K. de Meer

Nutritional support in 111 pediatric intensive care units: a European survey.

ObjectiveTo study current strategies in nutritional management of pediatric intensive care units (PICUs) in Europe, focusing on energy requirements.Design and settingSurvey by a 35-item questionnaire sent to representatives of 242 PICUs in 28 countries. Addresses were obtained from national PICU associations and the members’ list of the European Society of Pediatric and Neonatal Intensive Care.ParticipantsStaff members of 111 European PICUs (46%) from 24 countries.Measurements and resultsPredominantly physicians were reported to be responsible for nutritional support. In 73% of PICUs a multidisciplinary nutritional team was available. In most PICUs daily energy requirements were estimated using weight, age, predictive equations and correction factors. In 17% of PICUs energy expenditure was regularly measured by indirect calorimetry. Nutritional status was mostly assessed by weight, physical examination, and a wide range of biochemical blood parameters. Approximately 70% of PICUs used dedicated software for nutritional support. A similar percentage of PICUs regarded “nutrition” as a research topic and part of the residents’ training program.ConclusionsMost European PICUs regard nutritional support as an important aspect of patient care, as shown by the presence of nutritional teams, software, research, and education. However, energy requirements of pediatric intensive care patient were based predominantly on estimations rather than on measurements.

S‐adenosylhomocysteine and the ratio of S‐adenosylmethionine to S‐adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations

Background It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S‐adenosylhomocysteine, or of the ratio of S‐adenosylmethionine to S‐adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B6.

Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis

OBJECTIVE Glucocorticoid treatment of children often leads to growth retardation, and the precise target(s) in the growth plate responsible for this effect are unknown. Angiogenesis is an important part of the endochondral ossification process, and VEGF expressed in the growth plate is essential for proper angiogenesis to occur. Since glucocorticoid treatment down-regulates VEGF expression in cultured chondrocytes, we hypothesized that in vivo glucocorticoid treatment could result in VEGF down-regulation in the growth plate and disturbed angiogenesis, thus contributing to the growth retardation. DESIGN We treated 6-week-old prepubertal piglets (10 kg) for 5 days with prednisolone (50 mg/day). Tibial growth plate sections were studied for apoptosis and the expression of VEGF protein and mRNA and MMP-9 protein. Capillaries in the metaphysis were visualized by CD31 immunostaining. Growth plate morphology (width of various zones) was determined by interactive measurements on hematoxylin/eosin stained sections and apoptotic cells were detected by TUNEL assay. RESULTS In the prednisolone-treated animals, the total width of the growth plate decreased to 81% of controls (P<0.02), which was explained by a decrease of the width of the proliferative zone to 73% (P<0.05). The treatment had no effect on the orderly organization of the chondrocyte columns. In the growth plates of control animals, apoptosis was shown in 5.8% of the hypertrophic chondrocytes and was limited to the terminal hypertrophic chondrocytes. In prednisolone-treated animals, 40.5% of the hypertrophic chondrocytes was apoptotic (P<0.02), with apoptotic chondrocytes also appearing higher in the hypertrophic zone. We observed fewer capillaries and loss of their parallel organization in the metaphysis in the prednisolone-treated animals. The capillaries were shorter and chaotic in appearance. In contrast to controls, in prednisolone-treated animals VEGF mRNA and protein could not be detected in the hypertrophic zone of the growth plate. Trabecular bone length in the primary spongiosa was also diminished by the treatment. No changes were observed in the expression pattern of MMP-9, a matrix metalloproteinase, which is also important for angiogenesis and bone formation. CONCLUSIONS These results indicate that short-term glucocorticoid treatment of growing piglets severely disturbs the width of the growth plate, apoptosis of chondrocytes, VEGF expression by hypertrophic chondrocytes, the normal invasion of blood vessels from the metaphysis to the growth plate and bone formation at the chondro-osseous junction. These effects could alter the dynamics of endochondral ossification and thus contribute to glucocorticoid-induced growth retardation.

Research goals for folate and related B vitamin in Europe

In the past decade, the understanding of folate bioavailability, metabolism and related health issues has increased, but several problems remain, including the difficulty of delivering the available knowledge to the populations at risk. Owing to the low compliance of taking folic acid supplements, for example, among women of child-bearing age who could lower the risk of having a baby with a neural tube defect, food-based strategies aimed at increasing the intake of folate and other B-group vitamins should be a priority for future research. These should include the development of a combined strategy of supplemental folate (possibly with vitamin B12), biofortification using engineered plant-derived foods and micro-organisms and food fortification for increasing folate intakes in the general population. Currently, the most effective population-based strategy to reduce NTDs remains folic acid fortification. However, the possible adverse effect of high intakes of folic acid on neurologic functioning among elderly persons with vitamin B12 deficiency needs urgent investigation. The results of ongoing randomized controlled studies aimed at reducing the prevalence of hyperhomocysteinemia and related morbidity must be available before food-based total population approaches for treatment of hyperhomocysteinemia can be recommended. Further research is required on quantitative assessment of folate intake and bioavailability, along with a more thorough understanding of physiological, biochemical and genetic processes involved in folate absorption and metabolism.

