Pulmonary pharmacology最新文献

{"title":"Ovalbumin Challenge Following Immunization Elicits Recruitment of Eosinophils but not Bronchial Hyperresponsiveness in Guinea-pigs: Time Course and Relationship to Eosinophil Activation Status","authors":"Katharine H. Banner,&nbsp;William Paul,&nbsp;Clive P. Page","doi":"10.1006/pulp.1996.0021","DOIUrl":"10.1006/pulp.1996.0021","url":null,"abstract":"<div><p>Eosinophils are known to be present in the airways of allergic asthmatics, and have been suggested to contribute to the pathophysiological changes accompanying this condition, particularly hyperresponsiveness to airway spasmogens. However, a causal relationship between pulmonary eosinophil accumulation and bronchial hyperresponsiveness in asthma is not proven. In the present study, the time course of pulmonary cell influx was investigated in an immunized guinea-pig model. Eosinophil activation status was also determined together with the bronchial responsiveness to histamine. Guinea-pigs were sensitized [20 μg ovalbumin (OVA) per animal in Al(OH)₃(0.5 ml) ip] and subsequently challenged with aerosolized OVA (100 μg/ml) for 1 h 18–21 days later. At different time points (1 h to 72 h) after OVA challenge, bronchial responses to iv histamine were measured and bronchoalveolar lavage (BAL) was performed to assess pulmonary cell influx. Eosinophil peroxidase (EPO) and total protein levels were measured in BAL fluid supernatants. Exposure of sensitized animals to aerosolized OVA produced a significant increase (<em>P</em>&lt;0.05 vs. sham immunized) in eosinophil infiltration 24 h later which was sustained up to 72 h. Despite this, OVA challenge did not cause either eosinophil activation, as measured by EPO release, or bronchial hyperresponsiveness to histamine at any of the time points examined. These data show that allergen challenge of sensitized guinea-pigs can elicit airway eosinophil accumulation without accompanying airways hyperresponsiveness or eosinophil activation.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 3","pages":"Pages 179-187"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19911820","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 Chronic Glutathione Deficiency on Rat Lung Mitochondrial Function","authors":"Thanislass J. ,&nbsp;Raveendran M. ,&nbsp;Sivasithamparam N. ,&nbsp;Devaraj H.","doi":"10.1006/pulp.1996.0013","DOIUrl":"10.1006/pulp.1996.0013","url":null,"abstract":"<div><p>The effect of chronic glutathione deficiency on lung mitochondrial energy production using buthionine sulphoximine (BSO) as a depletor has been investigated. Prolonged depletion of mitochondrial glutathione produced an imbalance in the antioxidant defence and resulted in lipid peroxidation, which, in turn, damages the membranous structure, leading to the inactivation of inner membrane enzymes, matrix-bound enzymes and mitochondrial cytochrome content. Altered activities of energy-linked enzymes and electron transport resulted in the decreased rate of ADP-stimulated oxygen uptake, respiratory coupling ratio and ATP synthesis.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 119-122"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19846484","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":"The Endothelins in the Pulmonary System","authors":"Goldie R.G. ,&nbsp;Knott P.G. ,&nbsp;Carr M.J. ,&nbsp;Hay D.W.P. ,&nbsp;Henry P.J.","doi":"10.1006/pulp.1996.0010","DOIUrl":"10.1006/pulp.1996.0010","url":null,"abstract":"<div><p>No abstract.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 69-93"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19847172","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":"The Effect of Oxygen Tension on Responses Evoked by Methacholine and Bronchodilators in Bovine Isolated Bronchial Rings","authors":"Clayton R.A. ,&nbsp;Nally J.E. ,&nbsp;Thomson N.C. ,&nbsp;McGrath J.C.","doi":"10.1006/pulp.1996.0014","DOIUrl":"10.1006/pulp.1996.0014","url":null,"abstract":"<div><p>This study examined the effect of acute changes in oxygen tension on responses evoked by the bronchoconstrictor methacholine and the dilators salbutamol, atrial natriuretic peptide and isosorbide dinitrate in isolated bovine bronchi. Cumulative concentration–response curves to methacholine (10⁻⁹–3×10⁻⁴<span>M</span>) were constructed in three oxygen tensions; hyperoxia (95%), normoxia (20%) and hypoxia (4% O₂). Oxygen tensions of 20% and 4% each significantly enhanced contractions to methacholine compared to those in 95% O₂. There was no significant difference, however, between responses in 20 and 4%. The ability of salbutamol, atrial natriuretic peptide and isosorbide dinitrate to reverse methacholine induced tone was also compared in the three oxygen tensions (95%, 20% and 4%). Lowering the oxygen tension from 95% enhanced the ability of each of the drugs to reverse contraction, however the pattern differed between drugs; salbutamol was more effective in 20% O₂than 4%, atrial natriuretic peptide was more effective in 4% than either 95 or 20% O₂and isosorbide dinitrate was more effective in both 4 and 20% than 95% O₂. In conclusion, both bronchoconstrictor and bronchodilator responses in 95% O₂(hyperoxia) differed from those in 20% O₂(normoxia) and further changes occurred on moving to 4% (hypoxia), although the direction of the changes varied among the dilators. This suggests that the responses evoked by bronchodilators in 95% O₂may not necessarily predict those in the physiological range of oxygen tensions and that the relative effectiveness of bronchodilators may vary between normoxic and hypoxic conditions.