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Biomedical subjects

T Saijo

Publications and source records attributed to T Saijo.

At least 73 records · Page 4Linked to original sources
PubMed1986

The antiallergic agent amoxanox suppresses SRS-A generation by inhibiting lipoxygenase.

Amoxanox has potent antiallergic activity because it inhibits the release of chemical mediators such as histamine and leukotrienes. We studied the in vitro effect of amoxanox on arachidonic acid metabolism, including the lipoxygenase and cyclooxygenase pathways. Amoxanox inhibited calcium ionophore A23187-induced formation of 5-HETE, LTB4, SRS-A (LTC4, LTD4 and LTE4), and 12-HETE in rat peritoneal resident monocytes. These results indicate that amoxanox inhibits 5- and 12-lipoxygenases. The compound, however, did not affect the formation of TXB2 or 6-keto-PGF1 alpha in guinea pig lung fragments and PGE2 or PGF2 alpha in bovine seminal vesicles, suggesting that it did not inhibit cyclooxygenase. These results show that the antiallergic action of amoxanox is associated, at least in part, with the reduction of leukotrienes due to the inhibition of lipoxygenases.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1986

[Combination chemotherapy with MOPP and intrathecal methotrexate in children with brain tumors].

Five children with brain tumors, who had had no prior chemotherapy, were treated with combination chemotherapy including nitrogen mustard, vincristine sulfate, procarbazine, prednisolone (MOPP) and intrathecal methotrexate. Four had progressive tumor or metastatic deposits, (one medulloblastoma, one malignant choroid plexus papilloma, and two were not explored) but responded to chemotherapy. One child with medulloblastoma underwent resection, which was considered to be macroscopically radical, and demonstrated objective improvement of neurological findings after chemotherapy. Toxicities were not severe enough to require termination of the chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Inhibition by amoxanox (AA-673) of the immunologically, leukotriene D4- or platelet-activating factor-stimulated bronchoconstriction in guinea pigs and rats.

We studied the effects of amoxanox (AA-673) on allergic asthma and spasmogen-induced bronchoconstriction in guinea pigs and rats. Amoxanox given orally or parenterally inhibited allergic asthma mediated by IgE, IgG1, or heterologous IgG in guinea pigs and by IgE in rats. This compound also reduced leukotriene D4- and platelet-activating factor-induced bronchoconstriction in guinea pigs, strongly suggesting an antagonistic activity against slow reacting substance of anaphylaxis (SRS-A). Histamine- or acetylcholine-induced bronchoconstriction was not significantly affected by amoxanox. These antiasthmatic effects of amoxanox seem to be associated with an inhibition of the release of chemical mediators such as histamine and SRS-A and with an antagonism against SRS-A.

Aminopyridines↗
PubMed1985

Mechanism of the action of amoxanox (AA-673), an orally active antiallergic agent.

Amoxanox inhibited immunologically stimulated and LTD4-induced bronchoconstriction in laboratory animals. Amoxanox, like DSCG, inhibited rat IgE-mediated PCA and histamine release from rat peritoneal mast cells, and suppressed immunologically stimulated or calcium ionophore A23187-induced SRS-A generation in rat peritoneal cavity and guinea pig lung fragments. This compound also reduced the contractile response of guinea pig lung parenchymal and ileal strips to LTD4, but did not significantly affect the response of the ileum to either histamine or acetylcholine. Therefore, the antiallergic action of amoxanox seems to be associated with inhibition of chemical mediator release and antagonistic activity on SRS-A.

Aminopyridines↗
PubMed1983

Pharmacological profile of AA-861, a 5-lipoxygenase inhibitor.

AA-861, a selective 5-lipoxygenase inhibitor, suppressed A23187-induced formations of 5-HETE and LTB4 in rat peritoneal macrophages. Immunologically-stimulated generation of SRS-A was also inhibited in guinea pig lung and rat peritoneal cavity. AA-861 had no effects on histamine release from rat mast cells or passive cutaneous anaphylaxis in rats. Essentially no antagonistic activity to LTD4 or histamine was observed. This compound exerted an obvious inhibition of allergic bronchoconstriction in guinea pigs and a moderate reduction of carrageenin-induced paw edema and pleurisy in rats. These findings suggest that SRS-A plays an important role in asthmatic and inflammatory reactions.

Animals↗
PubMed1980

Interaction of the antiallergic agent AA-344 with biogenic amines and prostaglandins in production of cyclic AMP in rat mast cells.

AA-344, which has been evidenced to inhibit selectively IgE-mediated allergic reactions, exhibited an inhibitory effect on cyclic AMP phosphodiesterase (PDase) in the homogenates of purified rat peritoneal mast cells (RMC). AA-344 showed synergistic effects with epinephrine, isoproterenol or prostaglandin E2 and F2 alpha in increasing cyclic AMP level in RMC: the combinations caused an increase in cyclic AMP 30-160 times as much as that caused by the respective agent alone. In the latter effect, AA-344 was at least 1,000 times as potent as theophylline. On the other hand, histamine or serotonin with or without AA-344 had no effect on the RMC cyclic AMP. These results obtained in vitro suggest that AA-344 may exert antiallergic action by increasing cyclic AMP via an interaction with epinephrine or prostaglandins which might be endogenously involved in regulation of a function of RMC in allergic reactions.

