Varespladib Inhibits Secretory Phospholipase A2 in Bronchoalveolar Lavage of Different Types of Neonatal Lung Injury.

Autor:	De Luca, Daniele, Minucci, Angelo, Trias, Joaquim, Tripodi, Domenico, Conti, Giorgio, Zuppi, Cecilia, Capoluongo, Ettore
Předmět:	ANALYSIS of variance APGAR score BIOLOGICAL assay BIOPHYSICS BODY fluids BRONCHOALVEOLAR lavage STATISTICAL correlation ESTERASES HYALINE membrane disease INFECTION LUNGS LUNG injuries RESEARCH methodology MECONIUM aspiration syndrome RESEARCH funding STATISTICS DATA analysis ALBUMINS DATA analysis software INDOLE compounds DESCRIPTIVE statistics CHEMICAL inhibitors CHILDREN
Zdroj:	Journal of Clinical Pharmacology; May2012, Vol. 52 Issue 5, p729-737, 9p
Abstrakt:	Secretory phospholipase A2 (sPLA2), which links surfactant catabolism and lung inflammation, is associated with lung stiffness, surfactant dysfunction, and degree of respiratory support in acute respiratory distress syndrome and in some forms of neonatal lung injury. Varespladib potently inhibits sPLA2 in animal models. The authors investigate varespladib ex vivo efficacy in different forms of neonatal lung injury. Bronchoalveolar lavage fluid was obtained from 40 neonates affected by hyaline membrane disease, infections, or meconium aspiration and divided in 4 aliquots added with increasing varespladib or saline. sPLA2 activity, proteins, and albumin were measured. Dilution was corrected with the urea ratio. Varespladib was also tested in vitro against pancreatic sPLA2 mixed with different albumin concentration. Varespladib was able to inhibit sPLA2 in the types of neonatal lung injury investigated. sPLA2 activity was reduced in hyaline membrane disease (P < .0001), infections (P = .003), and meconium aspiration (P = .04) using 40 µM varespladib; 10 µM was able to lower enzyme activity (P = .001), with an IC50 of 87 µM. An inverse relationship existed between protein level and activity reduction (r = 0.5; P = .029). The activity reduction/protein ratio tended to be higher in hyaline membrane disease. Varespladib efficacy was higher in vitro than in lavage fluids obtained from neonates (P < .001). [ABSTRACT FROM PUBLISHER]
Databáze:	Complementary Index
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