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 123-128"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19846485","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":"Sodium Cromoglycate and Nedocromil Sodium in the Therapy of Asthma, a Critical Comparison","authors":"Parnham M.J.","doi":"10.1006/pulp.1996.0011","DOIUrl":"10.1006/pulp.1996.0011","url":null,"abstract":"<div><p>No abstract.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 95-105"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19847173","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":"Isolated, Electrically-stimulated Airway Preparations—Their Use in Determiningβ-Adrenoceptor Agonist Activity","authors":"Coleman R.A. ,&nbsp;Nials A.T. ,&nbsp;Rabe K.F. ,&nbsp;Vardey C.J. ,&nbsp;Watson N.","doi":"10.1006/pulp.1996.0012","DOIUrl":"https://doi.org/10.1006/pulp.1996.0012","url":null,"abstract":"<div><p>We have assessed the suitability of electrically-stimulated superfused preparations of guinea-pig trachea, cat trachea and human bronchus for investigating the relaxant activity of the<em>β</em>-adrenoceptor agonist, isoprenaline. Superfused strips of guinea-pig trachea, cat trachea and human bronchus all contracted in response to electrical stimulation. Guinea-pig trachea possesses inherent tone, and in its presence, electrical stimulation caused biphasic responses, comprising a modest, transient contraction, usually followed by a longer lasting relaxation. Human bronchus also possesses inherent tone, but responses were variable, generally monophasic, comprising a transient contraction of variable magnitude, but a longer lasting relaxation was occasionally observed after the transient contraction. Cat trachea possesses no inherent tone, and electrical stimulation of this preparation caused simple monophasic contractile responses. On guinea-pig trachea, addition of indomethacin (2.8 μ<span>M</span>) abolished the inherent tone, and under these conditions, electrical stimulation caused monophasic contractile responses similar to those observed in cat trachea. On human bronchus, however, indomethacin enhanced inherent tone, which tended to uncover or exaggerate any relaxant component in the responses to electrical stimulation. The 5-lipoxygenase inhibitor, zileuton (10 μ<span>M</span>), reduced, but did not abolish, the tone and converted the electrically-induced response to a monophasic contraction. In all preparations in which inherent tone was low or absent, whether naturally (cat trachea) or through pharmacological intervention (guinea-pig trachea with indomethacin, or human bronchus with zileuton), isoprenaline (1–100 n<span>M</span>) inhibited electrically-stimulated contractions in a concentration-related fashion (EC₅₀s: 9–100 n<span>M</span>). In preparations exhibiting inherent tone (guinea-pig trachea with indomethacin or human bronchus with or without indomethacin), this tone was inhibited by isoprenaline. This relaxant activity, on guinea-pig trachea at least, was concentration-related (EC₅₀: 5.4 n<span>M</span>). Such isoprenaline-induced relaxations complicated the analysis of inhibitory effects against electrically-induced contractions. Thus, in such experiments, only at higher concentrations did isoprenaline reliably inhibit these contractions (EC₅₀: 23–119 n<span>M</span>), lower concentrations of isoprenaline often resulting in an apparent enhancement. The enhancement was probably artefactual, resulting from the fact that the electrically-induced contractions originated from a lower baseline. These data suggest that electrically-stimulated airway preparations are suitable for evaluating the relaxant activity of<em>β</em>-adrenoceptor agonists, but the relaxant potency should be assessed in preparations lacking inherent tone, such as cat trachea, guinea-pig trachea in the presence of cyclo-o","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 107-117"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91980803","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":"Drug Induced Pulmonary Hypertension: Must History Repeat Itself?","authors":"Norbert F. Voelkel","doi":"10.1006/pulp.1996.0009","DOIUrl":"10.1006/pulp.1996.0009","url":null,"abstract":"<div><p>No abstract.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 2","pages":"Pages 67-68"},"PeriodicalIF":0.0,"publicationDate":"1996-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19847171","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":"Prostacyclin Modulates Granulocyte/Macrophage Colony-Stimulating Factor Release By Human Blood Mononuclear Cells","authors":"Luttmann W. ,&nbsp;Herzog V. ,&nbsp;Virchow jr J.-C. ,&nbsp;Matthys H. ,&nbsp;Thierauch K.