Differential expression of genes involved in the degeneration and regeneration pathways in mouse models for muscular dystrophies.

The genetically determined muscular dystrophies are caused by mutations in genes coding for muscle proteins. Differences in the phenotypes are mainly the age of onset and velocity of progression. Muscle weakness is the consequence of myofiber degeneration due to an imbalance between successive cycles of degeneration/regeneration. While muscle fibers are lost, a replacement of the degraded muscle fibers by adipose and connective tissues occurs. Major investigation points are to elicit the involved pathophysiological mechanisms to elucidate how each mutation can lead to a specific degenerative process and how the regeneration is stimulated in each case. To answer these questions, we used four mouse models with different mutations causing muscular dystrophies, Dmd (mdx), SJL/J, Large (myd) and Lama2 (dy2J) /J, and compared the histological changes of regeneration and fibrosis to the expression of genes involved in those processes. For regeneration, the MyoD, Myf5 and myogenin genes related to the proliferation and differentiation of satellite cells were studied, while for degeneration, the TGF-ß1 and Pro-collagen 1α2 genes, involved in the fibrotic cascade, were analyzed. The result suggests that TGF-ß1 gene is activated in the dystrophic process in all the stages of degeneration, while the activation of the expression of the pro-collagen gene possibly occurs in mildest stages of this process. We also observed that each pathophysiological mechanism acted differently in the activation of regeneration, with distinctions in the induction of proliferation of satellite cells, but with no alterations in stimulation to differentiation. Dysfunction of satellite cells can, therefore, be an important additional mechanism of pathogenesis in the dystrophic muscle.

Dosagem sérica de troponina I em cães com desnível do segmento ST utilizando quimioluminescência / Serum determination of troponin I in dogs with ST deviation by chemiluminescent

Com o intuito de verificar algum dano nas células do miocárdio, utilizaram-se 38 cães, 20 com traçado eletrocardiográfico normal, grupo 1, e 18 com desníveis do segmento ST, grupo 2, em registro na derivação II, velocidade de 50mm/s e sensibilidade N (1mV=1cm). No grupo 1, a dosagem sérica da troponina I (cTnI) destinou-se à obtenção dos valores referenciais (ng/mL) que seriam confrontados com os obtidos no grupo 2. A média e o desvio-padrão foram, respectivamente, 0,16ng/mL e 0,11ng/mL e 0,20ng/mL e 0,11ng/mL, nos grupos 1 e 2. A cTnI não apresentou evidências de associação com idade, massa corpórea, creatinafosfoquinase total e potássio nos dois grupos. Não houve diferenças significativas nos valores de cTnI entre os grupos. Conclui-se que é possível a utilização do kit de ensaio imunométrico quimioluminescente humano para a espécie canina e que a hipóxia-isquemia, revelada pelo desnível do segmento ST não acarreta dano miocárdico ou este é mínimo e indetectável.

In order to investigate myocardial cells injury, 38 dogs were evaluated, being 20 with a normal electrocardiogram (group 1) and 18 with ST segment elevation or depression (group 2), recorded in lead II, at paper speed of 50 mm/sec and N sensibility (1 mV = 1cm). Serum measurement of troponin I (cTnI) in group 1 was determined to obtain reference values (ng/mL). These values were compared to those obtained in dogs from group 2, to confirm or not myocardial injury. Mean cTnI values in groups 1 and 2 were 0.16ng/mL (SD±0.11ng/mL) and 0.20ng/mL (SD±0.11ng/mL), respectively. Three cTnI null values were found in group 1. cTnI was not related to age, mass, CK-T or serum potassium concentration in both animal groups, for each level varied in the group. There was no difference in cTnI values between groups 1 and 2. In conclusion, it is possible to use the human chemiluminescent immunometric assay kit in canine species and hypoxia/ischemia revealed by ST segment deviation does not mean significant myocardium injury.