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Biomedical subjects

I Arai

Publications and source records attributed to I Arai.

108 records · Page 6Linked to original sources
PubMed1984

Effects of sofalcone on necrotizing agents-induced gastric lesions and on endogenous prostaglandins in rats stomachs.

Attempts were made to investigate the effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (sofalcone) on necrotizing agents-induced gastric lesions and on prostaglandin E2 (PGE2)-like activity of the gastric tissue in rats. Sofalcone, 100 mg/kg i.p. and 300 mg/kg p.o., markedly suppressed 0.6 N HCl- or 100% EtOH-induced gastric lesions. Sofalcone, 100 mg/kg i.p., also significantly suppressed 0.2N NaOH-induced gastric lesions. Sofalcone suppressed 0.6 N HCl-induced gastric lesions with both oral and intraperitoneal routes, and the effect was particularly marked at 60 min. A dose of 100 mg/kg i.p. showed suppression lasting for up to 300 min. 0.6 N HCl-induced gastric lesions were significantly aggravated by indomethacin treatment (10 mg/kg s.c.). Oral sofalcone (300 mg/kg) significantly suppressed the aggravation of gastric lesions by indomethacin given before and after sofalcone, but the i.p. (100 mg/kg) did not show significant suppression in the case of pretreatment with indomethacin. PGs-like activity in the gastric tissue was increased in both of the fundus and the antrum by the administration of sofalcone without any dose-dependency. The increase was continuous and lasted for 6 h in the fundus of the stomach.

Animals↗
PubMed1984

Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (sofalcone) on chronic gastric ulcers in rats.

The anti-ulcer effect of sofalcone, an isoprenyl chalcone derivative, on acetic acid-induced gastric ulcers in rats was studied histologically and histochemically. After administrations of sofalcone at 50 and 200 mg/kg twice daily for 10 days, contraction of the ulcer, mucosal regeneration, accelerated development of the collagen fibers in the granulation tissue at the base of the ulcer, and increase of acid mucopolysaccharides, an alcian blue stain-positive substance covering the regenerated mucosa, were noted. The healing effect of sofalcone was balanced in mucosal regeneration and connective tissue proliferation (formation of the collagen fibers). Sofalcone of 50 mg/kg showed a greater healing effect than gefarnate at the same dose and had a similar healing effect as L-glutamine at 200 mg/kg.

Acetates↗
PubMed1984

[Anti-inflammatory activity of a non-steroidal anti-inflammatory agent, oxaprozin, in experimental models].

Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro tests. Anti-inflammatory potency of oxaprozin was almost equal to that of aspirin in acetic acid vascular permeability, carrageenin hind paw edema, cotton pellet granuloma and adjuvant arthritis tests in rats. On the other hand, in mice, oxaprozin was more potent than aspirin, ibuprofen and phenylbutazone, and it was as potent as sulindac and fenbufen in acetic acid vascular permeability and carrageenin hind paw edema tests. In adrenalectomized rats, the anti-edema activity of oxaprozin in the carrageenin hind paw edema test was the same as that in intact rats. Oxaprozin inhibited erythema formation induced by ultra-violet rays in guinea pigs. The inhibitory potency of oxaprozin against prostaglandin E2 biosynthesis in vitro was equal to that of ibuprofen. Oxaprozin showed a concentration-dependent inhibition of heat-induced denaturation of bovine serum albumin and lysis of rabbit erythrocytes in vitro. However, oxaprozin did not inhibit rat hind paw edemas induced by dextran, formalin and serotonin. It was suggested from these results that the mode of action of oxaprozin is similar to those of other acidic non-steroidal anti-inflammatory drugs. Ulcerogenicity of oxaprozin was weaker than those of phenylbutazone and aspirin in rats. Species differences in the metabolic rate of oxaprozin were shown. The blood concentration of oxaprozin in rats is extremely low because the metabolic rate of oxaprozin is rapid in rats. Therefore, in rats, oxaprozin exhibited a weak anti-inflammatory effect. However, in mice, oxaprozin had a low metabolic rate, and the effect of oxaprozin was as potent as sulindac and fenbufen. The elimination half-life of oxaprozin is extended, 49 to 69 hr, in humans. It was suggested from these findings that oxaprozin is a potent and long acting anti-inflammatory drug in clinical use.

Animals↗
PubMed1983

Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88) on gastric local blood flow.

Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88), a new anti-ulcer drug, on gastric tissue blood flow was investigated by using an inhaled hydrogen gas clearance method in rats. As a result, following the intravenous infusions of 10,20 and 30 mg/kg/h of SU-88, the gastric blood flow increased with an increase rate of 38.1, 70.5 and 61.7% as compared with the control value, respectively. Following the intraperitoneal administrations of 50 and 100 mg/kg of SU-88, the gastric blood flow increased by 59.8 and 51.2%, respectively, immediately after the administration.

