Intestinal and systemic illnesses have been linked to increased gut permeability. Bile acids, whose luminal profile can be altered in human disease, modulate intestinal paracellular permeability. We investigated the mechanism by which selected bile acids increase gut permeability using a validated in vitro model. Human intestinal Caco-2 cells were grown in monolayers and challenged with a panel of bile acids. Transepithelial electrical resistance and luminal-to-basolateral fluxes of 10-kDa Cascade blue-conjugated dextran were used to monitor paracellular permeability. Immunoprecipitation and immunoblot analyses were employed to investigate the intracellular pathway. Redistribution of tight junction proteins was studied by confocal laser microscopy. Micromolar concentrations of cholic acid, deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA) but not ursodeoxycholic acid decreased transepithelial electrical resistance and increased dextran flux in a reversible fashion. Coincubation of 50 μM CDCA or DCA with EGF, anti-EGF monoclonal antibody, or specific src inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP-2) abolished the effect. A concentration of 50 μM of either CDCA or DCA also induced EGF receptor phosphorylation, occludin dephosphorylation, and occludin redistribution at the tight junction level in the same time frame and in a reversible fashion. We conclude that selected bile acids modulate intestinal permeability via EGF receptor autophosphorylation, occludin dephosphorylation, and rearrangement at the tight junction level. The effect is mediated by the src family kinases and is abolished by EGF treatment. These data also support the role of bile acids in the genesis of necrotizing enterocolitis and the protective effect of EGF treatment.

BACKGROUND: Noninvasive ventilation is the treatment of choice for neonatal moderate respiratory distress (RD). Predictors of nasal ventilation failure are helpful in preventing clinical deterioration. Work on neonatal lung ultrasound has shown that the persistence of a hyperechogenic, “white lung” image correlates with severe distress in the preterm infant. We investigate the persistent white lung ultrasound image as a marker of noninvasive ventilation failure. METHODS: Newborns admitted to the NICU with moderate RD and stabilized on nasal continuous positive airway pressure for 120 minutes were enrolled. Lung ultrasound was performed and blindly classified as type 1 (white lung), type 2 (prevalence of B-lines), or type 3 (prevalence of A-lines). Chest radiograph also was examined and graded by an experienced radiologist blind to the infant’s clinical condition. Outcome of the study was the accuracy of bilateral type 1 to predict intubation within 24 hours from scanning. Secondary outcome was the performance of the highest radiographic grade within the same time interval. RESULTS: We enrolled 54 infants (gestational age 32.5 ± 2.6 weeks; birth weight 1703 ± 583 g). Type 1 lung profile showed sensitivity 88.9%, specificity 100%, positive predictive value 100%, and negative predictive value 94.7%. Chest radiograph had sensitivity 38.9%, specificity 77.8%, positive predictive value 46.7%, and negative predictive value 71.8%. CONCLUSIONS: After a 2-hour nasal ventilation trial, neonatal lung ultrasound is a useful predictor of the need for intubation, largely outperforming conventional radiology. Future studies should address whether including ultrasonography in the management of neonatal moderate RD confers clinical advantages.

Introduction: At birth, lung fluid is rapidly cleared to allow gas exchange. As pulmonary sonography discriminates between liquid and air content, we have used it to monitor extrauterine fluid clearance and respiratory adaptation in term and late preterm neonates. Ultrasound data were also related to the need for respiratory support. Methods: Consecutive infants at 60 to 120 minutes after birth underwent lung echography. Images were classified using a standardized protocol of adult emergency medicine with minor modifications. Neonates were assigned to type 1 (white lung image), type 2 (prevalence of comet-tail artifacts or B-lines) or type 3 profiles (prevalence of horizontal or A lines). Scans were repeated at 12, 24 and 36 hours. The primary endpoint was the number of infants admitted to the neonatal ICU (NICU) by attending staff who were unaware of the ultrasound. Mode of respiratory support was also recorded. Results: A total of 154 infants were enrolled in the study. Fourteen neonates were assigned to the type 1, 46 to the type 2 and 94 to the type 3 profile. Within 36 hours there was a gradual shift from types 1 and 2 to type 3. All 14 type 1 and 4 type 2 neonates were admitted to the NICU. Sensitivity was 77.7%, specificity was 100%, positive predictive value was 100%, negative predictive value was 97%. Four type 1 infants were mechanically ventilated. Conclusions: In the late preterm and term neonate, the lung ultrasound scan follows a reproducible pattern that parallels the respiratory status and can be used as a predictor of respiratory support.

Background and Aim: Discordant results that demand clarification have been published on diagnostic lung ultrasound (LUS) signs of transient tachypnea of the neonate (TTN) in previous cross-sectional, single-center studies. This work was conducted to correlate clinical and imaging data in a longitudinal and multicenter fashion. Methods: Neonates with a gestational age of 34–40 weeks and presenting with TTN underwent a first LUS scan at 60–180 min of life. LUS scans were repeated every 6–12 h if signs of respiratory distress persisted. Images were qualitatively described and a LUS aeration score was calculated. Clinical data were collected during respiratory distress. Results: We enrolled 65 TTN patients. Thirty-one (47.6%) had a sharp echogenicity increase in the lower lung fields (the “double lung point” or DLP sign). On admission, there was no significant difference between patients with and without DLP in Silverman scores (4 ± 1.5 vs. 4 ± 2.1; p = 0.9) or LUS scores (7.6 ± 2.6 vs. 5.6 ± 3.8; p = 0.12); PaO₂/FiO₂ (249 ± 93 vs. 252 ± 125; p = 0.91). All initial LUS scans (performed at the onset of distress) and 99.5% of all scans showed a regular pleural line with no consolidation, with only 1 neonate showing consolidation in the follow-up scans. The Silverman and LUS scores were significantly correlated (rho = 0.27; p = 0.02). Conclusion: A regular pleural line with no consolidation is a consistent finding in TTN. The presence of a DLP is not essential for the LUS diagnosis of TTN. A semi-quantitative LUS score correlates well with the clinical course and could be useful in monitoring changes in lung aeration during TTN.