ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen,n= 12), cow milk-based formula (low cholesterol, low phytoestrogen,n= 8), soy milk-based formula (zero cholesterol, high phytoestrogen,n= 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen,n= 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 ± 0.38), highest in soy milk-based formula (9.40 ± 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 ± 0.48 and 8.03 ± 0.28, respectively),p< 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula,p< 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Myo-inositol transport and metabolism were studied in cultured human skin fibroblasts exposed to potentially toxic levels of glucose or galactose. Although variable among 11 different cell lines, themyo-inositol level in confluent cells, ranging from 10–50 nmol/mg protein, was constant with passage. A high-affinity transport system for myo-inositol had an apparent K, of 55 μM and Vmaxof 16 pmol/min/mg protein. No obvious relationship existed between cellular levels and transport capacity. Dependency on sodium was complex. When medium sodium was lowered to 23 mM,myo-inositol uptake ceased after about 1 h. However, the initial rate ofmyo-inositol uptake only showed a sodium dependence at lowmyo-inositol concentrations. Both phloretin and phloridzin inhibitedmyo-inositol uptake. Phloridzin had a K1of 60 μM, and phloretin was either a noncompetitive or uncompetitive inhibitor. Glucose and galactose were only weak competitive inhibitors, with a K1of 30 mM and 65 mM, respectively. After 24 h of incubation withmyo-[2-3H]inositol, only 10% of the total cell label was incorporated into phospholipid. Compared with control media with 5 mM glucose, the incubation of confluent cells in media with 20 mM glucose had little effect on intracellular glucose and sorbitol, whereas cells incubated in control media supplemented with 5 mM galactose showed a large increase in galactose and polyol levels. In media with more than 200 μM ofmyo-inositol, neither treatment had an effect on wyo-inositol levels after 24 h. The uptake and incorporation of 11 μMmyo-[2-3H]inositol and incorporation into phospholipid were studied after cells had been previously exposed for 24 to 48 h to media supplemented with 15 mM glucose or galactose. Compared with controls, fibroblasts with a 24-h exposure to 20 mM glucose showed a 10% decrease inmyo-inositol uptake. When the exposure was extended to 48 h, preconditioning with galactose as well as glucose elicited the same 10% reduction in uptake. Phosphoinositide labeling in fibroblasts exposed to 20 mM glucose was reduced in parallel. These cells offer a unique opportunity for the study of sugar toxicity in human tissue: they can be exposed to high levels of glucose without significant glucose or polyol accumulation or can be made to accumulate polyol by exposure to moderate levels of galactose. The expression of a hexose-induced reduction inmyo-inositol transport required 24 to 48 h of exposure of the fibroblasts to elevated concentrations of glucose or galactose and may not be related to a competitive inhibitory effect of these sugars on transport.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The purpose of this study was to test the hypothesis that a high lactate signal and a lowN-acetyl-aspartate/choline ratio in neonates with postasphyxial encephalopathy indicated a high chance of an adverse outcomein vivowhen proton magnetic resonance spectroscopy was used. Twenty-one full-term asphyxiated neonates were examined at a mean postnatal age of 7.1 d. Five patients died, and five survivors had handicaps. Eleven of the 16 survivors (seven without handicaps and four with handicaps) had a second examination at 3 mo of age. After magnetic resonance imaging, spectra were obtained at 1.5 tesla. A 20-mm-thick slice was selected through the basal ganglia. After optimizing the B-0 field, we used a double spin-echo pulse sequence (90–180-180°) with a time to repeat of 2000 ms and a time to echo of 272 ms. Two-dimensional spectroscopic imaging was performed by 32 ± 32 phase encoding steps in two directions in a 225-mm field of view, resulting in 1-mL volumes, followed by computerized processing. Neuromotor development was examined at 6 wk, 3 mo, and every 3 mo thereafter. Lactate resonances were seen only in the five patients with grade 3 postasphyxial encephalopathy. Lactate was distributed diffusely (n= 4), or localized in areas of infarction (n= 1).N-acetyl-aspartate/choline ratios were significantly lower in the patients with an adverse outcome than in the survivors without handicaps, both neonatally (p< 0.005, Wilcoxon's rank sum test) and at 3 mo (p< 0.05). In conclusion, the presence of cerebral lactate and a lowN-acetyl-aspartate/choline ratio demonstratedin vivousing proton magnetic resonance spectroscopy in full-term neonates with postasphyxial encephalopathy indicate a poor outcome.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Very few data are available regarding the decreased susceptibility of the developing kidney to anoxia. Therefore, the purpose of this study was to develop an experimental system that would allow comparison of an anoxic insult in immature and mature proximal tubule segments and to investigate the hypothesis that the developing kidney is resistant to anoxia as compared with the mature kidney. Suspensions of proximal tubules from immature (age 8–10 d) and mature (8–10 wk) rats were obtained. The purity of the tubule suspension from the immature rats was documented by villin staining. A common buffer solution was developed to compare results from the immature and mature tubules. To study the response of the tubules to anoxia, we subjected the tubule suspension from both the immature and mature rats to 15, 30, 45, and 60 min of anoxia. Lactate dehydrogenase release was measured to assess plasma membrane damage, and ATP levels were determined as an index of cellular energy. After a short anoxic insult (15 or 30 min), the percentage of lactate dehydrogenase release was not significantly different from mature tubules. After prolonged anoxia (45 and 60 min) lactate dehydrogenase release continued to increase, whereas membrane integrity stabilized in the immature tubules. ATP levels decreased in both immature and mature tubules after anoxia, but the decline of ATP was greater in the mature tubules, with a plateau at 20% of basal ATP levels as compared with 40% in the immature tubules. Therefore, the developing kidney is resistant to prolonged anoxia.