Animals↗
PubMed1982

[Effects of the anti-ulcer drug SU-88 on the gastric blood flow and the cardiovascular system (author's transl)].

Effects of a newly synthetized anti-ulcer drug, 2'Carboxymethoxy-4,4'-bis(3-methyl-2-butenloxy)chalcone (SU-88), on gastric blood flow and the cardiovascular system were investigated. Intravenously administered SU-88 dose-dependently increased the blood flow of gastric tissues in rats. In anethetized dogs, i.a. administered SU-88 also increased the short gastric and the femoral arterial blood flows. SU-88 (i mg/kg, 3 mg/kg and 10 mg/kg i.v.) caused a mild fall in systemic blood pressure, an increase in heart rate, and a stimulation of respiration; however, these effects were only transient and recovered to the basal level within few minutes. No notable changes were observed in the electrocardiogram except for a shortening of the R-R interval accompanied by an increase in heart rate. The blood flow of the common carotid, the vertebral, the coeliac, the superipor mesenteric, and the femoral arteries in dogs were all increased by i.v. administration of SU-88, and among them an increase in the coeliac arterial blood flow was prominent. SU-88 increased the perfusates in isolated rabbit ear and relaxed the contraction of isolated rabbit aorta induced by noradrenaline, but showed no influences on the amplitude, heart rate, and coronary flow of isolated rabbit heart. The hypotensive effect of SU-88 was not abolished by i.v. administered atropine, diphendydramine, and propranolol and not influenced by vagotomy. Intraverterbrally administered SU-88increased the vertebral blood flow, but showed no influence on systemic blood pressure. Furthermore, SU-88 showed no influence on the rise in blood pressure by both common carotid occlusions. The increase in the femoral and the short gastric arterial blood flow induced by i.a. administration of SU-88 was not inhibited by atropine, diphenhydramine, and propranolol and not influenced by pretreatment with aminophylline. These results suggest that the hypotensive and vasodilative effects of SU-88 are not mediated by the central nervous system, autonomic nervous system, histamine and the action of adenosine augmentation and further experiments are necessary for precise explanations of its mechanism.

Animals↗
PubMed1981

[Studies on antigenicity, phototoxicity and other specific toxicities of hydrocortisone 17-butyrate 21-propionate (HBP) (author's transl)].

The present experiments were undertaken to determine the antigenicity and other toxicities of HBP; such as phototoxicity, photosensitivity, ulcerogenicity, adrogenic-myotropic, estrogenic and progestational activities, and mutagenicity. No antibody formation and delayed type skin reaction of HBP were seen in rabbits. Active systemic anaphylaxis was not observed in guinea pigs challenged by HBP. In the phototoxicity and photosensitivity test, 0.1% HBP ointment, 0.1% HBP cream and 10% HBP acetone solution did not show any skin reaction with or without irradiation of ultraviolet light. Repeated subcutaneous administration of HBP irritated the gastric and intestinal mucosa dose dependently in rats as hydrocortisone 17-butyrate and betamethasone 17-valerate (BV). HBP had neither androgenic-myotropic nor estrogenic activity, but antiestrogenic activity was observed. The progestational activity of HBP in immature rabbit pretreated with estrone was less potent than BV. In the mutagenicity test os HBP investigated by the reverse mutation according to the method by Ames, no significant increase in the number of revertants was observed in the presence or absence of S9 mixture.

Administration, Topical↗
PubMedDate not supplied

Buckthorn neuropathy: effects of intraneural injection of Karwinskia humboldtiana toxins.

Ingestion of the endocarp of the coyotillo fruit, Karwinskia humboldtiana, a shrub of the buckthorn family, causes "Buckthorn neuropathy" in man and animals. Two neurotoxic compounds T496 and T544 were isolated from the endocarp and each toxin was dissolved in sesame oil and injected into the sciatic nerve of rats. The nerves were subsequently examined by teasing and as sections by light and electron microscopy. During the first 3--4 days after injection, oil droplets, probably containing toxin, were observed in the cytoplasm of Schwann cells with intact myelin sheaths. Clinical signs of weakness in the limb first appeared at 5--6 days and were accompanied by segmental demyelination mainly of the larger fibres. These observations suggest that the toxins have a primary action on Schwann cell metabolism. The results of local injection of purified toxins are discussed in relation to reports of nerve damage in animals following oral administration of the endocarp where intramyelin vacuole formation and segmental demyelination are prominent features.

Animals↗
PubMedDate not supplied

A new test for evaluating nonsteroidal anti-inflammatory drugs in vitro: inhibition of prostaglandin E2 production in minced intestinal tissue.

