Effects of human urinary trypsin inhibitor (MTI) against operative stress were investigated. Laparotomy in a mouse caused suppression of immunological functions such as phagocytic activity and antibody formation, followed by loss of resistivity to bacterial infection and acceleration of growth of concealed tumor. The operation also caused damages to the body such as enhancement of protein catabolism and suppression of renal function, followed by increase of blood urea nitrogen, increase of protease activity in skeletal muscle and suppression of PSP clearance. Since MTI wholly ameliorated these undesirable conditions of the body caused by operative stress, it was suggested that MTI has an effect on maintaining the homeostasis of the living body as well as the ability to inhibit trypsin.

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Effect of Saiboku-to, which has been used for the therapy of bronchial asthma, on Type I hypersensitivity reactions was investigated. Forty eight-hr homologous PCA and antigen-induced histamine release in peritoneal cavities of rats passively sensitized with anti-DNP-As·IgE serum tended to be inhibited by the oral administration of Saibokuto. On the other hand, 7-day homologous PCA in guinea pigs mediated by anti-BPO-BGG·IgE serum was significantly inhibited with 200 and 500 mg/kg of Saiboku-to given orally 2 hr prior to challenge. In experimentally caused asthma in guinea pigs, 200 mg/kg of Saiboku-to dramatically inhibited decreases in the rate and volume of respiration, and 500 mg/kg of the drug inhibited even an increase in the ratio of expiration time to inspiration time. The Schultz-Dale reaction in guinea pig tracheal muscle was significantly inhibited by the pretreatment with 10^-4 g/ml of Saiboku-to. The antigen-induced histamine release from sensitized guinea pig lung tissue was inhibited by 10^-6 to 10^-4 g/ml of Saiboku-to in a dose-dependent fashion, though the release of SRS A was not affected. Saiboku-to did not show an antagonistic effect on allergic mediator-induced contraction in guinea pig ileum. From these results, it is considered that Saiboku-to shows an inhibitory activity on the Type I hypersensitivity reaction through the suppression of histamine release.

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Relationship between withdrawal time or naloxone injection time and withdrawal signs were examined in morphine-treated rats. Sixty-five rats were treated chronically with morphine-admixed food (1 mg/g food) for 7 days and were divided into 13 groups. The rats of 4 groups were abruptly withdrawn from morphine, and the rats of another 4 groups were given naloxone (3 mg/kg, s.c.) at 20:00 on the 8 th day and 2:00, 8:00 and 14:00 on the 9 th day after the morphine administration, respectively. Withdrawal signs were observed at intervals of 2 hr. After each naloxone injection, abnormal behaviors were observed for 60 min, and body weight was measured for 3 hr at intervals of 15 or 30 min. In the withdrawal test, weight loss at 24 hr after withdrawal in each group was approximately 10%, and there was no difference between each group. However, the body weight of non-treated rats and morphine-treated rats increased during the night period (20:00-8:00) and decreased during the daytime (8:00-20:00). Therefore, body weight reached the mimimum at 20:00, and then this time is appropriated for withdrawal. In the naloxone test, withdrawal signs in the night period were more potent than that in the daytime. The with-drawal signs induced by naloxone at 8:00 showed the maximum magnitude. Plasma morphine levels in rats treated with morphine-admixed food were high in the night period and low in the daytime. These results suggest that the magnitude of naloxone-precipitated withdrawal signs depends on the amount of morphine in the plasma.

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Molecular weights of mitochondrial type B monoamine oxidase (MAO) in guinea pig brain, liver and kidney were estimated, and their identities and multiplicity were studied. We ascertained what concentration of ³H-pargyline bound to type B MAO specifically from the inhibition curve toward serotonin (5-HT) and β-phenylethylamine (β-PEA) by pargyline. Pargyline irreversibly binds to FAD in MAO at a one to one molecular ratio. ³H-pargyline bound to type B MAO specifically and irreversibly by incubation for 5 hr at 37°C, and SDS-disc electrophoresis was carried out using ³H-pargyline as a tracer. The molecular weight of MAO was estimated after specific binding of pargyline was corrected for non-specific binding. The molecular weight of type B MAO in every organ was found to be 60, 000, giving a single peak after solubilization with 6% SDS, but several peaks at higher molecular weight were found in each organ after solubilization with 2% SDS. In the brain, there appeared to be a peak of 100, 000, and it was suggested that the MAO existed as a dimer which was composed of a FAD containing subunit and a low molecular weight subunit containing no FAD. In the liver, there appeared to be peaks of 120, 000 and 240, 000, and it was suggested that the MAO existed as a dimer and tetramer. In the kidney, there appeared to be a peak of 180, 000, and MAO was suggested to exist as a trimer.

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Effects of human calcitonin (HCT) on the responses of mice and rats to noxious stimuli of various types and morphineantinociception in the mice tail-pinch method were studied as compared with procine calcitonin (PCT). I.c.v. administration of HCT (0.007-0.071 mg/mouse) delayed response time to tail-pinch stimuli and suppressed acetic acid writhing dose-relatedly. PCT (0.5-3 U/mouse, i.c.v.) exerted a dose-related antinociceptive effect in the tailpinch and acetic acid writhing methods. The antinociceptive effect was also produced by s.c. administration of HCT (0.071-7.1 mg/kg) and PCT (10-1000 U/kg) in the tail-pinch and writhing methods, while the antinociceptive effect was not detected by the tail-flick method following i.c.v. and s.c. administration of HCT and PCT. Increase in response threshold in the hind paw pressure test was produced by 0.071-7.1 mg/kg, s.c. of HCT and 10-1000 U/kg, s.c. of PCT in rats. Inhibition of writhing due to i.c.v. administration of HCT and PCT was not antagonized by naloxone. Pre-drug control response time to tail-pinch stimuli tended to be shortened after 7-14 days of s.c. treatment with CT, especially with PCT. Pretreatment with HCT and PCT exerted no obvious influence on their acute effects. Morphine-antinociception in the tail-pinch method tended to be potentiated by single s.c. dose of HCT and to be decreased by 14 days chronic s.c. treatment with HCT. The role of calcium in HCT action was discussed.

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The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid were investigated using some experimental animal models. Anti-inflammatory potencies of aspirin were almost equal to those of sodium salicylate in the carrageenin hind paw edema, the cotton pellet granuloma and the adjuvant arthritis tests in rats. On the other hand, in the ultra-violet ray erythema and the arachidonic acid erythema tests in guinea pigs, aspirin was more potent than sodium salicylate. Aspirin and sodium salicylate exhibited almost the same inhibitions of the rat hind paw edema induced by a mixture of carrageenin and prostaglandin E₁. These results suggest that inhibition of cyclo-oxygenase by aspirin does not play any important roles for the prevention of the vascular permeability increment and the granulation in the inflamed tissue. Aspirin may exert its anti-inflammatory activity mainly as salicylic acid which is not an inhibitor of prostaglandins biosynthesis in vitro. Aspirin showed about 5 times more potent analgesic action than sodium salicylate in the lameness test using adjuvant arthritic rats. Analgesic potency of aspirin was decreased to the level of sodium salicylate by injection of prostaglandin E₂ into the inflamed rat paw in the adjuvant-induced lameness test. On the other hand, analgesic potency of sodium salicylate was not decreased by the same treatment. It is concluded that aspirin has two analgesic effects on the inflammatory pain, one is inhibition of prostaglandins biosynthesis by acetylation of cyclo-oxygenase and the other is an action due to salicylic acid, but the action of salicylic acid was not totally explained by the inhibition of prostaglandins synthetase.

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