Darcos Wattimena

The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids.

Infants fed formulas devoid of long-chain polyunsaturated fatty acids (LCP) exhibit low plasma LCP concentrations and have poorer retinal and neurologic development in comparison with their human milk-fed counterparts. It is not known whether the low plasma LCP concentrations result from an impaired biosynthetic capacity, a high need, or a low dietary intake. With stable isotope technology and high sensitivity tracer detection using gas chromatography-isotope ratio mass spectrometry we measured the conversion of[13C]linoleic acid (C18:2n-6) and [13C]linolenic acid (C18:3n-3) into their longer chain derivatives in five 1-mo-old formula-fed preterm infants (birth weight 1.17 ± 0.12 kg and gestational age 28.4 ± 1.3 wk). Carbon-13-labeled linoleic acid and inolenic were mixed with the formula and administered continuously for 48 h. Both tracers were rapidly incorporated in plasma phospholipids, and their metabolic products including arachidonic acid (C20:4n-6) and docosahexaenoic acid (C22:6n-3) became highly enriched. We demonstrate that the preterm infant is capable of synthesizing LCP from their 18-carbon precursors, and our data do not support the hypothesis that a reduced δ6 desaturation is a main factor leading to low arachidonic acid and docosahexaenoic acid levels.

Effect of minimal enteral feeding on splanchnic uptake of leucine in the postabsorptive state in preterm infants.

We conducted a controlled, randomized trial to study the effect of minimal enteral feeding on leucine uptake by splanchnic tissues, as an indicator of maturation of these tissues, in preterm infants in the first week of life. Within a few hours after birth, while receiving only glucose, a primed constant infusion of [1-13C]-leucine was started and continued for 5 h via the nasogastric tube, whereas 5,5,5 D3-leucine was infused intravenously (for both tracers, priming dose 2 mg/kg, continuous infusion 2 mg/kg/h). Patients were thereafter randomized to receive solely parenteral nutrition (C), parenteral nutrition and 20 mL breast milk/kg/d (BM), or parenteral nutrition and 20 mL formula/kg/d (F). On d 7, the measurements were repeated, after discontinuing the oral intake for 5 h. Fourteen infants were included in group C, 12 in group BM, and 12 in group F. There was no difference in energy intake or nitrogen balance at any time. On d 1, plasma enrichment for the nasogastric tracer was lower than for the intravenous tracer for all three groups, both for leucine and for α-keto-isocaproic acid. On d 7, the enrichment for leucine and α-keto-isocaproic acid for the nasogastric tracer was lower than for the intravenous tracer for the groups BM and F (BM: 3.65 ± 1.20 nasogastric versus 4.64 ± 0.64 i.v.; F: 4.37 ± 1.14 nasogastric versus 5.21 ± 0.9 i.v.). In the control group, there was no difference between tracers. The lower plasma enrichment for the nasogastric tracer compared with the intravenous tracer suggests uptake of leucine by the splanchnic tissues. We conclude that minimal enteral feeding—even in low volumes of 20 mL/kg/d—increases the leucine uptake by the splanchnic tissue. We speculate that this reflects a higher protein synthesis of splanchnic tissues in the groups receiving enteral nutrition.