Amines↗
PubMed1979

Studies on antianaphylactic agents. 6. Synthesis of some metabolites of 6-ethyl-3-(1H-tetrazol-5-yl)chromone and their analogues.

The metabolites of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) (1), an orally effective antiallergic agent, and their analogues were synthesized to confirm the proposed structures and to determine their activity in the rat passive cutaneous anaphylaxis (PCA) test. A glucuronic acid metabolite (6) was assigned the structure 24b, 1-deoxy-1-[5-(6-ethylchromon-3-yl)tetrazol-1-yl]-beta-D-glucopyranuronate, by the comparison of 13C NMR, mass spectra, and TLC of isomeric compounds. In 13C NMR spectra, the shift difference of the tetrazole ring carbons between a pair of isomers was more remarkable than that of the glycosidic carbons. Therefore, the former is a useful criterion for distinguishing between such isomers. Some of the metabolities and analogues were active when administered intravenously, and two metabolites (2 and 3) were also effective upon oral administration.

Animals↗
PubMed1979

Antiallergic action of 6-ethyl-3-(1h-tetrazol-5-YL) chromone (AA-344) on immediate hypersensitivity reaction in rats.

A newly synthesized compound, 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) given intravenously or orally inhibited considerably the 72-hr passive cutaneous anaphylaxis (72-hr PCA) induced by IgE in rats. The antiallergic action of AA-344 was neither due to the antihistamine or antiserotonin effect nor was it mediated via adrenergic mechanisms. The results obtained in a double sensitization with two IgE antibodies suggest that AA-344 may not impair antigen-antibody combination but probably prevents the release of chemical mediators including histamine. This assumption was supported by observation that AA-344 inhibited a reduction in the skin histamine content caused by the 72-hr PCA, without effect on the compound 48/80-induced histamine reduction. AA-344 also partially inhibited the IgGa-mediated 3-hr PCA in rats. These results indicate that the inhibitory action of AA-344 on the immediate hypersensitivity reactions is due to prevention of the release of chemical mediators from the mast cells, by acting on some process in sequential events leading to the mediator release following antigen-antibody combination.

Adrenalectomy↗
PubMed1979

Inhibitory action of 6-ethyl-3-(1H-tetrazol-5-YL)chromone (AA-344) on IgE, IgGa- or chemical agent-induced histamine release from isolated rat mast cells.

The antiallergic action of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) was studied on isolated rat peritoneal mast cells. AA-344 clearly inhibited the IgE-mediated release of histamine caused by various concentrations of antigen and the 50% inhibitory concentration was 0.1 microM. On the IgGa-mediated release of histamine, a peak inhibition of AA-344 was observed at 10 microM. The histamine release induced by chemical agents such as concanavalin A, dextran and compound 48/80 was depressed by AA-344 at the range of 0.1--1 mM. The results obtained in this study indicate that the antiallergic action of AA-344 is due to selective inhibition on the immunological release of the chemical mediator from mast cells.

Animals↗
PubMed1979

Effect of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the immediate and delayed hypersensitivity reactions.

Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complete-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.

Animals↗
PubMed1975

Studies on antianaphylactic agents. 4. Synthesis and structure-activity relationships of 3-(4-oxo-4H-1-benzopyran-3)acrylic acids, a new series of antiallergic substances, and some related compounds.

The syntheses of trans-3-(4-oxo-4H-1-benzypyran-3)acrylic acid and a number of analogs shown to be highly active in antiallergic bioassays are described. These compounds are of possible value in the treatment of asthma. The structural requirements for biological activity are discussed with reference to the type of the substituents on the chromone ring or positions of linkage of the acrylic acid on the pyrone ring.

Acrylates↗
PubMedDate not supplied

Type of lymphocytes affected by the islet-activating protein (IAP).

By flow cytometric analysis, we identified the subclass of lymphocytes that proliferates in response to islet-activating protein (IAP), both in vitro (human peripheral blood mononuclear cells, MNC, cultured with IAP) and in vivo (peripheral blood MNC derived from A/J mice treated with IAP). IAP caused a preferential proliferation of CD8+ T cells. These cells expressed the IL-2 receptors on their surface. CD4+ CD8+ T cells could also be detected in these cultures, IAP caused human MNC to produce IL-1 and to induce expression of HLA-DR antigen. These effects may play an important role in the T-cell proliferation induced by IAP, although IAP by itself suppressed the proliferative action of IL-1 in mouse thymocytes. IAP induced proliferation of the purified CD4+ cells but had a smaller effect on the purified CD8+ cells. This suggests that the proliferation of CD8+ cells in IAP-treated MNC depends on the function of other types of cell, e.g. CD4+ cell and macrophage.

Animals↗