L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.

Background: Prenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD.

Maturational effect of leptin on CO chemosensitivity in newborn rats.

Background: Leptin augments central CO chemosensitivity and stabilizes breathing in adults. Premature infants have unstable breathing and low leptin levels. Leptin receptors are on CO sensitive neurons in the Nucleus Tractus Solitarius (NTS) and locus coeruleus (LC).

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit ( = 12; 98 ± 4 days; 743 ± 350 g).

Adiponectin and the regulation of gastric content volume in the newborn rat.

Background: Oral intake is dependent on the gastric ability to accommodate the food bolus. Comparatively, neonates have a smaller gastric capacity than adults and this may limit the volume of their milk intake. Yet, we previously reported that the newborn rat gastric milk volume is greatest after birth and, when normalized to body weight, decreases with postnatal age.

Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus.

Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low-resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way.

Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxemic term and near-term neonates.

Approximately 40% of hypoxemic term/near-term neonates are nonresponders to inhaled nitric oxide (iNO). Phenotypic characterization of patients less likely to respond may improve diagnostic precision and therapeutic decisions. We conducted a retrospective cohort study of neonates born ≥35 weeks gestation with hypoxemia who received iNO in the first 72 h of life and classified them into responders and nonresponders according to changes in the fraction of inspired oxygen, saturations and/or arterial partial pressure of oxygen after 1 h of administration.

Necrotising enterocolitis in newborns receiving diazoxide.

Background: Frequent and severe gastrointestinal disturbances have been reported with the use of diazoxide in adults and older children. However, no studies have investigated the incidence of necrotising enterocolitis (NEC) in diazoxide-exposed newborns.

Objective: To evaluate a possible association between diazoxide treatment for neonatal hypoglycaemia and the occurrence of NEC.

Recombinant adiponectin protects the newborn rat lung from lipopolysaccharide-induced inflammatory injury.

Preterm infants are at high risk for developing bronchopulmonary dysplasia and pulmonary hypertension from inflammatory lung injury. In adult models, adiponectin (APN)-an adipocyte-derived hormone-protects the lung from inflammatory injury and pulmonary vascular remodeling. Cord blood APN levels in premature infants born < 26 weeks gestation are 5% of the level in infants born at term.

Acetaminophen increases pulmonary and systemic vasomotor tone in the newborn rat.

Background: Acetaminophen is widely prescribed to both neonates and young children for a variety of reasons. In adults, therapeutic usage of acetaminophen induces systemic arterial pressure changes and exposure to high doses promotes tissue toxicity. The pulmonary vascular effects of acetaminophen at any age are unknown.

A novel role for milrinone in neonatal acute limb ischaemia: successful conservative treatment of thrombotic arterial occlusion without thrombolysis.

Acute neonatal limb ischaemia (NLI) is most frequently an iatrogenic complication, however, may also occur in utero due to thromboembolism. There is no widely accepted protocol for treatment of NLI and limited evidence to guide management. Thrombolysis and surgical management have been attempted, though both are associated with significant morbidities.

Neonatal coning secondary to hypoxic ischaemic encephalopathy: A case study and literature review.

Introduction: Brain herniation is an extremely rare complication of hypoxic ischaemic encephalopathy (HIE) in the neonatal period with only a single report described. We report a 2-day-old term infant with severe HIE, who developed diffuse brain oedema and herniation.

Case Presentation And Description: A term female infant delivered by vacuum, required therapeutic hypothermia for severe encephalopathy.

GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis.

Gut mesenchyme provides key stem cell niche signals such as Wnt ligands, but how these signals are regulated is unclear. Because Hedgehog (Hh) signaling is critical for gut mesenchymal development and tumorigenesis, we investigated Hh-mediated mechanisms by analyzing mice deleted for key negative regulators of Hh signaling, Sufu and/or Spop, in the gut mesenchyme, and demonstrated their dosage-dependent roles. Although these mutants exhibit abnormal mesenchymal cell growth and functionally defective muscle layers, villification is completed with proper mesenchymal clustering, implying a permissive role for Hh signaling.

Chronic Intermittent Hypoxia in Premature Infants: The Link Between Low Fat Stores, Adiponectin Receptor Signaling and Lung Injury.

Premature infants have chronic intermittent hypoxia (CIH) that increases morbidity, and the youngest and the smallest premature infants are at the greatest risk. The combination of lung injury from inflammation/oxidative stress causing low functional residual capacity combined with frequent short apneas leads to CIH. Adiponectin (APN) is an adipose-derived adipokine that protects the lung from inflammation and oxidative stress.

Hydrogen peroxide promotes gastric motility in the newborn rat.

