摘要:

Surfactant proteins (SPs) play an important role in surfactant metabolism and function. Understanding their relative contribution to clinical outcome remains incomplete. Exogenous surfactants differ in their SP content and physiologic effects. The aims of this study were to measure bronchoalveolar lavage (BAL) SP concentrations from preterm infants ventilated for respiratory distress syndrome and to assess their association with clinical outcome. Fifty preterm infants randomized to receive a natural or synthetic surfactant were lavaged each day for the first week and twice weekly thereafter using a standardized nonbronchoscopic technique. BAL SP-A, SP-B, and SP-D concentrations were measured using ELISA. Median BAL SP-A, SP-B, and SP-D concentrations for the whole cohort rose significantly during the first postnatal week (p< 0.05). SP-A concentration did not differ between outcome groups. BAL SP-B concentration rose significantly in lungs that were not supplemented with SP-B. Infants dying had significantly lower BAL SP-B concentrations on d 2 and 6 compared with survivors. BAL SP-D concentrations were significantly lower on d 2 and 3 among infants in supplemental oxygen on d 28 compared with those in air. BAL SP-A and SP-D concentrations did not differ significantly between infants randomized to receive a natural or synthetic surfactant. Lower BAL SP-B and SP-D but not SP-A concentrations were associated with worse clinical prognosis.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Surfactant replacement is an effective therapy for neonatal respiratory distress syndrome. Full recovery from respiratory distress syndrome requires development of endogenous surfactant synthesis and metabolism. The influence of exogenous surfactant on the development of surfactant synthesis in premature lungs is not known. We hypothesized that different exogenous surfactants have different effects on the development of endogenous surfactant production in the premature lung. We treated organ cultures of d 25 fetal rabbit lung for 3 d with 100 mg/kg body weight of natural rabbit surfactant, Survanta, and Exosurf and measured their effects on the development of surfactant synthesis. Additional experiments tested how these surfactants and Curosurf affected surfactant protein (SP) SP-A, SP-B, and SP-C mRNA expression. Surfactant synthesis was measured as the incorporation of3H-choline and14C-glycerol into disaturated phosphatidylcholine recovered from lamellar bodies. Randomized-block ANOVA showed significant differences among treatments for incorporation of both labels (p< 0.01), with natural rabbit surfactant less than control, Survanta greater than control, and Exosurf unchanged. Additional experiments with natural rabbit surfactant alone showed no significant effects in doses up to 1000 mg/kg. Survanta stimulated disaturated phosphatidylcholine synthesis (173 ± 41% of control;p= 0.01), increased total lamellar body disaturated phosphatidylcholine by 22% (p< 0.05), and increased14C-disat-PC specific activity by 35% (p< 0.05). The response to Survanta was dose-dependent up to 1000 mg/kg. Survanta did not affect surfactant release. No surfactant altered the expression of mRNA for SP-A, SP-B, or SP-C. We conclude that surfactant replacement therapy can enhance the maturation of surfactant synthesis, but this potential benefit differs with different surfactant preparations.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Proinflammatory stimulation resulting from intraamniotic endotoxin improves lung function, increases surfactant protein mRNA expression and protein content, increases alveolar and lung saturated phosphatidylcholine pools, and accelerates lung morphometric maturation in fetal sheep. The mechanism for induction of lung maturation does not involve an increase in fetal cortisol. The effect of endotoxin on the maturation of a different lung system, the antioxidant enzyme (AOE) system, has not been examined. Therefore, we hypothesized that intraamniotic endotoxin would produce acceleration of AOE activity in fetal sheep at similar doses and schedule of administration to those producing lung functional and surfactant maturation. In a dose-response study, intraamniotic injections of 1, 4, 20, or 100 mg ofEscherichia coli055:&bgr;5 endotoxin were administered 7 d before preterm delivery of sheep at 125 d gestation. In a study examining time interval of administration before delivery, 20 mg of endotoxin was injected at either 1-, 2-, 4-, 7-, or 15-d intervals before preterm delivery at 125 d. Doses of 1–100 mg of endotoxin produced significant