Greater protein intakes are required than have been commonly used to achieve fetal in utero protein accretion rates in preterm neonates. To study the efficacy and safety of more aggressive amino acid intake, we performed a prospective randomized study in 28 infants [mean wt, 946 +/- 40 g (SEM)] of 1 (low amino acid intake, LAA) versus 3 g.kg(-1).d(-1) (high amino acid intake, HAA) at 52.0 +/- 3.0 h of life. After a minimum of 12 h of parenteral nutrition, efficacy was determined by protein balance and was significantly lower in the LAA versus HAA groups by both nitrogen balance (-0.26 +/- 0.11 versus 1.16 +/- 0.15 g.kg(-1).d(-1), p < 0.00005) and leucine stable isotope (0.184 +/- 0.17 versus 1.63 +/- 0.20 g.kg(-1).d(-1), p < 0.0005) methods. Leucine flux and oxidation and nonoxidative leucine disposal rates were all significantly higher in the HAA versus LAA groups (249 +/- 13 versus 164 +/- 8, 69 +/- 5 versus 32 +/- 3, and 180 +/- 10 versus 132 +/- 8 micro mol.kg(-1).h(-1), respectively, p < 0.005), but leucine appearance from protein breakdown was not (140 +/- 15 in HAA versus 128 +/- 8 micro mol.kg(-1).h(-1)). In terms of possible toxicity with HAA, there were no significant differences between groups in the amount of sodium bicarbonate administered, degree of acidosis as determined by base deficit, or blood urea nitrogen concentration. Parenteral HAA versus LAA intake resulted in increased protein accretion, primarily by increasing protein synthesis versus suppressing protein breakdown, and appeared to be well tolerated by very preterm infants in the first days of life.
Placental transport and fetal utilization of leucine were studied at 130 days of gestation in six control ewes and in seven ewes in which intrauterine growth retardation (IUGR) had been induced by exposure to heat stress. Leucine fluxes were measured during simultaneous intravenous infusion of L-[1-13C]leucine into the mother and L-[1-14C] leucine into the fetus. In the IUGR group, the following leucine fluxes, expressed as micromol/min/kg fetus, were reduced compared with control: net uterine uptake (3.44 vs. 8.56, P<0.01), uteroplacental utilization (0.0 vs. 4.7, P<0.01), fetal disposal rate (6.4 vs. 8.9, P<0.001), flux from placenta to fetus (5.0 vs. 7.1, P<0.01), direct transport from mother to fetus (1.6 vs. 3.4, P<0.01), flux from fetus to placenta (1.5 vs. 3.2, P<0.001), and oxidation of fetal leucine by fetus plus placenta (2.1 vs. 3.2, P<0.02). Uterine uptake, uteroplacental utilization, and direct transport were also significantly reduced per gram placenta. We conclude that maternal leucine flux into the IUGR placenta is markedly reduced. Most of the reduced flux is routed into fetal metabolism via a decrease in placental leucine utilization and a decrease in the leucine flux from fetus to placenta.
A relatively simple technique was used to estimate the size of the combined pools of zinc with which plasma zinc exchanges within 2 d (EZP). EZP size was determined from the amount of isotope introduced into the plasma and the coefficient of the simple exponential decay function fitting enrichment data between d 3 and 9 after isotope administration. Using data from 11 healthy adults, comparisons were made of EZP size estimations using oral and intravenous isotopes (r = 0.93 using urine) and urine and plasma enrichment (r = 0.85 for intravenous). EZP size estimations from urine and plasma enrichment following intravenous isotope administration were 2.35 +/- 0.84 and 2.83 +/- 0.86 mmol, respectively (mean +/- SD, P < 0.01). EZP size correlated with habitual dietary zinc intake (partial r = 0.74, P < 0.02). Cumulative declines in EZP size in two healthy adults after 3 wk of consuming a moderately zinc-restricted diet followed by 1 wk of severe zinc restriction were 26 and 32%. These results indicated that EZP size is dependent on dietary intake. We conclude that this technique is adequate to demonstrate EZP differences that are of nutritional and physiological interest. EZP size estimates can be obtained using orally or intravenously administered isotope and using plasma or urine enrichment data.
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