Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia

OBJECTIVES: To use stable isotopically labeled precursors of pulmonary surfactant phospholipids to measure precursor utilization and surfactant turnover in premature infants who required mechanical ventilation at birth, 2 weeks, and >4 weeks of age. STUDY DESIGN: Infants of < or =28 weeks' gestation received simultaneous 24-hour intravenous infusions of [1,2,3,4-13C4] palmitate and [1-13C1] acetate at birth, 2 weeks, and > or =4 weeks of life. Disaturated phospholipids were extracted from sequential tracheal aspirate samples obtained over a period of 2 weeks. Fractional catabolic rate (a measure of total turnover) and the fractional synthetic rates from plasma palmitate and de novo synthesis (acetate) were measured. RESULTS: The fractional catabolic rate increased from 25.3% +/- 7.0% per day at birth to 53.8% +/- 14.4% per day at 4 weeks (P=.001). The combined contribution from plasma palmitate and de novo synthesis to total synthesis increased from 44.2% +/- 19.8% at birth to 85.2% +/- 32.8% at 4 weeks (P=.03). CONCLUSIONS: Total surfactant turnover increased in premature infants with evolving bronchopulmonary dysplasia. The increasing contributions from acetate and plasma palmitate suggest a decrease in surfactant phospholipid recycling.     

15N-tracer investigations into the nitrogen metabolism of preterm infants fed mother's milk and a formula diet

Protein synthesis, protein breakdown, protein-N turnover, and other parameters describing the nitrogen metabolism were measured in five male preterm infants. The weight of the subjects at birth was 2,064 +/- 107 g and the measurements were performed at age 16.0 +/- 4.5 days in the case of the mother's milk diet and 27.4 +/- 6.8 days in the case of the formula diet containing 1.8% protein. The parameters were measured by means of the 15N-tracer technique using [15N]glycine (95 atom %) applied in a single oral dose of 20 mg/kg as a tracer. The three-pool model proposed by Winkler and Faust was used to calculate the whole body protein parameters. No difference in net protein gain, protein synthesis, protein breakdown, or the other protein metabolism parameters were recorded despite the different protein inputs. Renal nitrogen excretion and the rate of endogenous urea N excretion were significantly higher for the formula diet than for the mother's milk diet. The protein synthesis rate of 7.9 g X kg-1 X day-1 was, as has previously been observed, higher than in other age groups. The protein metabolism of the preterm infant older than 33 weeks of gestational age does not benefit from a formula diet based on cow's milk that is richer in protein than mother's milk.     

Parenteral amino acids increase albumin and skeletal muscle protein fractional synthetic rates in premature newborn minipigs

OBJECTIVES: Early administration of parenteral amino acids increases whole body nitrogen retention in premature infants. Tracer kinetic studies suggest an increase in whole body protein synthesis as a possible mechanism for this increase in nitrogen retention. However, the effect of early parenteral amino acids on synthesis of specific proteins remains uncertain. Using premature newborn minipigs as a model for human premature newborns, we investigated the effects of parenterally administered amino acids on albumin and skeletal muscle protein fractional synthetic rates. METHODS: Fifteen Yucatan minipigs were delivered by cesarean section 6 days before the mean expected delivery date (day 106 of gestation; expected gestation, 111-113 days) and randomized to two groups immediately after birth: 7 piglets received a mixture of amino acids (0.4 g. kg. h ) and glucose (0.8 g. kg. h ) for 5 hours, and 8 piglets (control group) received glucose only. All piglets received a continuous primed infusion of 1-[ C]valine. Arterial plasma free C-valine enrichment was measured by gas chromatography/mass spectrometry, and protein synthetic rates were determined by measuring incorporation of C-valine into albumin and skeletal muscle protein using gas chromatography/combustion/isotope ratio mass spectrometry. RESULTS: Administration of amino acids increased albumin (87.0% +/- 42.1% [mean +/- SD] vs. 37.6% +/- 6.8% per 24 hours; < 0.05) and skeletal muscle fractional synthetic rates (11.60% +/- 6.9% vs. 6.5% +/- 1.5% per 24 hours; < 0.05). CONCLUSION: We conclude that parenteral amino acids increase albumin and skeletal muscle fractional synthetic rates in premature piglets on the first day of life.     