A new method for evaluating the inhibitory effect of nonsteroidal anti-inflammatory drugs on prostaglandin E2 production is presented. Minced rat intestinal tissue was incubated with a nonsteroidal anti-inflammatory drug and homogenized. After centrifugation, prostaglandin E2 in the supernatant was measured by radioimmunoassay. The production of prostaglandin E2 was decreased by nonsteroidal anti-inflammatory drugs, in a concentration-dependent manner, the order of potency being diclofenac greater than loxoprofen greater than indomethacin greater than ibuprofen greater than TA-847 (imidazole derivative). Loxoprofen, a prodrug, inhibited the prostaglandin E2 production. In a classical enzyme assay with sheep seminal vesicle microsomal prostaglandin endoperoxide synthase, the order of inhibitory potency was TA-847 greater than diclofenac greater than indomethacin greater than ibuprofen. The inhibitory effect of loxoprofen was very weak. On the other hand, the potency order of these nonsteroidal anti-inflammatory drugs, with regard to their anti-inflammatory effect as determined in the rat carrageenin-induced paw edema model, was loxoprofen greater than indomethacin greater than diclofenac greater than ibuprofen greater than TA-847. The results of the new method with intestinal tissue showed thus a good correlation with the anti-inflammatory activity in vivo.

Animals↗
PubMedDate not supplied

Hepatoprotective effect of SY-640, a novel acetamide derivative, on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice.

The hepatoprotective effect of SY-640 on Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice and its protective mechanism were examined. Oral administration of SY-640, 150 mg/kg once daily for 7 days, significantly inhibited Propionibacterium acnes and lipopolysaccharide-induced liver injury, but a single administration was without effect. Liver-infiltrating cells (T-lymphocytes and macrophages) play an important role in Propionibacterium and lipopolysaccharide-induced liver injury and express a higher level of leukocyte function-associated antigen-1. SY-640 inhibited the number of liver-infiltrating cells and attenuated the increased expression of leukocyte function-associated antigen-1 on these cells. Tumor necrosis factor-alpha mediated Propionibacterium acnes and lipopolysaccharide-induced liver injury, and SY-640 inhibited the elevation of the serum tumor necrosis factor-alpha concentration after injection of lipopolysaccharide in Propionibacterium acnes-primed mice. The putative effects of SY-640 are inhibitory effects on infiltration into the liver and on activation of T-lymphocytes and macrophages after Propionibacterium acnes-priming, and attenuation of expression of cell adhesion molecules such as leukocyte function-associated antigen-1. The immunological effect of SY-640 is likely to be closely related to the inhibition of Propionibacterium and lipopolysaccharide-induced liver injury.

Acetamides↗
PubMedDate not supplied

Expression of prostaglandin H synthase-2 in endotoxic shock induced in rats.

We investigated the expression of prostaglandin H synthase-2 in rats subjected to endotoxic shock. The prostaglandin H synthase activities were assessed by measuring the plasma prostaglandins (PGE2 and 6-keto-PGF1 alpha) after arachidonic acid administration (3 mg/kg, i.v.). The plasma prostaglandin concentrations increased immediately after administration of arachidonic acid, reached a peak at 30-60 seconds, and then rapidly decreased. Lipopolysaccharide (1 mg/kg, i.v.) also increased the plasma prostaglandin concentrations, reached a peak 1 hour after administration, and then gradually decreased to normal levels. The production of plasma prostaglandin, induced by administration of arachidonic acid, was markedly enhanced in the lipopolysaccharide-treated rats. A low dose of acetylsalicylic acid (3 mg/kg, i.v.) blocked the prostaglandin production in the nontreated rats but not in the lipopolysaccharide-treated rats. In the latter group of rats, a high dose of acetylsalicylic acid (30 mg/kg, i.v.), given 10 to 30 minutes before administration of arachidonic acid, completely blocked the prostaglandin production, but recovery of this production was seen with acetylsalicylic acid (30 mg/kg) treatment at 1 to 2 hours before administration of arachidonic acid. These data suggest that pretreatment with lipopolysaccharide enhances the prostaglandin production by forming newly synthesized prostaglandin H synthase. Immunoblots of the levels of enzyme protein from rat aorta endothelial cells were analyzed. The enzyme protein cross-reacting with antibody against prostaglandin H synthase-2 was increased by lipopolysaccharide treatment in endothelial cells, and was constitutively expressed in the stomach, kidney and liver, but not in the lung and the intestine. The induction of prostaglandin H synthase-2 by lipopolysaccharide treatment was observed only in endothelial cells. The enhancement of the prostaglandin production in lipopolysaccharide-treated rats was blocked by pretreatment with dexamethasone, prior to administration of lipopolysaccharide, this suppression is apparently the result of a decrease of the prostaglandin H synthase-2 protein in endothelial cells, as determined by Western blotting. The enhanced production of prostaglandin, induced by lipopolysaccharide, seems to be due to the in vivo expression of prostaglandin H synthase-2.

Animals↗