabetes mellitus tipo 2 (DM2) podem apresentar fraqueza da musculatura inspiratória. O efeito do treinamento muscular inspiratório (TMI) nesses pacientes ainda é desconhecido. Objetivos. Avaliar os efeitos do TMI sobre a força muscular inspiratória, a função pulmonar, a capacidade funcional e a modulação autonômica em pacientes com DM2 com fraqueza da musculatura inspiratória. Métodos. A pressão inspiratória máxima (PImáx) foi avaliada em uma amostra de 148 pacientes com DM2 da qual 25 pacientes com PImáx < 70% do previsto foram randomizados para um programa de 8 semanas de TMI diário (n=12) ou TMI-placebo (n=13). A PImáx, a função pulmonar, o consumo máximo de oxigênio e a variabilidade da freqüência cardíaca foram avaliados antes e após o TMI. Resultados. Do total de pacientes avaliados, 29,05% (43 pacientes) apresentaram fraqueza muscular inspiratória. O TMI aumentou significativamente a PImáx (118%) e a resistência muscular inspiratória (320%), sem alterar a função pulmonar, a capacidade funcional e a modulação autonômica. Conclusões. O TMI, em pacientes com DM2 e fraqueza dos músculos inspiratórios, aumentou significativamente a PImáx sem modificar a função pulmonar, a capacidade funcional e a modulação autonômica.
Introduction. Subject with type 2 diabetes mellitus (DM2) can present weakness of the inspiratory muscle. The effect of the inspiratory muscle training (IMT) in these patients still is unknown. Objectives. To evaluate the effect of the IMT on the inspiratory muscle force, the pulmonary function, the functional capacity and the autonômica modulation in patients DM2 with weakness of the inspiratory muscle. Methods. The maximum inspiratory pressure (PImáx) was evaluated in a sample of 148 patients with DM2 of which 25 patients with PImáx < 70% of the foreseen one had been randomizeds for a program of 8 weeks of daily IMT (n=12) or IMT-placebo (n=13). The PImáx, the function pulmonary, the VO2 and the variability of the cardiac frequency had been evaluated before and after the IMT. Results. Of the total of evaluated patients, 29.05% (43 patients) had presented inspiratory muscle weakness. The IMT significantly increased the PImáx (118%) and the inspiratory muscle resistance (320%), without modifying the function pulmonary, the exercise capacity and the modulation autonomic. Conclusions. The IMT in patients with DM2 and weakness of the inspiratory muscles increased the PImáx without modifying the function pulmonary, the exercise capacity and the modulation autonomic significantly.

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Introdução: Pacientes com distrofia muscular de Duchenne (DMD) apresentam durante a evolucao natural da doenca dificuldades fisicas e funcionais progressivas. Ha dependencia de um cuidador, que geralmente e um familiar proximo. Todas as decisoes referentes a complexa rotina de tratamento e enfrentamento da doenca devem ser assumidas por esses familiares, por isso processos educativos sao importantes para aumentar o conhecimento sobre a doenca em suas diversas fases. Avaliar o grau de conhecimento dos familiares perante a doenca DMD pode ser uma boa estrategia para identificar os individuos que necessitem especialmente de intervencoes educacionais, aumentando a aderencia, e efetividade do tratamento e ainda podem contribuir para avaliar a efetividade dos programas de orientacao especificos da equipe interdisciplinar. Objetivo: Elaborar um questionario de conhecimento sobre distrofia muscular de Duchenne para familiares. Metodo: Foram entrevistados neste estudo 14 profissionais envolvidos no atendimento de pacientes com DMD (G1), 13 maes de pacientes com DMD (G2) e 10 pacientes com DMD (G3). O G1 recebeu uma pergunta aberta sobre quais informacoes da doenca DMD e seus tratamentos os familiares e pacientes de DMD deveriam ter acerca da doenca. Os G2 e G3 foram estimulados a relatar todo o conhecimento que possuem sobre DMD e seus tratamentos. Todos os discursos foram transcritos e organizados de acordo com quatro categorias pre-estabelecidas para elaboracao do conteudo do questionario: Genetica, Fisiopatologia, Tratamento e Atividades de vida pratica (AVP´s). Utilizou-se a tecnica do Discurso do Sujeito Coletivo (DSCÆs) para a analise dos dados, extrairam-se as expressoes chaves, as ideias centrais de cada grupo, em cada categoria e montaram-se os DSCÆs, tornando possivel a elaboracao das questoes. Resultados: Foram encontradas diferencas nos DSC´s dos tres grupos, que podem ser relacionados as caracteristicas sociodemograficas e nas diferencas