15N tracer kinetic studies on the validity of various 15N tracer substances for determining whole-body protein parameters in very small preterm infants

Reliable 15N tracer substances for tracer kinetic determination of whole-body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post-conceptual age was 32.2 +/- 0.8 weeks, and their body weight was 1670 +/- 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]glycine (Ib). In a second group of three infants with a post conceptual age of 15N-labeled 32.0 +/- 1.0 weeks and a body weight of 1,907 +/- 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three-pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 +/- 3.1 g kg-1 d-1 (Ia), 16.2 +/- 2.5 g kg-1 d-1 (Ib), and 10.8 +/- 3.0 g kg-1 d-1 (II). We were able to demonstrate an overestimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N-labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole-body protein parameters in very small preterm infants.     

Endogenous surfactant metabolism in newborn infants with and without respiratory failure

Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate is a direct precursor of de novo synthesized surfactant fatty acid, we measured [1-13C1]acetate incorporation into surfactant of term infants without respiratory dysfunction (control group), preterm infants with RDS, and term infants with primary respiratory failure to determine whether stable isotopically labeled acetate would yield similar results to previous studies of preterm infants with RDS and, furthermore, would distinguish normal from abnormal surfactant turnover. Despite similar amounts of phospholipids and acetate precursor enrichment, the control group had higher fractional synthetic rate and shorter half-life of clearance than preterm infants with RDS, (fractional synthetic rate, 15.4 +/- 2.4 versus 2.2 +/- 0.4%/d, p < 0.001; half-life of clearance, 27 +/- 3 versus 105 +/- 11 h, p < 0.001). Term infants with severe respiratory failure had a lower fractional synthetic rate than those with mild disease (2.9 +/- 0.6 versus 13.8 +/- 3.5%/d, p = 0.014) and a reduced amount of phospholipids recovered from tracheal aspirates (54 +/- 17 versus 300 +/- 28 nmol, severe versus mild disease, respectively, p < 0.001). The amount of phospholipids in tracheal aspirates correlated inversely with disease severity, (r = -0.75, p = 0.01). We conclude that normal surfactant turnover in term infants is faster than in preterm infants with RDS. Surfactant turnover in term infants with severe respiratory failure is similar to that of preterm infants with RDS, suggesting either delayed maturity of the surfactant system or disruption from the underlying disease process.     

Whole-body protein parameters in premature infants: a comparison of different 15N tracer substances and different methods.

[15N]glycine, [15N]leucine, and [15N]yeast protein thermitase hydrolysate (YPTH) as tracers for investigating the protein turnover rates in premature infants were studied in nine human milk-fed neonates (born after 32 to 34 wk of gestation) by paired comparison of the tracers. The 15N enrichment of total urinary nitrogen and ammonia after administration of a single oral dose of 15N was measured by emission spectrometry. Flux rates were calculated using a three-compartment model and the ammonia end product method. The mean whole-body protein synthesis rates, as determined by the three-compartment model derived from the three 15N tracers, differed significantly (p less than 0.01) among [15N]glycine (15.9 g/kg/d), [15N] leucine (9.1 g/kg/d), and 15N-YPTH (5.9 g/kg/d). When the corresponding rates were determined from the excretion of label in ammonia, the results showed the opposite tendency; the lowest apparent synthesis rates were found after [15N]glycine (7.5 g/kg/d), followed by [15N]leucine (14.4 g/kg/d), and the highest figure resulted after [15N] YPTH (16.7 g/kg/d). The results of this comparison substantiate the assumption that there are methodologic errors in connection with the use of different tracers and models for the calculation of whole-body protein parameters in preterm infants, with respect to the main requirement for tracer kinetic studies; the tracer nitrogen must be representative of total amino acid nitrogen. Seen in this light, mixtures of completely labeled amino acids such as YPTH may represent the most reliable tracer substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis

Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h [1-(13)C] acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants.     

Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation.

