Toshihiko Kaise

Accuracy of measurement of acoustic rhinometry applied to small experimental animals.

Nasal obstruction is one of the major symptoms of allergic rhinitis. In the study of the mechanism of nasal obstruction, experiments on animal are useful. In adult humans, acoustic rhinometry has been used to evaluate nasal obstruction by determining nasal cavity dimensions in terms of cross-sectional areas as a function of the distance from the nostril. We modified the equipment used on humans to assess dimensions of nasal airway geometry of small experimental animals. The purpose of this study was to investigate the accuracy of measurement of the modified acoustic rhinometry applied to small experimental animals using nasal cavity models and guinea pigs. Measurement of the nasal cavity models (made of cylindrical silicone tubes) showed that the acoustic rhinometry estimated 85.5% of actual area and 79.0% of actual volume. In guinea pigs, nasal cavity volume determined by the acoustic rhinometry was 73.7 ± 20.0% of actual volume. The actual volume was estimated by impression material instilled into the nasal cavity of the animals (IM volume), and volume determined by acoustic rhinometry significantly correlated with IM volume. Furthermore, there was a significant negative correlation between the volume and nasal airway resistance in guinea pigs. Measurement of the nasal airway resistance is the method frequently used in the evaluation of the nasal obstruction in guinea pigs. These results suggest that acoustic rhinometry is useful in evaluating nasal obstruction in small experimental animals.

Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats.

We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.

Erdosteine enhances mucociliary clearance in rats with and without airway inflammation

Erdosteine is a new homocysteine-derived expectorant and has been reported to have many mucolytic effects. In this report, we studied the activities of erdosteine on mucociliary clearance in normal and airway-inflammation-induced rats. In normal rats, erdosteine at doses of 100-600 mg/kg significantly promoted mucociliary clearance. However, erdosteine did not change the concentrations of mucopolysaccharides in bronchoalveolar lavage fluid (BALF). In the LPS-instillated rats, the mucociliary clearance was inhibited and the number of inflammatory cells, albumin concentration, and mucopolysaccharides concentration in BALF were increased. Erdosteine at doses of 100-600 mg/kg significantly attenuated the inhibition of mucociliary clearance and the increase of inflammatory cells, however, it did not prevent the increase of albumin and mucopolysaccharides. Other mucolytic drugs which are ambroxol and S-carboxymethylcysteine, had no effect. These results indicate that erdosteine promotes the mucociliary clearance in normal and airway-inflammation-induced rats.

Ability of Histamine to Increase Nasal Mucosal Permeability to Macromolecules in Guinea Pigs

The effect of histamine on nasal mucosal permeability against an antigen was investigated by using modified passive cutaneous anaphylaxis (PCA) reactions in normal and actively sensitized guinea pigs. The administration of a dinitrophenyl-coupled Ascaris (DNP-Ascaris) solution as an antigen into the nasal cavity caused PCA reactions in the dorsal skin of normal guinea pigs. The administration of histamine into the nasal cavity before the antigen treatment significantly enhanced the anaphylactic responses. The PCA reactions did not occur when ovalbumin (OA) was administered intranasally in normal guinea pigs. In guinea pigs sensitized against DNP-Ascaris, however, PCA reactions to anti-OA antiserum were elicited by the intranasal administration of OA. The intranasal administration of histamine before the antigen treatment also enhanced anaphylactic responses in sensitized guinea pigs. These results indicate that histamine increases nasal mucosal permeability and that this may be one of the causes of nasal hypersensitivity in nasal allergy.

Effect of Oxatomide Nasal Spray on Experimental Allergic Rhinitis in Guinea Pigs and Rats

We investigated the effect of topically applied oxatomide, an antiallergic agent, on the assault of allergic rhinitis in actively sensitized guinea pigs. Topical application of oxatomide nasal spray (0.025%) reduced the severity of allergic rhinitis which was assessed by determining dye leakage and histamine released to the nasal cavity of guinea pigs. Furthermore, oxatomide nasal spray treatment significantly prevented the increase in dye leakage induced by histamine administration in guinea pigs and rats. These results indicate that the topical application of oxatomide inhibits both the release and the action of histamine. Therefore, oxatomide nasal spray may be beneficial for treatment of allergic rhinitis.