Altered Sphingolipid Balance in Capillary Cerebral Amyloid Angiopathy.

Background: The majority of patients with Alzheimer's 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.

A stable isotope method for in vivo assessment of human insulin synthesis and secretion.

Aims: In vitro, beta cells immediately secrete stored but readily releasable insulin in response to a rise of glucose. During a prolonged insulin response, this is followed by newly synthesized insulin. Our aim was to develop an in vivo test to determine the ratio between readily available and newly synthesized insulin after a stimulus in humans by labelling newly synthesized insulin.

Familial hypercholesterolaemia: cholesterol efflux and coronary disease.

Background: Coronary heart disease (CHD) risk inversely associates with levels of high-density lipoprotein cholesterol (HDL-C). The protective effect of HDL is thought to depend on its functionality, such as its ability to induce cholesterol efflux.

Materials And Methods: We compared plasma cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM).

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation.

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO).

The gut takes nearly all: threonine kinetics in infants.

Background: Threonine is an essential amino acid that is abundantly present in intestinally produced glycoproteins. Animal studies show that intestinal first-pass threonine metabolism is high, particularly during a restricted enteral protein intake.

Objective: The objective of the study was to quantify intestinal first-pass threonine metabolism in preterm infants during full enteral feeding and during restricted enteral intake.

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life.

Background: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth.

Objective: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake.

Chemotherapy does not influence intestinal amino acid uptake in children.

Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis.

Intestinal amino acid metabolism in neonates.

The portal-drained viscera (stomach, intestine, pancreas and spleen) have a much higher rate of both energy expenditure and protein synthesis than can be estimated on the basis of their weight. A high utilization rate of dietary nutrients by the portal-drained viscera might result in a low systemic availability which determines whole-body growth. From studies in our multiple catheterized piglet model, we conclude that more than half of the dietary protein intake is utilized within the portal-drained viscera and that amino acids are a major fuel source for the visceral organs.

Effects of early amino acid administration on leucine and glucose kinetics in premature infants.

We previously showed that, in prematurely born infants, an anabolic state without metabolic acidosis can be achieved upon intravenous amino acid (AA) administration in the immediate postnatal phase, despite a low energy intake. We hypothesized that the anabolic state resulted from an increased protein synthesis and not a decreased proteolysis. Furthermore, we hypothesized that the energy needed for the higher protein synthesis rate would be derived from an increased glucose oxidation.

Amino acid administration to premature infants directly after birth.

Objectives: To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance.

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.

Splanchnic bed metabolism of glucose in preterm neonates.

Background: Glucose is a major oxidative substrate for intestinal energy generation in neonatal animals; however, few data in preterm infants are available. Early administration of enteral nutrition, including glucose, may be an effective strategy to support intestinal adaptation to extrauterine life in preterm neonates.

Objective: The purpose of the present study was to quantify the first-pass uptake and oxidation of glucose by the splanchnic tissues (intestine and liver) in human neonates.

Effects of antenatal steroids on protein metabolism in preterm infants on the first day of life.

Objective: To analyze, in an existing cohort of infants, whether antenatal administered corticosteroids influence protein metabolism in preterm infants on the first day of life. Study design Three groups of infants were studied. The mothers of 25 infants had received 2 or more doses of corticosteroids, the mothers of 5 had received 1 dose, and there was no antenatal steroid exposure for 8 infants.

Validation of the direct nasopharyngeal sampling method for collection of expired air in preterm neonates.

In clinical studies, the oxidation of 13C-labeled substrates to 13CO2 and the measurement of the appearance of excess 13CO2 in expiratory air has progressed to an increasingly common method as it is noninvasive and lacks the radiation exposure associated with the use of 14C. The collection of respiratory CO2 currently used occurs via trapping of CO2 in sodium hydroxide (trapping method), sometimes in conjunction with indirect calorimetry. The aim of the present study was to determine the accuracy of our direct nasopharyngeal sampling method for the collection of breath samples in preterm infants compared with the currently used trapping method.

Surfactant phosphatidylcholine pool size in human neonates with congenital diaphragmatic hernia requiring ECMO.

Objective: We measured surfactant phosphatidylcholine (PC) pool size and half-life in human congenital diaphragmatic hernia (CDH) patients who required extracorporeal membrane oxygenation (ECMO). Study design Surfactant PC pool size and half-life were measured by endotracheal administration of deuterium-labeled dipalmitoylphosphatidylcholine in 8 neonates with CDH on ECMO (CDH-ECMO), in 7 neonates with meconium aspiration syndrome on ECMO (MAS-ECMO), and in 6 ventilated infants (NON-ECMO).

Results: Lung PC pool size in the CDH-ECMO group was 73 +/- 17 mg/kg (mean +/- SEM), which was not significantly different from the MAS-ECMO (50 +/- 18 mg/kg) and the NON-ECMO group (69 +/- 38 mg/kg).

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-(13)C]-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).

The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes.

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome.

Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids.

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d.