Altered Sphingolipid Balance in Capillary Cerebral Amyloid Angiopathy

BACKGROUND The majority of patients with Alzheimers disease (AD) exhibit amyloid-β (Aβ) deposits at the brain vasculature, a process referred to as cerebral amyloid angiopathy (CAA). In over 51% of AD cases, Aβ also accumulates in cortical capillaries, which is termed capillary CAA (capCAA). It has been postulated that the presence of capCAA in AD is a specific subtype of AD, although underlying mechanisms are not yet fully understood. Sphingolipids (SLs) are implicated in neurodegenerative disorders, including AD. However, to date it remains unknown whether alterations in the SL pathway are involved in capCAA pathogenesis and if these differ from AD. OBJECTIVE To determine whether AD cases with capCAA have an altered SL profile compared to AD cases without capCAA. METHODS Immunohistochemistry was performed to assess the expression and localization of ceramide, acid sphingomyelinase (ASM), and sphingosine-1-phosphate receptors (S1P1, S1P3). In addition, we determined the concentrations of S1P as well as different chain-lengths of ceramides using HPLC-MS/MS. RESULTS Immunohistochemical analysis revealed an altered expression of ceramide, ASM, and S1P receptors by reactive astrocytes and microglial cells specifically associated with capCAA. Moreover, a shift in the balance of ceramides with different chain-lengths and S1P content is observed in capCAA. CONCLUSION Here we provide evidence of a deregulated SL balance in capCAA. The increased levels of ASM and ceramide in activated glia cells suggest that the SL pathway is involved in the neuroinflammatory response in capCAA pathogenesis. Future research is needed to elucidate the role of S1P in capCAA.

ENDOGENOUS SURFACTANT TURNOVER IN PRETERM INFANTS MEASURED WITH STABLE ISOTOPES, A NOVEL AND SAFE METHOD. |[dagger]| 1473

We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults.

DOES PRE-ECLAMPSIA IN THE MOTHER INFLUENCE LEUCINE METABOLISM IN THE INFANT?† 1423

Pre-eclampsia in the mother reduces blood flow to the conceptus, thereby reducing the amino acids transfer to the foetus. This reduced supply might impair fetal protein turnover and long-term growth.

Endogenous Surfactant Production in Preterm Infants Is Not Supressed By Exogenous Surfactant Administration

Aims. Whether endogenous surfactant production in preterm infants changes due to exogenous surfactant therapy is unknown. Therefore, we measured endogenous surfactant production with a new method using stable isotopes. Methods. Four preterm infants (992±88g, 27.9±0.8 wk) with mild neonatal RDS without exogenous surfactant treatment and 4 preterm infants (968±74 g, 27.6±1.3 wk) with severe RDS with exogenous surfactant treatment were included. All patients received a 24h [U-13C]glucose infusion, starting 4.2±1.1 h after birth. Tracheal aspirates were obtained and the surfactant phosphatidylcholine(PC) was isolated. The enrichment of plasma glucose and of palmitic acid in surfactant PC was measured by GC-IRMS. The fractional synthesis rate (FSR) which is the fraction of the total pool synthesised per day was calculated as the PC palmitate enrichment divided by the steady state plasma glucose enrichment. The absolute production rate was calculated as the FSR times the total pool size. Results. In the untreated patients the surfactant PC pool size is ≤ 87 mg/kg, after 2x surfactant treatment the total surfactant PC pool size is -179 mg/kg.Table

45 DIETARY SUPPLEMENTATION OF LONG CHAIN POLYUNSATURATED FATTY ACIDS (LCPs) IN THE PREMATURE INFANT: EFFECT ON ENDOGENOUS SYNTHESIS

Premature infants fed formulas devoid of LCPs exhibit low plasma levels in comparison with their human milk fed counterparts. Whether this results from a limited synthetic capacity or is merely a reflection of dietary intake is not known. With stable isotope technology and a high sensitivity tracer detection using gas-chromatography-isotope ratio mass spectrometry we have measured the conversion of LL and LN acid into their longer chain derivatives in 10 premature infants at one month of age. Five infants (BW 1.17±0.12 kg, GA 28.4±1.3 wks) were fed a standard formula (No LCP), while the other 5 (BW 1.07±0.09 kg, GA 28.8±0.6 wks) received a formula supplemented with ample amounts of LCP (Plus LCP). Uniformly labeled LL and LN acids were mixed with either formulas and administered continuously for 48 hours. Arachidonic (AA) and docosahexaenoic acid (DHA) content of plasma phospholipids (PL) at 48h from the beginning of the labeled diet are reported in table together with their isotopic enrichments, expressed in atom percent excess (APE)The premature infant docs desaturatc and elongate LL to AA and LN to DHA. LCP supplementation up to levels found in breast-fed infants seems not to suppress synthesis. Preterm infants probably have no, or immature regulation of desaturation and elongation of the 18 carbon atom essential fatty acids.