Ibuprofen-induced patent ductus arteriosus closure improved pulmonary mechanics, decreased total lung water, increased epithelial sodium channel expression, and decreased the detrimental effects of preterm birth on alveolarization.

A major mechanism for Na+ transport across epithelia occurs through epithelial Na+ channels (ENaC). ENaC is a multimeric channel consisting of three subunits (alpha, beta, and gamma). The alpha-subunit is critical for ENaC function. In specific culture conditions, the rat submandibular gland epithelial cell line (SMG-C6) demonstrates minimal Na+ transport properties and exposure to dibutyryl cAMP (DbcAMP) for up to 48 h caused an elevation of alpha-ENaC mRNA and protein expression and amiloride-sensitive short-circuit current (I(SC)). Here we examined the early signaling pathways evoked by DbcAMP which contribute to the eventual increase in Na+ transport is present. Treatment with either of the protein kinase A (PKA) inhibitors KT5720 or H-89 followed by exposure to 1 mM DbcAMP for 24 h markedly attenuated DbcAMP-induced alpha-ENaC protein formation and I(SC). Exposure of SMG-C6 cells to 1 mM DbcAMP induced a rapid, transient phosphorylation of the cAMP response element binding protein (CREB). This response was attenuated in the presence of either KT5720 or H-89. Dominant-negative CREB decreased DbcAMP-induced alpha-ENaC expression. Suppression of the extracellular signal-regulated protein kinase (ERK 1,2) with PD98059 or the p38 mitogen-activated protein kinase (MAPK) pathway with SB203580 reduced DbcAMP-induced alpha-ENaC protein levels in SMG-C6 cells. DbcAMP-induced phosphorylation of CREB was markedly attenuated by PD98059 or SB203580. DbcAMP-induced activation of the either the p38 or the ERK 1,2 MAPK pathways was abolished by either of the PKA inhibitors, H-89 or KT5720. Cross talk between these signaling pathways induced by DbcAMP via the activation of CREB appears to contribute to increased levels of alpha-ENaC observed after 24 h of treatment in SMG-C6 epithelial cells.

Changes in health care delivery have imposed more time constraints on community-based preceptors. However, this study identified underlying factors motivating physicians to volunteer as preceptors. Strategies to recruit new and retain current preceptors must be collaborative.

Previous studies have shown that the expression of cardiac angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors are developmentally regulated, although factors modulating these receptors have not been well investigated. The present study was designed 1) to characterize the ontogeny of cardiac AT1 and AT2 gene expression during the last third trimester of gestation in fetal sheep and newborn lambs, 2) to determine the influence of ANG II on modulating cardiac AT1 and AT2 gene expression during fetal life, and 3) to investigate the role of AT1 receptor activity on the regulation of AT1 and AT2 mRNA levels during fetal cardiac development. Using sheep AT1 and AT2 cDNA probes, we demonstrated that cardiac AT1 gene expression is relatively unchanged during fetal (90-135 d of gestation, term 145 d) and newborn life. In contrast, cardiac AT2 mRNA expression was high during fetal development and decreased rapidly after birth. Continuous i.v. infusion of ANG II (9.5 nM/h) for 24 h, which raised ANG II levels from 84+/-9 to 210+/-21 pg/mL had no effect on the expression of cardiac AT1 or AT2 mRNA, but increased adrenal and decreased liver AT1 mRNA levels. Administration of the AT1 receptor antagonist losartan (1.2 mg kg(-1) h(-1)) significantly decreased arterial blood pressure in fetuses at 110- and 135-d, but not 95-d gestation. Except for increased AT1 receptor gene expression in the right atrium at 95- and 135-d gestation, and left ventricle at 110-d gestation, cardiac AT1 and AT2 mRNA levels were unaltered by AT1 receptor blockade. In summary, this study demonstrates that cardiac AT2 but not AT1 receptor gene expression is regulated by the transition from fetal to newborn life. Neither ANG II nor blockade of AT1 receptors significantly alter the expression of AT1 or AT2 mRNA in the fetal heart. Endogenous ANG II also appears to significantly contribute to the maintenance of blood pressure homeostasis during the final third of gestation in fetal lambs.