da logica tecnico cientifica dos profissionais da area da Saúde e a logica da percepcao do senso comum da populacao alvo (familiares de paciente com DMD e pacientes com DMD). Elaboraram-se dez questoes de multipla escolha (duas questoes sobre genetica, tres sobre fisiopatologia, quatro sobre tratamento e uma sobre AVP´s). Conclusoes: O questionario de conhecimento sobre distrofia muscular de Duchenne foi elaborado e podera ser uma ferramenta de odialogo mensuravelo do nivel de informacoes pre-adquiridas por familiares de pacientes com DMD, fornecendo dados que poderao ser interpretados pela equipe envolvida, favorecendo estrategias de enfrentamento da doenca e promovendo maior aderencia ao tratamento proposto nas diversas fases da doenca. Necessita ser validado
Introduction: Patients with Duchenne muscular dystrophy (DMD) in the disease natural evolution present functional and progressive physical difficulties. Dependence on the caregiver is observed who usually is a close family member. All decisions to face the complex routine of therapy must be handled by these family members, so educational processes are important to increase disease awareness on the disease in its various phases. To assess the family’s degree of knowledge related to the DMD disease can be a good strategy to identify individuals who specially need educational interventions, increasing patient adherence, effectiveness of treatment and contributing to assess effectiveness of specific orientation programs of an interdisciplinary team. Objective: to develop a questionnaire to obtain the knowledge about Duchenne muscular dystrophy. Methodology: this study interviewed fourteen professionals involved in the care of patients with DMD (G1), thirteen mothers of patients with DMD (G2) and ten patients with DMD (G3). The G1 received an open question about what information family members and patients must know about the DMD disease and its treatment. The G2 and G3 were also encouraged to report all the knowledge they have about DMD and its treatment. All the answers were transcribed and organized according to four pre-established categories to elaborate the questionnaire content: Genetics, Pathophysiology, Treatment and Practical Life Activities. For data analysis, the technique of Collective Subject Discourse (DSCs) was used and key expressions, central ideas of each group, in each category, were obtained to elaborate the DSCs allowing performing the questions. Results: differences in DSCs were found in the three groups that can be related to sociodemographic characteristics and in the differences regarding scientific technical logic of healthcare professionals and the common sense perception of the target population (DMD patient’s family members and patients with DMD). Ten multiplechoice questions (two questions on genetics, three on Pathophysiology, four on treatment and one on practical life activities). Conclusions: the questionnaire on the knowledge about Duchenne muscular dystrophy was elaborated and it was built to be a tool of "measurable dialog" regarding prior information of the DMD patient’s family members, providing data that can be interpreted by the team involved, favoring strategies to deal with the disease and promoting greater adherence to the treatment proposed in the various stages of the disease. The questionnaire has to be validated.
BV UNIFESP: Teses e dissertações

Caffeine is the most widely consumed drug in the world. Research has suggested that caffeine can enhance aerobic performance. However, its benefits in the resistance training world are not fully understood. Due to caffeine's ability to alter pain perception and the onset of peripheral fatigue it may positively affect performance. This study examined the effects of caffeine on muscular strength, determined by the number of successfully completed reps at 85% of 1RM bench press. Fifteen recreationally trained males were tested for their 1RM on bench press. Subjects completed 3 randomized, double blind tria ls at 85% of their 1RM to failure after receiving caffeine, a placebo, or no treatment. Successful reps were recorded. Data was analyzed using a within group ANOVA (p = 0.05) to compare the differences in reps between trials. No significant differences were found between trials; however the mean number of reps completed was greater for the caffeine vs. placebo trials (7.27 vs. 7.2), suggesting no negative effect occurred as well. Further research is needed utilizing more complete training bouts and lower intensity/ higher repetition training.

