The anti-inflammatory effects of Glyteer (GL) were investigated by its local administration using the CMC-pouch method in rats, and the effects were compared with those of betamethasone 17-valerate (BV, 1 mg), phenylbutazone (PB, 10 mg), flufenamic acid (FA, 10 mg), bufexamac (BM, 10 and 20 mg), bendazac (BZ, 10 and 20 mg), icthammol (IT, 10 mg) and pine tar (PT, 10 mg). At three hours after CMC-treatment, GL (10 mg) significantly inhibited not only the protein exudation, but also the leucocyte migration.The inhibitory activity of GL on the leucocyte migration had the same potency as that of FA, but was stronger than those of PB, BV, BM, BZ, IT and PT. Furthermore, in relation to the leucocyte migration, GL markedly inhibited not only the neutrophil, but also the macrophage migration. At three hours after CMC-treatment, the inhibitory activity of GL on the neutrophil migration had the same potency as those of PB and FA, but was stronger than those of BV, BM, BZ, IT and PT. On the other hand, GL, BM, BZ, FA, IT and PT had an inhibitory activity on the macrophage migration, and the activity was more potent in GL, FA and IT. From these results, it is suggested that the inhibition of GL on increased vascular permeabiliy and leucocyte migration is one of the mechanisms of its anti-inflammatory action.

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Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb₁ on feeding behavior and endogenous chemical substances. Rb₁ infusion into the rat third cerebroventricle was started at 1930hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000hr. Rb₁ at doses of 0.05, 0.10 and 0.20 μmol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 μmol. Ambulatory activity was not affected in the doses tested. Infusion of Rb₁ increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 μmo1 Rb₁ into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb₁ was found to have a suppressive effect on feeding partly through the VMH.

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Characteristics of the antigen-induced contraction of the isolated esophageal muscularis mucosae of actively sensitized guinea-pigs to ovalbumin (OA) were examined in vitro, and they were compared with those of compound 48/80- or polymyxin B-induced contraction. OA, above 0.01 μg/ml, produced a sustained contraction of the sensitized esophageal muscularis mucosae, the amplitude of which was about 80 ?? 100% of the maximum contraction induced by carbachol (10 μM), while compound 48/80 and polymyxin B (10 ?? 300 μg/ml) produced less potent contractions of the non-sensitized esophageal muscularis mucosae. Contractions to OA or compound 48/80, but not to polymyxin B, were diminished by their repetitive applications. The contractile responses to OA, compound 48/80 and polymyxin B depended on the external calcium concentrations, and were abolished in the calcium-free medium. Pretreatment with tetrodotoxin (0.3 μM), atropine (0.3 μM), diphenhydramine (30 μM) or DSCG (300 μM) did not modify any of these contractions, whereas BW755C (100 μM) and quercetin (10 μM) significantly inhibited them. Indomethacin (10 μM) largely prevented only the polymyxin B-induced contraction, while FPL55712 (10 μM) inhibited both contractions to OA and compound 48/80. These findings indicate that the OA-induced anaphylactic contraction of the esophageal muscularis mucosae taken from the OA-sensitized guinea-pig may be an indirect action via the stimulation of releases of some mast cell-derived spasmogens. The spasmogens may involve the lipoxygenase products of arachidonic acid in part, but not histamine, acetylcholine or the cyclooxygenase products.

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Effects of the urinary enzyme inhibitor ulinastatin on experimental arthritis were investigated. Ulinastatin at the dose of 30, 000 units/kg/day, i.v., significantly restored the swelling of hind paw, inflammatory score and bone damage in adjuvant arthritic rats. Intraarticular administration of ulinastatin at 3000 units/site×3, significantly suppressed the articular swelling and the elevated inflammatory parameters in the synovial fluid of carrageenin-induced arthritic rabbits. Moreover, ulinastatin at the dose of 50000 units/kg/day, i.v., significantly prevented the elevation of serum rheumatoid factor and articular lesions in MRL/1 mice. In addition, ulinastatin significantly inhibited human granulocyte elastase and cathepsin G. These findings indicate that ulinastatin may be a useful therapeutic agent for arthritis.

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The effects of daily oral administration of imipramine (IM) hydrochloride (50 mg/kg) and/or oxazepam (OZ, 20 mg/kg) or diazepam (DZ, 5 mg/kg) in a 1% aqueous solution of carboxymethylcellulose sodium salt (CMC) on the activities of drug metabolizing enzyme systems and steady state plasma levels of IM, desmethylimipramine (DIM), DZ, desmethyldiazepam (DDZ) and OZ were investigated in rats during a 15-day period. In addition, the effect of a single intravenous administration of IM hydrochloride (5 mg/kg), DZ (0.5 mg/kg) and OZ (2 mg/kg) on plasma concentration-time profiles of IM, DIM, DZ, DDZ and OZ was investigated in rats given the same drug treatments by the oral route for 14 days. The group treated with IM hydrochloride plus OZ group showed a great increase in drug-metabolizing enzyme activities, but the difference for the group given IM hydrochloride was not statistically significant. The steady-state plasma levels of DZ after oral administration for 15 days suggested that the group given IM hydrochloride plus DZ did show accumulated DZ. In terms of the area under the concentration-time curve of IM, DZ and OZ after intravenous administration of IM hydrochloride, DZ and OZ, there were significant differences between each of the mono-treatment groups and the IM hydrochloride plus DZ or OZ treatment groups. In conclusion, we have found that the drug interaction for IM hydrochloride by OZ is markedly lower than that by DZ.

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Effects of cysteamine (2-mercaptoethylamine) on vocalization responses, a parameter of nociceptive response, was studied in conscious guinea pigs. Intra-arterial injection of bradykinin (3 μg), acetylcholine (300 μg), capsaicin (3 μg) and vanillyl n-nonoylamide (3 μg, VNA) induced severe vocalization responses. Three hours after an administration of cysteamine (300mg/kg, s.c.), a significant suppressive effect was observed for bradykinin and acetylcholine-evoked vocalization. A weak suppressive effect appeared in capsaicin and VNA-evoked vocalization, but there were not statistically significant changes on vocalization counts when compared with the value of the saline-treated animals. However, consecutive pretreatment of guinea pigs with VNA led to a complete suppression of capsaicinoids-evoked vocalization only. Cysteamine completely suppressed bradykinin, acetylcholine, capsaicin and VNA-evoked vocalization responses in VNA desensitized guinea pigs. These findings suggest that the mechanisms of bradykinin and acetylcholine-evoked vocalization response differ from that of capsaicinoids.

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