Effect of one-time high load exercise on skeletal muscle injury in rats of different genders: oxidative stress and mitochondrial responses

Purpose: To evaluate the impact of one-time high load exercise on skeletal muscle injury and analysis its mechanism in different genders. Methods: Twenty-four male and 24 female rats were divided randomly into four groups respectively: control, 0 h, 6 h, and 24 h after exercise. The activities of creatine kinase (CK), lactate dehydrogenase (LDH), and myohemoglobin (MYO) in serum, the expression level of oxidative stress markers, mitochondrial respiratory chain complex enzyme, and the apoptosis related protein in quadriceps were detected. Results: The results showed that the activities of CK, LDH and MYO in serum increased immediately after exercise and restored faster in female rats. More obvious structural disorder and apoptosis in male rats were showed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were increased while catalase (CAT) and glutathione (GSH) were decreased in male rats. SOD, CAT and GSH were increased in female rats. Mitochondrial complex enzyme activity was decreased in males and increased in females. Conclusions: The skeletal muscle injury in both genders of rat could be induced by one-time high load exercise due to the mitochondrial respiratory enzyme dysfunction and oxidative stress, which was relatively mild and recovered quicker in female rats.

Miopatia mitocondrial e deficiência auditiva neurossensorial: estudo de caso / Mitochondrial myopathy and sensorineural hearing loss: case study

Resumo A miopatia mitocondrial é causada pela ausência e/ou insuficiência de uma enzina quaternária, L-carnitina, responsável por transportar ácidos graxos livres para a parte interna da mitocôndria. A função da mitocôndria é produzir energia, contribuindo para o bom funcionamento das células. A Lipidose Muscular é uma doença que provoca anomalias em enzimas que metabolizam gordura e por consequência causa acúmulo de toxinas de subprodutos com gordura nos tecidos. O objetivo deste trabalho é apresentar o estudo de caso da paciente B.D., 37 anos, diagnosticada com Lipidose Muscular aos seis anos, com deficiência de L-Carnitina e relatar o acompanhamento fonoaudiológico realizado em um serviço de saúde auditiva. A abertura de prontuário da paciente foi realizada em 05/03/1989. Foi prescrito pelo neurologista o uso contínuo de 2g/dia de L-carnitina. A mãe relatou que B.D. apresentava dificuldades em ouvir, pois era muito desatenta, o que foi mais evidente quando começou a frequentar a escola. Em 1988, a paciente foi diagnosticada com perda auditiva neurossensorial de grau moderado bilateral e começou a fazer uso de aparelhos de amplificação sonora individual retroauriculares em 1989. O desempenho escolar e comunicação melhoraram. Em 1998, passou a utilizar aparelhos tipo micro canal, o que a favoreceu esteticamente, promoveu melhora da localização sonora e maior ganho em altas frequências. Os limiares de audibilidade apresentaram uma leve piora e a paciente atualmente é pós-graduada e trabalha em uma grande instituição financeira. Conclui-se que o diagnostico neurológico e a intervenção fonoaudiológica precoces possibilitaram o adequado desenvolvimento de linguagem da paciente.

Abstract Mitochondrial myopathy is caused by the absence and/or insufficiency of L-carnitine, a quaternary enzyme responsible for transporting free fatty acids into the mitochondria. The primary function of the mitochondria is to produce energy, contributing to proper cell functioning. Muscular lipidosis causes abnormalities in enzymes that metabolize fat, resulting in the accumulation of harmful amounts of fats in tissues. The aim of this study was to present the case study of patient B.D., a 37-year-old woman diagnosed with muscular lipidosis with L-carnitine deficiency at 6 years old, and describe the speech-language follow-up performed at a hearing care clinic. The first entry in the patient's medical chart was on 03/05/1989, with continuous use of 2g/day of L-carnitine prescribed by a neurologist. The mother reported that B.D. had difficulty hearing and was inattentive, which became more evident when she started school. In 1988 the patient was diagnosed with moderate bilateral sensorineural hearing loss and began using behind-the-ear (BTE) hearing aids in 1989, after which her academic performance and communication improved. In 1998 she switched to Completely in Canal (CIC) hearing aids, which are more discreet, provided better sound localization and greater high frequency gain, although her hearing thresholds worsened slightly. She completed her graduate studies and currently works at a large financial institution. It was concluded that early neurological diagnosis and speech-language intervention enabled adequate language development in the patient.

