The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes. Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ET(A)) antagonist) and CSE+bosentan (a mixed ET(A)/ET(B) receptor antagonist). ⋯ Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ET(A) receptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-alpha and IL-1beta, and improved the biological antioxidant activity in the serum. Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress.
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Obstructive sleep apnoea (OSA) is common in children and leads to multiple end-organ morbidities. Myeloid-related protein (MRP) 8/14 plays an important pathophysiological role in atherosclerosis, and plasma levels correlate with endothelial cell dysfunction. We hypothesised that MRP8/14 levels would be altered in children with OSA. 255 children (aged 7.6+/-1.5 yrs) were included after a sleep study and a morning blood sample. ⋯ Children with the highest MRP levels (>1.34 ug x mL(-1)) had 2.4- and 5.4-fold increased odds of mild OSA and moderate-to-severe OSA, respectively, after adjusting for confounding variables. Plasma MRP8/14 levels are associated with paediatric OSA and may reflect increased risk for cardiovascular morbidity. The short- and long-term consequences of elevated MRP8/14 on cardiovascular function in the context of paediatric OSA remain to be defined.
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We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development. 45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (DeltaPCT, DeltaCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables. ⋯ VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330-5.715). Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.
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Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague-Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise. An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15-20 min breaks every 4 h. ⋯ In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling/disruption. Our study established a direct link between histological and physiological evidence of HAPE-like symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPE-like symptoms in Sprague-Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.