Biology of the neonate最新文献

Background: Insufficient cerebral O2 supply leads to cellular energy failure and loss of brain cell function. The relationship between the severity of cellular energy failure due to hemorrhagic hypotension and the loss of electrocortical brain activity (ECBA), as a measure of brain cell function, is not yet fully elucidated in near-term born lambs.

Objectives: To study the relationship between cerebral purine and pyrimidine metabolism, as a measure of brain cell energy failure, and brain cell function after hemorrhagic hypotension in near-term born lambs.

Methods: Eight near-term lambs (term 147 days) were delivered at 131 days of gestation. After a stabilization period, mean arterial blood pressure was reduced till 30% of baseline by withdrawal of blood. Cerebrospinal fluid (CSF) was obtained at the end of the hypotensive period (2.5 h). CSF from 8 siblings was used for comparison. HPLC was used to determine purine and pyrimidine metabolites in CSF, as a measure of cellular energy failure. ECBA was calculated as the root mean square value of a band-filtered (2-16 Hz) one-channel EEG.

Results: Values of guanosine, inosine, hypoxanthine, xanthine and uridine were significantly higher, while ECBA was significantly lower after hemorrhagic hypotension than control values. The concentrations of inosine, hypoxanthine, xanthine and uridine were significantly negatively linearly related to ECBA.

Conclusions: Brain cell function is negatively related to concentrations of inosine, hypoxanthine, xanthine and uridine in the CSF after hemorrhagic hypotension in near-term born lambs.

Although neonatal morbidity and mortality are less than in the past, the risk of pre-natal and neonatal brain damage has not been eliminated. In order to optimize pre-natal, perinatal and neonatal care, it is necessary to detect factors responsible for brain damage and obtain information about their timing. Knowledge of the timing of asphyxia, infections and circulatory abnormalities would enable obstetricians and neonatologists to improve prevention in pre-term and full-term neonates. Cardiotocography has been criticized as being too indirect a sign of fetal condition and as having various technical pitfalls, though its reliability seems to be improved by association with pulse oximetry, fetal blood pH and electrocardiography. Neuroimaging is particularly useful to determine the timing of hypoxic-ischemic brain damage. Cranial ultrasound has been used to determine the type and evolution of brain damage. Magnetic resonance has also been used to detect antenatal, perinatal and neonatal abnormalities and timing on the basis of standardized assessment of brain maturation. Advances in the interpretation of neonatal electroencephalograms have also made this technique useful for determining the timing of brain lesions. Nucleated red blood cell count in cord blood has been recognized as an important indication of the timing of pre-natal hypoxia, and even abnormal lymphocyte and thrombocyte counts may be used to establish pre-natal asphyxia. Cord blood pH and base excess are well-known markers of fetal hypoxia, but are best combined with heart rate and blood pressure. Other markers of fetal and neonatal hypoxia useful for determining the timing of brain damage are assays of lactate and markers of oxidative stress in cord blood and neonatal blood. Cytokines in blood and amniotic fluid may indicate chorioamnionitis or post-natal infections. The determination of activin and protein S100 has also been proposed. Obstetricians and neonatologists can therefore now rely on various methods for monitoring the risk of brain damage in the antenatal and post-natal periods.

With the technical progress made in fetal and neonatal intensive care, perinatal mortality has decreased by 25% over the last decade and has expanded the surviving premature population. Prematurity drastically changes the environment of the developing organism. Striking evidence from a number of disciplines has focused attention on the interplay between the developing organism and the circumstances in which it finds itself. The environmental event during a sensitive period in development, induces injury and/or biological adaptations that lead to altered differentiation of tissues. The organism can express specific adaptive responses to its environment which include short-term changes in physiology as well as long-term adjustments. This review addresses these short-term as well as longer-term changes occurring in lung and brain tissue and illustrates how these changes can be studied using advanced imaging techniques such as magnetic resonance imaging

Background and objectives: Different types of surfactant preparations were shown not to exert uniform response in preterm infants suffering from respiratory distress syndrome (RDS). Therefore, the effects of a recombinant surfactant protein C (rSP-C) based preparation and a natural surfactant were compared applying different levels of positive end-expiratory pressure (PEEP) in experimental RDS.

Methods: Preterm rabbits (n = 7-14 per group; 27 days gestation; term 30 days) were randomized for receiving either 100 mg/kg rSP-C or natural bovine surfactant and were compared with saline treated controls. Animals were ventilated for 30 min with either 0.3 or 0 kPa PEEP at standardized tidal volumes and lung mechanics were measured as well as lung histology and mRNA expression of surfactant associated proteins B and C by real-time PCR.