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Purpose Difficulty in recruiting and retaining community preceptors for medical student education has been described in the literature. Yet little, if any, information is known about community outpatient preceptors who have stopped or decreased teaching time with students. This study aimed to examine these preceptors’ perspectives about this phenomenon. Method Using a phenomenology framework, this multi-institutional qualitative study used semistructured interviews with community pediatric preceptors who had stopped or reduced teaching time with medical students. Interviews were conducted between October 2017 and January 2018 and transcribed verbatim. Interviews explored factors for engaging in teaching, or decreasing or ceasing teaching, that would enable future teaching. An initial code book was developed and refined as data were analyzed to generate themes. Results Twenty-seven community pediatricians affiliated with 10 institutions participated. Thirty-seven codes resulted in 4 organizing themes: evolution of health care, personal barriers, educational system, and ideal situations to recruit and retain preceptors, each with subthemes. Conclusions From the viewpoints of physicians who had decreased or stopped teaching students, this study more deeply explores previously described reasons contributing to the decline of community preceptors, adds newly described barriers, and offers strategies to help counter this phenomenon based on preceptors’ perceptions. These findings appear to be manifestations of deeper issues including the professional identify of clinical educators. Understanding the barriers and strategies and how they relate to preceptors themselves should better inform education leaders to more effectively halt the decline of community precepting and enhance the clinical precepting environment for medical students.

At birth, lung fluid clearance is coupled to Na+ transport through epithelial Na+ channels (ENaC) in the distal lung epithelium. We evaluated the effect of postnatal glucocorticoids (GC) on lung α-ENaC expression in preterm 29-day gestational age (GA) fetal rabbits. Postnatal treatment of 29-day GA fetuses with 0.5 mg/kg of dexamethasone (Dex) iv resulted in a 2- and 22-fold increase in lung α-ENaC mRNA expression compared with saline-treated fetuses after 8 and 16 h, respectively. Lung α-ENaC protein levels in Dex-treated fetuses were also elevated compared with saline-treated counterparts. The extravascular lung water (EVLW)/dry lung tissue weight ratios of 29-day GA fetuses treated with either saline or Dex decreased over 24 h compared with that observed at birth; however, at 24 h, the EVLW/dry lung tissue weight ratios of saline- and Dex-treated fetuses were similar. Dex-induced α-ENaC mRNA and protein levels were attenuated by glucocorticoid receptor (GCR) antagonist RU-486 in fetal distal lung epithelial cells isolated from 29-day GA fetuses, indicating that GC-dependent augmentation of lung α-ENaC requires the presence of functional GCR. Lung GCR mRNA expression and protein levels were elevated in 29-day GA fetuses compared with fetuses at earlier GA. Exposure of 29-day GA fetuses to Dex for 16 h caused a 2.1-fold increase in lung GCR mRNA expression, but GCR protein levels were decreased in Dex-treated fetuses after 24 h. We conclude that postnatal treatment of preterm 29-day GA fetal rabbits with GC results in an elevation of lung α-ENaC accompanied by an autoregulation of pulmonary GCR.

Glucocorticoid levels increase greatly at the time of birth in humans and sheep, coinciding with an increased ability of the kidney to reabsorb sodium. Cortisol induces proximal tubule apical membrane Na+/H+exchanger maturation in near-term fetal sheep. Proximal tubule salt transport is ultimately dependent on Na+ pump activity, so we studied the effects of cortisol treatment on renal cortical Na+-K+-ATPase. We first looked at six 140 day gestation fetal sheep (term is 145) and compared their renal cortical Na+-K+-ATPase to that of six 1-day-old lambs. Na+-K+-ATPase activity increased 80% after birth. Then nine pairs of twin fetal sheep were chronically instrumented at 127 days gestation. After 72 h recovery, one twin was given a 48-h continuous intraperitoneal infusion of cortisol. Both twins were then killed, and their renal cortices were studied. Na+-K+-ATPase activity increased 122% with cortisol treatment; activity equaled that of 1-day-old lambs. Protein abundance of the α1-subunit of the Na+-K+-ATPase increased 19%; the β1-subunit increased 39% with cortisol treatment. mRNA abundance of the α1-subunit increased 58%; the β1-subunit increased 72%. These results indicate that cortisol matures Na+-K+-ATPase activity.