Giuseppe Cirino

Nitric oxide-releasing NSAIDs inhibit interleukin-1beta converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFalpha.

: Nitric oxide (NO)‐releasing NSAIDs are a new class of NSAID derivatives with markedly reduced gastrointestinal toxicity. Although it has been demonstrated that NO‐NSAIDs spare gastric mucosal blood flow, molecular determinants involved in this effect are unknown.

Pharmacological characterization of polycation-induced rat hind-paw oedema.

1 The inflammatory response induced by poly‐l‐arginine in the rat hind‐paw was studied both by measuring paw oedema and histologically. 2 The paw volume was measured with a hydroplethysmometer at 0.5, 1, 2, 4, 6 and 18 h after the subplantar injection of the polycation. Protein extravasation was evaluated with Evans blue and the histology studied by light microscopy. 3 Poly‐l‐arginine (12, 24, 43 and 115 kD) caused dose‐ and molecular weight‐dependent oedema which had a rapid onset and long duration. Evans blue extravasation paralleled the oedema induced by poly‐l‐arginine. Microscopic examination of the paws at early stages of oedema formation showed exuberant liquid exudate with no inflammatory cells. After 18 h, a cellular infiltrate was present, consisting mainly of mononuclear cells. 4 Indomethacin, dexamethasone, BW755c or the PAF‐antagonist WEB 2086 caused no significant inhibition of the poly‐l‐arginine‐induced oedema. Cyproheptadine had inhibitory effects only on the early stages of the polycation‐induced oedema. Similar results were observed with rats depleted of histamine and 5‐hydroxytryptamine. 5 Heparin, a polyanion, injected in the rat paw caused a marked inhibition of the polycation‐induced oedema. NG‐monomethyl‐l‐arginine (LNMMA), an inhibitor of EDRF synthesis, injected locally also produced a marked inhibition, but this inhibition was reversed by iloprost. 6 These results suggest that the oedema induced by polycations was due to their cationic charge. The inhibitory effect of LNMMA is probably due to a decrease in vascular flow rather than a decrease in vascular permeability.