Results: The PEEP level applied (0.3 vs. 0 kPa) largely influenced dynamic compliance after administration of rSP-C surfactant (4.45 vs. 2.58 ml/kg), whereas natural surfactant improved compliance regardless of the PEEP applied (4.86 vs. 4.24 ml/kg) compared to controls (2.41 vs. 1.55 ml/kg). Accordingly, administration of PEEP significantly increased alveolar count in all groups as well as SP-C mRNA expression, whereas SP-B expression and protein content both remained unchanged.

Conclusion: Response to rSP-C surfactant depends on the PEEP level applied in our model of neonatal RDS. These findings should be considered for the conception of clinical trials regarding treatment strategies in neonatal RDS.

A patent ductus arteriosus (PDA) results in increased pulmonary blood flow and redistribution of flow to other organs. Several co-morbidities (i.e., necrotizing enterocolitis, intracranial hemorrhage, pulmonary edema/hemorrhage, bronchopulmonary dysplasia, and retinopathy) are associated with the presence of a PDA, but whether or not a PDA is responsible for their development is still unclear. In this review, comparative physiology between the full term and preterm newborn and the barriers preventing the necessary cascade of events leading to permanent constriction of the PDA are reviewed.

Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.

Background: Recent investigations demonstrating that pseudoglandular-stage airspaces contract spontaneously suggest that the production of contractile proteins by airway wall smooth muscle (ASM) is an important factor in the functional and structural differentiation of ASM.

Aims: Ouraim was to determine if smooth muscle (SM)-myosin heavy chain (MHC) myofilaments, the 'motor' underlying SM contraction, and SM-alpha-actin myofilaments were distributed simultaneously in pseudoglandular-stage human lungs and to further define the nature of fetal airway contractions.

Methods: Immunohistochemically stained sections of fetal lung (14 fetuses, 10.1-17 weeks gestation) were analysed by computer-assisted morphometry to determine airspace dimensions and detect SM-MHC- and SM-alpha-actin-ASM. Lung tissue from the same fetuses was also placed in explant culture to observe airway contractions using videomicroscopy. We found that the smallest airspaces were just as likely to be invested by a layer of SM-MHC-positive ASM as by a layer of SM-alpha-actin-positive ASM. In addition, larger airways or airways from more mature fetal lungs were more likely to be invested by either SM-MHC- or SM-alpha-actin-positive ASM. Spontaneous airspace contractions were peristalsis-like and variable in amplitude. The time interval between contractions was temperature dependent (mean+/-SEM, 44+/-7.5 s at 37 degrees C), shortened by carbachol and increased by nitric oxide (NO)-donating drugs.

Conclusions: These observations suggest that ASM differentiation is characterised by the simultaneous production of SM-alpha-actin and SM-MHC myofilaments and that the presence of these proteins is likely to be responsible for cholinergic- and NO-sensitive spontaneous contractions of fetal human airspaces.

Background: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia.

Objective: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment.

Methods: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24-28 weeks) infants collected every 4 h for up to 10 days.

Results: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 microg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 microg/l, respectively. In 5/8 VLBW infants, urinary S-100B was> microg/l in samples obtained on the first day of life (range 1.2-44.9 microg/l, median 6.8 microg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R(s)=-0.882, p=0.009). Three of the 8 preterm infants had peak urinary concentrations>0 microg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age.

Conclusions: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity.

Based on preliminary studies that contractile efficacy was altered in vertebral and basilar arteries from neonatal donors treated with postnatal glucocorticoids, we examined the hypothesis that postnatal dexamethasone (DEX), a glucocorticoid used for respiratory disease in neonates, can alter vascular reactivity. Using near-term fetal lamb carotids, we measured 5-hydroxytryptamine (5-HT) dose-response relationship in DEX-treated and untreated arteries. We found that DEX incubation for 1 h had no effect on 5-HT sensitivity and agonist affinity but significantly reduced 5-HT contractile efficacy, a response that became even more pronounced after 4 h of DEX treatment. Coincubation of DEX-treated arteries with INDO for 4 h reversed this DEX-induced attenuation in 5-HT contractile efficacy, although DEX had no significant effects on cyclooxygenase (COX)-1 and COX-2 protein abundance. This data suggests that DEX alters vascular reactivity through a COX-related mechanism, with possible repercussions to neurological injury.