ABSTRACT
INTRODUCTION: Patients with preeclampsia (PE) exhibit different serum concentrations of sFlt-1 and PlGF. The sFlt-1/PlGF ratio can be used as an aid in the diagnosis of preeclampsia. OBJECTIVES: The objective of this study was to explore the use of the sFlt-1/PlGF ratio as an aid in the prediction of preeclampsia in women with a high risk of the condition. METHODS: 150 patients with high risk of preeclampsia were included in this prospective study. Groups were compared according to the outcome of pregnancy: healthy pregnant women (controls, n=114), pregnancies complicated by intrauterine growth restriction without PE (IUGR, n=14), early PE<34 weeks of gestation (early PE, n=6) and late PE⩾34 weeks of gestation (late PE, n=16). Measurements of sFlt-1 and PlGF were performed on the automated Elecsys system. Statistical comparison of the sFlt-1/PlGF ratio in different outcome groups and multilevel analysis for logistic data using the random slope model was performed. RESULTS: We found significant differences in the sFlt-1/PlGF ratio between the outcome groups in weeks 24-36 of gestation (p=0,05). A significant difference in the sFlt-1/PlGF ratio between controls, IUGR and PE (early and late PE) could be measured up to six weeks before diagnosis (PE) or birth (IUGR, controls) (p=0,05). The random slope model showed significant different slopes (p=0,05) for individual outcome groups (controls 0,657; IUGR 1,786; early PE 1,951; late PE 0,881). CONCLUSION: The sFlt-1/PlGF ratio is able to identify pathologic pregnancy outcomes in gestational weeks 24-36. Prediction is feasible up to six weeks before clinical diagnosis (PE) or 6 weeks before birth (IUGR, controls). Repeated measurements are necessary beginning in 24 weeks of gestation with a maximum distance of six weeks. The slope between two measurements of the sFlt-1/PlGF ratio is predictive of further pregnancy outcome and the risk of developing preeclampsia.
ABSTRACT
Lung transplantation is hampered by bronchiolitis obliterans syndrome (BOS), although recently azithromycin treatment has a published response rate of about 42% in patients with established BOS. We linked this improvement to a reduction in airway neutrophilia and IL8. In the present study, we further investigated the intracellular mechanisms of azithromycin, looking at the possible involvement of mitogen-activated-protein kinases (MAPK) and oxidative stress. Simultaneously, currently used immunosuppressive agents were investigated. Human primary airway smooth muscle cells were stimulated with IL17 and incubated with increasing concentrations of steroids, immunosuppressive agents (tacrolimus, cyclosporine and rapamycin) or macrolides (erythromycin and azithromycin). We measured supernatant IL8 protein, 8-isoprostane and cell lysate MAPK. IL17-induced IL8 production was decreased by both erythromycin and azithromycin. In nonstimulated condition, IL8 production only increased at the highest dose of azithromycin. Dexamethasone failed to attenuate IL8 production, whereas immunosuppressive agents significantly increased IL8 production in both IL17-stimulated and nonstimulated conditions. 8-isoprostane production and MAPK activation proved to be decreased by the macrolides. We conclude that macrolides (but not steroids/immunosuppressive agents) inhibit IL17-induced IL8 production in human primary airway smooth muscle cells via a reduction in MAPK activation and 8-isoprostane production. In BOS patients, these phenomena may explain the anti-inflammatory effects of azithromycin.
