N-Acetylcysteine prevents baker's-yeast-induced inflammation and fever.

OBJECTIVE AND DESIGN: To investigate whether N-acetylcysteine (NAC) alters baker's-yeast-induced fever and inflammation. MATERIAL OR SUBJECTS: Male Wistar rats (26-28 days old) injected with baker's yeast (135 mg/kg, intraperitoneal) or prostaglandin E(2) (300 ng/100 µL, intrathecal). TREATMENT: Rats were injected with NAC (500 mg/kg, subcutaneous, or 50 µg/100 µL, intrathecal) 1 h before, or 2 h after, pyrogen injection. METHODS: Rectal temperature changes induced by baker's yeast, PGE(2) and NAC were followed up over time. Four hours after baker's yeast injection, total leukocytes, protein, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and nonprotein thiol content were assessed in peritoneal lavage and hypothalamus. RESULTS: Systemic administration of NAC decreased leukocytes, protein, IL-1ß and TNF-α levels in peritoneal lavage, and decreased IL-1ß levels in the hypothalamus. The central administration of NAC prevented baker's-yeast-induced fever, but did not alter the febrile response elicited by prostaglandin E(2). CONCLUSION: These results suggest an anti-inflammatory and antipyretic role for NAC in yeast-induced peritonitis.

General pathway for a convenient one-pot synthesis of trifluoromethyl-containing 2-amino-7-alkyl(aryl/heteroaryl)-1,8-naphthyridines and fused cycloalkane analogues.

A convenient and general method for the synthesis in 26-73% yields of a new series of 7-alkyl(aryl/heteroaryl)-2-amino-5-trifluoromethyl-1,8-naphthyridines from direct cyclocondensation reactions of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF3C(O)CH=C(R¹)OR, where R¹ = H, Me, Ph, 4-MePh, 4-OMePh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl, 2-thienyl and R = Me, Et] with 2,6-diaminopyridine (2,6-DAP), under mild conditions, is described. Another synthetic route also allowed the synthesis of 2-amino-5-trifluoromethyl-cycloalka[b][1,8]naphthyridines in 33-36% yields, from direct or indirect cyclo-condensation reactions of five-, six- and seven-membered 2-trifluoroacetyl-1-methoxy-cycloalkenes with 2,6-DAP.

Diacerein decreases TNF-alpha and IL-1beta levels in peritoneal fluid and prevents Baker's yeast-induced fever in young rats.

OBJECTIVE: To investigate the effect of diacerein, an anti-inflammatory drug, on body temperature and protocols of fever induction in male Wistar rats. METHODS: The effect of diacerein (5.0 mg/kg, s.c.) on rectal temperature (T (R)) changes induced by Baker's yeast (0.135 g/kg, i.p.) and PGE(2) (10 ng/animal, i.t.) was evaluated. T (R) changes were recorded over time. The leukocyte count and TNF-alpha and IL-1beta content were evaluated in the peritoneal fluid by means of optical microscopy and enzyme immunoassay (ELISA kits), respectively. RESULTS: The administration of diacerein to febrile animals attenuated Baker's yeast-induced fever but did not alter prostaglandin E(2)-induced fever. Diacerein prevented the development of Baker's yeast-induced fever and significantly attenuated the increase in peritoneal leukocytes and decreased IL-1beta and TNF-alpha levels in peritoneal fluid. CONCLUSIONS: These data suggest that diacerein partially protects against Baker's yeast-induced fever and peritoneal leukocyte migration, and indicate that this effect appears to be due to inhibition of release of cytokines (such as TNF-alpha and IL-1beta).