Matrix metalloproteinase-8 and tissue Inhibitor of metalloprotinases-2 in tracheal aspirates from ventilated preterm neonates with respiratory distress syndrome

Matrix metalloproteinases [MMPs] are a family of endoproteinases that act in remodeling and destruction of extracellular matrix and basement membrane. An imbalance among their inducers, activators and specific inhibitors is believed 10 generate parenchymal destruction in pulmonary inflammatory diseases. In this study the concentrations of MMP-8 and tissue inhibitor of metalloprotinases [TIMP]-2 were assessed in tracheal aspirate fluids [TAFs] obtained from ventilated preterm neonates during the first postnatal week. The aim was to investigate their possible role in acute inflammatory lung injury associating respiratory distress syndrome [RDS], assess their relation to disease severity and their possible contribution to the development of chronic lung disease [CLD].Clinical and radiographic assessments of respiratory distress were attempted for 90 ventilated preterm neonates who were defined in 3 groups. Group A comprised 32 neonates with RDS, group B constituted 28 neonates with bronchopneumonia while group C included 30 ventilated neonates for extrapulmonary disorders. The median values for fraction of inspired oxygen [FiO[2]] and arterial/alveolar O[2] tension ratio [a/A O[2]] during the first 24 hours of ventilation, as measures of initial severity of respiratory distress, were calculated. TAF samples were collected for measurement of MMP-8 and TIMP-2 levels by ELISA with calculation of MMP-8/TIMP-2 ratio. Clinical outcome was determined in terms of evolution to CLD. A significant increase in MMP-8/TIMP-2 ratio was found in group A as compared to groups B and C [p<0.01, respectively]. Meanwhile, no significant change in MMP-8/TIMP-2 ratio was encountered in group B in comparison to group C [p>0.05]. Among neonates with RDS, MMP-8 was positively correlated to FiO[2] [r=0.64, p<0.01] and was inversely related to a/A O[2] [r=-0.72, p<0.01]. Nineteen [59%] of RDS neonates developed CLD and those were found to have significantly higher MMP-8, MMP-8/TIMP-2 ratio and initial FiO[2] and significantly lower initial a/A O[2] ratio as compared to RDS neonates with no CLD [p<0.01, respectively]. MMP-8 at an optimum cut-off value of 188 ng/mL was the best to predict RDS progression to CLD with a positive predictive value [PPV] of 94.1% and an efficacy of 87.5%. An imbalance between tracheal aspirate MMP-8 and TIMP-2 levels during the early postnatal period could play a role in the acute inflammatory lung injury in neonatal RDS. This imbalance is associated with disease severity and probably contributes to subsequent evolution of CLD. It could also be speculated that early assessment of tracheal aspirate MMP-8 in preterm neonates with RDS might help prediction of later CLD development

Biochemical studies on blood platelets of chronic renal failure patients and their relations to impairment of platelet function

Abnormal bleeding is a major complication of chronic renal failure. Among the multiple causes of this defect is impaired platelet function as reduced platelet adhesiveness defective aggregation by thrombin and adenosine diphosphate, and inhibition of release reaction. The aim of this study was to find a correlation between impaired platelet function and changes of the biochemical structure of the plaselets. The platelets of 15 patients with chronic renal failure and ten normal subjects [controls] were studied for total proteins, lipids, phospholipids, cholesterol and total carbohydrates, and protein components separated by electrophoresis. Also the enzyme activities of Na[+]-K[+]-Mg[+2] adenosine triphosphatase and monoamine oxidase were studied. The results showed increased concentration of total lipids, phospholipids and a qualitative change in protein components of uremic platelets. On the other hand, the activities of Na[+]-K[+]-Mg[+2] adenosine triphosphatase and monoamine oxidase were decreased. These results were discussed in the light of their effect on platelet physiological functions