increases in glutathione peroxidase activity; doses of 4–100 mg significantly increased catalase activity, whereas doses of 20–100 mg resulted in significant increases in total superoxide dismutase activity. Glutathione peroxidase activity was elevated within 2 d, whereas superoxide dismutase was increased by 4 d and catalase activity increased by 7 d after endotoxin. No AOE increases were sustained for 15 d. Endotoxin increased fetal lung AOE activity at similar dosing amounts and intervals to those producing maturation of lung function and surfactant. Thus, mechanisms involving proinflammatory stimulation, unrelated to glucocorticoid hormones, can induce maturation of the AOE system of the fetal lung.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Determining total energy expenditure (TEE) and its components in children treated with home parenteral nutrition (CHPN) under free-living conditions is an important consideration in the assessment of energy requirements and the maintenance of health. The aim of this study was to assess TEE and physical activity in CHPN. Eleven CHPN (three girls and eight boys; median age, 6.0 y; range, 4.5–15.0 y) were compared with 11 healthy children (three girls and eight boys; median age, 6.0 y, range, 4.5–14.0 y) after pairing for sex, age, and weight. Underlying diseases included chronic intractable diarrhea (n= 5), short bowel syndrome (n= 3), and intestinal dysmotility (n= 3). None of these children had inflammatory disease or recent infection when studied. Fat-free mass (FFM), measured by body impedance analysis, fat mass (FM), measured by skinfold thickness, and energy intake were similar between the two groups, suggesting that CHPN had normal body composition and energy intake. Resting energy expenditure (REE), measured by indirect calorimetry, and TEE, assessed by a technique using 24-h heart-rate monitoring calibrated against indirect calorimetry and physical activity using a triaxial accelerometer, were simultaneously recorded and were also similar in the two groups. Sleeping energy expenditure (SEE), expressed per kilogram of FFM, was significantly greater in the CHPN group (median, 0.15; range, 0.10–0.23 kJ/min/kg FFMversusmedian, 0.12; range, 0.09–0.21 kJ/min/kg FFM for controls;p< 0.05, Wilcoxon rank test). These findings were explained by the high correlation between the energy flow infused by parenteral nutrition and sleeping energy expenditure (p< 0.05, Spearman test) and also-diet induced thermogenesis (p< 0.05 Spearman test). These results suggest that the energy requirements of children on long-term home parenteral nutrition programs do not differ from controls and that cyclic parenteral nutrition does not interfere with physical activity.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Prematurity is associated with delayed postnatal activation of mitochondrial oxidative phosphorylation and impaired switch from glycolytic to oxidative metabolism. Fatty acids (FA), which represent a major energy substrate in mature muscle cells, are engaged in the postnatal activation of genes of energy metabolism and lipid oxidation. To understand the mechanism activating mitochondria in human newborns, expression of the genes for mitochondrial uncoupling proteins (UCP) was characterized in autopsy samples of skeletal (n= 28) and cardiac (n= 13) muscles of preterm neonates, who mostly died during the first postnatal month, and two aborted fetuses. Transcripts levels for UCP2, UCP3, and also for genes engaged in the transport of FA between cytoplasm and mitochondria were measured using real-time reverse transcriptase PCR. In accordance with studies in mice, our results document postnatal induction of UCP3 gene expression in skeletal muscle, involvement of nutritional FA in the induction, and a role of UCP3 in mitochondrial FA oxidation. They suggest impaired postnatal activation of UCP3 gene in neonates delivered before approximately 26 wk of gestation. Mean levels of the UCP3 transcript in skeletal muscle were by two orders of magnitude higher than in the heart. In contrast to UCP3, the UCP2 gene was active in fetuses, and its expression was not affected by nutrition. Our results support a role of UCP3 in postnatal activation of lipid oxidation in skeletal muscle and suggest the involvement of UCP3 in the delayed activation of mitochondrial energy conversion in very immature preterm neonates.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated byEscherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring.

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2003

数据来源: OVID