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Y Oyanagui

Publications and source records attributed to Y Oyanagui.

33 records · Page 2Linked to original sources
PubMed1986

Vasoregulin, a glucocorticoid-inducible vascular permeability inhibitory protein.

A vascular permeability inhibitory protein 'Vasoregulin' was induced by dexamethasone and other glucocorticoids in Namalva cells. Precipitates produced by trichloroacetic acid from cultured supernatant (crude released vasoregulin) suppressed serotonin-induced paw edema of mice (ID30 = 750 micrograms/mouse) when dosed 30 min. before serotonin. Carrageenan paw edema of rats was also suppressed (ID30 = 9 mg/rat, s.c. and i.p., not by oral dosing) when the compound was injected at the same time as carrageenan and the edema determined after 3 hrs. The possible effect of glucocorticoid itself being contained in the vasoregulin preparation was excluded. The presence of Cu, Zn-superoxide dismutase (SOD), spermidine and spermine also gave good yields of vasoregulin in culture; SOD protected the inactivation of vasoregulin from superoxide radical in vitro. Vasoregulin partially purified by Sephadex G-75 columns had no malonaldehyde-formation inhibitory capacity. Thus, vasoregulin is a glucocorticoid-inducible anti-inflammatory protein which differs from lipocortin.

Animals↗
PubMed1984

Reevaluation of assay methods and establishment of kit for superoxide dismutase activity.

Superoxide dismutase (SOD) activity was measured by seven assay methods. The nitrite method was found to be the best for our SOD assay kit. This method was then modified to give better sensitivity and minimize interference by coexisting protein, a factor which has been previously ignored. Hydroxylamine or its O-sulfonic acid, xanthine oxidase, hypoxanthine, EDTA, and the sample were incubated with or without KCN at pH 8.2, 37 degrees C, for 30 min. Diazo dye-forming reagent was added and the absorption was measured at 550 nm. Human plasma and erythrocyte lysate from healthy adults and Down's syndrome patients were assayed by this SOD kit and by the cytochrome c method. Our kit gave 8.5 times higher sensitivity than the cytochrome c method. This high sensitivity allowed the use of a simple spectrophotometer and, moreover, only one dilution was needed to determine the SOD unit with the help of our formulas. Good recovery, reproducibility, and stability of reagents were demonstrated.

Adult↗
PubMed1984

Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata - possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical.

Serotonin paw edema of mice and carrageenan paw edema of rats were inhibited by subcutaneously or orally administered certain polyamines. They must be given at least 2 h before serotonin challenge to get inhibitions which were blocked by the concomitant injections of cycloheximide. Thirty percent inhibitory dose (ID30) of polyamines (s.c.) 3 h before serotonin (s.c.) were: spermidine (8 mg/kg), spermine 28 mg/kg) and putrescine (55 mg/kg). Agmatine, cadaverine, ornithine, citrulline, lysine and arginine were not inhibitory even at 200 mg/kg. Three inhibitory polyamines were effective by oral administration but were not inhibitory by local administration into the paws. Intravenous injections of spermidine also required 2 h of lag period for inhibitions. Serotonin edema was inhibited by dexamethasone (1 mg/kg), prednisolone (1 mg/kg) or by superoxide dismutase (SOD, 5 mg/kg) in lag period requiring manner (s.c. and i.v.). High dose of cyclo-oxygenase inhibitors indomethacin and diclofenac sodium, lipo-oxygenase inhibitor BW755C (30 mg/kg s.c., respectively) and phospholipase A2 inhibitor quinacrine (100 mg/kg s.c.) failed to inhibit serotonin edema, suggesting that arachidonate metabolites are not participating in this model. ID30 of polyamines which were administered (s.c. and oral) to rats 3 h before carrageenan and determined at 3 h by paw weight were: spermidine (28 and 100 mg/kg), spermine (18 and 90 mg/kg) and putrescine (both greater than 200 mg/kg). Adrenalectomized rats responded to polyamines just as normal rats. Local vascular permeability, irritancy and acute toxicity were also tested in mice. Polyamines were proved to be glucocorticoid-type anti-inflammatory drugs. Polyamines may be mediators of glucocorticoids for the synthesis of the postulated vascular permeability inhibitory protein (called as 'vasoregulin' for convenience). Anti-inflammatory effect of glucocorticoid is recently explained by its capacity to induce phospholipase A2 inhibitory protein(s) (macrocortin or lipomodulin). However, this hypothesis has not yet been proved by in vivo experiment and our data suggest that there is induction by glucocorticoid of another kind of protein which does not inhibit phospholipase A2 activity.

