The ultrastructural evidence of intercalated discs remodelling in ARVC, together with the positive screening of D protein encoding genes in half of probands, are in keeping with an intercellular junction cardiomyopathy.

No abstract

Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor-alpha (TNF-alpha) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei. Proapoptotic agents, caspase-3 and -9, were increased, as well as serum levels of TNF-alpha and its second messenger sphingosine. Treatment of rats with L-carnitine, known for its protective effect on muscle metabolism injuries, was found to inhibit caspases and to decrease the levels of TNF-alpha and sphingosine, as well as the number of apoptotic myonuclei. Staurosporine was used in in vitro experiments to induce apoptosis in skeletal muscle cells in culture. When L-carnitine was applied to skeletal muscle cells, before staurosporine treatment, we observed a reduction in apoptosis. These findings show that L-carnitine can prevent apoptosis of skeletal muscles cells and has a role in the treatment of congestive heart failure-associated myopathy.

✓Arachnoid cysts are frequent incidental findings on neuroimaging studies and in clinical practice. Theories of their origin, still matter for debate, compose four categories: 1) a ball-valve mechanism; 2) an osmotic gradient between the intra- and extracystic medium; 3) primary malformation of the arachnoid membrane or cerebral lobe agenesis; and 4) fluid hypersecretion by the lining cells of the cyst wall. The cause of cyst enlargement is also debatable, although there is strong controversial evidence supporting the last two theories rather than the former. Brain water homeostasis and its regulatory pathways are weakly understood at the molecular level. In this brief report the authors attempt to add new insights into the pathogenesis of arachnoid cysts by considering aquaporin expression in the cyst wall and discuss possible future research directions and molecular targets.

Our data point to Wnt/β-catenin as the final common pathway underlying different desmosomal AC forms and support the zebrafish as a suitable model for detecting early signalling pathways involved in the pathogenesis of DSP-associated diseases, possibly responsive to pharmacological or genetic rescue.