Background: When compared with infant formula, human milk enhances gastric emptying in preterm infants. Hydrogen peroxide (HO) is present in large quantities in human milk that has an antimicrobial role for the mother and infant. In vitro adult rat studies suggest that HO facilitates gastric motor contraction.

Gavage Feed Volume Determines the Gastric Emptying Rate in Preterm Infants.

Objective: Feeding intolerance, manifesting as increased gastric residual, is a common finding in preterm neonates. Little is known about the regulation of gastric emptying early in life and the extent to which this plays a role in the preterm infants' feeding tolerance. The goal of this study was to evaluate clinically stable 28- to 32-week gestation neonates during the first 4 weeks of life and noninvasively determine their gastric emptying rate.

The effect of a single anti-Vascular Endothelial Growth Factor injection on neonatal growth and organ development: In-vivo study.

Retinopathy of prematurity (ROP) is one of the leading causes of blindness in preterm Infants. Anti-vascular endothelial growth factor (VEGF) is emerging as a promising treatment, but there is insufficient evidence on their safety. We investigate the effect of systemic anti-VEGF in rat pups with equivalent maturity to a 32 week neonate.

Human milk HO content: does it benefit preterm infants?

BackgroundHuman milk has a high content of the antimicrobial compound hydrogen peroxide (HO). As opposed to healthy full-term infants, preterm neonates are fed previously expressed and stored maternal milk. These practices may favor HO decomposition, thus limiting its potential benefit to preterm infants.

Tetrahydrobiopterin (BH4) deficiency is associated with augmented inflammation and microvascular degeneration in the retina.

Background: Tetrahydrobiopterin (BH4) is an essential cofactor in multiple metabolic processes and plays an essential role in maintaining the inflammatory and neurovascular homeostasis. In this study, we have investigated the deleterious effects of BH4 deficiency on retinal vasculature during development.

Methods: hph-1 mice, which display deficiency in BH4 synthesis, were used to characterize the inflammatory effects and the integrity of retinal microvasculature.

Early Empiric Antibiotic Use Is Associated With Delayed Feeding Tolerance in Preterm Infants: A Retrospective Analysis.

The causative factors of neonatal feeding intolerance are poorly understood, but potentially related to clinical practices such as empiric antibiotic usage. The objective of this study was to evaluate whether early empiric antibiotic exposure negatively affects preterm infants' enteral feeding tolerance. Data from infants without risk factors for sepsis, 500 to 1499 g birth weight and 24 to 34 weeks gestational age were analyzed.

Finding NeMO-Nerve-sparing Mid-urethral Obstruction: A Pathophysiologically Accurate Model of Rodent Partial Bladder Outlet Obstruction.

Objective: To develop and evaluate a novel technique modeling partial bladder outlet obstruction (pBOO) using a nerve-sparing mid-urethral obstruction (NeMO) approach.

Materials And Methods: Female unoperated rats were compared to rats after NeMO, NeMO sham, proximal urethral (PU) obstruction, or PU sham. Residual volume, bladder capacity, voiding volume, and bladder mass were recorded; the contractile characteristics of isolated bladder strips were also analyzed.

Gastric emptying is reduced in experimental NEC and correlates with the severity of intestinal damage.

Purpose: The aim of this study is to assess gastric emptying in experimental necrotizing enterocolitis (NEC) and its diagnostic significance using non-invasive ultrasound imaging.

Methods: Fourteen neonatal mice (C57BL/6) were randomized into two groups: NEC [n=10] and control [n=4]. NEC was induced by gavage feeding of hyperosmolar formula, hypoxia, and lipopolysaccharide between postnatal day 5 (P5) and 9 (P9).

Intestinal microbiota as a tetrahydrobiopterin exogenous source in hph-1 mice.

Tetrahydrobiopterin (BH4) is a cofactor of a number of regulatory enzymes. Although there are no known BH4 exogenous sources, the tissue content of this biopterin increases with age in GTP cyclohydrolase 1-deficient hyperphenylalaninemia-1 (hph-1) mice. Since certain bacteria are known to generate BH4, we hypothesize that generation of this biopterin by the intestinal microbiota contributes to its tissue increase in hph-1 adult mice.

Effect of the I/E ratio on CO2 removal during high-frequency oscillatory ventilation with volume guarantee in a neonatal animal model of RDS.

Unlabelled: The objective of this study was to analyze the effect of I/E ratio on carbon dioxide (CO2) elimination during high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG). Five 2-day-old piglets were studied before and after a bronchoalveolar lavage (BAL). The effect of an I/E ratio of 1:1 and 1:2 with (VG-ON) and without VG (VG-OFF) on PaCO2, as well as delta and mean airway pressures at the airway opening (∆Phf-ao, mPaw-ao) and at the tracheal level (∆Phf-t, mPaw-t) were evaluated at frequencies of 5, 8, 11, and 14 Hz.