Biology of the neonate最新文献

Background: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is crucial to cell-migration, proliferation, apoptosis and remodeling of tissues, with a potential role in pathobiology of pulmonary hypertension. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial to the integrity of the extracellular matrix. TN-C and MMPs are counter-regulatory molecules, which influence the vascular integrity through modulations of elastin. We have a murine model of pulmonary hypoplasia with coexistent diaphragmatic hernia, vascular abnormalities and excessive arterial smooth muscle cell (SMC) proliferation.

Objectives: Our objective was to investigate modulations of TN-C and MMPs in hypoplastic lungs and their possible contribution to the observed pulmonary vascular abnormalities.

Methods: We addressed our objectives by pursing immunoblotting and immunohistochemistry and zymography/reverse zymography to assess the alterations in activities of MMPs and their inhibitors.

Results: We observed significant down-regulation of MMP-9 activity in hypoplastic lungs at the later fetal developmental stages, whereas MMP-2 activity assessed by gelatin zymography remained unaltered. Reverse zymography revealed up-regulation of activities of TIMP-1, -2, -3 and -4 in hypoplastic lungs during later fetal development, with pronounced increases in TIMP-3 and -4 activities. Furthermore, immunoblot analyses and immunohistochemistry revealed that TN-C protein was down-regulated in developing hypoplastic lungs, compared to normal lungs.

Conclusions: (1)TN-C is known to inhibit vascular SMC proliferation. But, decrease in TN-C in hypoplastic lungs may support the observed arterial SMC proliferation. (2) Our studies showed that in hypoplastic lungs the SMC apoptosis is not affected, thus suggesting that SMC proliferation and apoptosis may be two separate processes in pulmonary hypoplasia with coexistent diaphragmatic hernia. Together, our data showed an imbalance in the extracellular matrix proteins, which may contribute to the pulmonary vascular abnormalities.

Background: Elevated blood lactate levels are common in the critically ill neonate; however, sometimes they are difficult to interpret. Persistent or recurrent lactic acidemia might point to an inborn error of metabolism, like disturbances of the oxidative phosphorylation. Chronic lactic acidemia results in increased serum alanine levels. Serum alanine levels in newborns with transient lactic acidemia have not yet been studied.

Objective: We designed a pilot study to evaluate the use of serum alanine levels as an additional metabolic marker to differentiate the transient effect of circulatory failure from a possible mitochondrial dysfunction.

Methods: We prospectively evaluated 10 newborns with transient lactic acidemia after mild dysoxia, and 10 newborns with recurrent lactic acidemia consecutively diagnosed with a disorder in oxidative phosphorylation.

Results: No significant serum alanine level elevation was found in transient lactic acidemia. Increased serum alanine was a sensitive marker in mitochondrial dysfunction.

Conclusions: We propose to measure the serum alanine level in hypotonic newborns with lactic acidemia to facilitate the decision making in further diagnostics and management.

Background: Advances in neonatal intensive care have led to an increased survival of very low birth weight (VLBW, <1,500 g) and extremely low birth weight infants (ELBW, <1,000 g). Several abnormalities may occur in these children, e.g. esophageal atresia (EA), imperforate anus or abdominal wall defects. Correction of EA is often performed as a staged procedure in this group of patients.

Objectives: To evaluate the feasibility of a primary correction of EA in 4 ELBW and VLBW infants.

Methods: Between 2002 and 2004, 4 infants below 1,200 g were operated on in our institution with a diagnosis of EA with lower tracheoesophageal fistula. Birth weight ranged from 780 to 1,120 g (median: 920 g), gestational age from 28 to 30 weeks. Treatment included closure of the tracheoesophageal fistula and primary anastomosis of the esophagus in a one-step procedure.

Results: Primary correction of EA and fistula repair was feasible in all children. Initially, all children had a normal passage of the esophagus as observed in barium swallowing. One child suffering from a leakage of the anastomosis was managed conservatively. Another infant suffered from spontaneous small bowel perforation 6 days after surgery, which was treated by laparotomy. One child developed stenosis of the esophagus and required a single dilatation 14 months after initial treatment. In the 4th child, a type II cleft syndrome was subsequently diagnosed, requiring secondary cleft repair together with semifundoplication. This child eventually died from cytomegalovirus pneumonia.

Conclusions: Primary repair of EA and closure of a tracheoesophageal fistula is technically feasible and offers a good treatment option for ELBW and VLBW infants. Staged repair can be avoided. Infants with cleft syndrome are still a diagnostic and therapeutic challenge.

Objective: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH.

Material and methods: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to normal CSF samples. The IVH group (n = 21, group III) consisted of neonates who had been diagnosed by cranial ultrasonography or computed tomography scans. Data are presented as median (range).

Results: There was no significant difference between groups with respect to serum UA levels. While no significant difference was observed between CSF UA levels of the control [0.6 (0.1-1.8) mg/dl] and traumatic tap group [0.5 (0.3-1.1) mg/dl], the IVH group [1.6 (0.7-6.9) mg/dl] was found to have significantly higher CSF UA levels than groups I and II. Furthermore, although there were significant correlations between serum and CSF UA levels in the control and traumatic tap groups, no correlation was observed in the IVH group.

Conclusion: CSF UA levels are increased in neonates with IVH and they may be used to differentiate a real hemorrhage from a traumatic tap.

