Background and objective: Bile acid (BA) aspiration is associated with various lung diseases. It was hypothesized that BA may induce changes in alveolar epithelium permeability and contribute to the pathogenesis of lung injury. Methods: Human alveolar epithelial cells were grown in monolayer and stimulated with a major component of BA, chenodeoxycholic acid (CDCA). Transepithelial electrical resistance (TER) and paracellular fluxes were measured to assess permeability alteration. Prostaglandin E2 (PGE2) production was measured, and its effect on TER and junctional proteins (JP) was also examined. Reverse transcription polymerase chain reaction and Western blots were used to investigate the expression of messenger RNA and JP. Results: CDCA induced significant p38 and c-Jun N-terminal kinase (JNK) phosphorylation, cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) messenger RNA expression, PGE2 production, TER reduction and decay of JP (including occludin, zonula occludens-1 (ZO-1) and E-cadherin, in which ZO-1 had maximal change). CDCA also increased paracellular fluxes, which was abolished by dexamethasone. Both CDCA and PGE2 contributed to TER reduction in an identical trend and a dose-response manner. PGE2 also reduced ZO-1 expression, which was similar to that observed by CDCA stimulation. Pretreatment with inhibitors of p38 (SB203580), JNK (SP600125), cPLA2 (mepacrine) and COX-2 (NS398) as well as dexamethasone reversed the CDCA-induced PGE2 production, TER reduction and decay of ZO-1.
Conclusions:The increase in alveolar permeability was associated with decay of JP. BA may induce permeability alteration through the upregulation of mitogenactivated protein kinase, cPLA2, COX-2, PGE2 and JP, which may contribute to the pathogenesis of BA-associated lung injury. made equal contributions to this study.
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BackgroundMonitoring of fetal heart rate (FHR) is important during labor since it is a sensitive marker to obtain significant information about fetal condition. To take immediate response during cesarean section (CS), we noninvasively derive FHR from maternal abdominal ECG.MethodsWe recruited 17 pregnant women delivered by elective cesarean section, with abdominal ECG obtained before and during the entire CS. First, a QRS-template is created by averaging all the maternal ECG heart beats. Then, Hilbert transform was applied to QRS-template to generate the other basis which is orthogonal to the QRS-template. Second, maternal QRS, P and T waves were adaptively subtracted from the composited ECG. Third, Gabor transformation was applied to obtain time-frequency spectrogram of FHR. Heart rate variability (HRV) parameters including standard deviation of normal-to-normal intervals (SDNN), 0V, 1V, 2V derived from symbolic dynamics of HRV and SD1, SD2 derived from Poincareé plot. Three emphasized stages includes: (1) before anesthesia, (2) 5 minutes after anesthesia and (3) 5 minutes before CS delivery.ResultsFHRs were successfully derived from all maternal abdominal ECGs. FHR increased 5 minutes after anesthesia and 5 minutes before delivery. As for HRV parameters, SDNN increased both 5 minutes after anesthesia and 5 minutes before delivery (21.30±9.05 vs. 13.01±6.89, P < 0.001 and 22.88±12.01 vs. 13.01±6.89, P < 0.05). SD1 did not change during anesthesia, while SD2 increased significantly 5 minutes after anesthesia (27.92±12.28 vs. 16.18±10.01, P < 0.001) and both SD2 and 0V percentage increased significantly 5 minutes before delivery (30.54±15.88 vs. 16.18±10.01, P < 0.05; 0.39±0.14 vs. 0.30±0.13, P < 0.05).ConclusionsWe developed a novel method to automatically derive FHR from maternal abdominal ECGs and proved that it is feasible during CS.
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