Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice.

Muscle wasting, as occurring in cancer cachexia, is primarily characterized by protein hypercatabolism and increased expression of ubiquitin ligases, such as atrogin-1/MAFbx and MuRF-1. Myostatin, a member of the TGFbeta superfamily, negatively regulates skeletal muscle mass and we showed that increased myostatin signaling occurs in experimental cancer cachexia. On the other hand, enhanced expression of follistatin, an antagonist of myostatin, by inhibitors of histone deacetylases, such as valproic acid or trichostatin-A, has been shown to increase myogenesis and myofiber size in mdx mice. For this reason, in the present study we evaluated whether valproic acid or trichostatin-A can restore muscle mass in C26 tumor-bearing mice. Tumor growth induces a marked and progressive loss of body and muscle weight, associated with increased expression of myostatin and ubiquitin ligases. Treatment with valproic acid decreases muscle myostatin levels and enhances both follistatin expression and the inactivating phosphorylation of GSK-3beta, while these parameters are not affected by trichostatin-A. Neither agent, however, counteracts muscle atrophy or ubiquitin ligase hyperexpression. Therefore, modulation of the myostatin/follistatin axis in itself does not appear sufficient to correct muscle atrophy in cancer cachexia.

Play-back theatre, theatre laboratory, and role-playing: new tools in investigating the patient-physician relationship in the context of continuing medical education courses.

AIM: The aim of this study was to report on the validation of a role-playing approach, using play-back and theatre laboratory in the context of a continuing medical education (CME) course on predialysis and transplantation, to discuss the patient-physician relationship. METHODS: The course was developed with the help of a theatre director. The role-playing 2-day course was designed to be highly interactive for a small group (15-20 participants), based on a core of case reports (dialysis, transplantation, and return to dialysis after graft failure). Two stages were included: play-back theatre in which experiences told by the participants were mimed by a group of actors, and theatre laboratory in which different aspects of voice and touch were explored. Opinions were gathered by an anonymous semistructured questionnaire completed by all participants. RESULTS: The course obtained a high score from The Ministry of Health (14 credits, 1 per teaching hour). The opinions of the 18 participants were highly positive; all liked the courses. Sixteen of 18 asked to repeat the experience. The strong emotional involvement was an advantage for 15 of 18, sharing emotional aspects of the profession for 10 of 18, and usefulness in clarifying opinions on "dark sides" of our profession for 10 of 18. CONCLUSION: The positive opinions recorded during this experience, the first experiment with a "psycho-theatrical approach" developed in a CME course in our country, suggest the benefit of implementing nonconventional, educational approaches in a multidisciplinary discussion of the patient-physician relationship in transplantation medicine.