This research aimed at assessing respiratory muscle function, electrical activity of the accessory inspiratory muscles, diaphragmatic range of movement (DROM), the palate dimensions and nasal patency in adults with mouth breathing mode (MB), comparing with adults with nasal breathing mode (NB). In the study, 77 adults were selected, from 18 to 30 years old, of both sexes, according the inclusion criteria, allocated in MB (n=38) and NB (n=39) groups. The breathing mode (MB/NB) was diagnosed, based on physical characteristics, the signs and symptoms and on the otorhinolaryngologic examination. It was evaluated anthropometric measurements, maximal inspiratory and expiratory pressures (MIP, MEP), peak nasal inspiratory flow (PNIF), spirometry, nasal obstruction symptoms (NOSE scale), vertical and transverse palate dimensions , ultrasonography of the diaphragm muscle during breathing at Tidal Volume (TV), inspiration at Lung Total Capaciy (LTC) and sniff test. Yet, it was carried out the surface electromyographic (sEMG) of the sternocleidomastoid (SCM) and upper trapezius (UT) for evaluation of the amplitude and symmetry activity (POC%) during rest, inspiration at LTC and in the sniff, MIP and MEP tests. For statistical analysis, SPSS statistical software (version 17.0) was utilized, adopting a significance level of 5 % and the tests Shapiro-Wilk (data normality), Student t and Mann-Whitney (comparison between groups), Intraclass Correlation Coefficient (inter and intra-examiner reproducibility), Pearson and Spearman (correlation between variables) and the chi-square test for nominal variables. In the comparison between groups, the MB had significantly higher mean values for NOSE scale and lower mean values for MIP, MEP, PNIF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and sEMG activity of SCM in the sniff, PNIF and MIP tests. There was no difference in sEMG activity during rest, inspiration TLC, as well as for the POC%. The DROM was lower in the MB group in all tests, with significant difference at rest and TLC. Palate dimensions, in the MB group, showed significantly smaller transverse distance in intercanine region and, bigger in the vertical distance at the premolars and molars regions. The PNIF correlated inversely with the NOSE scale, with the UT sEMG at rest and LTC and, positively, with the FVC, the palate transversal distance, MIP and DROM. The MIP was positively correlated with MEP and FVC. The MB group presented smaller nasal patency, smaller width and higher height of hard palate than NB. The mouth breathing reflected in the smaller values of respiratory pressures, accessory inspiratory muscle electrical activity and diaphragmatic amplitude. As smaller the nasal patency, smaller the respiratory muscle pressure, the diaphragm amplitude and the width of hard palate.
Esta pesquisa teve por objetivo verificar a função muscular respiratória, atividade elétrica dos músculos inspiratórios acessórios, amplitude do movimento diafragmático (AMD), dimensões do palato e patência nasal em adultos com modo respiratório oral (RO), comparando-os com adultos com modo respiratório nasal (RN). Foram selecionados 77 adultos, entre 18 e 30 anos de idade, de ambos os sexos, de acordo com os critérios de inclusão, sendo alocados nos grupos RO (n=38) e RN (n=39). O modo respiratório foi diagnosticado baseado nas características físicas, sinais e sintomas e no exame otorrinolaringológico. Avaliou-se medidas antropométricas, pressões inspiratórias e expiratórias máximas (PImáx, PEmáx), pico de fluxo inspiratório nasal (PFIN), espirometria, sintomatologia de obstrução nasal (escala NOSE), dimensões vertical e transversal do palato e ultrassonografia do diafragma durante respiração em volume corrente (VC), inspiração na capacidade pulmonar total (CPT) e teste de sniff. Ainda, realizou-se eletromiografia de superfície (sEMG) dos músculos esternocleidomastoideo (ECM) e trapézio superior (TS), para avaliação da amplitude e índice de simetria da atividade elétrica (POC%) no repouso, inspiração na CPT, sniff, PImáx e PFIN. Para a análise estatística utilizou-se o programa estatístico SPSS (versão 17.0), com nível de significância de 5% e os testes Shapiro-Wilk (normalidade dos dados), t-student e Mann-Whitney (comparação entre os grupos), Coeficiente de Correlação Intraclasse (reprodutibilidade inter e intra-examinadores), Pearson e Spearman (correlação entre as variáveis) e o qui-quadrado (variáveis nominais). Na comparação entre os grupos, os RO apresentaram valores significativamente maiores para a escala NOSE e menores para PImáx, PEmáx, PFIN, capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e amplitude da sEMG dos músculos ECM nos testes de sniff, PFIN e PImáx. Não houve diferença na sEMG no repouso e na inspiração em CPT, assim como no POC%. A AMD foi menor no grupo RO em todas as situações testadas, com diferença significante durante o repouso e CPT. O grupo RO apresentou distância transversal do palato significativamente menor na região intercanina e maior na distância vertical, na região dos pré-molares e molares. A medida do PFIN se correlacionou inversamente com a escala NOSE e com a sEMG do TS durante o repouso e CPT. Correlações positivas foram encontradas na medida do PFIN com CVF, distância transversal do palato, PImáx e AMD. A PImáx se correlacionou positivamente com a PEmáx e CVF. O grupo RO apresentou menor patência nasal, menor largura e maior altura do palato duro que o RN. A respiração oral repercutiu em menores valores de pressões respiratórias, de atividade elétrica dos músculos inspiratórios acessórios e de amplitude diafragmática. Quanto menor a patência nasal, menores os valores das pressões respiratórias, a amplitude de movimento do diafragma e a largura do palato duro.

