Pulmonary pharmacology最新文献

{"title":"Speeds of Action of Single Doses of Formoterol and Salbutamol Compared with Placebo in Reversing Methacholine-induced Bronchoconstriction","authors":"J.R. Beach ,&nbsp;C.L. Bromly,&nbsp;A.J. Avery,&nbsp;R.W.E.C. Reid ,&nbsp;E.H. Walters ,&nbsp;D.J. Hendrick","doi":"10.1006/pulp.1996.0031","DOIUrl":"10.1006/pulp.1996.0031","url":null,"abstract":"<div><p>We compared the speeds of action of two doses of the long acting<em>β</em>-agonist formoterol (12<em>μ</em>g and 24<em>μ</em>g) with those of salbutamol (400<em>μ</em>g) and placebo using a double-blind, randomized, cross-over study design in 16 asthmatic subjects. A methacholine test was used on four separate study days to produce a standardized degree of bronchoconstriction (a decrement in FEV1 ≥20%) and one of the study medications as dry powder was administered immediately afterwards via an Aerolizer^TMinhaler device. The speeds of recovery were estimated from measurements of FEV1 over the following 2–90 min. All active treatments produced significantly greater bronchodilation than placebo as early as 2 min after administration, and their peak effects within 10 min; and no significant differences were noted between them. Mean recovery times by 50% of the FEV1 decrement provoked by methacholine were significantly shorter for the active medications: 5.7 min (formoterol 24<em>μ</em>g), 6.4 min (salbutamol 400<em>μ</em>g), 10.2 min (formoterol 12<em>μ</em>g), and 53.1 min (placebo); the respective times for recovery by 80% being 18.0, 17.4, 22.1, and 83.3 min. We conclude that single doses of the dry powder formulations of all three active treatments produce rapid and effective bronchodilation. This conclusion should not, however, be extrapolated to the regular use of these medications, since differential down-regulation and tachyphylaxis may then exert an influence.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 245-249"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucolytic and Mucokinetic Therapy","authors":"P.J. Wills ,&nbsp;P.J. Cole","doi":"10.1006/pulp.1996.0024","DOIUrl":"10.1006/pulp.1996.0024","url":null,"abstract":"<div><p>No abstract</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 197-204"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Inhibition by Selective Phosphodiesterase Inhibitors of Antigen, LTC4and Histamine-induced Contraction of Guinea-pig Isolated Trachea","authors":"J.-M. Planquois ,&nbsp;Y. Ruffin-Morin ,&nbsp;V. Lagente ,&nbsp;A.N. Payne ,&nbsp;S.G. Dahl","doi":"10.1006/pulp.1996.0032","DOIUrl":"10.1006/pulp.1996.0032","url":null,"abstract":"<div><p>Antigen (ovalbumin)-induced contraction of guinea-pig isolated trachea, which largely resulted from the endogenous release of peptidoleukotrienes, was strongly inhibited by the non-selective phosphodiesterase (PDE) inhibitor theophylline and, more potently, by the selective PDE type IV inhibitors rolipram and Ro 20-1724. It was also strongly inhibited by the PDE type V inhibitor zaprinast, but much less so by the PDE type III inhibitor siguazodan and milrinone. Similar results were obtained in trachea minus epithelium. In contrast to their effects vs. allergic airway smooth muscle contraction, both milrinone and siguazodan potently relaxed leukotriene C₄(LTC₄)-induced contraction in isolated trachea from non-sensitized animals. In this assay, rolipram, Ro 20-1724 and zaprinast were less active compared to their effects vs. ovalbumin-induced contraction, whereas theophylline had equivalent potency in the two tests. The relative potencies of rolipram and siguazodan in relaxation of trachea were similar when added prior to or after either LTC₄or histamine. These results suggest that the higher potency of selective PDE type IV &amp; V inhibitors compared with PDE type III inhibitors vs. ovalbumin-induced contraction is due to their greater inhibition of anaphylactic mediator release. The converse is true if we consider their bronchodilator actions, although the superior efficacy of selective PDE type III inhibitors over PDE type IV inhibitors may vary in sensitized vs. non-sensitized animals. The present results are in agreement with a previous study showing that low concentrations of a<em>β</em>₂-agonist increased the relaxant effect of selective PDE type IV inhibitors in guinea-pig trachea. The present data indicate that prophylactic use of selective PDE type IV inhibitors combined with therapeutic use of low dose inhaled<em>β</em>-agonists might represent an alternative to the use of anti-allergic or steroid therapy in asthma.