ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Arachidonic acid (AA) is a long-chain polyunsaturate (LCP) present in human breast milk as both triglyceride (TG) and as phospholipid (PL). There has been little attention to the metabolic consequences of lipid form of AA in infant formulas. Our objective was to investigate the efficacy of dietary TG and PL as carriers of AA for accretion in the brain and associated organs of term baboon neonates consuming a formula with LCP composition typical of human milk. TG and phosphatidylcholine (PC) with [U-13C]-AA in the sn-2 position and with unlabeled 16:0 in the remaining positions (TG-AA* or PL-AA*, respectively) were used as tracers to study the tissue AA* incorporation. Baboon neonates received a single oral dose of either TG-AA* (n= 3) or PL-AA* (n= 4) at 18–19 d of life. Tissues were obtained 10 d later (28–29 d of life) and isotopic enrichment was measured. In the brain, 4.5% of the PL-AA* dose and 2.1% of the TG-AA* dose were recovered as brain AA*, respectively, indicating that PL was about 2.1-fold more effective than TG as a substrate for brain AA accretion. Preferential incorporation of PL-derived AA* over TG source of AA* was also observed in the liver, lung, plasma, and erythrocytes. Because of the quantitative predominance of TG-AA in formula, total brain AA accretion, expressed as absolute weight, was 5.0-fold greater from TG-AA than from PL-AA. We estimate that about half of postnatal brain AA accretion is derived from dietary preformed AA in term baboon neonates consuming a formula with lipid composition similar to that of human milk.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly concentrated in CNS tissues. Although breast milk contains the fatty acids DHA and arachidonic acid, infant formulas marketed in North America do not contain these nutrients. The potential deleterious effects of rearing infants with formulas devoid of these nutrients was assessed by comparing nursery-reared rhesus macaque infants (Macaca mulatta) fed standard formula with infants fed standard formula supplemented with physiologically relevant concentrations of DHA (1.0%) and arachidonic acid (1.0%). Neurobehavioral assessments were conducted on d 7, 14, 21, and 30 of life using blinded raters. The 30-min assessment consisted of 45 test items measuring orienting, temperament, reflex capabilities, and motor skills. Plasma concentrations of DHA in standard formula-fed infants were significantly lower than those fed supplemented formula or mother-raised (breast-fed) infants; however, infants fed the supplemented formula exhibited higher arachidonic acid levels than either mother-reared infants or infants fed standard formula. Infant monkeys fed the supplemented formula exhibited stronger orienting and motor skills than infants fed the standard formula, with the differences most pronounced during d 7 and 14. This pattern suggests an earlier maturation of specific visual and motor abilities in the supplemented infants. Supplementation did not affect measures of activity or state control, indicating no effect on temperament. These data support the assertion that preformed DHA and arachidonic acid in infant formulas are required for optimal development.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The primary objective of this study was to determine whether exogenous arachidonic acid (AA) in a supplemented formula substitute for piglets or sow milk would attenuate reductions in AA status, growth, and bone mineral content (BMC) as a result of exogenous glucocorticoid excess using dexamethasone (DEX). A secondary objective was to confirm a positive effect of exogenous AA on growth and BMC of piglets fed formula and not treated with DEX as well as to determine whether the elevation in BMC was related to greater production of prostaglandin E2in bone. Forty-eight 5-d-old male piglets were randomized to be suckled or receive either a standard formula or the same formula, but containing AA (0.5% wt/wt total fat) for 15 d in addition to either treatment with DEX or placebo. Piglets treated with DEX grew slower and had lower BMC of whole body, lumbar spine, and femur in addition to lower proportions of AA, but those fed standard formula had the greatest reductions. Piglets in the supplemented group weighed more than piglets fed standard formula or suckled in both the DEX and placebo groups. Suckled piglets had the highest BMC of whole body and femur compared with standard formula, and the supplemented group was intermediate for whole body but similar to suckled pigs for femur. Release of prostaglandin E2was elevated only with supplementation of AA. These data indicate that supplemental AA is associated with elevated whole body and femur BMC but that BMC is not enhanced during glucocorticoid treatment.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Infections withCandida albicanshave become a significant problem among very low birth weight infants in the neonatal intensive care unit. Risk factors are multiple and include administration of antibiotics and glucocorticoids, such as dexamethasone. Experiments were designed to study the combined effect of oral broad-spectrum antibiotics and parenteral dexamethasone on cecal colonization and extraintestinal dissemination ofC. albicansin separate groups of mice that were orally inoculated with one of fourC. albicansstrains that were either wild-typeINT1/INT1or had one or more disruptions of theINT1gene. Intestinal colonization was monitored by quantitative culture of the mouse cecum, and extraintestinal invasion was monitored by quantitative culture of the draining mesenteric lymph nodes and kidneys. At sacrifice, the average numbers of cecalC. albicansdiffered from 7.7 log10/g to 6.7 log10/g (p< 0.01) in mice orally inoculated withC. albicanscontaining two functional copies ofINT1and no functional copies ofINT1, respectively. The incidence of extraintestinal dissemination to mesenteric lymph nodes and kidneys correspondingly varied from 57 to 13% (p< 0.01) and 83 to 4% (p< 0.01) in mice inoculated with these twoC. albicansstrains. Mice orally inoculated withC. albicanscontaining one functional copy ofINT1had intermediate levels of cecal colonization and extraintestinal dissemination. Thus, cecal colonization and extraintestinal dissemination ofC. albicanswas facilitated in antibiotic-treated mice given dexamethasone. In addition, the presence of two functional copies of theINT1gene was associated with the greatest levels of cecal colonization and extraintestinal dissemination ofC. albicans.