Resumo: A tensão muscular excessiva representa um obstáculo bastante comum enfrentado por músicos frente à necessidade de expressar fisicamente o conteúdo de uma obra musical. Pesquisadores vêem o problema da tensão na execução não apenas como limitador da qualidade da performance, mas como um dos mais importantes fatores de risco para o desenvolvimento de lesões neuromusculares em nstrumentistas. A literatura apresenta o problema como produto de uma diversidade de fatores, físicos e emocionais, o que aponta para a necessidade de um enfoque interdisciplinar, envolvendo áreas como a medicina, a fisioterapia, a psicologia e a pedagogia do ensino instrumental. Em nossa pesquisa, nos propomos a investigar o fenômeno da tensão excessiva no universo da performance pianística. Uma survey de pequeno porte, realizada por meio de um questionário aplicado a 14 estudantes de graduação em piano, levantou dados acerca de suas opiniões e experiências relacionadas ao tema. Os resultados revelaram a tensão excessiva como um problema bastante relevante e com elevada incidência: afeta a todos os respondentes, sendo que 57,15% experimentam-na freqüentemente ou sempre em suas execuções. Na visão dos entrevistados, a questão se constitui numa das principais causas de dificuldades enfrentadas por pianistas, apenas superada pela maneira de estudar, técnica e ansiedade. A ansiedade e a maneira de estudar foram apontadas como os fatores mais responsáveis pelo próprio excesso de tensão muscular. Tal percepção é concordante com outras pesquisas já desenvolvidas sobre este tema e, além de revelar o grau de consciência acerca do problema, é indicadora de que estratégias que visem minimizar e eliminar a tensão muscular excessiva requerem a abordagem da ansiedade e a avaliação dos procedimentos usados na prática diária do piano. Os dados obtidos podem indicar possíveis direcionamentos para novas pesquisas nas modalidades qualitativas e exploratórias, ou mesmo quantitativas, que investiguem populações e amostras maiores.

Muscular dystrophy is a collective group of genetic disorder that results in progressive wasting of skeletal muscle. Dysferlin, the gene responsible for Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi Myopathy (MM) was found to be a member of a newly identified protein family named the ferlins. Recent work has suggested that dysferlin is necessary for efficient calcium sensitive membrane resealing therefore is involved in membrane repair, a mechanism which if defective results in progressive muscle wasting. In this project, the involvement of other genes that could possibly be associated with muscular dystrophy is investigated. Myoferlin, a member of the ferlin protein family is highly homologous to dysferlin and is also a plasma membrane protein with six C2 domains and a C-terminus transmembrane domain. To date no disease has been associated with mutations in the myoferlin gene but its high similarity to dysferlin means that it could be a potential muscular dystrophy associated gene. Results obtained from this study strongly suggest that myoferlin like dysferlin is enriched at plasma membrane disruption sites and during myoblast differentiation, two processes which involve the fusion of two opposed bilayers, a process vital in membrane repair. In addition, a fifth member of the ferlin protein family is reported in this project and the primary results obtained are consistent with it being a potential muscular dystrophy associated gene. Finally, a group of MM affected families that were previously excluded for mutations in their dysferlin gene were analysed for muscular dystrophy associated genes other than dysferlin.

