dinoprost and Lung-Diseases--Obstructive

Most of the studies linking chronic obstructive pulmonary disease (COPD) with oxidative stress are in vitro, using invasive techniques, or measuring systemic oxidative stress. The aim of this study was to quantify oxidative stress in the lungs in patients with COPD and in healthy smokers, as reflected by 8-isoprostane concentrations in breath condensate. This is a noninvasive method to collect airway secretions. 8-Isoprostane is a prostaglandin-F(2alpha) isomer that is formed in vivo by free radical-catalyzed peroxidation of arachidonic acid. We also studied the acute effect of smoking on exhaled 8-isoprostane in healthy smokers. Exhaled 8-isoprostane was measured by a specific enzyme immunoassay in 10 healthy nonsmokers and 12 smokers, 25 COPD ex-smokers, and 15 COPD current smokers. 8-Isoprostane concentrations were similar in COPD ex-smokers (40 +/- 3.1 pg/ml) and current smokers (45 +/- 3.6 pg/ ml) and were increased about 1.8-fold compared with healthy smokers (24 +/- 2.6 pg/ml, p < 0.001), who had 2.2-fold higher 8-isoprostane than healthy nonsmokers (10.8 +/- 0.8 pg/ml, p < 0.05). Smoking caused an acute increase in exhaled 8-isoprostane by about 50%. Our study shows that free radical production is increased in patients with COPD and that smoking causes an acute increase in oxidative stress.

Topics: Aged; Biomarkers; Breath Tests; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Female; Forced Expiratory Volume; Humans; Lung; Lung Diseases, Obstructive; Male; Middle Aged; Oxidative Stress; Smoking; Vital Capacity

To test whether isoprostanes could be used as markers of oxidative stress in horses, their concentration was determined in plasma and in pulmonary epithelial lining fluid (PELF) in 3 models of oxidative stress: (1) strenuous exercise, (2) acute COPD crisis and (3) exercise combined with COPD crisis. Four horses were investigated twice, once in crisis and once in remission. The animals underwent a standardised treadmill exercise test. Isoprostane assessment was performed in plasma and bronchoalveolar lavage fluid 24 h before and 1 h after exercise and in plasma also immediately after exercise. Exercise in remission induced a significant increase of isoprostanes in plasma and in PELF. In horses in crisis, the isoprostane concentrations did not increase in plasma, while they did increase in PELF. Lastly, exercise in crisis increased plasma levels of isoprostanes, but did not change PELF isoprostanes. In conclusion, 1) isoprostanes are increased by systemic oxidative stress induced by strenuous exercise in COPD horses in remission either in PELF or in plasma; 2) only PELF and not plasma isoprostanes are increased by pulmonary oxidative stress induced by COPD crisis and 3) unexpectedly, exercise in crisis increased plasma but not PELF isoprostanes.

Topics: Animals; Bronchoalveolar Lavage Fluid; Dinoprost; Epithelial Cells; Exercise Test; Heart Rate; Horse Diseases; Horses; Lung Diseases, Obstructive; Models, Biological; Oxidative Stress; Physical Conditioning, Animal

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2alpha-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2alpha-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2alpha-III were significantly higher in patients with COPD (median, 84 pmol/ mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = -0.38, p = 0. 019). Aspirin treatment failed to decrease urinary levels of iPF2alpha-III (102 +/- 8 versus 99.2 +/- 7.3 pmol/ mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0.0001). Elevated levels of iPF2alpha-III (median, 125 pmol/mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2alpha-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arachidonic Acids; Aspirin; Case-Control Studies; Creatinine; Cross-Sectional Studies; Cyclooxygenase Inhibitors; Dinoprost; Female; Follow-Up Studies; Free Radicals; Humans; Lipid Peroxidation; Lung Diseases, Obstructive; Male; Middle Aged; Oxidative Stress; Oxygen; Sex Factors; Smoking; Thromboxane B2; Time Factors

The bronchoconstrictive effect of prostaglandin F2 alpha was investigated in 24 school children suffering from obstructive lung disease. In all the investigated substance was administered by 2-minute inhalation, consecutively in doses of 0.06-0.12-0.25 and 0.5 mg with subsequent evaluation of pulmonary functions 1, 3, 6 and 10 minutes following inhalation. The trial was terminated when a drop of values indicating obstruction of the bronchial system by 20%, as compared with initial values, was recorded. While in healthy children the resistance of the air current did increase even after a high concentration of the administered substance, a provocation concentration in the patients was achieved already with the dose of 0.06 mg. The bronchodilating effect of prostaglandin E2 administered in a dose of 0.05 mg in eight asthmatic patients was very intensive but short and disappeared within 3 minutes after administration. From a therapeutic aspect the tussigenic effect of prostaglandin E2 played a more important role.

Topics: Bronchial Provocation Tests; Child; Dinoprost; Dinoprostone; Humans; Lung Diseases, Obstructive; Spirometry

Topics: Adult; Aged; Alprostadil; Connective Tissue Diseases; Diabetes Mellitus; Dinoprost; Factor Analysis, Statistical; Female; Humans; Kidney Failure, Chronic; Lung Diseases, Obstructive; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Middle Aged; Neoplasms; Prostaglandins E; Prostaglandins F

Chronic bronchitis was induced in 6 mongrel dogs by chronic exposure to SO2 gas; the degree of chronic airway obstruction and the effects on airway responsiveness to inhaled histamine, carbachol, and prostaglandin F2 alpha were examined. Five dogs developed chronic airway obstruction, as indicated by an increase in pulmonary resistance, and clinical mucous hypersecretion. In addition, in each of the animals in which chronic airway obstruction developed there was a decrease in the airway responsiveness to inhaled mediators. Those findings demonstrate that induction of chronic bronchitis in dogs results in hyporesponsiveness to inhaled mediators, a finding distinctly different from that reported in human subjects with naturally occurring disease.

Topics: Airway Resistance; Animals; Bronchitis; Carbachol; Chronic Disease; Dinoprost; Dogs; Histamine; Lung Compliance; Lung Diseases, Obstructive; Prostaglandins F; Sulfur Dioxide