RESUMEN
Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.
Asunto(s)
Distrofia Muscular Animal/patología , Fenotipo , Animales , Modelos Animales de Enfermedad , Perros , Músculo Esquelético/patologíaRESUMEN
Concomitant tumor immunity evinced by C57BL/6 mice, bearing a MC-induced sarcoma, was evaluated by graded challenge doses for different primary tumor sizes (2-3,4-6,8-12% tumor weight of the total body weight TW/TBW). 100% of mice bearing tumors, representing 2--6% of total body weight, rejected doses from 0.2--1 X 10(4) cells. The gradual curtailment of the concomitant tumor immunity, depending on increasing TW/TBW ratio, could be evaluated, using adequately increasing challenge doses. The immune equipotency of the whole s.c. body area, the failure to modify the concomitant tumor immunity by drainin node excision and the demonstration of its dependency upon the total challenge-dose and its independency upon fractionated multilocular inoculation of the challenge, showed clearly that the concomitant tumor immunity is a local expression of general immunity. The experimental model allows a valuable biological assessment of the tumor-beareer immune status and represents likewise an adequate tool for immunotherapeutic effects estimation.