Ex Vivo Effect of Varespladib on Secretory Phospholipase A2 Alveolar Activity in Infants with ARDS
Autor: | Ettore Capoluongo, Daniele De Luca, Leonarda Gentile, Marco Piastra, Bruno Giardina, Angelo Minucci, Francesca Vendittelli, Laura Marzano, Paola Cogo, Giorgio Conti |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Genetics and Molecular Biology (all)
ARDS Anatomy and Physiology Critical Care and Emergency Medicine Indoles Pulmonology Respiratory System lcsh:Medicine RESPIRATORY-DISTRESS-SYNDROME Phospholipase Acetates Pediatrics Biochemistry chemistry.chemical_compound Pulmonary surfactant Enzyme Inhibitors lcsh:Science chemistry.chemical_classification Respiratory Distress Syndrome Multidisciplinary Medicine (all) Ventilatory Support Keto Acids Medicine Dose-Response Relationship Drug Humans Infant Infant Newborn Phospholipases A2 Secretory Respiratory Distress Syndrome Newborn Bronchoalveolar Lavage Fluid Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) medicine.symptom Drug Research Article Pediatric Critical Care Pediatric Pulmonology Inflammation ACUTE LUNG INJURY Dose-Response Relationship Respiratory Failure medicine Respiratory Physiology Settore BIO/10 - BIOCHIMICA Biology business.industry Catabolism lcsh:R medicine.disease Newborn Secretory Phospholipases A2 Enzyme chemistry Immunology Varespladib lcsh:Q business Ex vivo |
Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 10, p e47066 (2012) |
Popis: | Background Secretory phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available. Methods We studied varespladib in broncho-alveolar lavage (BAL) fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10–40–100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance. Results Varespladib reduces sPLA2 activity (p |
Databáze: | OpenAIRE |
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