The Ras antagonist farnesylthiosalicylic acid ameliorates experimental myocarditis in the rat.

BACKGROUND: Myocarditis is an inflammatory disorder of the heart in which T lymphocytes have a central role. No effective treatment is currently at hand for management of the myocarditis. Lymphocyte function requires the active signal transducer Ras. We thus hypothesized that S-farnesylthiosalicylic acid (FTS), a synthetic small molecule that detaches Ras from the inner cell membrane and induces its rapid degradation, will attenuate experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: Two groups of Lewis rats were induced to develop EAM by immunization with porcine cardiac myosin. Group A received 5 mg/kg of FTS, and group B received phosphate-buffered saline (PBS) according to two protocols: FTS or PBS was given 2 days before myosin immunization in protocol 1 and FTS or PBS was given 14 days after myosin immunization in protocol 2. FTS significantly suppressed myocarditis, and this effect was accompanied by a reduction in myosin-specific cellular and humoral immune responses. In the longer regimen, FTS treatment for 6 weeks was associated with preservation of myocardial function made evident by echocardiography. In vitro, FTS significantly attenuated the proliferation of lymphocytes from untreated myocarditic rats to myosin. CONCLUSIONS: FTS is effective in suppressing the progression of EAM and its consequent functional myocardial dysfunction. The effect may be mediated by suppression of the cellular and humoral responses to myosin.

Depressive personality styles and interpersonal problems in young adults with difficulties in establishing long-term romantic relationships.

This research examined Blatt's personality styles in relation to overall interpersonal distress and problems in affiliation and dominance of young adults with difficulties in establishing long-term romantic relationships. Participants were 141 (73 males and 68 females) young adults comprising two groups: with difficulties in establishing long-term romantic relationships and without such difficulties. They completed the Depressive Experiences Questionnaire and the Mental Health Index (MHI), and they and their friend completed the Inventory of Interpersonal Problems (IIP-C). Self-criticism and dependency contributed to greater self-reported interpersonal distress, over and above MHI depression and anxiety, while efficacy moderated the effects of these vulnerabilities. Self-criticism contributed to the friend's report of interpersonal distress only for those without difficulties in long-term romantic relationships. The findings are discussed in terms of Blatt's theory on interpersonal relatedness and self-definition in young adult's personality development and the complementary ways the personality styles influence the interpersonal world.