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Effect of a calcium sensitization modulator, Y-27632, on isolated human bronchus and pulmonary artery.

A recently developed pyridine derivative, Y-27632, has been reported to inhibit smooth muscle contraction by inhibiting Ca(2+)sensitization in animal experiments. However, the effect of this compound in human tissues has not yet been elucidated. The aim of the present study was to evaluate the effect of Y-27632 on human bronchi and pulmonary arteries. The tissues were obtained from lung cancer patients undergoing lung resection. Tissue responses were assessed by isometric tension measurement. Y-27632 relaxed the bronchi at basal tone with an IC(50)(concentration causing 50% relaxation of the maximal response) of 2.0+/-0.3x10(-6)M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC(50)was 3.0+/-0.4x10(-6), 2.5+/-0.5x10(-6)and 1.8 +/-0.3x10(-6)M, respectively. The dilatory effect of Y-27632 was significantly smaller in ACh-precontracted tissues compared with those of basal or histamine- and neurokinin A-induced precontracted bronchi (P<0.05). Further, Y-27632 showed an inhibitory effect on cholinergic nerve stimulation- and ACh-induced bronchial contraction to the same degree, suggesting that a modulatory effect of this compound on ACh release from nerve terminals was unlikely. Y-27632 also dilated the pulmonary arteries precontracted by phenylephrine (IC(50)= 1.6+/-0.1x10(-6)M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries.

Amides↗

Gut and bronchus associated lymphoid tissue: an overview.

The mucosal lymphoid aggregates in lung and gut contain precursor cells destined to seed mucosal tissues with IgA containing cells. It is likely that both tissues also are sources of both IgE B cell precursors as well as the cells responsible for their regulation (38). Although the traffic of B cells is relatively well understood from the standpoint of IgA, the factors responsible for localization in mucosal tissue are at best unclear. Furthermore, little is known about the migration patterns of helper or suppressor cells of any kind and these may have, if derived from mucosal tissue, a preferential site of action in the mucosa. The mucosal mast cell may well be a cell of different lineage than the mast cell from the peritoneal cavity and may itself have a mucosal localization pattern. Much more work needs to be done to render some of these speculations onto a better factual base, and to harness these systems in provision of better approaches to vaccination and control of disease.

Animals↗

Preferential uptake of soluble antigen by respiratory tract epithelium overlying bronchus-associated lymphoid tissue in the rat.

Soluble protein antigen (Horseradish peroxidase - HRP) administered to rats intratracheally is predominantly phagocytosed by alveolar macrophages and Type-II pneumonocytes. A proportion, after localization on the lumenal surface of the bronchiolar epithelium is transported across the epithelium via the apical cytoplasm and the intercellular space to the region of the basement membrane. The rate of transfer is faster in the epithelium closer to areas of BALT than elsewhere and in these areas there is further significant penetration below the basement membrane into the BALT tissue to facilitate the contact of antigen and of lymphoid cells. No evidence of alveolar macrophage re-entry to the lymphatic system after phagocytosis of HRP could be seen.

Animals↗

The effect of thiorphan and epithelium removal on contractions and tachykinin release produced by activation of capsaicin-sensitive afferents in the guinea-pig isolated bronchus.

(1) We have studied the effect of epithelium removal (rubbing) and the endopeptidase 24.11 inhibitor, thiorphan, on the contractile response of the guinea-pig isolated bronchi (atropine and indomethacin in the bath) produced by electrical field stimulation, capsaicin or exogenously administered tachykinins (substance P and neurokinin A). (2) The response to field stimulation, thought to involve release of endogenous tachykinins, was potentiated by thiorphan in both epithelium-free and intact bronchi. However, at low frequencies (1-5 Hz), the effect of thiorphan was more evident in intact preparations. (3) The response to capsaicin was enhanced by both epithelium removal and thiorphan administration. (4) The response to exogenous substance P or neurokinin A was potentiated by thiorphan both in epithelium-free and intact bronchi. (5) Capsaicin (1 microM) evoked a consistent release of substance P-like immunoreactivity (determined by radioimmunoassay) and tachykinin-like immunoreactivity (determined by a novel immunoenzyme assay), which was enhanced by thiorphan in both epithelium-free and intact bronchi. (6) These findings suggest that a thiorphan-sensitive mechanism, presumably 'enkephalinase' (endopeptidase 24.11), plays a major role in inactivating endogenous tachykinins released from sensory nerves and that this enzymatic activity is still present after removal of the bronchial epithelium.

Animals↗

[Surgery of bronchus carcinoma (author's transl)].

The results of surgery for bronchial carcinoma can be improved by further stressing of early diagnosis, by operative methods adapted to oncological needs and assessment of techniques which increase operability as well as by adequate and general additional therapy. Based on our material of 8,423 patients of which 2,773 (i.e. 23%) have been operated the results of the operation in relation to type of operation, histology, Feinstein's classification, TNM stages and other are demonstrated.

Austria↗