RESUMEN
Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.
Asunto(s)
Ácidos Indolacéticos/uso terapéutico , Mitocondrias Musculares/metabolismo , Miositis por Cuerpos de Inclusión/tratamiento farmacológico , Fenilbutiratos/uso terapéutico , Adenosina Trifosfato/biosíntesis , Anciano , Anciano de 80 o más Años , Butionina Sulfoximina/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , ADN Mitocondrial/genética , Evaluación Preclínica de Medicamentos , Dinaminas/biosíntesis , Dinaminas/genética , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Fibroblastos/efectos de los fármacos , GTP Fosfohidrolasas/biosíntesis , GTP Fosfohidrolasas/genética , Factor 15 de Diferenciación de Crecimiento/biosíntesis , Factor 15 de Diferenciación de Crecimiento/sangre , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Ácidos Indolacéticos/farmacología , Masculino , Persona de Mediana Edad , Mitocondrias Musculares/patología , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Mioblastos/ultraestructura , Miositis por Cuerpos de Inclusión/metabolismo , Miositis por Cuerpos de Inclusión/patología , Consumo de Oxígeno , Fenilbutiratos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Estudios RetrospectivosRESUMEN
Martial arts, such as judo, kendo, and karate, are popular worldwide, not only among adults but also among children and adolescents. Although low back pain (LBP) is considered to be a common problem in these sports, it has been scarcely studied, especially in young athletes. The purpose of this study was to elucidate the point prevalence of and factors related to LBP among school-aged athletes in judo, kendo, and karate. A cross-sectional study was conducted in school-aged athletes (age, 6-15 years; n = 896) using a self-reported questionnaire. Multiple logistic regression models were used to assess the factors related to LBP along with the odds ratio (OR) and 95% confidence interval (95% CI). Variables included in the analysis were sex, age, body mass index, team level, number of days and hours of training, frequency of participation in games, practice intensity, and lower extremity pain. The prevalence of LBP was 6.9% in judo, 4.7% in kendo, and 2.9% in karate. Older age was significantly associated with LBP in judo (adjusted OR, 2.12 [95% CI, 1.24-3.61]), kendo (1.77 [1.27-2.47]), and karate (2.22 [1.14-4.33]). Lower extremity pain was significantly associated with LBP in judo (6.56 [1.57-27.34]) and kendo (21.66 [6.96-67.41]). Coaches should understand the characteristics of LBP in each martial art to develop strategies to prevent LBP among school-aged martial arts athletes.