Current Issue : July - September Volume : 2016 Issue Number : 3 Articles : 4 Articles
Background: Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality.\nAlthough aspiration-induced local lung inflammation has been studied in animal models, little is known about\nextrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric\nfluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins\nhaving antiprotease activity.\nMethods: In anesthetized Sprague-Dawley rats receiving whole gastric fluid, we studied at different times after\ninstillation (4 h âË?â??7 days): changes in blood cytokines and acute phase proteins (fibrinogen and the antiproteases\nalpha1-antitrypsin and alpha2-macroglobulin) as well as liver mRNA expression of the two antiproteases. The impact of\nthe systemic changes on lung antiprotease defense was evaluated by measuring levels and bioactivity of antiproteases\nin broncho-alveolar lavage fluid (BALF). Markers of alveolar-capillary barrier derangement were also studied.\nNon-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used.\nResults: Severe peribronchiolar injury involving edema, intra-alveolar proteinaceous debris, hemorrhage and PMNn cell\ninfiltration was seen in the first 24 h and later resolved. Despite a large increase in several lung cytokines, only IL-6 was\nfound elevated in blood, preceding increased liver expression and blood concentration of both antiproteases. These\nchanges, with an acute phase response profile, were significantly larger for alpha2-macroglobulin (40-fold increment in\nexpression with 12-fold elevation in blood protein concentration) than for alpha1-antitrypsin (2ââ?¬â??3 fold increment in\nexpression with 0.5-fold elevation in blood protein concentration). Both the increment in capillary-alveolar antiprotease\nconcentration gradient due to increased antiprotease liver synthesis and a timely-associated derangement of the\nalveolar-capillary barrier induced by aspiration, contributed a 58-fold and a 190-fold increase in BALF alpha1-antitrypsin\nand alpha2-macroglobulin levels respectively (p < 0.001).\nConclusions: Gastric contents-induced acute lung injury elicits a liver acute phase response characterized by increased\nmRNA expression of antiproteases and elevation of blood antiprotease concentrations. Hepatic changes act in concert\nwith derangement of the alveolar capillary barrier to enrich alveolar spaces with antiproteases. These findings may\nhave significant implications decreasing protease burden, limiting injury in this and other models of acute lung injury\nand likely, in recurrent aspiration....
Chronic obstructive pulmonary disease (COPD) is characterized by fixed air flow limitation and progressive decline of lung function\nand punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating\nmobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular\nendothelial progenitor cells (VEPCs) are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex smokers\nwith diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted\nprimitive hemopoietic progenitors (HPCs) and VEPC were enumerated by flow cytometry. Migration and adhesive responses to\nfibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood,\nVEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups\nin either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal\ncell-derived factor-1alpha (SDF-1...
Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associatedwith high-altitude pulmonary hypertension (HAPH).\nAsymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in\nthe ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric\nchamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days\nof normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine\nand ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed (...
The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats.\nTwenty-fourWistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin +\nnaringin 80) were used. Rats were administered a single dose of bleomycin (5mg/kg; via the tracheal cannula) alone or followed\nby either naringin 40mg/kg (orally) or naringin 80mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were\nweighed to determine the lung index. TNF-...
Loading....