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants

OBJECTIVES: To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period. STUDY DESIGN: Premature infants < or =32 weeks gestation with a birth weight from 694 to 1590 g were randomly assigned to either a glutamine-supplemented group (n = 10) or to a control group (n = 10). Tracer isotope studies were performed when the infants were 6 to 7 days old and had been receiving an amino acid intake of approximately 3.0 g.kg -1 .d -1 for at least 3 days. Whole body glutamine and nitrogen kinetics were measured with [5-15N]glutamine, [2H5]phenylalanine, [1-13C, 15 N]leucine, [15N2]urea, and GC-mass spectrometry. RESULTS: Supplemental glutamine was associated with a lower rate of appearance of glutamine ( P = .003), phenylalanine ( P = .001), and leucine C ( P = .003). There was no significant difference in leucine N turnover, urea turnover and plasma cortisol, and C-reactive protein levels in the 2 groups. CONCLUSION: Parenteral glutamine supplement in LBW infants was associated with lower whole-body protein breakdown. Because the decrease in whole body proteolysis is associated with protein accretion, parenteral glutamine supplement may be beneficial in selected populations of LBW infants.     

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of different 15N-tracer substances for calculation of whole body protein parameters in infants

The validity of using different 15N-tracer substances to measure whole body protein parameters, i.e., protein synthesis, protein breakdown, net protein gain, protein turnover, metabolic pool, and reutilization, was assessed by comparing the results obtained with: [15N]glycine, a mixture of 10 15N-labeled amino acids, and a 15N-labeled chicken egg protein in two infants, 9 and 12 weeks old, who were fed human milk. The tracer substances were fed orally as a single dose corresponding to a 15N-excess quantity of 0.2 mmol X kg-1 body weight. 15N Excretion in the urine was measured cumulatively by emission spectrometry, and the data on the protein metabolism were calculated by means of a three-pool model. All three tests yielded consistent net protein gains. The protein synthesis, protein breakdown, protein turnover, and nitrogen reutilization values produced by the [15N]glycine tracer study were higher than those produced by application of the 15N-amino acid mixture and the 15N-labeled egg protein. However, in our opinion, this discrepancy does not justify the replacement of [15N]glycine by expensive 15N-amino acid mixtures as tracer substances.     

The effect of energy intake and expenditure on the recovery of 13CO2 in the parenterally fed neonate during a 4-hour primed constant infusion of NAH13CO3

The use of 13CO2 excretion to measure the oxidation of 13CO2 labeled substrates is increasing as it is both noninvasive and lacks the radiation exposure associated with the use of 14C. No standards are available for 13CO2 recovery in breath from the bicarbonate pool in the neonate. A primed constant infusion of NaH13CO3 over 4 h was used with open circuit indirect calorimetry in 15 appropriate for gestational age newborn infants (gestational age 28-39 wk; postnatal age 2-52 days), on varying amounts of intravenous feeding (37-114 kcal X kg-1 X day-1). Following a bolus of 6.9 mumol X kg-1 of NaH13CO3, a maintenance infusion of 4.6 mumol X kg-1 X h-1 was started. The 13C enrichment in breath rose rapidly to reach a plateau by 90 min with less than 5% variation of the plateau. Recovery of the tracer in breath ranged from 69.6-83.5% and was significantly correlated with 1) energy intake (37-114 kcal X kg-1 X day-1); 2) metabolic rate (34.6-56.1 kcal X kg-1 X day-1); 3) VCO2 (4.86-7.43 ml X kg X -1 X min-1). There was no correlation with the level of protein or fat intake. We provide an equation that can be used to calculate the correction factor when doing constant infusion substrate oxidation studies with a 13C label in neonates.     

Plasma glutamate concentrations in 1-year-old infants and adults ingesting monosodium L-glutamate in consommé

This study tested the hypothesis that infants metabolize glutamate more slowly than adults. Eight 1-yr-old infants ingested 160 ml of a beef consommé providing monosodium L-glutamate at 0, 25, and 50 mg/kg body weight. Plasma glutamate and aspartate concentrations were measured sequentially for the next 2 h. The results were compared to values noted in nine adult subjects ingesting equivalent doses of monosodium L-glutamate in consommé. In adults, mean (+/- SD) peak plasma glutamate concentrations were 5.59 +/- 1.56, 10.2 +/- 2.08, and 17.0 +/- 8.06 mumol/dl, respectively; the area under the plasma glutamate concentration time curves were 96 +/- 42, 257 +/- 80, and 442 +/- 303 mumol/dl X min, respectively. In infants, the mean (+/- SD) peak plasma glutamate concentrations were 6.94 +/- 1.43, 10.6 +/- 2.36, and 12.0 +/- 1.16 mumol/dl, respectively; the plasma glutamate area under the curve values were 47 +/- 28, 191 +/- 85, and 358 +/- 105 mumol/dl X min, respectively. The data indicate that the plasma glutamate concentration response in 1-yr-old infants ingesting MSG at these glutamate doses is no higher than values observed in adult subjects.     

