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Biomedical subjects

K Ohuchi

Publications and source records attributed to K Ohuchi.

At least 127 records · Page 7Linked to original sources
PubMed1987

The effect of diphenylamine derivatives on arachidonic acid metabolism in rat peritoneal macrophages.

The effect of diphenylamine derivatives such as diclofenac sodium, mefenamic acid and lobenzarit disodium on arachidonic acid metabolism in rat peritoneal macrophages was examined. Lobenzarit disodium has no effect on prostaglandin E2 production as measured by radioimmunoassay although two other diphenylamine derivatives have a potent inhibitory activity. Three diphenylamine derivatives have no effect on Ca2+ ionophore-stimulated release of radioactivity from (3H)arachidonic acid-labeled macrophages. HPLC analysis revealed that lobenzarit disodium had no effect on the synthesis of lipoxygenase products as observed in diclofenac sodium and mefenamic acid. It is concluded that lobenzarit disodium, although its fundamental chemical structure resembles diclofenac sodium and mefenamic acid, has no inhibitory activity on arachidonic acid metabolism, suggesting that immunomodulatory activities of lobenzarit disodium are manifested without interfering with arachidonic acid metabolism.

Aniline Compounds↗
PubMed1987

Mechanism of antianaphylactic action of beta-agonists in allergic inflammation of air pouch type in rats.

Using an experimental model of allergic inflammation of air pouch type in rats, the mechanism of antiallergic action of beta-agonists was examined. In this model an immediate increase in vascular permeability and histamine level in the pouch fluid was observed after injecting the antigen (azobenzene arsonate-conjugated acetyl bovine serum albumin) solution into the preformed air pouch on the back of the sensitized rats. The same type of reaction was inducible by injecting anti-rat IgE into the preformed air pouch, but not IgG2a. This fact indicates that the immediate increase in vascular permeability and histamine level is an IgE-mediated anaphylactic reaction. When beta-agonists such as isoproterenol, procaterol and salbutamol were injected into the air pouch together with the antigen, the anaphylactic increase in vascular permeability was suppressed dose-dependently without concomitant decrease in histamine level in the pouch fluid. In contrast, disodium cromoglycate, an inhibitor of degranulation of mast cells, the anaphylactic vascular permeability increase was suppressed in parallel with a decrease of the histamine level. Propranolol, a beta-antagonist, counteracted the effect of beta-agonists. Serotonin-induced vascular permeability was also suppressed dose-dependently by treatment with beta-agonists. Furthermore, vascular permeability in the postanaphylactic phase of the present experimental model was also suppressed by isoproterenol. These results indicate that beta-agonists exert their antiallergic effect by inhibiting the reactivity of local vasculature to chemical mediators released from mast cells.

Adrenergic beta-Antagonists↗
PubMed1987

Recurrence of an allergic inflammation of air-pouch type in rats and possible participation of prostaglandin E2.

The recurrence of allergic inflammation, as examined by exudate accumulation, infiltration of polymorphonuclear leukocytes into the exudate, edema formation, vascular permeability and prostaglandin E2 levels in the exudate, was induced by injecting the antigen, azobenzene arsonate-conjugated acetyl bovine serum albumin, into the capsule of the proliferative granulation tissue which had been formed by the first-time antigenic challenge injection into an air pouch in the dorsum of the sensitized rat. The recurrence of the allergic inflammation 4 and 24 h after the antigenic challenge was inhibited dose-dependently by treatment with cyclooxygenase inhibitors, suggesting the possible participation of cyclooxygenase products, especially prostaglandin E2. The difference in the allergic inflammatory responses induced by the first-time antigenic challenge and the second-time antigenic challenge was discussed from the viewpoint of chemical mediators.

Animals↗
PubMed1987

Platelet-activating factor in the inflammatory exudate in the anaphylactic phase of allergic inflammation in rats.

Using a model of allergic inflammation of air pouch type in rats, the platelet-activating factor (PAF) in the pouch fluid in the anaphylactic phase was analyzed. Anaphylactic reaction was induced by injecting an antigen (azobenzene-arsonate-conjugated acetyl bovine serum albumin) solution into a subcutaneous air pouch preformed on the dorsum of immunized rats. The pouch fluid was collected 30 min after the antigenic challenge, and chloroform extract was subjected to normal phase high-performance liquid chromatography to isolate two fractions, PAF and lyso-PAF. In the pouch fluid, however, there was little activity of PAF as examined by the aggregation of guinea pig platelets. The lyso-PAF fraction obtained was acetylated to PAF chemically with pyridine and acetic anhydride. This acetylated lyso-PAF fraction induced the aggregation of guinea pig platelets, which was inhibited dose-dependently by a PAF antagonist, CV-3988. The amount of lyso-PAF in the pouch fluid of the immunized group in the anaphylactic phase was significantly higher than that of the nonimmunized group. When (3H-)PAF was incubated with the supernatant fraction of the pouch fluid it was metabolized into lyso-PAF time-dependently. The significance of the higher level of lyso-PAF in the pouch fluid in the anaphylactic phase of allergic inflammation is discussed.