Thesis: S.M., Massachusetts Institute of Technology, School of Engineering, Center for Computational Engineering, Computation for Design and Optimization Program, 2015.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 75-78).
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood and affects 1 in 3600 male births. The disease is caused by mutations in the dystrophin gene leading to progressive muscle weakness which ultimately results in death due to respiratory and cardiac failure. Accurate, practical, and painless tests to diagnose DMD and measure disease progression are needed in order to test the effectiveness of new therapies. Current clinical outcome measures such as the sixminute walk test and North Star Ambulatory Assessment (NSAA) can be subjective and limited by the patient's degree of effort and cannot be accurately performed in the very young or severely affected older patients. We propose the use of image-based biomarkers with suitable machine learning algorithms instead. We find that force-controlled (precise acquisition at a certain force) and force-correlated (acquisition over a force sweep) ultrasound helps to reduce variability in the imaging process. We show that there is a high degree of inter-operator and intra-operator reliability with this integrated hardware-software setup. We also discuss how other imaging biomarkers, segmentation algorithms to target specific subregions, and better machine learning techniques may provide a boost to the performance reported. Optimizing the ultrasound image acquisition process by maximizing the peak discriminatory power of the images vis-à-vis force applied at the contact force is also discussed. The techniques presented here have the potential for providing a reliable and non-invasive method to discriminate, and eventually track the progression of DMD in patients.
by Sisir Koppaka.
S.M.

Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by progressive degeneration of muscle fibers and dystrophic changes on muscle biopsy¹. DMD accounts for approximately 50% of all dystrophinopathies, with around 21,000 male babies born with the disease each year², ³, ⁴, ⁵. It is also the most lethal X-linked recessive disorder as phenotypic traits are not immediately present at birth¹¹, ³. Patients usually do not live past their 20's without medical intervention to treat associated respiratory and cardiac dysfunctions¹¹, ³. For these reasons DMD remains one of the greatest threats, amongst a range of pediatric pathologies, to the normalcy of child development and parental care. Although treatment options have shown to mitigate the progression of DMD, most are controversial and costly - the estimated annual treatment cost of DMD per patient is $50,953⁵⁸. In light of this, disease awareness and public health education are critical components for acquiring funds needed for research towards a cure¹². My hope is that through this integrated overview of DMD, the medical layman will better understand the depths of this lethal disease, and how it can be detrimental to both the affected child and his caretaker.

Mounting evidence suggests that synaptic connections are early pathological targets in many neurodegenerative diseases, including motor neuron disease. A better understanding of synaptic pathology is therefore likely to be critical in order to develop effective therapeutic strategies. Spinal muscular atrophy (SMA) is a common autosomal recessive childhood form of motor neuron disease. Previous studies have highlighted nerve- and muscle-specific events in SMA, including atrophy of muscle fibres and postsynaptic motor endplates, loss of lower motor neuron cell bodies and denervation of neuromuscular junctions caused by loss of pre-synaptic inputs. Here I have undertaken a detailed morphological investigation of neuromuscular synaptic pathology in the Smn-/- ;SMN2 and Smn-/-;SMN2;Δ7 mouse models of SMA. Results imply that synaptic degeneration is an early and significant event in SMA, with progressive denervation and neurofilament accumulation being present at early symptomatic time points. I have identified selectively vulnerable motor units, which appear to conform to a distinct developmental subtype compared to more stable motor units. I have also identified significant postsynaptic atrophy which does no correlate with pre-synaptic denervation, suggesting that there is a requirement for Smn in both muscle and nerve and pathological events can occur in both tissues independently. Rigorous investigation of lower motor neuron development, connectivity and gene expression at pre-symptomatic time points revealed developmental abnormalities do not underlie neuromuscular vulnerability in SMA. Equivalent gene expression analysis at end-stage time points has implicated growth factor signalling and extracellular matrix integrity in SMA pathology. Using an alternative model of early onset neurodegeneration, I provide evidence that the processes regulating morphologically distinct types of synaptic degeneration are also mechanistically distinct. In summary, in this work I highlight the importance and incidence of synaptic pathology in mouse models of spinal muscular atrophy and provide mechanistic insight into the processes regulating neurodegeneration.

