The Role of Ureaplasma Species in Prenatal and Postnatal Morbidity of Preterm Infants: Current Concepts.

Background: Ureaplasma species are considered commensals of the adult urogenital tract. Yet, in pregnancy, Ureaplasma parvum and Ureaplasma urealyticum have been associated with chorioamnionitis and preterm birth. In preterm infants, Ureaplasma respiratory tract colonization has been correlated with the development of bronchopulmonary dysplasia and has been implicated in the pathogenesis of other complications of prematurity.

Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells.

Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression.

Albumin Stimulates Epithelial Na Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway.

Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na transport drives alveolar fluid clearance (AFC), enabling air breathing.

Y It Matters-Sex Differences in Fetal Lung Development.

Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted.

Development and Functional Characterization of Fetal Lung Organoids.

Preterm infants frequently suffer from pulmonary complications due to a physiological and structural lung immaturity resulting in significant morbidity and mortality. Novel and models are required to study the underlying mechanisms of late lung maturation and to facilitate the development of new therapeutic strategies. Organoids recapitulate essential aspects of structural organization and possibly organ function, and can be used to model developmental and disease processes.

Epidermal growth factor strongly affects epithelial Na transport and barrier function in fetal alveolar cells, with minor sex-specific effects.

Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na transport. The epidermal growth factor (EGF) is important during fetal lung development with possible influence on Na transport.

Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells.

Background: Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as bronchopulmonary dysplasia (BPD), the most common sequel of preterm birth. In these studies, cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD.

Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan.

We investigated the mechanisms involved in the development of airway hyperresponsiveness (AHR) following exposure of mice to halogens. Male mice (C57BL/6; 20-25 g) exposed to either bromine (Br) or Cl (600 or 400 ppm, respectively, for 30 min) developed AHR 24 h after exposure. Nifedipine (5 mg/kg body wt; an L-type calcium channel blocker), administered subcutaneously after Br or Cl exposure, produced higher AHR compared with Br or Cl alone.

Glucocorticoids Equally Stimulate Epithelial Na Transport in Male and Female Fetal Alveolar Cells.

Preterm infants frequently suffer from respiratory distress syndrome (RDS), possibly due to lower expression of epithelial Na channels (ENaC). RDS incidence is sex-specific, affecting males almost twice as often. Despite the use of antenatal glucocorticoids (GCs), the sex difference persists.

Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Permissive Hypercapnia.

Background: Ventilator-induced lung injury is considered to be a main factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Optimizing ventilator strategies may reduce respiratory morbidities in preterm infants. Permissive hypercapnia has been suggested to attenuate lung injury.

Signaling Cascade Involved in Rapid Stimulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Dexamethasone.

Impairment of mucociliary clearance with reduced airway fluid secretion leads to chronically inflamed airways. Cystic fibrosis transmembrane conductance regulator (CFTR) is crucially involved in airway fluid secretion and dexamethasone (dexa) has previously been shown to elevate CFTR activity in airway epithelial cells. However, the pathway by which dexa increases CFTR activity is largely unknown.

Sex-specific effects of sex steroids on alveolar epithelial Na transport.

Alveolar fluid clearance mediates perinatal lung transition to air breathing in newborn infants, which is accomplished by epithelial Na channels (ENaC) and Na-K-ATPase. Male sex represents a major risk factor for developing respiratory distress, especially in preterm infants. We previously showed that male sex is associated with reduced epithelial Na transport, possibly contributing to the sexual dimorphism in newborn respiratory distress.

Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide.

Background: Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing.

Methods: Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation.

Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth.

Preterm infants frequently suffer from pulmonary complications resulting in significant morbidity and mortality. Physiological and structural lung immaturity impairs perinatal lung transition to air breathing resulting in respiratory distress. Mechanical ventilation and oxygen supplementation ensure sufficient oxygen supply but enhance inflammatory processes which might lead to the establishment of a chronic lung disease called bronchopulmonary dysplasia (BPD).

Male Sex is Associated with a Reduced Alveolar Epithelial Sodium Transport.

Respiratory distress syndrome (RDS) is the most frequent pulmonary complication in preterm infants. RDS incidence differs between genders, which has been called the male disadvantage. Besides maturation of the surfactant system, Na+ transport driven alveolar fluid clearance is crucial for the prevention of RDS.

Glucocorticoids Distinctively Modulate the CFTR Channel with Possible Implications in Lung Development and Transition into Extrauterine Life.

During fetal development, the lung is filled with fluid that is secreted by an active Cl- transport promoting lung growth. The basolateral Na+,K+,2Cl- cotransporter (NKCC1) participates in Cl- secretion. The apical Cl- channels responsible for secretion are unknown but studies suggest an involvement of the cystic fibrosis transmembrane conductance regulator (CFTR).

The interaction of glucocorticoids and progesterone distinctively affects epithelial sodium transport.

Purpose: Glucocorticoids and progesterone exert stimulatory effects on epithelial Na(+) transport, including increased mRNA expression of the participating ion transporters (epithelial Na(+) channels [ENaC] and Na,K-ATPases) and their electrophysiological activity. Fetuses threatened by preterm labor may receive high doses of glucocorticoids to stimulate lung maturation and are naturally exposed to high levels of female sex steroids. However, it is still unknown how the combination of both hormones influences the epithelial Na(+) transport, which is crucial for alveolar fluid clearance.

Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells.

Abstract Alveolar fluid clearance is driven by vectorial Na(+) transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na(+) transport was studied in isolated alveolar cells from 18-19-day gestational age rat fetuses. Equivalent short-circuit currents (ISC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation.

Differential regulation of voltage-gated Ca2+ currents and metabotropic glutamate receptor activity by measles virus infection in rat cortical neurons.

Measles virus (MV) infection may lead to severe chronic CNS disease processes, including MV-induced encephalitis. Because the intracellular Ca(2+) concentration ([Ca(2+)](i)) is a major determinant of the (patho-)physiological state in all cells we asked whether important Ca(2+) conducting pathways are affected by MV infection in cultured cortical rat neurons. Patch-clamp measurements revealed a decrease in voltage-gated Ca(2+) currents during MV-infection, while voltage-gated K(+) currents and NMDA-evoked currents were unaffected.

Modulation of sodium transport in alveolar epithelial cells by estradiol and progesterone.

The effects of estradiol (E2) and progesterone (P) on alveolar epithelial Na+ transport were studied in isolated alveolar epithelial cells from 18- to 19-d GA rat fetuses, grown to confluence in serum-free media supplemented with E2 (0-1 μM) and P (0-2.8 μM). Short-circuit currents (ISC) were measured, showing an increase by E2 and P in a dose-dependent manner.

Community dynamics within a bacterial consortium during growth on toluene under sulfate-reducing conditions.

A sulfate-reducing bacterial consortium was enriched from an anoxic aquifer contaminated with BTEX compounds, using toluene as a growth substrate. Total cell counts, protein contents and sulfide production were determined to follow growth at the in situ temperature (14 degrees C) and at 25 degrees C, respectively. Community members were identified by 16S rRNA gene cloning and sequencing.