We examined the effects of exercise on diaphragm degeneration and cardiomyopathy in dystrophin-deficient mdx mice. Mdx mice (11 months of age) were exercised (swimming) for 2 months to worsen diaphragm degeneration. Control mdx mice were kept sedentary. Morphological evaluation demonstrated increased fibrosis in the diaphragm of exercised mdx mice (33.3 ± 6.0% area of fibrosis) compared with control mdx mice (20.9 ± 1.7% area of fibrosis). Increased (26%) activity of MMP-2, a marker of fibrosis, was detected in the diaphragms from exercised mdx mice. Morphological evaluation of the heart demonstrated a 45% increase in fibrosis in the right ventricle (8.3 ± 0.6% in sedentary vs. 12.0 ± 0.6% of fibrosis in exercised) and in the left ventricle (35% increase) in the exercised mdx mice. The density of inflammatory cells-degenerating cardiomyocytes increased 95% in the right ventricle (2.3 ± 0.6 in sedentary vs. 4.5 ± 0.8 in exercised) and 71% in the left ventricle (1.4 ± 0.6 sedentary vs. 2.4 ± 0.5 exercised). The levels of both active MMP-2 and the pro-fibrotic factor transforming growth factor beta were elevated in the hearts of exercised compared with sedentary mdx mice. The wall thickness to lumen diameter ratio of the pulmonary trunk was significantly increased in the exercised mdx mice (0.11 ± 0.04 in sedentary vs. 0.28 ± 0.12 in exercised), as was the thickness of the right ventricle wall, which suggests the occurrence of pulmonary hypertension in those animals. It is suggested that diaphragm degeneration is a main contributor to right ventricle dystrophic pathology. These findings may be relevant for future interventional studies for Duchenne muscular dystrophy-associated cardiomyopathy.

In Duchenne muscular dystrophy (DMD), the search for new biomarkers to follow the evolution of the disease is of fundamental importance in the light of the evolving gene and pharmacological therapies. In addition to the lack of dystrophin, secondary events including changes in calcium levels, inflammation and fibrosis greatly contribute to DMD progression and the molecules involved in these events may represent potential biomarkers. In this study, we performed a comparative evaluation of the progression of dystrophy within muscles that are differently affected by dystrophy (diaphragm; DIA and quadriceps; QDR) or spared (intrinsic laryngeal muscles) using the mdx mice model of DMD. We assessed muscle levels of calsequestrin (calcium-related protein), tumour necrosis factor (TNF-α; pro-inflammatory cytokine), tumour growth factor (TGF-β; pro-fibrotic factor) and MyoD (muscle proliferation) vs. histopathology at early (1 and 4 months of age) and late (9 months of age) stages of dystrophy. Fibrosis was the primary feature in the DIA of mdx mice (9 months: 32% fibrosis), which was greater than in the QDR (9 months: 0.6% fibrosis). Muscle regeneration was the primary feature in the QDR (9 months: 90% of centrally nucleated fibres areas vs. 33% in the DIA). The QDR expressed higher levels of calsequestrin than the DIA. Laryngeal muscles showed normal levels of TNF-α, TGF-β and MyoD. A positive correlation between histopathology and cytokine levels was observed only in the diaphragm, suggesting that TNF-α and TGF-β serve as markers of dystrophy primarily for the diaphragm.

These findings suggest that suramin may be a new adjunctive therapy to help improve cardiomyopathy in DMD.

This study suggests that P2Y may participate in cardiomyopathy in mdx mice. P2-selective drugs with specific actions in the dystrophic heart may ameliorate cardiomyopathy in dystrophinopathies. Muscle Nerve 55: 116-121, 2017.

Fisioterapia: uma ciência baseada em evidências O surgimento da Fisioterapia no Brasil foi in luenciado pela vinda da Família Real ao país e ao uso das chamadas "Casas de Duchas". Durante muitos anos, os recursos isioterápicos faziam parte da terapêutica médica e a forma de atuação nesse período (século XIX) parecia restringir a Fisioterapia como apenas "reabilitadora" e não como ramo da ciência 1. Os isioterapeutas baseavam-se em livros de reabilitação os quais, em sua maioria, eram importados e que descreviam "receitas prontas", o que restringia o discernimento crítico diante do grande arsenal de recursos terapêuticos disponíveis e tornava a tomada de decisão clínica um ato complexo. Hoje, devidamente regulamentada, a Fisioterapia é uma Ciência da Saúde que estuda, previne e trata os distúrbios cinéticos funcionais intercorrentes em órgãos e sistemas do corpo humano, gerados por alterações genéticas, por traumas e por doenças adquiridas 2 , além de ser uma prática clínica totalmente alicerçada em evidências e pesquisas. O pro issional é dotado de habilidades que o possibilita atuar em todos os níveis de atenção à saúde e em equipes multidisciplinares, contribuindo para a manutenção da saúde, bem estar e qualidade de vida. Cabe ao isioterapeuta avaliar, estabelecer o diagnóstico isioterapêutico, de inir as intervenções e realizar as reavaliações necessárias. A pró-atividade é o princípio da pesquisa e certamente contribui e continuará sendo a base para os avanços no setor. Nesta edição, a Revista Fisioterapia em Movimento contempla o leitor com artigos originais que evidenciam a atuação isioterápica nas áreas de Ortopedia, Dermatofuncional, Cardiorrespiratória, Saúde Coletiva e Neurofuncional. Ainda, conta com revisões no âmbito da Fisioterapia Pediátrica Neonatal e Terapia Intensiva. Estas publicações são um retrato da pesquisa na área e objetos motivacionais para a busca contínua por aprimoramento e a produção de novos conhecimentos.