Orientador: Rui Errerias Maciel
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-18T11:27:31Z (GMT). No. of bitstreams: 1 Barros_MariliaMantovaniSampaio_M.pdf: 5610094 bytes, checksum: 3c8fc3572780a9ebbb0dc49aa4b3bf4b (MD5) Previous issue date: 1993
Resumo: Detectou-se o conteúdo histamínico nos tecidos muscular-esquelético (músculo gastrocnêmio) e cardíaco de ratos sedentários (controles). Estes índices foram comparados aos de animais treinados, sacrificados, respectivamente, a partir da condição de repouso e após 60 minutos de exercício agudo de natação em que ambos os grupos (sedentários ¿ SED e treinados ¿ TER) foram subemtidos. Para esta finalidade, foram utilizados 94 ratos (Rattus norvegicus albinus, Wistar) machos, distribuídos em grupos assim esquematizados: 1- SED-R: Animais mantidos em condições sedentárias; 2 ¿ SED-A: animais mantidos em condições sedentárias, que realizaram 60 minutos de exercício agudo de natação, imediatamente antes do sacrifício. 3 ¿ TER-R: animais que realizaram o treinamento de natação com resistência (8% do peso corporal), 60 min/dia, 5 dias/semana, durante 45 dias, mantidos em repouso de 24 horas após a última sessão de natação, até o sacrifício; 4 ¿ TRE-A: animais que realizaram o mesmo treinamento do grupo anterior e que se submeteram a 60 minutos de exercício agudo de natação, imediatamente antes do sacrifício. Após o sacrifício por decapitação em guilhotina, foram dissecados e pesados o coração e os músculos gastrocnêmio de ratos submetidos ao treinamento físico adotado. A HA pode participar da hemostasia microcirculatoria de músculos esqueléticos e corrações de ratos sedentários durante o exercício agudo de natação e de corações de ratos treinados em repouso
Abstract: Dynamic physical exercise and those realised in long time can result in an elevation of histamine (HA) level in blood and other tissues, besides of classic hormones. This research compared the HA levels in gastrocnemius and cardiac muscles on physical exercise: short term (SEG-SRC) and long term swimmg (T). The efficacy of long-term swimming was confirmed by histologic method (H/E). The determination of the HA levels was done by fluorimetric assay. Regarding the short-term exercise, the increase of the HA level in basal levels in SRC 1,43..
Mestrado
Fisiologia
Mestre em Ciências Biológicas

Indivíduos com hipertensão arterial sistêmica podem apresentar o metaborreflexo muscular inspiratório exacerbado comparado a indivíduos normotensos. No primeiro estudo, comparamos as respostas hemodinâmicas e respiratórias da ativação deste reflexo entre hipertensos e normotensos. Em uma amostra de conveniência, 31 participantes realizaram o protocolo de indução do metaborreflexo muscular inspiratório com carga e o protocolo controle. No protocolo de indução com carga houve maior aumento da pressão arterial média e redução do fluxo sanguíneo da perna para os hipertensos em relação aos normotensos. Conclui-se que o metaborreflexo muscular inspiratório pode estar exacerbado nos indivíduos hipertensos. O segundo estudo, protocolo de ensaio clínico randomizado duplo cego, foi publicado e tem como objetivo testar a eficácia do treinamento muscular inspiratório sobre a redução dos níveis pressóricos de hipertensos.
Individuals with systemic arterial hypertension may present exacerbated inspiratory muscle metaboreflex compared to normotensive individuals. In the first study, we compared the hemodynamic and respiratory responses of the activation of this reflex between hypertensive and normotensive individuals. In a convenience sample, 31 participants performed the induction protocol of inspiratory muscle metaborreflex with load and the control protocol. In the protocol of induction with load there was a greater increase in mean arterial pressure and reduction of blood flow from the leg to hypertensive patients in relation to the normotensive ones. It is concluded that inspiratory muscle metaboreflex may be exacerbated in hypertensive subjects. The second study, a randomized double-blind clinical trial protocol, was published and aims to test the effectiveness of inspiratory muscle training on the reduction of blood pressure levels in hypertensive patients.