thiourea and Pleurisy

Some evidence indicates that nitric oxide (NO) contributes to inflammation, while other evidence supports the opposite conclusion. To clarify the role of NO in inflammation, we studied carrageenin-induced pleurisy in rats treated with an NO donor (NOC-18), a substrate for NO formation (L-arginine), and/or an NO synthase inhibitor (S-(2-aminoethyl) isothiourea or N(G)-nitro-L-arginine). We assessed inflammatory cell migration, nitrite/nitrate values, lipid peroxidation and pro-inflammatory mediators. NOC-18 and L-arginine reduced the migration of inflammatory cells and edema, lowered oxidative stress, and normalized antioxidant enzyme activities. NO synthase inhibitors increased the exudate formation and inflammatory cell number, contributed to oxidative stress, induced an oxidant/antioxidant imbalance by maintaining high O(2) (-), and enhanced the production of pro-inflammatory mediators. L-arginine and NOC-18 reversed the proinflammatory effects of NO synthase inhibitors, perhaps by reducing the expression of adhesion molecules on endothelial cells. Thus, our results indicate that NO is involved in blunting-not enhancing-the inflammatory response.

Topics: Animals; Antioxidants; Arginine; Carrageenan; Disease Models, Animal; Male; Malondialdehyde; Nitrates; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitrites; Pleurisy; Rats; Rats, Wistar; Thiourea

The bulk of published data has shown that NO is proinflammatory. However, there also exists the conflicting notion that NO may be protective during an inflammatory insult. In an attempt to resolve this issue, we have compared the effects on inflammation of a range of NO synthase (NOS) inhibitors given either directly to the site of the inflammatory lesion or systemically. It was found that in the carrageenin-induced pleurisy, a single intrapleural injection of the selective inducible NO inhibitors S-(2-aminoethyl) isothiourea (AE-ITU; 3 and 10 mg/kg) and N-(3-(aminomethyl)-benzyl) acetamidine (1400W; 10 mg/kg) or the selective endothelial cell NOS inhibitor L-N(5)(1-iminoethyl)-ornithine (10 mg/kg) not only exacerbated inflammation at the very early stages of the lesion (1-6 h), but also prevented inflammatory resolution. By contrast, administering NOS inhibitors systemically ameliorated the severity of inflammation throughout the reaction. To elucidate the mechanisms by which inhibition of NO synthesis locally worsened inflammation, we found an increase in histamine, cytokine-induced neutrophil chemoattractant, superoxide, and leukotriene B(4) levels at the inflammatory site. In conclusion, this work shows that the local production of NO is protective by virtue of its ability to regulate the release of typical proinflammatory mediators and, importantly, that NOS inhibitors have differential anti-inflammatory effects depending on their route of administration.

Topics: Acute Disease; Amidines; Animals; Antioxidants; Benzylamines; Carrageenan; Disease Models, Animal; Drug Administration Schedule; Edema; Enzyme Inhibitors; Free Radical Scavengers; Inflammation; Inflammation Mediators; Injections; Injections, Intraperitoneal; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; omega-N-Methylarginine; Pleura; Pleurisy; Rats; Rats, Wistar; Superoxides; Thiourea

The importance assumed by local treatment in non-tuberculous purulent pleurisy has suggested that intrapleural applications of a broad spectrum antiseptic could be as useful as in peritonitis. Fifteen adult patients with empyema secondary, in most cases, to local, usually Gram-negative, infections were treated with combined antibiotic therapy and locally administered noxytioline. The patients underwent 3 to 30 intrapleural lavages (average 9) via a pleurotomy drainage tube (11 cases) or after pleural puncture (4 cases). Results were very satisfactory in 12 out of 15 cases, with mild pleural sequelae in 8 cases. No local or systemic reactions were observed. This treatment proved particularly effective in 5 difficult cases.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Noxythiolin; Pleurisy; Suppuration; Thiourea

Topics: Animals; Dogs; Edema; Lung; Pleural Effusion; Pleurisy; Pulmonary Edema; Rats; Thiourea

Topics: Animals; Blood; Cholesterol; Dogs; Plasma; Pleural Effusion; Pleurisy; Thiourea