Neumopatía crónica secundaria al trastorno de la deglución en un paciente con miopatía mitocondrial / Chronic pneumopathy secondary to swallowing disorder in a patient with mitochondrial myopathy

RESUMEN Introducción: la enfermedad pulmonar crónica secundaria a la disfagia es una complicación frecuente en los pacientes con enfermedades neuromusculares. Las miopatías mitocondriales son un conjunto de enfermedades que pueden conducir a daño pulmonar progresivo, secundario al síndrome aspirativo crónico. Caso clínico: niño de 7 años con signos clínicos y radiológicos de enfermedad pulmonar crónica; además, con desnutrición crónica, debilidad muscular, disfonía y oculoparesia externa crónica multiplanar. Su padre tuvo síntomas similares desde la infancia y requirió alimentación con dieta espesa por trastorno de la deglución. Se confirma en el paciente la presencia de disfagia como la causa de la neumopatía crónica y se sospecha miopatía congénita hereditaria. En consecuencia, se realiza el diagnóstico de enfermedad mitocondrial con oculoparesia externa crónica, mediante la secuenciación del gen polimerasa gamma del ADN mitocondrial (POLG). Conclusiones: en los pacientes con neumopatía crónica se deben considerar las enfermedades neuromusculares en el diagnóstico diferencial. La miopatía mitocondrial con oculoparesia externa crónica progresiva, se asocia con trastorno de la deglución hasta en un 50 % de los casos. El diagnóstico temprano es importante para retardar el deterioro de la función pulmonar.

SUMMARY Introduction: Chronic lung disease secondary to dysphagia is a frequent complication in patients with neuromuscular diseases. Mitochondrial myopathies could lead to progressive lung damage due to chronic aspiration syndrome. Clinical case: Seven-year-old male with clinical and radiological signs of chronic lung disease, as well as low weight, weakness, dysphonia and multiplanar external oculoparesis. His father had similar symptoms during infancy and needed thickened liquid diet due to swallowing disorder. Dysphagia was confirmed as the cause of chronic lung disease and, therefore, hereditary congenital myopathy was suspected. Mitochondrial disease with chronic external oculoparesis was confirmed by molecular sequencing of the mitochondrial DNA gamma polymerase gene (POLG). Conclusion: Neuromuscular disorders may cause chronic lung disease. Mitochondrial myopathy with progressive chronic external oculoparesis is associated with swallowing disorder in 50 % of the cases. Early diagnosis is important to slow decline in lung function.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Abstract Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

The Newcastle Pediatric Mitochondrial Disease Scale: translation and cultural adaptation for use in Brazil / Escala Pediátrica de Doença Mitocondrial de Newcastle: tradução e adaptação cultural para uso no Brasil

ABSTRACT Objective The aim of this study was to translate and adapt the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to Portuguese for use in Brazil. Methods The scale was applied in 20 pediatric patients with mitochondrial disease, in three groups: myopathy (n = 4); Leigh syndrome (n = 8); and encephalomyopathy (n = 8). Scores were obtained for the various dimensions of the NPMDS, and comparisons were drawn between the groups. Results There was a statistically significant difference between the myopathy group and the Leigh syndrome group (p = 0.0085), as well as between the myopathy and encephalomyopathy groups (p = 0.01). Conclusions The translation of the NPMDS, and its adaptation to the socioeconomic and cultural conditions in Brazil, make the NPMDS score useful as an additional parameter in the evaluation and monitoring of pediatric patients with MD in Brazil.

RESUMO Objetivo O objetivo do presente estudo foi realizar a tradução e adaptação da escala NPMDS para a população brasileira. Métodos A escala foi aplicada em 20 crianças e adolescentes com doença mitocondrial (DM) divididos em três grupos: miopatia (n=4), síndrome de Leigh (n=8) e encefalomiopatia (n=8). Obteve-se os escores separados das dimensões da escala NPMDS, foram realizadas comparações entre os escores da NPMDS nos diferentes grupos. Conclusão A tradução da escala NPMDS e sua adequação as condições socioeconômicas e culturais de nossa população tornam este instrumento um parâmetro adicional na avaliação e acompanhamento de pacientes pediátricos com DM.

MELAS en el Perú: reporte de caso / MELAS in Peru: case report

El síndrome de MELAS es una rara citopatía mitocondrial de difícil diagnóstico. Reportamos el caso de una niña de 10 años, que ingresó al Instituto Nacional de Ciencias Neurológicas de Lima, Perú, quien presentó episodios bruscos similares a accidentes cerebrovasculares y crisis epilépticas. Los estudios de neuroimágenes mostraron infartos y el examen genético fue positivo para MELAS identificando la mutación más frecuente A3243G...

