LPS depresses contractility of isolated rat hearts by inducing TNF-alpha synthesis and subsequently activating the sphingomyelinase pathway, whereas no evidence for a role of NOSII- or NOSIII-generated NO was found. Moreover, Cox-2-derived TxA(2) appears to facilitate TNF-alpha synthesis in response to LPS.

Purified staphylococcal alpha-toxin provokes coronary vasoconstriction and loss in myocardial contractility. The responses appear to be largely attributable to the generation of thromboxane and are even enhanced when the endogenous nitric oxide synthesis is blocked. Bacterial exotoxins, such as staphylococcal alpha-toxin, may thus be implicated in the loss of cardiac performance encountered in Gram-positive septic shock.

Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthdayEleven new indole alkaloids were isolated from cultures of the human pathogenic yeast Malassezia furfur after addition of l-tryptophan as the sole N-source: pityriacitrin B (2), the malassezindoles A (3) and B (4), malassezialactic acid (6), the malasseziazoles A (7), B (8), and C (9), pityriazole (10), malasseziacitrin (11), and malassezione (12), along with the known d-indole-3-lactic acid ( (aR)-a-hydroxy-1H-indole-3-propanoic acid 5), and 2-hydroxy-1-(1H-indol-3-yl)ethanone (13). The structural elucidation of these compounds was performed by spectroscopic methods (MS as well as 1D-and 2D-NMR). The biogenetic relationships (Scheme) and biological activities of the new metabolites are discussed.