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
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