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Notes: Lesions of trachea cuticles are a pathological histological characteristic of bronchial asthma. Furthermore, collected tracheal cuticles desquamated from the respiratory tract are found in patients’ sputum when asthma attacks occur or after the induction of allergen inhalation. From these facts, it is assumed that desquamation of trachea cuticle cells is a pathological symptom of bronchial asthma. However, there has not been any chronological report of desquamation of trachea cuticles through the process of bronchial asthma attacks.For this report, we made an experimental bronchial asthma model using guinea pigs, and conducted chronological examinations of trachea cuticle lesions related to pathological symptoms of bronchial asthma using a transmission electron microscope and a scanning electron microscope.The experimental asthma models were made by injection of ovalbumin into the abdominal cavity of guinea pigs. Then the airway responses to inhaled aerosolized ovalbumin were induced. The trachea were enucleated and examined under an optical microscope, a transmission electron microscope (hereafter abbreviated as TEM), and a scanning electron microscope (hereafter abbreviated as SEM) after 1, 2, 4, 8, 12, 24 h and 7 days after the immediate airway responses.Intercellular oedema of ciliated epithelium was observed in the sensitization groups immediately after the immediate airway response. SEM observation revealed increased mucus secretion and shortening of cilium. A slight case of desquamation or deciduation of ciliated epithelium was also beginning to appear. TEM observation revealed a dilation of ciliated epithelium intervals. Infiltration of eosinophilic leucocytes was already detectable beneath the ciliated epithelium. The degree of ciliated epithelium desquamation and infiltration of eosinophilic leucocytes progressed with time. When the late airway response occurred 4 hours later, eosinophilic leucocytes had increased drastically, and ciliate epithelium had desquamated to the extent that basal cells were exposed. Seven days after the immediate airway response, epithelium intercellular oedema had improved, and cilium had been reproduced.These results suggest that desquamation of epithelium caused by trachea cuticle lesions appears at an early stage of an asthma attack, owing to the contraction of the trachea, and that the damage is intensified by the infiltration of eosinophilic leucocytes.

Notes: Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.Objective To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR).Methods After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 µg/day), were randomly assigned to one of two treatments – placebo (n = 98) or montelukast 10 mg once daily (n = 93) – for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and β-agonist use.Results After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 ± 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 ± 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 ± 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group.Conclusion These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.

Notes: Background TMK688 is being developed as ati anti-allergic drug having both 5-lipoxygenasc inhibitory activity atid anti-histaminc activity.Method We compared the inhibition ol the late asthmatic rcsponses by TMK688 with that by other anti-allergic agents in actively sensitized guinea pigs, and examined the relationship between 5-lipoxygetiase inhibition and the late asthmatic responsesResults At 1–3.2 mg/kg, TMK688 inhibited the increases in respiratory resistance, leukotriene (LT) B4 and C4 production in the lungs and eosinophil infiltralion into the alveoli during the late asthmatic response, whereas the eliects tended to lessen at the dose of 10mg/kg. These effects are thought to be caused by the 5-lipoxygenase inhibitory activity of TMK688 because Azelastine. an anti-allergic drug having potent antihistamine activity, exhibited no effect. ONO-1078. a peptide LT antagonist. inhibited the late-phase bronchoconstriction at a dose of 100mg/kg p.o., but not the increase in the infiltration of inflammatory cells into the alveoli, suggesting that the late-phase bronchoconstriction is induced, in part, by peptide LTs, i.e. LT C4, D4 and E4 atid that the inflammatory cell infiltration may be caused by LTB4, TMK688 inhibited the immediate bronchoconstriction dose-dependently, and the effect was significant at a dose of 10mg/kg orally. Since Azelastine, Ketotifen and Oxatomide suppressed the bronchoconstriction at far lower doses than did TMK688, the inhibitory effect was mainly caused by its antihistamine activity.Conclusions TMK688 appears to be a novel anti-allergic drug having inhibitory effects on both the bronchoconstriction and the infiltration of inflatnmutory cells during late asthmatic responses.

Notes: Abstract— Fatigue strength, crack initiation and small crack growth behaviour in two kinds of squeeze-cast aluminium alloys, AC8A-T6 and AC4C-T6 were investigated using smooth specimens subjected to rotatary-bending fatigue at room temperature. Fatigue resistance of these alloys was almost the same as that of the wrought aluminium alloys because of their fine microstructure and of the decrease in defect size due to squeeze-casting. Fatigue crack initiation sites were at the eutectic silicon particles on the surface of specimens or at internal microporosity in the specimens. Crack initiation life, defined as a crack length of 50 μm on the specimen surface, was successfully estimated from an evaluation of initiation sites using fracture mechanics and the statistics of extrema. Small fatigue crack growth in the two kinds of alloys obeys the relation proposed by Nisitani et al., namely that d(2c)/dN = C(σa/σB)n· (2c), where C is a constant and σB is the ultimate tensile strength. It is pointed out that an improvement in fatigue strength of cast aluminium alloys can be expected by refining the eutectic silicon rather than by an increase in static strength.