MELAS syndrome is a rare mitochondrial cytopathy difficult to diagnose. We report the case of a 10 year old girl who was admitted to the National Institute of Neurological Sciences of Lima - Peru, who presented sudden stroke like episodes and seizures. Neuroimaging studies showed infarction and genetic testing was positive for identifying the most common MELAS mutation (A3243)...

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Melas: Aproximación diagnóstica y experiencia terapéutica reporte de dos casos. Hospital de San José, Bogotá DC / Melas syndrome: A diagnostic and therapeutic approach - a report of two cases Hospital de San José, Bogotá DC

La ocurrencia de encefalopatía, miopatía mitocondrial, acidosis láctica y episodios de strokelike es un raro síndrome clínico que se manifiesta por encefalopatía con convulsiones, acidosis láctica y episodios de strokelike (apoplejía) que constituyen una causa de enfermedad cerebrovascular en el adulto joven. Tiene expresión clínica distinta entre los mismos miembros de una familia y su base fisiopatológica se encuentra en la alteración de la fosforilación oxidativa con la subsecuente depleción de ATP en la célula, secundaria a una mutación en el ADNmt, siendo la 3243 A>G la más frecuente. No se ha establecido un protocolo de tratamiento adecuado para los pacientes con MELAS y lo recomendado está basado en reportes de casos o estudios abiertos no aleatorios. Se debe brindar una terapia apropiada a las comorbilidades encontradas, teniendo en cuenta el potencial de algunos fármacos para exacerbar la enfermedad.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare syndrome featured by encephalopathy with seizures, lactic acidosis and stroke-like episodes which constitute a cause of cerebrovascular disease (CVC) in young adults. MELAS has extreme variability of clinical expressions in members of the same family. Its pathophysiology is based on cellular ATP depletion caused by impaired oxidative phosphorylation secondary to a mtDNA mutation. A mutation of nucleotide pair 3243 A>G is found in most cases. An adequate treatment protocol for MELAS has not yet been established and recommendations are based on case reports or open randomized clinical trials. Coexisting conditions must receive adequate treatment considering that some medications can exacerbate the disease.

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( VO2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the VO2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The ΔVO2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak VO2 and muscle performance were lower in patients than controls (P < 0.05). Patients had significantly lower ΔVO2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P < 0.001). There were significant relationships between ΔVO2/ΔWR (S T) and muscle endurance, MRT-VO2, GET and peak VO2 in MM patients (P < 0.05). In fact, all patients with ΔVO2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak VO2 values (<60 percent predicted). Moreover, patients with higher cardiopulmonary stresses during exercise (e.g., higher Δ ventilation/carbon dioxide output and Δ heart rate/ΔVO2) had lower ΔVO2/ΔWR (P < 0.05). In conclusion, a readily available, effort-independent index of aerobic dysfunction during dynamic exercise (ΔVO2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress.

Facilitação neuromuscular proprioceptiva (FNP) na miopatia mitocondrial: estudo de caso / Proprioceptive neuromuscular facilitation (PNF) on mitochondrial myopathy: case study

Introdução: As miopatias mitocondriais são consideradas um grupo de desordens que podem comprometer uma variedade de órgãos e apresentar fenótipos variáveis. Frequentemente afetam o sistema nervoso central e a musculatura esquelética e cardíaca. Objetivo: Investigar os efeitos de um programa individualizado, baseado nas técnicas de facilitação neuromuscular proprioceptiva (FNP), no gerenciamento da fraqueza muscular e habilidades funcionais de um paciente com miopatia mitocondrial de início tardio e distribuição atípica. Material e métodos: O paciente foi submetido a uma avaliação da força muscular e da capacidade funcional antes e após 12 semanas de tratamento, composto por exercícios de intensidade leve/moderada, com duração de 60 minutos/sessão e frequência de 2 atendimentos semanais. Resultados e Discussão: Ganhos relacionados à força muscular foram obtidos em determinados grupamentos musculares. O nível de independência funcional não sofreu alterações após a proposta terapêutica, entretanto manteve-se estabilizado. Conclusão: O programa reabilitativo atuou na minimização das complicações geradas pela fraqueza muscular e na otimização das atividades quotidianas. A reabilitação física faz-se necessária para um melhor gerenciamento da fraqueza muscular e da habilidade do paciente na execução de atividades básicas e instrumentais da vida diária.

