ABSTRACT
Las distrofias musculares de origen genético son muy diversas y, tanto su diagnóstico preciso como su manejo, suponen un reto importante. En cuanto a este último aspecto, no obstante el desarrollo en proceso de nuevas estrategias a nivel molecular para su tratamiento, las herramientas con que se cuenta para este propósito son limitadas, y pocas veces pueden influir de manera efectiva para evitar el deterioro progresivo que muchos de estos pacientes experimentan. Además, las terapias de última generación no abarcan la gran diversidad de estas patologías y no se espera que estén disponibles a corto plazo para la mayoría de los pacientes. El propósito del artículo es mostrar el papel de las poliaminas, actores ubicuos en el metabolismo in tracelular tal vez poco conocidos; cómo están involucrados en los procesos fisiológicos y patológicos, y cómo también pudiesen estar involucrados en la fisiopatología de las distrofias musculares. Su inhibición controlada, mediante Difluorometilornitina (DFMO), pudiese constituir un mecanismo para en lentecer o eliminar el deterioro muscular de estos pacientes, al utilizarse como una herramienta dentro del arsenal de las ya existentes
Muscular dystrophies of genetic origin are very diverse and, both their precise diagnosis and their management represent an important challenge. Regarding this last aspect, despite the development in process of new strategies at the molecular level for its treatment, the tools available for this pur pose are limited, and can rarely influence effectively to avoid the progressive deterioration that many of these patients experience. In addition, the lates tgeneration therapies do not cover the great diversity of these pathologies and are not expected to be available in the short term for most patients. The purpose of the article is to show the role of polyamines, ubiquitous actors in intracellular meta bolism, perhaps little known; how they are involved in physiological and pathological processes, and how they could also be involved in the physiopathology of muscular dystrophies. Its controlled inhi bition, by difluoromethylilitin (DFMO), could be a mechanism to slow or eliminate the muscle deterio ration of these patients, by being used as a tool within the arsenal of those already existing.
Subject(s)
Humans , Male , Female , Ornithine/pharmacology , Polyamines/pharmacology , Muscular Dystrophies/diagnosis , Polyamines/chemistry , Chemical Compounds , Muscular Dystrophy, Duchenne/history , Muscular Dystrophy, Duchenne/prevention & controlABSTRACT
A distrofia muscular de Duchenne (DMD) é uma alteração neuromuscular caracterizada por contínua necrose muscular e degeneração, com eventual fibrose e infiltração por tecido adiposo. O aumento progressivo da fibrose intersticial no músculo impede a migração das células miogênicas, necessárias para a formação muscular. O modelo canino constitui-se nas melhores fenocópias da doença em humanos, quando comparados com outros modelos animais com distrofia. O tratamento antifibrose de pacientes DMD, tendo como alvo os mediadores da citocina, TGF-beta, e o tratamento com antiinflamatórios, podem limitar a degeneração muscular e contribuir para a melhora do curso da doença. O presente estudo teve como objetivo observar os possíveis efeitos adversos na fisiologia renal, por meio de avaliação bioquímica sanguínea e da pressão arterial, verificando a viabilidade do uso do Losartan (um inibidor de TGF-beta) nos cães afetados pela distrofia muscular. Foram utilizados quatro cães adultos, sendo dois machos e duas fêmeas. Utilizou-se a dose de 50mg de Losartan, administrada via oral, uma vez ao dia. Os exames clínicos, bem como alterações na função renal, o nível do potássio sérico e a pressão arterial não evidenciaram reação adversa durante todo o período do experimento. O uso de Losartan, por um período de 9 semanas, mostrou-se como uma terapia segura para o tratamento antifibrótico em cães adultos, não afetando a função renal ou pressão arterial dos animais.
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder characterized by a continuous muscle necrosis and degeneration with eventual fibrosis and fatty tissue infiltration. Progressive increase in muscle interstitial fibrosis prevents the movement of myogenic cells, which is necessary for myotube formation. Canine model is the best phenocopies of the disease in humans when comparing with others animal models with dystrophy. Anti-fibrotic treatment of DMD patients, targeting the cytokine mediators, TGF-beta, and the treatment with antiinflammatories, may limit muscle degeneration and contribute for the improvement of the course of the illness. This work aimed to verify the possible adverse effects in renal physiology by means of evaluation sanguineous biochemist and arterial pressure, in order to verifying the viability of Losartan (a TGF-beta inhibiter) in affected dogs by muscle dystrophy. It was used four adults dogs, two of each gender. A dose of 50mg of Losartan was orally given once a day. The clinical exams, the kidney function, arterial blood pressure and potassium level did not show any adverse effect through the experimental period. Losartan utilization showed to be a safe therapy for the antifibrotic treatment in adults dogs, not affecting neither the kidney function nor the arterial blood pressure.
Subject(s)
Animals , Angiotensins/adverse effects , Dogs , Muscular Dystrophy, Duchenne/prevention & control , Muscular Dystrophy, Duchenne/therapy , Arterial Pressure , Kidney , Kidney/physiologyABSTRACT
Las personas con discapacidad representan alrededor del 10 por ciento de la población, por ello su atención va desde su prevención, mejorar su calidad de vida y la integración social. De estas discapacidades una de las más frecuentes en aparecer son las físico-motoras y causa de éstas son las Distrofias Musculares, por lo que en este trabajo se realizó una revisión bibliográfica actualizada sobre la Distrofia Muscular de Duchenne previa identificación de un caso afectado en una familia del consejo popular Boca de Camarioca del municipio de Varadero, y se propuso una metodología para el Asesoramiento Genético Preconcepcional de esta enfermedad, dado que el afectado tiene dos hermanas en edad reproductiva. Se tomaron como base los principios básicos de este proceso mostrando así la interrelación dinámica entre sus elementos y se elaboró un documento educativo-informativo para una mayor comprensión de la enfermedad y que pueda ser discutido en el seno de la familia.
Disabled people represent around 10 percent population. Their attention covers prevention, life quality improvement, and social integration. One of the most frequent disabilities is the physic-motor one and muscular dystrophies are their cause. To make this work we carried out an up-dated bibliographic review on Duchenne muscular dystrophy after being identified a case in a family living in the popular council Boca de Camarioca, municipality of Varadero. We proposed a methodology for the Preconception Genetic Management of this disease, taking into account that the patient has two sisters in reproductive age. As a base we took the main principles of this process, showing the dynamic interrelation between its elements and elaborated an informative-educative document for a better comprehension of the disease to be discussed by the members of the family.