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This study aims to evaluate the diagnostic utilities of four leukocyte surface antigens—two lymphocyte antigens (CD25 and CD45RO) and two neutrophil antigens (CD11b and CD64)—for identification of late-onset nosocomial bacterial infection in preterm, very low birthweight infants, and to define the optimal cutoff value for each marker so that it may act as a reference with which future studies can be compared. Very low birthweight infants in whom infection was suspected when they were >72 h of age were eligible for the study. A full sepsis screen was performed in each episode. IL-6, C-reactive protein, and leukocyte surface antigens (CD25, CD45RO, CD11b, and CD64) were measured at 0 (at the time of sepsis evaluation), 24, and 48 h by standard biochemical methods and quantitative flow cytometric analysis. The diagnostic utilities including sensitivity, specificity, and positive and negative predictive values of each marker and combination of markers for predicting late-onset neonatal infection were determined. One hundred twenty-seven episodes of suspected clinical sepsis were investigated in 80 infants. Thirty-seven episodes were proven infection. The calculated optimal cutoff values for CD25, CD45RO, CD11b, and CD64 were 3,100, 2,900, 10,450, and 4,000 phycoerythrin-molecules bound per cell, respectively. An interim analysis of data after 68 episodes suggested that CD25 and CD45RO were poor predictors of neonatal infection with sensitivity or specificity <75% during a single measurement. Thus, these two markers were excluded from further investigation. In the final analysis, CD64 has the highest sensitivity (95–97%) and negative predictive value (97–99%) at 0 and 24 h after the onset. The addition of IL-6 or C-reactive protein (0 h) to CD64 (24 h) further enhanced the sensitivity and negative predictive value to 100%, and has the specificity and positive predictive value exceeding 88% and 80%, respectively. Neutrophil CD64 expression is a very sensitive marker for diagnosing late-onset nosocomial infection in very low birthweight infants. If further validated, the use of CD64 as an infection marker should allow early discontinuation of antibiotic treatment at 24 h without waiting for the definitive microbiologic culture results. The quantitative flow cytometric analysis applied in this study could be developed into a routine clinical test with high comparability and reproducibility across different laboratories.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Neonatal bacterial sepsis is often characterized by a fulminant clinical course and highly elevated plasma levels of proinflammatory cytokines. To evaluatein vitroactivation of the neonatal immune system by specific infectious stimuli, cord blood cells from healthy neonates were examined for expression of tumor necrosis factor-&agr; (TNF-&agr;), IL-1&bgr;, IL-6, and IL-8 in response toStreptococcus agalactiae(GBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). Cytokine-expression was compared in mononuclear cells from cord and adult peripheral blood. TNF-&agr; and IL-6 levels in the supernatant of cord blood cell cultures were significantly higher after stimulation with heat-killed GBS (107/mL) than with LPS (2 &mgr;g/mL) or LTA (2 &mgr;g/mL) (TNF-&agr;: 2215versus267.5versus40 pg/mL,p= 0.001; IL-6: 9667versus4909versus919 pg/mL,p= 0.006). mRNA expression of TNF-&agr;, IL-1&bgr;, IL-6, and IL-8 was equally pronounced after stimulation with either GBS, LPS, or LTA in cord or adult blood cells at various times. A MAb directed against the monocyte receptor molecule CD14 did not inhibit the release of cytokines in cord blood mononuclear cells after stimulation with GBS. In summary, activation of cord blood cells by infectious stimuli is comparable to the adult immune response in terms of expression of proinflammatory cytokines. GBS in particular proves to be a potent activator of the neonatal immune system when compared with LPS and LTA. CD14 seems not to be a crucial molecule for activation of cord blood cells by GBS.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25–31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1&bgr;, and tumor necrosis factor-&agr; were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 ± 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p< 0.001), IL-1&bgr; (p= 0.035), and heart rate (p= 0.027); and with decreased mean and diastolic blood pressure (p= 0.026 andp= 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p= 0.028) in infants with fetal vessel inflammation. Maternal temperature ≥38.0°C and newborn immature-to-total white blood cell ratio ≥0.4 were associated with significant decreases in left ventricular fractional shortening (p= 0.001 andp= 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

There is growing evidence that sepsis-related complications in neonates are crucially mediated by the action of proinflammatory cytokines. It has previously been demonstrated that elevated IL-6 and IL-8 levels can predict brain damage and chronic lung disease in preterm infants. However, it is the current view that neonates have a reduced capability to produce proinflammatory cytokines. To clarify this issue, we analyzed the inflammatory response in term and preterm infants directly at the single cell level by flow cytometry. Endotoxin challenge was performed under defined conditions on monocytes obtained from 50 healthy adults and 119 neonates, which consist of 45 term infants, 63 preterm infants (26.1–36.7 wk of gestational age), and 11 preterm infants with proven infection (24.6–29.9 wk). Our results challenge the existing view of an immature inflammatory response by demonstrating that term infants and preterm infants display a higher percentage of IL-6– and IL-8–positive cells than adults. After preincubation with dexamethasone the number of cytokine-positive cells decreased in all groups, but the number of IL-8–positive cells remained higher in term and preterm infants >32 wk compared with adults. These observations demonstrate not only a well-developed but also an enhanced inflammatory response in term and preterm infants. Under consideration of several detrimental effects of IL-6 and IL-8, our data may have major implications on the pathophysiology of inflammatory-triggered neonatal diseases.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of Silver-Russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID