Search

Human activated protein C (APC) is a serineprotease and one of the most important physiological inhibitors of the coagulation system. Apart from anticoagulative effects, profibrinolytic and anti-inflammatory modes of action have been reported for APC. The administration of recombinant human activated protein C (rhAPC), drotrecogin alfa (activated), Xigris, to patients with severe sepsis and sepsis-induced multi-organ failure reduced mortality in large clinical trials. Anti-apoptotic and immunomodulatory effects of rhAPC have been examined in in vitro experiments and in experimental animal studies. Moreover, a reduction of endothelial cell permeability, enhanced endothelial cell survival as well as improvements of microcirculatory disorders have been proposed for rhAPC. The manifold mechanisms of action of APC may give reasons for its application in diseases other than sepsis, which are characterized by endothelial and microcirculatory dysfunction, e.g. acute pulmonary or renal failure, ischemic stroke, ischemia-reperfusion injury and acute pancreatitis. A better understanding of the anti-inflammatory, anti-apoptotic and immunomodulatory modes of action of APC could be relevant for dosing and mode of application and may lead to a broadening of the indication field for rhAPC.

Background: Nonrheumatic, calcific aortic stenosis is the main heart valve disease and the main cause of heart valve replacement in the elderly. Recent studies suggest that it is based on a chronic inflammatory process. The pathogenetic mechanisms, however, are unclear., Methods: A MEDLINE search was conducted for the phrases "chlamydia pneumoniae" and "aortic valve", and all articles published between 1966 and May 2004 were evaluated. Data presented as letter or congress abstract was also included., Results: Clinical and histopathologic studies demonstrate an association of calcific aortic stenosis and cardiovascular risk factors similar to atherosclerosis. As for atherosclerosis, infection with Chlamydia (C.) pneumoniae is also discussed as a further potential risk factor for calcific aortic stenosis. Previous seroepidemiologic and pathologic studies using various detection methods yielded heterogeneous results., Conclusion: Thus, data suggesting a pathogenetic association of C. pneumoniae and calcific aortic stenosis should be interpreted cautiously.