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 4","pages":"Pages 251-258"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20107268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical Responses of Tracheal Tissue In Vitro: Dependance on the Tissue Preparation Employed and Relationship to Smooth Muscle Content","authors":"Chiara Florio,&nbsp;Angela Styhler,&nbsp;Seymour Heisler ,&nbsp;James G. Martin","doi":"10.1006/pulp.1996.0018","DOIUrl":"10.1006/pulp.1996.0018","url":null,"abstract":"<div><p>We examined the relationship between the quantity of smooth muscle in isolated tracheal preparations and their responses to contractile agonists. The responses of two different tracheal preparations, rings and tubes, to carbachol and serotonin were compared both intra-species (Fisher vs. Lewis strain rats) and inter-species (rat vs. guinea-pig). The rank order for carbachol-induced maximal isometric tensions was Fisher&gt;Lewis&gt;guinea-pig and for serotonin Fisher&gt;guinea-pig&gt;Lewis for tracheal rings. The sensitivities to carbachol and serotonin were greater in Fisher than in Lewis rats. Guinea-pig tracheal rings were comparable to Fisher in sensitivity to carbachol, but were more sensitive to serotonin than either Fisher or Lewis rings. In both species, agonist-independent differences were found in the maximal tension of rings taken from different regions of trachea. For whole tracheal tubes under isovolumetric conditions, the rank order for carbachol-induced changes in the intraluminal pressure was guinea-pig&gt;Lewis≥Fisher. The sensitivity to carbachol was greater in guinea-pig tubes than in rat. The quantity of tracheal smooth muscle estimated from myosin was greater in guinea-pigs than in either Fisher or Lewis rats. In addition, the area of cartilage determined by morphometry in guinea-pig trachea was greater than that in the rat. We conclude that a concordance between the magnitude of contraction and the amount of tracheal smooth muscle is obtained only in whole tracheal tubes and not in tracheal rings. Several factors could contribute to the observed discrepancies in tracheal rings, including regional differences in efficacy and sensitivity to contractile agonists and the thickness of cartilage.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 157-166"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of [3H]α, β-Methylene ATP Binding Sites in Pulmonary Blood Vessels of Different Species","authors":"M. Zhao ,&nbsp;X. Bo ,&nbsp;G. Burnstock","doi":"10.1006/pulp.1996.0019","DOIUrl":"10.1006/pulp.1996.0019","url":null,"abstract":"<div><p>Purinergic neurotransmission has been reported to take part in the regulation of pulmonary vascular resistance in many species. The receptor which mediates the contraction of blood vessels by ATP was defined as P2X-purinoceptors in pharmacological studies. In the present study, autoradiographic localization of P2X-purinoceptors was carried out in pulmonary blood vessels from rat, guinea-pig, rabbit, piglet and human by using [³H]α,β-methylene ATP ([³H]α,β-MeATP) as the radioligand. Autoradiographs showed that all the pulmonary arteries had been labelled with [³H]α,β-MeATP. The specific binding sites were only associated with the smooth muscle of the blood vessels. Semi-quantitation of the autoradiographs revealed significant differences in the densities of P2X-purinoceptors amongst the vessels studied, both regional and interspecific. Generally, intrapulmonary arteries were labelled more heavily than the main pulmonary arteries, and the medium- and small-sized arteries had higher densities of P2X-purinoceptor than the large muscular arteries. The veins were sparsely labelled, except that rat intrapulmonary veins were labelled moderately. The results from this study provide: (1) direct evidence for the existence of P2X-purinoceptors in pulmonary vasculature, (2) a semi-quantitative estimation of the relative density of P2X-purinoceptors in pulmonary vessels of different sizes; and (3) a comparison of the P2X-purinoceptor densities among the species studied. Furthermore, the distribution of the P2X-purinoceptors is consistent with known pharmacological responses elicited by ATP in these vessels.