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

Objectives:To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups.Design:A randomized, double-blind intervention study.Subjects:A total of 12 young (<30 y) and 12 middle-aged (≥50 y) healthy volunteers were recruited.Methods:Volunteers were randomized to receive daily supplementation with 400 μg folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [2H2]folic acid test doses using isotope kinetics in plasma.Results:Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P=0.03) and after (P=0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P=0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P=0.05) but not in the middle-aged (+18%; P=0.5) adults.Conclusions:Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults.Sponsorship:Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

Increasing fat in the diet does not improve muscle performance in patients with mitochondrial myopathy due to complex I deficiency

SummaryFour myopathic patients with complex I deficiency followed diets containing 55 energy per cent (En%) as fat or 25 En% as fat, both for three weeks. Maximal workload and muscle force were not different on either diet. Exercise endurance time, oxygen consumption and lactate levels were also not different, but one patient had diminished endurance time on 25 En% as fat. Our observations do not support the use of increasing the fat in the diet of patients with mitochondrial complex I deficiency.

Determination of 13C and 15N enrichments of urea in plasma by gas chromatography–combustion isotope ratio mass spectrometry and gas chromatography–mass spectrometry using the 2-methoxypyrimidine derivative

We describe a GC-MS and GC-c-IRMS method for the determination of labeled urea tracer enrichments in plasma as a result of combined 13C- and 15N(2)-urea infusion experiments in piglets. Urea was converted into 2-methoxypyrimidine, a stable derivative, suited for analyses by both GC-MS and GC-c-IRMS. Using calibration curves for the respective working ranges (13C-urea: 0-1% APE; 15N(2)-urea: 0-7% MPE) enrichments were established in single point measurements; for 15N(2)-urea as values+/-0.15% MPE (95% confidence interval); for 13C-urea as values+/-0.02% APE (95% confidence interval). 15N(1)-urea enrichments were determined by measurement of the same sample with GC-c-IRMS and GC-MS. Subtraction of the 13C specific GC-c-IRMS data from the nondiscriminating GC-MS data for the sum of 13C- and 15N(1)-urea resulted in 15N(1)-urea enrichments+/-0.15% MPE (95% confidence interval). Application of the method in a combined 13C-urea bolus and 15N(2)-urea primed constant infusion experiment in piglet was demonstrated.

NEW DIETARY APPROACH FOR TREATMENT OF MITOCHONDRIAL RESPIRATORY CHAIN DISORDER • 598

Complex I Deficiency (CID) is a disorder of oxidative phosphorylation characterized by impaired mitochondrial ability to oxidize NADH. Triglyceride compared to glucose oxidation provides a higher non-NADH vs. NADH electron flow to the respiratory chain; we thus postulated that supplying more fat would improve exercise tolerance and oxygen consumption in CID patients. In 3 CID patients with decreased maximal workload (mean (Wmax; mean (SD) 53 (7) W) and in 3 control subjects (Wmax 197 (15) W), we studied the effects of intravenous infusion of isoenergetic amounts of Intralipid (3.6 mg triglyceride/kg/min) or glucose (10 mg/kg/min) during steady-state bicycle ergometry at 15% Wmax. Results showed that the exercise was tolerated for the nominal 90 minutes in all control studies, and also in the CID patients during triglyceride infusion. However, during glucose infusion all CID patients suffered from premature muscle fatigue (mean endurance time 58 (95% CI: 36-80) min). Oxygen consumption in the CID patients during cycling was higher with triglyceride infusion compared to glucose infusion (difference: 1.0 (95% CI: 0.4-1.5) ml/kg/min); in the controls no significant difference was found (0.1(-0.2 to 0.4) ml/kg/min). In the exercising CID patients (but not in controls), plasma lactate concentrations rose substantially (with glucose to 8.6 (5.0) mM, with triglyceride to 8.9 (2.8) mM; infusion effect not significant) above baseline. Effects of high fat/low carbohydrate vs. high carbohydrate/low fat diets (Protein: 15 energy%; Fat: 55 vs. 25 energy%, respectively) were studied in the CID patients in a cross-over design, during at least 2 weeks for each dietary period. Steady-state bicycle ergometry at 15% of initial Wmax showed reduced endurance time on the low fat/high carbohydrate diet in two (28 and 23 min) but normal endurance (90 min) in one patient. Endurance time on the high fat diet was 90 min in all patients. We conclude that fat as compared to carbohydrates improves mitochondrial performance in affected muscle in patients with Complex I Deficiency. The results suggest the preferential use of fat, or avoidance of carbohydrate-rich meals before exercise, by patients with this respiratory chain disorder.