epiglucan and pimagedine

Circulatory failure in multiple organ dysfunction syndromes (MODS) is characterized with systemic vasodilation, diminished blood flow to various vascular beds. The aim of this study was to investigate the effects of selective inhibition of nitric oxide on the mesenteric arterial blood flow (MABF), survival and organ injury of the liver, kidney, lung and spleen in zymosan-induced MODS.. Forty Swiss albino mice (20-40 g), 7 to 9 weeks old, were obtained. Animals were randomly divided into four groups. The first group were treated intraperitoneally (i.p) with vehicle (saline) and served as a sham group for aminoguanidine (AG) (n=10). The second group was treated with zymosan (500 mg/kg, suspended in saline solution, i.p). The mice in the third and fourth group received AG (15 mg/kg) 1 h and 6 h after zymosan or saline administration, respectively. Eighteen hours after the administration of zymosan, animals were assessed for MODS described subsequently. The signals from the flowmeter were also recorded on mesenteric arterial blood flow values.. In zymosan-treated animals, the MABF was significantly lower than that of solvent (saline)-treated controls (ml min(-1), controls: 4.6 +/- 0.6; zymosan: 1.6 +/- 0.9, P <0.05). When animals were treated with AG, there were no significant differences in MABF values between AG group and solvent (saline)-treated control group. However AG prevented zymosan-induced mesenteric MABF decrease. Treatment with aminoguanidine also decreased mortality.. AG is capable of inhibiting both the induction and the activity of the already iNOS; it remains a potential therapeutic agent in patients with MODS.

Topics: Animals; beta-Glucans; Enzyme Inhibitors; Guanidines; Kidney; Liver; Lung; Mice; Multiple Organ Failure; Nitric Oxide Synthase; Splanchnic Circulation; Spleen; Survival Analysis; Zymosan

We have studied the cytotoxic effect of stimulated macrophages on Meth A tumor cells in vitro. When stimulated with interferon-gamma and soluble beta-1,3-D-glucan, macrophages exerted cytotoxicity towards syngeneic Meth A tumor cells. This cytotoxicity was associated with a high level of nitric oxide production. Both cell death and nitric oxide production were significantly inhibited by the addition of aminoguanidine, a specific inhibitor of inducible nitric oxide synthase (iNOS), to the culture medium. The cytotoxic effect was accompanied by internucleosomal cleavage of DNA as shown by electrophoresis and DNA fragmentation assay.

Topics: Animals; Apoptosis; beta-Glucans; Cells, Cultured; Coculture Techniques; Female; Glucans; Guanidines; Interferon Inducers; Interferon-gamma; Macrophage Activation; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microscopy, Electron; Microscopy, Electron, Scanning; Nitric Oxide; Nitrites; Nitroprusside; Recombinant Proteins; Sarcoma, Experimental; Tumor Cells, Cultured