To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

Stimulation of bovine alveolar macrophages with calcium ionophore A23187 resulted in marked production of leukotriene (LT)B4 and a lesser increase in thromboxane (TX)B2, whereas opsonized zymosan (OPZ) resulted in production of TXB2 and relatively small increases in LTB4 and prostaglandin (PG)F2 alpha. Alveolar macrophages incubated with recombinant bovine interferon-gamma or lipopolysaccharide, and subsequently stimulated with A23187 or OPZ, had altered arachidonic acid metabolism, producing markedly increased amounts of TXB2 and PGF2 alpha, and slightly increased LTB4. Incubation of alveolar macrophages with lipopolysaccharide had a more profound effect on the increased amounts of TXB2 and PGF2 alpha, observed in response to stimulation with A23187 or OPZ, than did incubation with interferon-gamma. Alveolar macrophages incubated with recombinant bovine interferon-alpha 1-1 also produced slightly increased amounts of LTB4 when stimulated with A23187 or OPZ. Altered arachidonic acid metabolism by alveolar macrophages exposed to interferons and lipopolysaccharide may contribute to the development of pulmonary inflammation, such as in the early stages of bacterial pneumonia following viral infections that induce interferon production.

A study was performed to determine the effect of proadifen hydrochloride on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TxA2) synthesis by equine peritoneal macrophages and the effect of proadifen on endotoxin-induced synthesis of PGI2 and TxA2 by equine macrophages. Peritoneal macrophages (2.5 X 10(6)/ml) were incubated for 6 hours in tissue culture media containing 1) nothing (nontreated control), 2) proadifen hydrochloride (20, 100, 250, and 500 micromol/L, 3) endotoxin (5 ng/ml), or 4) the calcium ionophore A23187 (0.95 micromol/L). In a second series of experiments, peritoneal macrophages were incubated with endotoxin (5 ng/ml) and proadifen (250 micromol/L), for 6 hours. Concentrations of 6-keto-prostaglandin F 1alpha (6-keto-PGF 1alpha) and thromboxane B2, the stable metabolites of PGI2 and TxA2, were determined in the incubation media by radioimmunoassay. Proadifen caused increased synthesis of PGI2 by equine macrophages, without affecting TxA2 production. The increased PGI2 production was similar to that induced by endotoxin and calcium ionophore; however, the latter 2 agents significantly stimulated TxA2 production as well (P less than 0.05). There were no significant differences among mean concentrations of 6-keto-PGF 1alpha in media from macrophages treated with 100, 250, or 500 micromol/L proadifen, but there was a significant curvilinear regression between their concentrations. The ratio of thromboxane B2 to 6-keto-PGF 1alpha was significantly lower than baseline in incubation media from macrophages exposed to proadifen, endotoxin, and calcium ionophore. Proadifen hydrochloride did not significantly change equine peritoneal macrophage production of PGI2 or TxA2 in response to endotoxin.

The fatty acid composition of muscle were investigated to compare muscle composition among the 9 domestic animals including cattle. In major domestic animals, analyzed the effects of age, part and sex of the animal on their fatty acid composition. The content of 4 types of major fatty acids of muscle was determined and calculated their ratio. Myristic acid and palmitic acid levels were high in chicken and sheep. Besides dog muscle contained a lot of stearic acid. Linoleic acid content showed evident difference in the content depending on the animal species. The ratios of linoleic acid/palmitic acid (L/P ratio) and linoleic acid/stearic acid(L/S ratio) were characteristically high in horse and pig, whereas the ratio of palmitic acid/stearic acid(P/S ratio) was 0.7+_0.17, showing very low level in dog. As for the content of steric acid, in cattle and chicken it was higher in young animal than adults. In duck, the contents of all fatty acids and ratio were increased by the age. As for the content of fatty acids according to the part of chicken, high level was shown in thigh than in breast and wing, while there was no remarkable variation by the part in other animal. The differences in the content of myristic acid, palmitic acid and linoleic acid among some animal could be verified in muscle lipid composition. The L/P ratio which maintained certain level regardless of age, part, sex shown distinctive pattern between the species.