Adrenalectomy↗
PubMed1983

Physiological regulation of vascular permeability by endogenous glucocorticoids and active oxygen.

A copper chelator, diethyldithiocarbamate (DDC), injection and adrenalectomy induce significant paw swelling by low doses of serotonin, histamine, or bradykinin, which can result in mild swelling in non-treated mice. Dexamethasone, Cu,Zn-superoxide dismutase (SOD), and hydroxyl radical scavengers suppressed the DDC-provoked edema, but only dexamethasone suppressed the edema of adrenalectomized mice. Adrenal stimulation by SOD is exclusive in that the suppression of edema by SOD began about 1 h prior to that by glucocorticoid. In order to explain the data obtained, the existence of a vascular permeability inhibitory protein (called "vasoregulin") was assumed. This protein must be synthesized constantly somewhere in the body and continuously inactivated by active oxygen in vivo. Local levels of vasoregulin may limit the responses of vascular permeability against the chemical mediators. This hypothesis was also supported by the edema-enhancing effects of protein/RNA synthesis inhibitors.

Adrenalectomy↗
PubMed1983

Platonin, a photosensitizing cyanine dye, suppresses acute inflammation.

Platonin is believed to be an immunomodulator, because it has been shown to be effective only in chronic inflammation models in rat adjuvant arthritis. Platonin did not suppress the serotonin-, histamine- and bradykinin-induced paw edemata of mice when injected 0-1 hr before these irritants in the standard methods. When platonin was administered 3 hr before challenge, however, all of these inflammations were significantly suppressed. Platonin required at least 1 hr of lag for onset of inhibition, just as dexamethasone, and was effective only in the range of 10-320 micrograms/kg. Inhibition of serotonin-induced paw edema by platonin was impaired by concomitant injection of cycloheximide and was not affected by adrenalectomy. Platonin was concluded to suppress the vascular permeability principally through enhancing the endogenous anti-inflammatory protein (vasoregulin) synthesis without changing arachidonate metabolism, lymphocyte transformation or antibody production. Rat carrageenan paw edema was also suppressed when this drug was administered 2-4 hr before challenge.

Acute Disease↗
PubMed1980

Inflammation and superoxide production by macrophages.

Superoxide (.O-2) is demonstrated to participate at the prostaglandin phase swelling (2-4 h) of carrageenan paw edema. Superoxide production is inhibited in vitro by typical anti-inflammatory drugs, but these drugs did not scavenge superoxide which was produced by xanthine oxidase. Phosphate, pyrophosphate, ATP, ADP and sulfate were essential for superoxide production by macrophages. These anions can induce paw swelling and are reported to increase in rheumatic patients. A mixture of macrophages and lymphocytes from BCG sensitized guinea-pigs was cultured for 2 days with SOD or D-mannitol. Nitroblue tetrazolium reduction (formazan formation) was inhibited by these agents, suggesting that the hydroxyl radical (.OH) is necessary for metabolic activation of macrophage. Lympholine-like factor of which production or release is enhanced by hydroxyl radical, activates macrophage. Production of oxygen radicals may increase rapidly by this chain cycle reaction. Possible relations of oxygen radicals to prostaglandin(s) biosyntheses, chemotaxis, lysosomal enzyme release protease participation, were discussed. Endogenous SOD, epinephrine, ceruloplasmin, blood plasma proteins, inflammatory fluid, may modulate the amount of superoxide by their superoxide scavenging capacities.

Animals↗
PubMed1977

Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema.

The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (-O-2) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of -O-2 by the xanthine oxidase system, suggesting that they serve only as activators of -O-2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5'-triphosphate (ATP) reported to be in the synovial fluid, -O-2 was produced efficiently and was inhibited by diclofenac sodium. These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling.

Adenine Nucleotides↗
PubMedDate not supplied

Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice.

Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L-NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L-NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema.

Animals↗