Glycogen storage disease: effects of glucose infusions on [15N]glycine kinetics and nitrogen metabolism

The effects of intragastric glucose infusions on [15N]glycine kinetics and whole body protein turnover were investigated in four children with type I and two children with type III glycogen storage disease. Either fasting or the administration of insufficient glucose was associated with a diminution in the glycine pool size relative to values observed when patients received adequate glucose. The cause of the smaller pool size was an increased fractional glycine turnover. Simultaneous determination of whole body protein turnover, using a stochastic model based on [15N]urea excretion, showed higher rates of protein synthesis, nitrogen flux, net tissue protein retention, and reutilization of amino acid nitrogen derived from protein catabolism, in patients receiving sufficient exogenous glucose. Depletion of amino acid pools, presumably because of intensive utilization of these gluconeogenic precursors when inadequate glucose is administered, was associated with a lower rate of whole body protein synthesis.     

Effect of two amino acid solutions on leucine turnover in preterm infants

OBJECTIVE: To assess the effect of two different parenteral amino acid mixtures, Trophamine and Primene, on leucine turnover in preterm infants. METHOD: Leucine kinetics were measured with [5,5,5 D3]leucine tracer in 15 infants receiving Trophamine (group 'T') (mean birth weight 1,263 g) and 22 who received Primene (group 'P') (mean birth weight 1,336 g) during two study periods, within a few hours after birth but before introduction of parenteral amino acid solution, and again at postnatal day 7. The rate of appearance of leucine was calculated from the enrichment of alpha-ketoisocaproic acid in plasma. RESULTS: There were no significant differences in leucine turnover within a few hours after birth in the two groups. In the infants who received Primene leucine turnover on day 7 was significantly lower than in those who received Trophamine (269 +/- 43 vs. 335 +/- 27, p < 0.05). Despite a higher intake of leucine in the Trophamine group (108 +/- 10 vs. 77 +/- 8 micromol.kg(-1).h(-1)), leucine released from proteins at day 7 was higher in this group compared to Primene (227 +/- 27 vs. 192 +/- 42 micromol.kg(-1).h(-1)). CONCLUSIONS: Primene administration results in lower leucine released from proteins, an estimate of protein breakdown, than Trophamine in preterm infants. Increases in whole body leucine turnover in response to administration of i.v. amino acids is influenced by the composition of the amino acid mixture. The factors responsible for this difference remain to be elucidated.     

Ontogenetic changes in the rates of protein synthesis and leucine oxidation during fetal life

Studies of fetal leucine metabolism and protein synthetic rate, using L-(1-14)leucine as tracer, were carried out in 12 pregnant ewes at midgestation and compared with similar studies in late gestation. The disposal rate of fetal plasma leucine ranged between 3.07 and 9.06 mumol/min and was correlated (r = 0.89) to fetal dry weight. The fluxes to CO2 excretion and to protein synthesis were 18.6 +/- 2.6 and 37.2 +/- 2.6% of disposal rate, respectively. The flux of leucine molecules into the placenta was relatively large and correlated to the placental/fetal dry weight ratio (r = 0.84). The mean fractional protein synthetic rate was 0.216 +/- 0.01 day-1. Comparison with late gestation data showed that fractional protein synthetic rate is inversely correlated (r = 0.87) to gestational age and that fetal protein synthetic rate (PRs, g/day) is related to fetal dry weight (DW,g) by the allometric equation: log PRs = -0.503 + 0.754 log DW The 0.754 exponent is similar to the exponent relating fetal oxygen consumption to dry weight (0.729). This indicates that protein synthesis and energy metabolism per g dry weight decrease during fetal growth at approximately the same rate so that the protein synthesis/oxygen consumption ratio tends to remain constant.     

Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover, we studied the leucine turnover in preterm infants soon after birth and again after 7 days. Ten infants from preeclamptic mothers (birth weight 1,280 +/- 240 g, gestational age 31 +/- 2 weeks) and 15 control patients (birth weight 1,320 +/- 210 g, gestational age 30 +/- 2 weeks) were enrolled. The leucine turnover was measured using a primed constant 5-hour intravenous infusion of [1-(13)C]leucine within the first 24 h after delivery and again on day 7 of life. The turnover (leucine flux; micromol.kg(-1).h(-1)) was calculated from the enrichment in alpha-ketoisocaproic acid in plasma. The leucine turnover on day 1 was 300 +/- 65 in the preeclampsia group and 358 +/- 70 in the controls (ANOVA, p < 0.05). The values on day 7 were 474 +/- 73 in the preeclampsia group and 485 +/- 80 in the control group (n.s.). To conclude, the leucine turnover on day 1 is lower in infants of preeclamptic mothers as compared with controls. This difference has disappeared on day 7 of life after receiving the same protein and energy intake.     

Whole body protein turnover measured with 13C-leucine and energy expenditure in preterm infants

Our study was undertaken in preterm infants to examine the relationship of whole body protein kinetics with protein intake and energy expenditure. Leucine kinetics were determined in seven low birth wt preterm infants fed human milk or human milk enriched with protein (2.5 to 4.3 g protein/kg.d). The infants received a short (4-h) constant infusion of L-[1-13C]leucine and leucine turnover and oxidation were calculated from 13C-plasma leucine and expired 13CO2 enrichments measured by mass spectrometry. Energy expenditure was measured by indirect calorimetry. Nonoxidative leucine disposal (an estimate of protein synthesis) and leucine derived from protein (an estimate of protein breakdown) were, respectively, 2.98 +/- 0.82 and 2.06 +/- 0.74 mumol/kg.min. Whole body protein turnover and deposition, derived from leucine kinetics, were 8.22 +/- 2.31 and 2.17 +/- 0.50 g/kg.d, whereas energy expenditure was 56.3 kcal/kg.day. Protein turnover was correlated with protein intake but not with protein deposition. Energy expenditure was correlated with protein turnover, synthesis, and breakdown but not with protein deposition. These data are in agreement with the fact that protein deposition depends upon protein intake, but they also suggest that an elevated protein deposition is not necessarily the result of a rapid protein turnover or associated with an elevated energy expenditure.     

The effect of neonatal sepsis on bone turnover in very-low birth weight premature infants

Neonatal sepsis is very common in preterm infants, and severe morbidity during the neonatal period is a major cause of osteopenia of prematurity. We examined the effect of neonatal sepsis on bone turnover markers in premature infants. Twenty-four premature infants participated in the study. Ten of the premature infants developed sepsis during their hospitalization in the neonatal intensive care unit (mean gestational age [GA] 27.3 +/- 0.4 weeks; mean birth weight [BW] 898 +/- 82 g). Fourteen infants who did not develop sepsis served as controls (GA: 26.8 +/- 0.8 weeks, BW: 892 +/- 66 g). Blood samples for bone turnover markers were collected during the initial sepsis workup, and at the end of the first week of treatment, and were compared to the corresponding weekly changes in bone markers in the controls. In addition, samples were collected at the end of the 10th week of life to determine long-term effects of sepsis on bone turnover. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of circulating carboxy terminal cross-links telopeptide of type I collagen (ICTP). There were no significant differences in the weekly changes of all bone turnover markers in premature infants who developed or did not develop sepsis. No significant differences were found in bone turnover markers at the age of 10 weeks between the groups. Neonatal sepsis in premature infants was not associated with biochemical evidence of reduced bone turnover.     

Nutritional rehabilitation increases resting energy expenditure without affecting protein turnover in patients with cystic fibrosis.

The effect of nutritional rehabilitation on several nutritional parameters was studied in eight malnourished patients with cystic fibrosis during the first year after gastrostomy tube insertion. Body composition was studied by fat skinfold measurements and by total body potassium count, resting energy expenditure (REE) by indirect calorimeter, and protein turnover by a single dose administration of [15N]glycine. Weight gain was accompanied by a significant increase in the various body compartments: weight 41.4 +/- 7.5 to 46.1 +/- 8.4 kg (p less than 0.0002), fat body mass 5.6 +/- 2.8 to 7.7 +/- 3.4 kg (p less than 0.005) and fat-free body mass (FFBM) 35.7 +/- 6.3 to 38.3 +/- 6.9 kg (p less than 0.0003). REE increased significantly per kg of body weight as well as per kg of FFBM. No significant differences were found in protein turnover during refeeding nor in pulmonary function. We conclude that nutritional support restores body composition, but is accompanied by an increase in energy expenditure. This increase could not be attributed to increased protein turnover.