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Fluoride pharmacokinetic data are presented for infants given a fluoride supplement. Seventeen infants participated in a total of 20 studies. On one day, 0.013 mmol (0.25 mg) fluoride was given as a supplement (fluoride supplement study), and on another day a placebo was given (control study). Samples of plasma and urine were collected for 5 h and analyzed for fluoride. During control studies fluoride intake averaged 0.15 μmol/kg (2.9 Mg/kg), and plasma fluoride concentrations ranged from 0.05 to 0.11 μmol/L (10 to 20 μg/L). In nine instances, the quantity of fluoride excreted in the urine was more than twice that consumed. When the fluoride supplement was given, total fluoride intake averaged 1.93 μmol/kg (36.6 μg/kg). Plasma peak concentration was reached by 30 min in 14 studies and by 60 min in six studies. Mean plasma peak fluoride concentration was 3.3 μmol/L (63 ng/mL). Area under the plasma concentration curve averaged 236 nmolm−1min (4479 ngmL−1min) and was not related to the dose of fluoride. The rate of urinary excretion was significantly correlated with rate of urinary flow. When the dose of fluoride was expressed per unit of body weight, fluoride retention was strongly related to the dose. Retention of the fluoride absorbed from the fluoride dose ranged from 75.4 to 87.6%. Plasma clearance averaged 6.8 mLkg−1min−1and decreased significantly with age. Net fractional clearance (renal clearance of the fluoride dose/GFR) averaged 56.7%, which was significantly greater than the 29% observed during the control studies. The greater percentage retention of fluoride by infants than by adults is probably explained by a greater capacity of the infant to deposit fluoride in hard tissues.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Impaired neutrophil responses contribute to the neonate's increased susceptibility to infection. Because granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance granulocyte and macrophage number and function, their use in the management of neonatal sepsis may be beneficial. Little is known about the endogenous levels of G-CSF and GM-CSF. In adults, raised values for G-CSF, but not GM-CSF, have been demonstrated in patients with infection, and conflicting data has emerged regarding CSF levels in neonates. We have used an ELISA to measure maternal and cord serum G-CSF and GM-CSF at the time of delivery, with gestational age between 25 and 42 wk. In mothers, an inverse linear relationship between gestational age and GM-CSF levels (p= 0.049) was found, but no association with G-CSF levels was observed. In neonates, a quadratic association was found between GM-CSF levels and gestational age (p= 0.019), whereas G-CSF levels showed an inverse linear association (p= 0.015). In addition, an association was found between maternal and cord GM-CSF (p= 0.007) but not G-CSF levels in paired samples. The effect of gestational age on the cytokine levels could not be explained by the white cell count, the absolute neutrophil count, pregnancy-induced hypertension, or the presence of infection. We suggest that 1) GM-CSF levels in mothers vary throughout gestation and may have a role in the maintenance of normal pregnancy; 2) G-CSF and GM-CSF levels in neonates vary with gestational age and may have a developmental role; and 3) G-CSF has theoretical benefit in the management of neonatal neutropenia and sepsis; clinical trials are now needed to establish its optimal use.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In the human fetus, liver macrophages appear to be the primary source of erythropoietin (Epo). Epo production shifts from the liver to peritubular cells in the kidney sometime during the 3rd trimester. Some preterm infants experience a hyporegenerative anemia that appears to be caused by inadequate Epo production. It is not clear whether this anemia is due to deficient Epo production by liver macrophages or renal peritubular cells. To assess this situation, we measured Epo mRNA and protein in macrophages obtained from cord blood of preterm and term infants and from peripheral blood of adults. Macrophages from preterm infants generated Epo mRNA and protein as effectively as those from term infants and adults. It appears that the anemia of prematurity is not due to defective Epo production by macrophages.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Children with leukemia receive CNS therapy to improve long-term survival. Neurotoxic effects, such as cognitive impairment, have been associated with this therapy. A rat model was developed to determine which agent, or combination of agents, in CNS therapy causes neurotoxicity. The agents examined were cranial irradiation (1000 cGy), methotrexate (2 or 4 mg/kg, intraperitoneally), and prednisolone (18 or 36 mg/kg, intraperitoneally). Young Sprague-Dawley rats were exposed to each agent alone or to two- or three-agent combinations. Each therapy had matched controls that received sham radiation and/or intraperitoneal saline. Subsequent to exposure, spontaneous behavior was tested using a computer pattern recognition system, which recorded and classified behavior in a novel environment. Behavioral initiations, total times, and time structures were compared in therapy and control groups. Combined rather than single-agent therapies had more behavioral effects, and these were dose- and sex-dependent. Synergistic interactions between agents caused behavioral deficits, and components of the combination determined the abnormality. Some combinations interacted antagonistically, and thus mitigated behavioral deficits. Prednisolone was clearly pivotal to behavioral outcome. A low prednisolone dose antagonized methotrexate preventing deficits, whereas a higher prednisolone dose altered behavior by enhancing effects of methotrexate and radiation. These findings emphasize that steroids are important in agent interactions. Their role in morbidity associated with leukemia treatment protocols may be equally important as that of methotrexate and cranial irradiation.

ISSN:0031-3998    

出版商:OVID    

年代:1994

数据来源: OVID