Adenosine Diphosphate↗
PubMed1987

Role of endogenous histamine in postanaphylactic phase of allergic inflammation in rats.

Role of endogenous histamine in postanaphylactic phase of allergic inflammation was examined by using a rat model of allergic inflammation of air pouch type. Histamine in the exudate revealed a biphasic increase. The anaphylactic increase was followed by rapid decrease and then by a gradual rising in postanaphylactic phase with the maximum attained around 24 hr after the antigenic challenge. It again decreased gradually. The histamine increase in the postanaphylactic phase was accompanied by the increase of histidine decarboxylase activity in inflammatory tissues. Local administration of pyrilamine, an H1 antagonist, together with either methysergide, a serotonin antagonist, or cimetidine, an H2 antagonist, was unable to inhibit vascular permeability response in the postanaphylactic phase. When histaminase was administered locally in the postanaphylactic phase to reduce histamine in the exudate, neutrophil accumulation in the exudate was enhanced without any change in exudate accumulation. Enhancement of the neutrophil accumulation was also inducible with local administration of cimetidine but not with pyrilamine. Local administration of histamine inhibited the neutrophil accumulation dose-dependently. These results suggest that endogenous histamine released in the postanaphylactic phase contributes to downward regulation of neutrophil accumulation in the inflammatory site without affecting the vascular permeability.

Amine Oxidase (Copper-Containing)↗
PubMed1986

Synergistic stimulation of histamine release from rat peritoneal mast cells by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters.

Thapsigargin, a non-TPA (12-O-tetradecanoylphorbol 13-acetate)-type tumor promoter, provoked histamine release from rat peritoneal mast cells at concentrations above 30 ng/ml, but not at 10 ng/ml. TPA-type tumor promoters such as TPA, teleocidin and aplysiatoxin released very little, if any, histamine even at 100 ng/ml. When mast cells were incubated in medium containing thapsigargin at 10 ng/ml and varying concentrations of TPA-type tumor promoters, histamine release was increased synergistically. Maximum synergistic effects were observed at 10 ng/ml of each TPA-type tumor promoter. Palytoxin, another non-TPA-type tumor promoter, having no effect on histamine release at up to 10 pg/ml, also induced histamine release in the presence of 10 ng/ml of each TPA-type tumor promoter. However, no synergistic effect on histamine release was observed when mast cells were incubated in medium containing two different non-TPA-type tumor promoters, e.g., 10 ng/ml thapsigargin and 10 pg/ml palytoxin, or in medium containing two different TPA-type tumor promoters, e.g., TPA and teleocidin, TPA and aplysiatoxin, or teleocidin and aplysiatoxin (all at 10 ng/ml). These results suggest that the release of histamine from mast cells is stimulated synergistically under the mutual influence of TPA-type tumor promoters and non-TPA-type tumor promoters.

Animals↗
PubMed1986

Vascular permeability responses and the role of prostaglandin E2 in an experimental allergic inflammation of air pouch type in rats.

Rats were sensitized with azobenzene arsonate-conjugated acetyl bovine serum albumin. An allergic inflammation was induced in the preformed air pouch in the dorsum of the sensitized rats by injecting the antigen dissolved in a 2% sodium carboxymethyl cellulose solution into the air pouch. Time course changes of vascular permeability, accumulated pouch fluid volume and prostaglandin E2 (PGE2) levels in the pouch fluid were compared in sensitized and non-sensitized rats to characterize the allergic inflammatory reaction. Effects of three cyclo-oxygenase inhibitors (indomethacin, diclofenac sodium and tiaprofenic acid) on vascular permeability and accumulated pouch fluid volume 4 and 24 h after the immunological challenge injection were examined to elucidate a possible role of PGE2 in the inflammatory response. Four h after initiating the allergic reaction, although the level of PGE2 in the pouch fluid reached a high level, the vascular permeability response, measured over the period 3.5-4 h, was not suppressed by treatment with the three cyclo-oxygenase inhibitors and neither was the pouch fluid volume measured over the period 0-4 h. However, vascular permeability and accumulated pouch fluid volume at 24 h were suppressed by the cyclo-oxygenase inhibitors in a dose-dependent manner. These observations suggest that in this model, endogenous PGE2 does not affect oedema formation measured at 4 h. However, oedema formation measured at 24 h may be dependent on PGE2 generation.

Animals↗
PubMed1986

Orosomucoid as the accelerator of hepatic fibrosis.

The administration of orosomucoid to rats with chronic liver injury accelerated hepatic fibrosis. An increase of hepatic fibres was seen histologically and the content of hydroxyproline in the liver collagen fraction increased. Moreover, the incorporation of 3H-proline into the collagen fraction of injured liver was increased by the administration of orosomucoid.

Animals↗
PubMed1985

Pharmacological analysis of the vascular permeability response in the anaphylactic phase of allergic inflammation in rats.