Transposição da rima palpebral em ptose miogênica mitocondrial / Tarsal switch levator for mitochondrial myogenic ptosis

OBJETIVO: Relatar o uso da ressecção do tarso da pálpebra superior e enxerto na pálpebra inferior para a elevação da rima palpebral e liberação do eixo visual, sem causar complicações corneanas em pacientes portadores de ptose miogênica mitocondrial. MÉTODOS: Estudo prospectivo. A técnica cirúrgica consiste na tarsectomia da pálpebra superior e autoenxerto do tarso na lamela posterior da pálpebra inferior. As cirurgias foram realizadas sob anestesia local. No caso de diplopia, a cirurgia foi realizada em apenas um olho. RESULTADOS: O procedimento foi realizado em 9 olhos de 6 pacientes com miopatia mitocondrial. Cinco pacientes eram do sexo feminino, a média de idade foi de 59,8 anos e o seguimento variou de 30 a 60 meses. A rima palpebral elevou em todos os pacientes, descobrindo o eixo visual na posição primária do olhar e melhorando a posição viciosa de cabeça. Não houve complicações decorrentes da exposição do globo ocular. CONCLUSÃO: A técnica de transposição da rima palpebral é útil na correção do mau posicionamento das pálpebras em pacientes sem mecanismos de proteção porque eleva a pálpebra superior e a inferior, diminuindo ou eliminando o risco de causar lagoftalmo com complicações corneanas.

PURPOSE: To report the use of tarsal switch levator resection procedures that lift the palpebral fissure to visual axis without causing corneal complications in patients with mitochondrial myogenic ptosis. METHODS: Prospective study. The technique consists of an upper eyelid tarsectomy, with transfer of the autologous tarsoconjunctival graft to the posterior lamella of the lower eyelid. The surgeries were performed under local anesthesia. In case of diplopia, the surgery was performed in one eye. RESULTS: Tarsal switch procedure was performed in 9 eyes of 6 patients with mitochondrial myopathy. There were 5 women; the average age was 59.8 years and the follow-up ranged from 30 to 60 months. The palpebral fissure was moved cephalad in all patients, unmasking their visual axis in primary position and improving their head position. There was no patient with exposure symptoms after surgery. CONCLUSION: The tarsal switch procedure is useful in managing the eyelid malpositions in patients with poor eye protective mechanisms because it elevates both the upper and the lower eyelids, decreasing or eliminating the risk of lagophthalmos with corneal complications.

Miopatias inflamatórias idiopáticas: relato de caso / The idiopathic inflammatory myopathies: case report

JUSTIFICATIVA E OBJETIVOS: As miopatias inflamatórias idiopáticas, também conhecidas como síndrome de miosite, são da família de doenças sistêmicas adquiridas do tecido conjuntivo, caracterizadas por efeitos clínicos e patológicos de inflamação muscular crônica de causa desconhecida. As formas mais comuns são a polimiosite e a dermatomiosite, que tem seu diagnóstico com base em uma combinação de achados clínicos, laboratoriais e histopatológicos. O objetivo deste estudo foi abordar a característica clínica da dermatopolimiosite e demonstrar a evolução e o tratamento da doença. RELATO DO CASO: Paciente do sexo feminino, 66 anos, apresentando quadro de dor no abdômen e nos membros superiores e inferiores, associada com diminuição da força muscular. Presença de dispnéia acompanhada de tosse produtiva. Foi submetida à avaliação reumatológica, levantando-se a hipótese de dermatopolimiosite, concluindo-se o diagnóstico após avaliação clinica e laboratorial. CONCLUSÃO: O tratamento da doença ocorreu de acordo com o padrão evolutivo que a paciente se encontrava.

BACKGROUND AND OBJECTIVES: The idiophatic inflammatory myopathies - or syndrome myositis - are a group of acquired systemic diseases of connective tissue with characteristic of clinical and pathological effect of chronic inflammatory of muscle whose your pathogenesis is strange. The types habitual are the polymyositis and the dermatomyositis. For diagnosis is necessary a arrangement of clinical, laboratory and histopathologic founds. In this article we approach the characteristics of idiopathic inflammatory myopathies, aiming to demonstrate the evolution and treatment of disease. CASE REPORT: Female patient, 66 years, presenting chart of pain in abdomen and lower and upper members, associated with diminution of the muscular force. Presence of dyspnea accompanied of productive cough. It was submitted to Rheumatologic clinical evaluation being raised the hypothesis of dermatopolymyositis, concluding the diagnosis after evaluation is in clinical practice and laboratory. CONCLUSION: The handling of the illness occurs according to the developing standard that the patient is found.

