Biomedical subjects

K Takenouchi

Publications and source records attributed to K Takenouchi.

31 records · Page 2Linked to original sources

PubMed1988

Effects of antiallergic drugs on bronchial and cutaneous anaphylaxis in Lewis rats.

Effects of antiallergic agents on 2,4-dinitrophenylated Ascaris extract (DNP-As)-induced bronchial asthma were studied in Lewis rats, and compared with those on passive cutaneous anaphylaxis (PCA). Effects of methysergide and chlorpheniramine on the bronchial asthma model were also investigated. Rats were actively sensitized with DNP-As antigen and with killed Bordetella pertussis. After 8 d, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As caused a marked asthmatic bronchoconstriction without significant effect on systemic blood pressure and heart rate. Disodium cromoglycate (DSCG), 10 mg/kg, i.v., trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) and tranilast at doses of 30 and 100 mg/kg, intraduodenally, significantly inhibited the asthmatic response. Chlorpheniramine and methysergide at a dose of 1 mg/kg, i.v. also significantly inhibited it. The above doses of NCO-650 and tranilast significantly inhibited 48 h PCA, while DSCG almost abolished the PCA. These results indicate that 1) NCO-650 and tranilast inhibited both the asthmatic response and PCA in almost the same degree, 2) DSCG inhibited PCA much more strongly than asthmatic response, and 3) histamine and 5-hydroxytryptamine may be involved in this asthmatic response.

Anaphylaxis↗

PubMed1987

The effect of trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) on Ascaris suum antigen-induced bronchoconstriction in dogs.

Antiallergic asthma effect of trans-4-guanidinomethylcyclohexane-carboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650), a new anti-allergic drug, was investigated in comparison with those of tranilast and disodium cromoglycate (DSCG) in anesthetized dogs. The asthmatic bronchoconstriction was induced by inhalation of Ascaris suum antigen (Asc-Ag) to naturally Ascaris-sensitive dogs. The airway resistance was determined using the modified Konzett-Rössler method. Both intravenous (1 and 5 mg/kg) and intraduodenal (10, 30 and 100 mg/kg) administrations of NCO-650 prior to the antigen challenge markedly inhibited the asthmatic bronchoconstriction induced by Asc-Ag inhalation. The antiasthmatic effect of NCO-650 was much stronger than that of DSCG (10 mg/kg, i.v.) and was about three-fold stronger than that of tranilast. On the other hand, when NCO-650 was administered after the antigen challenge, the agent had no inhibitory effect on the Asc-Ag induced bronchoconstriction. As for the effects on increased airway secretion at the time of asthmatic attack, NCO-650 inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. NCO-650 had no effect on the bronchoconstriction induced by inhalation of acetylcholine, suggesting that NCO-650 appears to have no anti-cholinergic effect and thus no effect on the vagal reflex that occurred during the asthmatic responses. The above findings show that NCO-650 may be useful for the treatment of bronchial asthma as an orally active drug.

Acetylcholine↗

PubMed1987

The effects of chlorpheniramine and antiallergic drugs on Ascaris suum antigen-induced active cutaneous anaphylaxis in dogs.

Effects of chlorpheniramine and two antiallergic drugs on the active cutaneous anaphylaxis (ACA) reaction induced by intradermal injection of Ascaris suum antigen in naturally sensitized dogs were investigated. Chlorpheniramine (10 mg/kg, intraduodenally (i.d.)) almost abolished the ACA reaction. NCO-650 (100 mg/kg, i.d.) had no inhibitory effect, while tranilast (300 mg/kg, i.d.) showed a weak inhibitory effect. These findings show that the ACA reaction is almost totally mediated by histamine and ACA reaction is considerably resistant to antiallergic drugs such as tranilast and NCO-650.

Anaphylaxis↗

PubMed1987

Effects of mast cell stabilizers on a new bronchial asthma model using compound 48/80 in dogs.

Development of a nonimmunologically induced experimental asthma model using compound 48/80 was attempted. Male mongrel dogs anesthetized with pentobarbital-Na were immobilized with decamethonium bromide under artificial respiration. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of compound 48/80 caused no change in VO even in high concentrations up to a 1% solution. Infusion of compound 48/80 into the bronchial artery at a dose of 0.2 mg/min for 10 min by using the right bronchial perfusion method caused a marked increase in VO accompanied by decreases in perfusion pressure and systemic blood pressure. The compound 48/80-induced bronchoconstriction was inhibited 58% by surgical vagotomy and was almost abolished by chlorpheniramine (10 mg/kg, intraduodenally (i.d.)). Disodium cromoglycate (inhalation of 1% solution along with 5 mg/kg, i.v.), tranilast (300 mg/kg, i.d.) and NCO-650, a new antiallergic drug (100 mg/kg, i.d.) significantly inhibited the compound 48/80-induced bronchoconstriction. These results indicate that compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, the main chemical mediator involved in this response would be histamine acting through H1-receptors, and effects of mast cell stabilizers can be evaluated with this model.

Airway Resistance↗

PubMed1987

Strain difference in an allergic asthma model in rats.

A new rat asthma model was devised, and with the model, allergic bronchoconstrictor responses and effects of disodium cromoglycate (DSCG) were compared among Wistar, Lewis and Fischer 344 rats. Rats were actively sensitized with DNP-Ascaris antigen (DNP-As) and killed Bordetella pertussis vaccine. After eight days, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As using a newly devised apparatus caused a marked asthmatic response with negligible effects on systemic blood pressure and heart rate. The extent of the bronchoconstriction provoked was of the following order: Wistar greater than Lewis = Fischer 344. There was no relationship between the individual 48 hr PCA titer and the bronchoconstriction that occurred in any strain of rats. The bronchoconstrictions were inhibited by DSCG (10 mg/kg, i.v.) and the inhibition ratios were 28%, 36% and 33% in Wistar, Lewis and Fischer 344 rats, respectively. The inhibitions were statistically significant in the latter two strains. Fischer 344 rats were more susceptible to the damage resulting from the operative procedures. The above findings suggest that Lewis rats are the most suitable among the above strains as a model for studying the effects of antiallergic agents.

Animals↗

PubMed1982