Allergic inflammation was induced by injecting an antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into a preformed air pouch in the dorsum of sensitized rats. There was a marked increase of vascular permeability during the first 30 min, i.e. the anaphylactic phase, after the antigenic challenge injection. In an attempt to define the mediators responsible for the vascular permeability increase, series of experiments were performed with the aid of various pharmacologic agents. The combined treatment with pyrilamine and methysergide almost completely suppressed the anaphylactic vascular permeability response. However, FPL 55712, a specific antagonist to leukotrienes C4 and D4, components of slow-reacting substance, exerted no effect at doses sufficient to suppress the leukotriene C4-or leukotriene D4-induced vascular permeability increase. Indomethacin treatment was also ineffective. These results suggest that the anaphylactic increase in vascular permeability was mediated primarily by histamine and serotonin, while slow-reacting substance or prostaglandins did not play any significant role. A potent anti-inflammatory steroid, dexamethasone, exerted a dose-dependent inhibitory effect on the anaphylactic increase in vascular permeability without interfering with the liberation of histamine from mast cells. The mechanism of the steroid action is discussed.

Anaphylaxis↗
PubMed1985

Stimulation of prostaglandin E2 production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide.

The effects of TPA (12-O-tetradecanoylphorbol 13-acetate)-type and non-TPA-type tumor promoters on prostaglandin E2 production by peritoneal macrophages of rats were examined. Among the TPA-type tumor promoters, aplysiatoxin was most potent in stimulating prostaglandin E2 production followed by dihydroteleocidin B, teleocidin, TPA and debromoaplysiatoxin. Prostaglandin E2 production by aplysiatoxin treatment was stimulated at doses up to 0.1 ng/ml. Palytoxin, a non-TPA-type tumor promoter, also stimulated both prostaglandin E2 production and the release of radioactivity from [3H]arachidonic acid-labeled macrophages. However, the dose required for the expression of these effects by palytoxin was up to 3 pg/ml. It was suggested that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism, irrespective of their type. Cycloheximide, a protein synthesis inhibitor, inhibited both prostaglandin E2 production and the release of radioactivity from prelabeled macrophages stimulated either by the TPA-type tumor promoters or by the non-TPA-type tumor promoter. It is possible that the tumor promoters may induce the synthesis of some proteins responsible for the stimulation of arachidonate metabolism.

Acrylamides↗
PubMed1984

Reduction by dexamethasone of chemotactic activity in inflammatory exudates.

Using an experimental model for allergic inflammation of the air pouch type in rats, the effects of dexamethasone and indomethacin on leukocyte infiltration and level of chemotactic activity in the inflammatory exudate were examined to clarify the mechanisms of anti-inflammatory effects of glucocorticoids. Both dexamethasone and indomethacin when locally administered inhibited leukocyte infiltration, while chemotactic activity of the exudate was reduced by dexamethasone only. Indomethacin failed to reduce the level of chemotactic activity. Suppression by dexamethasone of the level of chemotactic activity became evident prior to the decrease in the number of leukocytes in the inflammatory exudate. These results suggest that the anti-inflammatory steroids manifest their inhibitory effect on leukocyte infiltration by inhibiting the generation of chemotactic factors in the inflammatory site. Besides this, the possible production of some inhibitory factors by the steroids may be considered as an alternative mechanism.

Animals↗
PubMed1984

Dexamethasone inhibits generation in inflammatory sites of the chemotactic activity attributable to leukotriene B4.

Effects of dexamethasone on chemotactic activity to polymorphonuclear leukocytes (PMN) of a lipophilic fraction collected with the aid of octadecylsilyl silica cartridge from exudates of an allergic inflammation were investigated. The chemotactic activity of this fraction was attributable to leukotriene B4 fraction separated by means of a reversed phase high performance liquid chromatography. Local application of dexamethasone suppressed dose-dependently the chemotactic activity of the lipophilic fraction in parallel with the inhibition of PMN infiltration in the inflammatory sites.

Animals↗
PubMed1984

Lectins modulate prostaglandin E2 production by rat peritoneal macrophages.

The effect of Aloctin A (Alo A), a lectin having anti-inflammatory activities, on prostaglandin (PG) E2 production by activated rat peritoneal macrophages was compared with that of concanavalin A (Con A), wheat germ agglutinin (WGA), plsum sativum agglutinin (PSA) and soybean agglutinin (SBA). Alo A, WGA, Con A and PSA at 10 micrograms per ml inhibited PG E2 production. But SBA, even at a dose of 1 microgram per ml, stimulated PG E2 production. The inhibition by Alo A treatment of the release of radioactivity from (3H)arachidonic acid-labeled macrophages and the stimulation of this release by SBA treatment were observed. The uptake of (51Cr)-labeled sheep red blood cells by the macrophage was inhibited by Alo A, Con A, and PSA, all at 10 micrograms per ml and SBA at 1 microgram per ml, however, WGA at 10 micrograms per ml stimulated the uptake of the sheep red blood cells. The mechanism of the anti-inflammatory properties of Alo A was discussed.

Animals↗