Síndrome de Kearns-Sayre / Kearns-Sayre syndrome

A síndrome de Kearns-Sayre é uma patologia rara, que acarreta piora da qualidade de vida; caracteriza-se por oftalmoplegia externa progressiva, fraqueza muscular e distúrbios na condução cardíaca. A entidade integra um grupo de desordens do metabolismo mitocondrial, denominadas miopatias mitocondriais ou citopatias mitocondriais.

Kearns-Sayres syndrome is a rare pathology which leads to a worse quality of life of the individual; it is characterized by progressive external ophthalmoplegia, muscular weakness, and cardiac conduction defects. The disease belongs to a group of mitochondrial metabolic disorders, named mitochondrial myopathies of mitochondrial cytopathies.

Miopatias inflamatórias no idoso / Infl ammatory myopathies in the elderly

As miopatias inflamatórias foram analisadas em suas diferentesformas, incluindo a dermatomiosite, polimiosite e miosites porcorpúsculos de inclusão, especialmente focalizadas em relação àpopulação idosa. Foram apresentados aspectos relativos à incidência,etiologia, quadro clínico, diagnóstico, diagnóstico diferencial,tratamento em suas várias modalidades e prognóstico. A associaçãodas miopátias infl amatórias com neoplasias foi particularmenteavaliada.

Miopatia mitocondrial - efeito do treinamento aerobico e de equilibrio: estudo de caso / Mitochondrial myopathy - effects of aerobic and balance training: reported case

Individuos com miopatia mitocondrial apresentam quadro caracteristico de intolerancia ao exercicio, fadiga e acidose latica. Foram avaliados as adaptacoes fisiologicas, a capacidade aerobica e a performance muscular de um paciente portador dessa doenca, submetido a treinamento aerobico realiazdo em cicloergometro e exercicios em solo. O treinamento aerobico foi realizado totalizando 20 minutos de exercicio dentro da zona de frequencia cardiaca (FC) submaxima durante 8 semanas, exercicios de solo estimularam coordenacao e equilibrio da paciente durante 18 semanas. A capacidade aerobica foi estimada antes e apos o treinamento aerobico por meio do teste de esforco submaximo, realizado em esteira com implemento de carga, dada a partir de 0,5 Km/h a cada intervalo de 2 min. A interrupcao do teste baseou-se no alcance da FC submaxima e na percepcao subjetiva de esforco, segundo a escala de Borg. O consumo de oxigenio foi determinado a partir da analise direta dos gases. A performance muscular foi avaliada antes e depois dos exercicios em solo e o programa de treinamento aerobio, pela analise das variaveis pico de torque e trabalho total, nas velocidades de 60/seg e 120/seg. os resultados observados para a capacidade aerobica demonstraram um acrescimo de 33,9 (por cento) nos indices aerobicos e de 33,8 (por cento) para requivalentes metabolicos. O joelho direito do paciente apresentou melhora na forca de flexao e extensao concentricas (60 e 120/seg), e o esquerdo apresentou melhora na forca de extensao concentrica (60 e 120/seg). Esse estudo suger que o treinamento aerobico associado a exercicios em solo pode beneficiar individuos com miopia mitocondrial, auxiliando-os no desempenho das atividades de vida diaria por reduzir a fraqueza e a intolerancia aos exercicios

Muscle cell outside and inside: the nascent approach of a clinician

Understanding muscle cell in disease and health is an unfinished process. Following the lead of Jaime Alvarez, I have had the opportunity of working on two complementary approaches to this field. One is the study of muscle cell surface molecules. Both synaptic muscle molecules, such as the asymmetric form of acetylcholinesterase, and extrasynaptic molecules, such as the extracellular matrix proteoglycans, are regulated by the motor nerve activity. This illustrates one of Jaime's teachings: cell phenotypes are a dynamic process that reflects the influence of other cells (Alvarez, 2001). Proteoglycans have many functions, including growth factor receptors. Studying them in muscular dystrophy will contribute to the comprehension of the muscle regeneration failure, characteristic of this disease. Muscle cells are highly dependent upon energy production, and the mitochondriae produce most of it. These organelles are unique in having their own genome. Mutations in these genes have recently been recognized as the cause of human disease and originally in muscle pathology. The physiopathology of these diseases is summarized here