Insulin-like growth factor (IGF)-I is a polypeptide that mediates the growth-promoting action of growth hormone in postnatal animals. The present study was conducted to examine whether orally administered IGF-I would be absorbed into the general circulation and also whether ingested IGF-I would enhance the growth of whole body as well as internal organs, and tissues in 3-week-old ICR-strain female weanling mice. In experiment (Exp) 1, a total of 70 mice received IGF-I orally at 1 microg.g-1 in 0.2-ml PBS or the vehicle alone. Concentrations of IGF-I and glucose in heart blood were measured after killing 5 animals in each group every fourth hour during a 24-hour period. In Exp 2, a total of 40 mice received oral IGF-I administration at 1 microg.g-1 or vehicle every third day beginning from day 0 for a 13-day period. Half the animals were killed at day 7 and the other half at day 13. Weights of whole body and organs/tissues (small intestine, liver, thigh muscle, and brain) were measured every day and at slaughter, respectively. In Exp 1, following the oral IGF-I administration, serum IGF-I concentration increased at hour 4 (p<0.01) and returned to the hour 0 level by hour 8, whereas glucose concentration was lowest at hour 4 and returned to the hour 0 level by hour 16. In the PBS-fed group, neither IGF-I nor glucose concentration changed during the 24-hour period. In Exp 2, weight of small intestine increased (p<0.05) in response to the oral IGF-I, whereas weights of liver and thigh muscle of the IGF-I-fed group were greater (p<0.01) and tended to be greater (p=0.06), respectively, than those of the PBS-fed only at day 13. However, brain weight and serum concentrations of IGF-I and IGF-II were not affected by oral IGF-I administration. Results suggest that although orally administered IGF-I mainly acts at the intestine, a portion of ingested IGF-I is absorbed into the general circulation to enhance the growth of selective organs/tissues in weanling mice.

Background: This study aimed to evaluate the diagnostic utilities of monocyte HLA-DR as an infection marker in the identification of early-onset clinical infection and pneumonia in newborn infants.

Methods: Term newborns in whom infection was suspected when they were <72 h of age were eligible for enrollment in the study. C-reactive protein (CRP), monocyte HLA-DR and neutrophil CD64 expressions were quantitatively measured at the time of sepsis evaluation (0 h) and 24 h afterwards by flow cytometry and standard laboratory method.

Results: A total of 288 infants with suspected sepsis were investigated, and 93 were found to be clinically infected. There were no significant differences in monocyte HLA-DR expression between the infected, non-infected and control groups at 0 h (median (interquartile range): 13,986 (10,994-18,544), 14,234 (12,045-17,474) and 18,441 (14,250-21,537) antibody phycoerythrin (PE) molecules bound/cell), and between infected and non-infected infants at 24 h (median (interquartile range): 17,772 (12,933-25,167) and 19,406 (14,885-24,225) antibody PE molecules bound/cell). The areas under the receiver operating characteristics (ROC) curves for HLA-DR, CD64 and CRP were 0.52-0.54, 0.88-0.94 and 0.75-0.77, respectively. We were unable to determine an optimal cutoff value for HLA-DR, as the diagnostic utilities of any cutoff point on the ROC curves were unable to satisfy the criteria (i.e. sensitivity and specificity >or=80%) for consideration as an useful diagnostic marker of infection.

Conclusions: Our findings did not support the use of monocyte HLA-DR alone or in combination with other infection markers in the diagnosis of early-onset clinical infection and pneumonia in term newborns.

The human lung is born with a fraction of the adult complement of alveoli. The postnatal stages of human lung development comprise an alveolar stage, a stage of microvascular maturation, and very likely a stage of late alveolarization. The characteristic structural features of the alveolar stage are well known; they are very alike in human and rat lungs. The bases for alveolar formation are represented by immature inter-airspace walls with two capillary layers with a central sheet of connective tissue. Interalveolar septa are formed by folding up of one of the two capillary layers. In the alveolar stage, alveolar formation occurs rapidly and is typically very conspicuous in both species; it has therefore been termed 'bulk alveolarization'. During and after alveolarization the septa with double capillary networks are restructured to the mature form with a single network. This happens in the stage of microvascular maturation. After these steps the lung proceeds to a phase of growth during which capillary growth by intussusception plays an important role in supporting gas exchange. In view of reports that alveoli are added after the stage of microvascular maturation, the question arises whether the present concept of alveolar formation needs revision. On the basis of morphological and experimental findings we can state that mature lungs contain all the features needed for 'late alveolarization' by the classical septation process. Because of the high plasticity of the lung tissues, late alveolarization or some forms of compensatory alveolar formation may be considered for the human lung.

Background: Partial liquid ventilation (PLV) with perfluorochemical (PFC) has been advocated as a new therapy for acute respiratory distress syndrome in both clinical and animal studies, meconium aspiration syndrome, and RDS. PFC is referred to as liquid PEEP because it gets distributed to the most gravity-dependent regions of the lung due to its density. High-frequency oscillation (HFO) has been shown to prevent both acute and chronic lung injury in the management of very low birth weight infants with RDS, with gentle ventilation approach. Specifically, HFO with aggressive and adequate lung volume recruitment has been shown to reduce the incidence of chronic lung disease in very low birth weight infants. We hypothesized that PLV along with HFO might be effective in ARDS in an adult rabbit model.

Objectives: To examine the efficiency of low-dose PLV with with HFO on pulmonary gas exchange and lung compliance in a surfactant-depleted rabbit model.

Methods: After induction of severe lung injury by repeated saline lung lavage, 19 adult white Japanese rabbits were randomized into two groups that received PLV with HFO (n=9) or HFO gas ventilation (n=10). Physiological and blood gas data were compared between the two groups by analysis of variance.

Results: The HFO-PLV group showed improved total lung compliance with maintenance of significantly lower mean airway pressure as compared with the HFO-GAS group so as to keep SpO2>90%.

Conclusions: The addition of a low dose of PFC with HFO was effective in achieving adequate oxygenation, with a reduction in further lung injury in neonates.