Biology of the neonate最新文献

Background: Tumor necrosis factor (TNF) is a central mediator of sepsis. The NcoI polymorphism within the TNF locus has been described as a prognostic marker for mortality in adult patients with sepsis.

Objectives: The aim of our study was to investigate the genotype and allele distribution of 2 TNF gene polymorphisms in preterm infants <32 weeks of gestational age, who developed early-onset sepsis.

Methods: A double-blinded retrospective cohort study was carried out on stored Guthrie blood spot cards with group A including 67 premature infants <32 weeks of gestational age with proven early-onset sepsis and group B including 102 healthy newborn infants (>32 + 0 weeks of gestation). The genotype andallele distribution of the study population were also compared to reference groups of healthy adult volunteers (n = 252 for TNF-beta NcoI and n = 233 for -308 TNF-alpha promoter). Polymorphisms of the TNF-alpha promoter -308 region and the NcoI site of the TNF-beta gene were assessed using PCR followed by melting curve analysis or NcoI digestion. The groups were compared by estimation of Hardy-Weinberg equilibrium.

Results: The overall allele frequency and genotype distribution of the -308 TNF-alpha and NcoI polymorphism of the TNF-beta gene were comparable to the values found in the controls.

Conclusion: The study results suggest that none of the analyzed TNF gene polymorphisms may serve as a prognostic marker for preterm infants at high risk of sepsis.

Surfactant is now standard of care for infants with respiratory distress syndrome. Surfactant treatments are effective because of complex metabolic interactions between surfactant and the preterm lung. The large treatment dose functions as substrate; it is taken up by the preterm lung and is reprocessed and secreted with improved function. The components of the treatment surfactant remain in the preterm lung for days. If lung injury is avoided, then surfactant inhibition is minimized. Prenatal corticosteroids complement surfactant to further enhance lung function. The magic of surfactant therapy results from the multiple interactions between surfactant and the preterm lung.

Background: The medicinal benefits of Echinacea sp. plants in several disease conditions, including insect bites, respiratory ailments, and even cancer and AIDS, have been touted for decades. Echinacea sp.-based phytoceuticals are among the top selling herbals in the Western marketplace today. However, evidence is very scant concerning the effects of using Echinacea species herbals during pregnancy. While available data indicates that fetal malformations do not occur during pregnancy in humans consuming this herb, there are no formal studies aimed at assessing the possibility that consuming Echinacea herbals may promote spontaneous abortions, thereby reducing the number of live births upon which to assess the presence or absence of malformations.

Objectives: We undertook a study in which pregnant mice were fed daily Echinacea purpurea from pregnancy onset until gestational days 10, 11, 12, 13, and 14.

Methods: Maternal spleen and bone marrow were taken for enumeration of cells in each of five separate hemopoietic lineages/organ, and fetal status was recorded.

Results: The data indicate that the significant, pregnancy-induced elevation in splenic lymphocytes and nucleated erythroid cells was all but eliminated in those females which consumed E. purpurea daily throughout their pregnancy. Moreover, consuming E. purpurea during pregnancy reduced the number of viable fetuses.

Conclusions: The data may be extrapolated to suggest that in humans, abstention from consuming Echinacea products during the early/mid stages of pregnancy, may be prudent.

Background: Hyperoxia and tidal volume mechanical ventilation are independent factors in the genesis of lung injury, but it remains unclear the extent to which each is responsible or contributes to this process in newborns.

Objectives: To study the independent and combined effects of hyperoxia and tidal volume mechanical ventilation on the induction of lung inflammation in a newborn piglet model of ventilator-induced lung injury.

Methods: Following exposure to either ambient air or F(I)O2 = 1.0 for a period of 3 days, newborn piglets were randomized to receive mechanical ventilation with either high tidal volume (20 ml/kg) or low tidal volume (6 ml/kg) for 4 h while controlling for pH.

Results: Monocyte chemoattractant protein-1 level in the lungs of animals randomized to hyperoxia with high tidal volume ventilation was significantly elevated, compared to all other groups (p < 0.05). Myeloperoxidase assayed in lung homogenate was found to be significantly higher in nonventilated animals exposed to hyperoxia (p < 0.01). Only in animals previously exposed to hyperoxia did the addition of high tidal volume ventilation further increase the level of myeloperoxidase present (p < 0.05). Pulmonary vascular resistance was significantly elevated after 4 h of mechanical ventilation compared to 1 h (p < 0.001).

Conclusions: We conclude that in neonatal piglets undergoing hyperoxic stress, superimposition of high tidal volume ventilation exacerbates the lung inflammation as assessed by lung monocyte chemoattractant protein-1 and level of myeloperoxidase.

Background: The closing mechanisms of the ductus venosus (DV) have not yet been revealed.

Objectives: The aims of this study were to document the perinatal closing process of the DV, to study the suppression of prostaglandins by indomethacin, and to determine the effects of umbilical blood flow to the fetal DV.

Methods: The proximal and distal DV diameters were studied in near-term fetal and neonatal rats with the rapid whole-body freezing method.

