The cardinal manifestations of the pregnancy-specific disorder preeclampsia, new-onset hypertension and proteinuria that resolve with placental delivery, have been linked to an extracellular protein made by the placenta, sFlt1 (soluble fms-like tyrosine kinase 1), that injures the maternal vasculature. However, the mechanisms by which sFlt1, which is heavily matrix-bound, gains access to the systemic circulation remain unclear. Here we report that the preeclamptic placenta’s outermost layer, the syncytiotrophoblast, forms abundant “knots” that are enriched with sFlt1 protein. These syncytial knots easily detach from the syncytiotrophoblast, resulting in free, multinucleated aggregates (50–150 μm diameter) that are loaded with sFlt1 protein and mRNA, are metabolically active, and are capable of de novo gene transcription and translation. At least 25% of the measurable sFlt1 in 3rd trimester maternal plasma is bound to circulating placental microparticles. We conclude that detachment of syncytial knots from the placenta results in free, transcriptionally active syncytial aggregates that represent an autonomous source of sFlt1 delivery into the maternal circulation. The process of syncytial knot formation, shedding of syncytial aggregates, and appearance of placental microparticles in the maternal circulation appears to be greatly accelerated in preeclampsia and may contribute to the maternal vascular injury that characterizes this disorder.
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Background: Endobronchial administration of local anesthetics such as lidocaine is often used for cough suppression during bronchoscopy. To achieve a better distribution of lidocaine in the tracheobronchial tree, spray catheters have been developed, allowing nebulization of the local anesthetic solution. However, there are little data on the efficacy and safety of this approach, or on the consumption of sedative drugs and lidocaine during nebulized administration. Objectives: To investigate the tolerability of nebulized lidocaine compared to conventional lidocaine administration via syringe through the working channel of the bronchoscope in patients undergoing bronchoscopy. Consumption of sedative drugs and lidocaine was also compared between the two lidocaine administration approaches. Methods: Patients requiring bronchoscopy with endobronchial or transbronchial biopsy were randomly assigned to receive topical lidocaine either via syringe or via nebulizer. Endpoints were consumption of lidocaine and sedative drugs, as well as patient tolerance and safety. Results: Thirty patients were included, 15 in each group. Patients in the nebulizer group required lower doses of endobronchial lidocaine (184.7 ± 67.98 vs. 250.7 ± 21.65 mg, p = 0.0045) and intravenous fentanyl (0.033 ± 0.041 vs. 0.067 ± 0.045 mg, p = 0.0236) than those in the syringe group; midazolam or propofol dosages did not differ between the two groups. In addition, there were no between-group differences in patient tolerance or safety (all p > 0.05). Conclusion: Endobronchial administration of lidocaine during bronchoscopy via nebulizer was found to be well tolerated and safe and was associated with reduced lidocaine and fentanyl dosages compared to administration via syringe.
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