Decreased FOXP3 expression in small airways of smokers with COPD.

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients. A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways. Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction. To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.

A simple method of bronchoprovocation using a valved holding chamber.

This study was undertaken to ascertain whether the use of a valved holding chamber (VHC) during bronchial provocation testing might increase lung deposition and repeatability of the test relative to the tidal breathing method. The 2-min tidal breathing results were compared to five inhalations from a VHC device in patients using the Pari-provoII nebulizer (MMD = 2.1mkm). Lung and mouth deposition, losses though the exhaled air and losses before aerosol delivery to the patient's mouth were measured in patients using a radiolabeled 99Tc-DTPA solution and gamma camera. The study revealed that lung deposition was 67% with the VHC method, and losses with exhaled air were 29% of the inhaled amount. The tidal breathing method resulted in lung deposition of 20.9 +/- 3.4%, and losses with exhaled air were 77.5 +/-3.5%. Mouth deposition did not differ significantly between methods. Variability in lung deposition was 15.3% for the VHC and 32.0% for the tidal breathing method. In addition to greater lung deposition and reproducibility, the VHC method allows easier calculation of the inhaled dose.

[Studies of kinin-like properties of a new peptide isolated from bovine brain]. / Issledovanie kininopodobnykh svoistv novogo peptida, vydelennogo iz mozga krupnogo rogatogo skota.

Kinin-like properties of two new peptides NRP-11 and P7 which have structural similarity with neurotensin (NT) and kallidin (K) were investigated. It was found that, unlike NT and K, the new peptides possess reduced myotropic and hypotensive activity. On the other hand, similarly to NT and K, the new peptides exhibited a high histamine-releasing activity in rat peritoneal mast cells. Possible central effects are implied for peptide NRP-11 isolated from bovine brain and its fragment P7.

[Antagonistic properties of tetra-substituted analog of vasopressin with selective antidiuretic effects]. / Antagonisticheskie svoistva chetyrekhzameshchennogo analoga vazopressina s selektivnym antidiureticheskim deistviem.

Biological properties of a novel vasopressin analogue were investigated. It was found that this analogue has no vasopressor and oxytocic activities but it exhibits a selective antidiuretic effect which is weaker than that of adiuretin (DDAVP). Novel analogue inhibits vasopressor, oxytocic and antidiuretic effects caused by arginine--vasopressin. The usefulness of novel compound as a pharmacological tool--vasopressin antagonist is suggested.

[Cyclic analogs of substance P. III. Cyclo (6(sup)gamma----oligomethylenediamine----11) substance P(6-11)-hexapeptides]. / Tsiklicheskie analogi veshchestva P. III. Cyclo(6(sup)gamma----oligometilendiamin----11) veshchestvo P(6-11)-geksapeptidy.

Cyclic analogues of substance P of the formula cyclo-[Glu-Phe-Phe-Gly-Leu-Met-NH(CH2)nNH-], where n = 3-10, 12, and open-chain analogues (XVIIIa, b) H-Glu.(NHR)-Phe-Phe-Gly-Leu-Met-NHR, where R = -CH3, -CH2CH2CH3, were synthesized. By NMR spectroscopy it was found that cyclo-compounds with n = 3-8 have regularly arranged structures, stabilized by intramolecular hydrogen bonds. Substances of this type showed less than or equal to 0.1% of the substance P activity on the guinea pig ileum, but some of them antagonize the natural peptide (for compound with n = 5 IC50 = 3.2.10(-6) M). The open-chain compounds proved to have rather high myotropic activity, viz., 22% (R = -CH3) and 8% (R = -CH2CH2CH3) of the substance P activity.

[Cyclic analogs of bradykinin, containing a carboxyl group]. / Tsiklicheskie analogi bradikinina, soderzhashchie karboksil'nuiu gruppu.

1 alpha-beta-carboxypropionyl-cyclo(9----1 epsilon)-[Lys1, Gly6]bradykinin (Suc-c[Lys1, Gly6]B), 1 alpha-beta-carboxypropionyl-cyclo(10----1 epsilon)kallidin (Suc-cK), cyclo(10 gamma----1 epsilon)-[Glu10]kallidin (c[Glu10]K) and cyclo(11 gamma----1 epsilon)kallidylglutamic acid (cKG) were synthesized. Suc-c[Lys1, Gly6]B and Suc-cK were prepared by acylating the appropriate cyclopeptides with succinic anhydride. c[Glu10]K and cKG were obtained by the classic peptide synthesis, the cyclization being carried out with 61 and 42% yields, respectively. The protecting groups were then eliminated by catalytic hydrogenation. c[Glu10]K and cKG exerted myotropic action on isolated rat uterus (alpha 0.73 and 0.89, pD2 6.61 and 8.61, respectively). cKG displayed direct myotropic activity with respect to electrically stimulated rat vas deferens and guinea-pig ileum, potentiating the contractions (by 100%) in response to electric stimuli. c[Glu10]K and cKG elicit histamine release in isolated rat mast cells (EC30 4.91.10(-5) and 1.47.10(-6) M, respectively). Both cyclopeptides alter arterial pressure following intravenous administration to anaesthetized rats, cats and dogs and affect heart rate. In all assays cKG is more active than c[Glu10]K. Suc-c[Lys1, Gly6]B and Suc-cK do not possess myotropic, histamine-releasing or hypotensive activity, though they were found to elicit a transient increase of bloodflow in cats and dogs.