-H. ,&nbsp;Kroegel C.","doi":"10.1006/pulp.1996.0005","DOIUrl":"10.1006/pulp.1996.0005","url":null,"abstract":"<div><p>Although production and immunological activity of granulocyte–macrophage colony stimulating factor (GM-CSF) have been implicated in the pathogenesis of various disorders, little has been reported concerning the factors involved in the regulation of GM-CSF release. Therefore, we examined the effect of the stable prostacyclin agonist, cicaprost, on the in vitro production of GM-CSF by peripheral blood mononuclear cells (PBMC) obtained from normal subjects by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Incubation of PBMC (10⁶cells/ml¹) with the bacterial lipopolysaccharide (LPS; 0.1 μg/ml) for 24 h caused a more than 10-fold concentration-dependent increase of GM-CSF release (401±58 pg/ml×10⁶cells⁻¹). Addition of cicaprost (0,01 ng/ml to 1 μg/ml) resulted in a concentration- and time-dependent reduction of LPS-induced GM-CSF secretion by PBMC with a mean IC₅₀of 6.7 ng/ml (n=9). Furthermore, cicaprost also inhibited the LPS-elicited expression of GM-CSF mRNA, as determined by RT-PCR. These results demonstrate that prostacyclin inhibits LPS-induced GM-CSF release and that its effects are related to the level of transcription. Hence, our data suggest that cicaprost or related PGI₂agonists may represent immunomodulators of mononuclear cell function and may offer a therapeutic approach to GM-CSF-mediated inflammatory disorders.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 1","pages":"Pages 43-48"},"PeriodicalIF":0.0,"publicationDate":"1996-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19810749","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":"Uncoupling in the Wall of the Cartilaginous Bronchus of the Pig Produced by Smooth Muscle Contraction","authors":"Mitchell H.W.,&nbsp;Gray P.R.","doi":"10.1006/pulp.1996.0003","DOIUrl":"10.1006/pulp.1996.0003","url":null,"abstract":"<div><p>Studies in small non-cartilaginous airways suggest that the cross sectional area of the airway wall (comprising the smooth muscle and mucosa) is unaltered during the contraction–relaxation cycle produced by bronchial provocation. In the present study we examined whether the wall area of large cartilaginous bronchi remained constant during bronchoconstriction produced by acetylcholine (ACh, 10⁻⁴–10⁻²<span>M</span>), and if not the effect of this on the narrowing of the bronchial lumen. Narrowing of the lumen and adventitia of bronchial segments, 3.6 mm id from pigs, was simultaneously recorded using endoscopy and video imaging of the airway lumen. Concurrently, the shortening of the smooth muscle was estimated morphometrically from the same bronchi fixed during muscle contraction. In individual bronchi, ACh produced from 5 to 60% shortening of the smooth muscle, which caused up to 64% narrowing of the bronchial lumen, but only approximately 10% narrowing of the adventitia. Lumen narrowing was greater than predicted. Morphological assessment showed a doubling of the area between the smooth muscle and the cartilage, in response to maximum smooth muscle contraction by ACh. In contrast the area of the smooth muscle and mucosa did not change. Similar changes in bronchial morphology were produced in whole lung slices, incubated in ACh or histamine. We conclude that the inner airway wall uncouples from the outer wall during muscle contraction and that this increases the narrowing of the airway lumen relative to the adventitia.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 1","pages":"Pages 29-34"},"PeriodicalIF":0.0,"publicationDate":"1996-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19810747","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 Isoenzyme Selective Phosphodiesterase Inhibitors on the Proliferation of Murine Thymus and Spleen Cells","authors":"Banner K.H. ,&nbsp;Bertin B. ,&nbsp;Moodley I. ,&nbsp;Page C.P.","doi":"10.1006/pulp.1996.0004","DOIUrl":"10.1006/pulp.1996.0004","url":null,"abstract":"<div><p>The effects of isoenzyme selective phosphodiesterase inhibitors on mitogen-stimulated proliferation of murine thymus and spleen cells was determined. The type 4 phosphodiesterase inhibitors, (rolipram, RO 20-1724 and denbufylline) and the mixed type 3/4 inhibitors, (zardaverine and benzafentrine) produced a concentration-related inhibition of mitogen stimulated thymus and spleen cell proliferation. Combined addition of the type 4 inhibitor, rolipram and the type 3 inhibitor, SK&amp;F 94836 had no antiproliferative effect additional to that of rolipram alone. The thymus cells were more sensitive to the type 4 inhibitors than the spleen cells. The type 3 phosphodiesterase inhibitor, SK&amp;F 94836 significantly inhibited cell proliferation, but only at high concentrations. The type 1 (vinpocetine) and the type 5 (zaprinast) phosphodiesterase inhibitor had no significant effect on proliferation. These results suggest that thymus and to a lesser extent spleen cell proliferation is dependent on the activity of the type 4 phosphodiesterase isoenzyme.</p></div>","PeriodicalId":74618,"journal":{"name":"Pulmonary pharmacology","volume":"9 1","pages":"Pages 35-41"},"PeriodicalIF":0.0,"publicationDate":"1996-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/pulp.1996.0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19810748","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}