Results: The DV diameter changed sensitively at birth, and decreased by 10% immediately after the cessation of the umbilical circulation. Umbilical hemorrhage caused an additional decrease in the DV diameter compared with neonate without the hemorrhage. The neonates showed a DV diameter decreased by 20% at 30 min and 30% at 60 min after birth. The fetal DV was tubular, and the neonatal DV was horn-shaped with a smaller inlet than outlet. A small dose (0.1 mg/kg) of indomethacin administered to the pregnant rats induced a reduction in prostaglandins and decreased the fetal DV diameter to 80% of the control. Indomethacin at a large dose (10 mg/kg), administered to the dams, induced a reduction in prostaglandins, severe constriction of the ductus arteriosus, and decreased blood flow through the descending aorta umbilicus, and caused a further reduction in the DV diameter to 70-80% of the control. A large dose of nifedipine (10 mg/kg), which causes cardiac suppression and heart failure in the fetus, was administered to near-term rats to study the effect of decreased fetal cardiac output and blood flow passing through the DV. Nifedipine induced a 20% decrease in the DV diameter for 2-8 h. In all 1-hour-old neonates with or without pretreatment, the inlet diameter of the DV was reduced more than the outlet diameter, and the DV showed a horn-shaped morphology.

Conclusion: In conclusion, perinatal cessation of the umbilical circulation and umbilical hemorrhage are associated with an immediate decrease in DV diameter. The DV diameter is also reduced in other conditions associated with decreased umbilical blood flow, such as induced by nifedipine which leads to heart failure and constricting of the ductus arteriosus induced by indomethacin. The constricting effect of a small dose of indomethacin suggests that prostaglandins dilate the DV physiologically.

Background: Mechanical ventilation results in acute lung trauma that can stimulate processes that alter lung development. Activation of matrix metalloproteinases (MMPs) and their tissue-produced inhibitors (TIMPs) is initiated by the inflammatory response to mechanical ventilation and are involved in breakdown of the basement membrane and parenchymal modeling.

Objectives: The aim of this study was to test the hypothesis that rhCC10, a lung anti-inflammatory mediator, would foster improved lung function, structural preservation, and a reduction in net MMP activity in a juvenile model of acute lung injury.

Methods: Twenty-four juvenile rabbits were saline-lavage-injured and treated with 100 or 25 mg/kg surfactant (Survanta, Ross Labs) with or without rhCC10 (Claragen, Inc.; n=6 per group). Animals were ventilated for 4 h, then euthanized for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, MMP-7, and MMP-9 and TIMPs 1 and 2 in the lung.

Results: Apical lung expansion, reduced with the lower dose of surfactant, was partially restored with the addition of rhCC10. Alveolar septal wall thickness was reduced (p<0.05) with low-dose surfactant plus rhCC10 compared to high-dose surfactant alone. Increased within-group variance in MMP-2 and MMP-9 proteolytic activity was found with the low-dose surfactant and was abolished with rhCC10. MMP-7 was reduced (p<0.05) with rhCC10 administration, independent of surfactant dose.

Conclusions: Intratracheal administration of the anti-inflammatory rhCC10 resulted in preserved lung structure and MMP/TIMP profile after 4 h of mechanical ventilation, in a surfactant dose-dependent manner.

Background: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment.

Objective: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34(pos) cells, either cultured alone or in conjunction with CD34(neg) light density mononuclear cells (LDMCs).

Methods: CD34(pos) cells and CD34(neg) LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34(pos) cells were obtained from healthy adults. CD34(pos) cells were then cultured alone or co-cultured with CD34(neg) LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10-12 days. Mk colonies were then quantified following immunohistochemical staining.

Results: Pure CD34(pos) cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O(2) concentrations.

Conclusions: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34(pos) cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.

Background: Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants.

Methods: A prospective study included 125 infants with gestational age 23-29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late.

Results: Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH.

Conclusions: These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.

Objectives: We investigated the effect of human growth hormone (GH) on newborn rat brain superoxide dismutase, glutathione and malondialdehyde (MDA) levels in hypoxic-ischemic (H-I) newborn rats.

Methods: Fourty-eight 7 days old newborn rats were randomized to a healthy (n: 15), H-I (n: 18) and GH administered H-I (GH-H-I, n: 15) group. Permanent, left common carotid ligation was performed in the H-I groups. In the GH-H-I group, 50 mg/kg human GH (Norditropin Simplex, Novo Nordisk A/S) was administered subcutaneously just before carotid artery ligation. Two hours after ligation, rats were subjected to 2 h of hypoxemia and then were decapitated. Right and left cerebral hemispheres (CHs) and cerebellum-brain stem (C-BS) were separated.

Results: Glutathione levels of each region were not statistically different from each other in and between the groups. Superoxide dismutase levels were higher in C-BSs compared to CHs (for each comparison p < 0.01). CHs and C-BS MDA levels were similar in the control and H-I groups but MDA levels of both CHs of the GH-H-I group were significantly higher than the levels of the H-I group (p = 0.01; p = 0.024, respectively). Left CH MDA level of GH-H-I group was higher compared to left CH MDA of the control group (p = 0.045) while there was no difference between right CHs. In the GH-H-I group, left CH MDA level was higher than the C-BS (p = 0.03). MDA levels of the C-BSs did not differ between the groups (p > 0.05).

Conclusion: Although we have not evaluated the effect of GH histopathologically, increased lipid peroxidation especially in the H-I (left) hemisphere of the GH treated rats might suggest that GH treatment may be harmful in H-I encephalopathy.