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 167-174"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extravasation, Lamina Propria Flooding and Lumenal Entry of Bulk Plasma Exudate in Mucosal Defence, Inflammation and Repair","authors":"C.G.A. Persson ,&nbsp;J.S. Erjefält,&nbsp;M. Andersson,&nbsp;L. Greiff,&nbsp;C. Svensson","doi":"10.1006/pulp.1996.0015","DOIUrl":"10.1006/pulp.1996.0015","url":null,"abstract":"<div><p>No abstract</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 129-139"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Release of Adenosine from Human Sensitized Lung Fragments and its Effect on Antigen-induced Mediator Release","authors":"K. Konnaris ,&nbsp;H.G.E. Lloyd,&nbsp;D.M. Temple","doi":"10.1006/pulp.1996.0016","DOIUrl":"10.1006/pulp.1996.0016","url":null,"abstract":"<div><p>Adenosine may play a role in asthma as a pro-inflammatory mediator. In this study, the release of adenosine from human sensitized lung fragments and its effect on antigen-induced histamine and leukotriene release has been explored. Antigen challenge increased histamine and leukotriene release five-fold but was without effect on adenosine release. In contrast, the adenosine deaminase inhibitor EHNA (10 μ<span>M</span>) and the adenosine kinase inhibitor 5-iodotubericidin (10 μ<span>M</span>) increased adenosine concentration 45-fold (<strong><em>P</em></strong>≤ 0.001; n= 4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 μ<span>M</span>) decreased histamine and leukotriene release by 25% (<strong><em>P</em></strong>≤ 0.001) and 40%, respectively (<strong><em>P</em></strong>≤ 0.05; n= 9 patients). Additionally, the non-selective adenosine agonist NECA (10 μ<span>M</span>) markedly inhibited antigen-induced leukotriene release by 80– 90% (<strong><em>P</em></strong>≤ 0.001) and marginally inhibited histamine release by approximately 10% (<strong><em>P</em></strong>≤ 0.05; n=9); the A_2a-selective agonist DPMA (10 μ<span>M</span>) was without effect on either histamine or leukotriene release. These results are consistent with adenosine having a biphasic effect on antigen-induced mediator release with low concentrations potentiating release and high concentrations inhibiting release. The overall stimulatory effect of endogenous adenosine supports the proposal that adenosine may act as a pro-inflammatory mediator in asthma.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 141-148"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Modulators of Tyrosine Kinase Activity on Agonist-induced Contraction in the Rat Pulmonary Vascular Smooth Muscle","authors":"J.P. Savineau ,&nbsp;P. Gonzalez De La Fuente,&nbsp;R. Marthan","doi":"10.1006/pulp.1996.0022","DOIUrl":"10.1006/pulp.1996.0022","url":null,"abstract":"<div><p>In the rat isolated main pulmonary artery, we investigated the effect of a tyrosine kinase inhibitor (genistein) and that of a tyrosine phosphatase inhibitor (phenylarsine oxide) on agonist-induced contraction. Genistein (10 μM) reduced the amplitude of the contraction evoked by noradrenaline (0.1–10 μM) or angiotensin II (1–100 nM). Phenylarsine oxide (0.5 μM) increased the amplitude of the contraction evoked by these agonists. The effects of genistein and phenylarsine oxide on agonist-induced contractions were also observed in the presence of verapamil (10 μM). Thapsigargin (0.5 μM) increased the amplitude of the contraction induced by noradrenaline (1–10 μM) or angiotensin II (10–100 nM). Subsequent addition of genistein counteracted the effect of thapsigargin on noradrenaline- and angiotensin II-induced contraction. Dantrolene alone (100 μM) reduced noradrenaline- and angiotensin II- but not KCl-induced contraction. In the presence of dantrolene, genistein and phenylarsine oxide failed to modify noradrenaline- and angiotensin II-induced contraction. Finally, in β-escin skinned preparations, genistein (10–20 μM) and phenylarsine oxide (0.5–1 μM) did not alter Ca²⁺-induced contraction. These results suggest that a tyrosine kinase activity is involved in the vasoconstrictor action of noradrenaline and angiotensin II in the pulmonary circulation. The stimulation of the tyrosine kinase activity appears to be linked to the depletion of an intracellular Ca²⁺store.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 189-195"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Bacterial Lipopolysaccharides (LPS) and Tumour Necrosis Factor-α (TNFα) on Rat Tracheal Epithelial Cells in Culture: Morphology, Proliferation and Induction of Nitric Oxide (NO) Synthase","authors":"A. Freitag ,&nbsp;A. Reimann ,&nbsp;I. Wessler ,&nbsp;K. Racké","doi":"10.1006/pulp.1996.0017","DOIUrl":"10.1006/pulp.1996.0017","url":null,"abstract":"<div><p>Rat tracheal epithelial cells were cultured and the effects of LPS and TNFα on cell morphology, rate of proliferation and NO synthase activity were studied. NO synthase activity was determined by measuring the accumulation of³H-L-citrulline during incubation of confluent monolayer with³H-L-arginine. In untreated cells no significant³H-L-citrulline formation was detected, and bradykinin and the calcium ionophore A 23187 failed to stimulate³H-L-citrulline formation excluding a constitutively expressed, calcium-dependent NO synthase activity. After culturing the cells for 18 h in the presence of LPS (10 μg/ml) and TNFα (500 U/ml) a marked formation of³H-L-citrulline could be detected, which was largely inhibited by N^G-monomethyl-L-arginine (L-NMMA) indicating the induction of NO synthase activity which could be prevented by dexamethasone. Exposure of confluent monolayer to LPS and TNFα for up to 4 days resulted in a reduction in cell density by 20% within 1 to 2 days and in additional marked changes in cell morphology. The normal honeycomb-like structure of the culture was lost and a considerable number of cells developed ‘dendritic’ outgrowths. These morphological changes as well as the reduction in cell density was attenuated by dexamethasone, but not by the NO synthase inhibitor L-NMMA. The rate of cell proliferation was determined in non-confluent cultures 24 h after passage by determination of the incorporation of tritium into DNA during 24 h of incubation with³H-thymidine.³H-thymidine incorporation was reduced by about 40–45% when LPS or TNFα was present during exposure to³H-thymidine, and by about 65%, when LPS and TNFα were present in combination. Neither L-NMMA nor dexamethasone significantly affected the³H-thymidine incorporation nor the inhibitory effects of LPS and TNFα. In conclusion, airway epithelial cells are markedly affected by LPS and TNFα and the various responses (changes in the cell morphology, inhibition of cell proliferation and induction of NO synthase activity) appear to be caused by different (dexamethasone-sensitive and -insensitive), cellular mechanisms. An enhanced formation of endogenous NO may not be responsible for the observed morphological changes or the inhibition of cell proliferation.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 149-156"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Pharmacokinetics of Theophylline in Rabbits and in Humans with Hyperlipidemia","authors":"J. Wójcicki ,&nbsp;W. Górnik,&nbsp;A. Pawlik,&nbsp;M. Droździk,&nbsp;B. Gawrońska-Szklarz","doi":"10.1006/pulp.1996.0020","DOIUrl":"10.1006/pulp.1996.0020","url":null,"abstract":"<div><p>The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose. Blood was sampled after 5, 10, 15, 30 and 45 min and 1, 2, 4, 6, 8, 12 and 24 h following theophylline administration. FPIA method was used to determine blood serum concentrations of theophylline. Considerable alterations of theophylline pharmacokinetics in humans suffering from mixed form of hyperlipidemia were observed. Marked decrease in area under the concentration–time curve (AUC), diminished volume of distribution, increased total body clearance, and shortened elimination half-life were observed. On the contrary, in rabbits with alimentary induced lipid metabolism disturbances<em>t</em>_1/2of theophylline was practically unchanged and AUC only slightly increased. In conclusion: (1) hyperlipidemia affects the pharmacokinetics of theophylline in human beings, (2) rabbit model with dietetary induced lipid metabolic disturbances is not a suitable subject for estimation of pharmacokinetics of xanthine derivatives.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 175-178"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}