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Biomedical subjects

Alexandre Lapillonne

Publications and source records attributed to Alexandre Lapillonne.

13 recordsLinked to original sources

Rapid cortical oscillations and early motor activity in premature human neonate.

Delta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in the human cortex during the third trimester of gestation. Here, we studied the relationship between delta-brushes in the somatosensory cortex and spontaneous movements of premature human neonates of 29-31 weeks postconceptional age using a combination of scalp electroencephalography and monitoring of motor activity. We found that sporadic hand and foot movements heralded the appearance of delta-brushes in the corresponding areas of the cortex (lateral and medial regions of the contralateral central cortex, respectively). Direct hand and foot stimulation also reliably evoked delta-brushes in the same areas. These results suggest that sensory feedback from spontaneous fetal movements triggers delta-brush oscillations in the central cortex in a somatotopic manner. We propose that in the human fetus in utero, before the brain starts to receive elaborated sensory input from the external world, spontaneous fetal movements provide sensory stimulation and drive delta-brush oscillations in the developing somatosensory cortex contributing to the formation of cortical body maps.

Biological Clocks↗

The role of essential fatty acids in development.

The presence of docosahexaenoic acid (DHA) and arachidonic acid (ARA) in human milk but not in infant formula, coupled with lower plasma and brain lipid contents of DHA in formula-fed than in breast-fed infants and reports of higher IQ in individuals who were breast-fed versus formula-fed as infants, suggest that exogenous DHA (and ARA) may be essential for optimal development. Thus, since 1990, several studies have examined the impact of formulas containing DHA or DHA plus ARA on visual function and neurodevelopmental outcome. Some of these studies have shown benefits but others have not. These results leave largely unanswered the question of whether these fatty acids are beneficial for either the term or preterm infant. However, evidence that preterm infants might benefit is somewhat more convincing than that for term infants. Despite the limited evidence for efficacy, formulas supplemented with DHA and ARA are now available and appear to be safe.

Arachidonic Acid↗

Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term.

BACKGROUND: Because recent data on the effects of mineral concentrations in preterm infant formula on bone mineralization are lacking, recommendations for the mineral content of preterm infant formula differ greatly between committees. OBJECTIVE: The goal of the study was to assess the effects of an isocaloric, nutrient-enriched preterm formula, which was fed from the age when full enteral feedings were tolerated through expected term, on bone mineralization in preterm infants. DESIGN: We conducted a prospective, randomized, double-blind study in healthy, preterm infants (gestational age of 28-32 wk) who were fed either a control preterm formula (n=20) or an isocaloric, nutrient-enriched preterm formula (n=21) until 3 mo of age (ie, approximate expected term). Serum calcium indexes were taken throughout the study, and bone mass was determined by using dual-energy X-ray absorptiometry at hospital discharge and expected term. RESULTS: A total of 37 infants (experimental formula, n=19; control formula, n=18) completed the study. Compared with control subjects, infants fed the experimental formula had 25% and 40% higher intakes of calcium and phosphorus, respectively. Serum calcium, phosphorus, osteocalcin, and alkaline phosphatase concentrations and urinary collagen type I cross-linked N-telopetide concentrations were not significantly different between the groups at any time point. The bone mineral content of infants fed the experimental formula was 23% (P=0.039) and 35% (P=0.002) higher at hospital discharge and expected term, respectively. CONCLUSIONS: Bone mineralization at hospital discharge and expected term was significantly higher in preterm infants fed the isocaloric, nutrient-enriched formula than in those fed control formula. Continuation of the experimental formula beyond hospital discharge, through expected term, further improved bone mineralization.

Absorptiometry, Photon↗

Polyunsaturated fatty acids and gene expression.

PURPOSE OF REVIEW: This review focuses on the effect(s) of n-3 polyunsaturated fatty acids on gene transcription as determined by data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneously and, hence, is a potentially powerful tool for studying the regulation of physiological mechanisms that are triggered or inhibited by nutrients. RECENT FINDINGS: Recent data generated with cDNA microarrays not only confirm the effects of n-3 polyunsaturated fatty acids on regulation of lipolytic and lipogenic gene expression as determined by more traditional methods but also emphasize the tissue specificity of this regulation. cDNA microarray experiments also have expanded our understanding of the role of n-3 polyunsaturated fatty acids in regulation of expression of genes involved in many other pathways. These include: oxidative stress response and antioxidant capacity; cell proliferation; cell growth and apoptosis; cell signaling and cell transduction. SUMMARY: The cDNA microarray studies published to date show clearly that n-3 polyunsaturated fatty acids, usually provided as fish oil, modulate expression of a number of genes with such broad functions as DNA binding, transcriptional regulation, transport, cell adhesion, cell proliferation, and membrane localization. These effects, in turn, may significantly modify cell function, development and/or maturation.

Animals↗

Plausible mechanisms for effects of long-chain polyunsaturated fatty acids on growth.

A few studies conducted over the past decade suggest that formulas supplemented with long-chain polyunsaturated n-3 fatty acids may adversely affect growth of preterm infants. Others suggest that a high intake of alpha-linolenic acid (ALA; 18:3 n-3), the precursor of the long-chain polyunsaturated n-3 fatty acids, also may limit growth. The majority of studies, however, have not shown an effect of either long-chain polyunsaturated n-3 fatty acids or their precursor on growth. Nonetheless, the importance of growth during infancy and the possibility that these fatty acids may inhibit growth under some circumstances makes the issue worthy of further consideration. At the very least, plausible mechanisms for such an effect of n-3 PUFA on growth should be considered. These include (1) altered nutrient intake, absorption, and/or utilization; (2) low plasma and tissue contents of arachidonic acid (ARA;20:4 n-6); (3) an imbalance between n-6 and n-3 LCPUFA eicosanoid precursors and, hence, the eicosanoids produced from each; (4) altered membrane characteristics; and (5) effects on gene expression. Each of these is discussed. It is concluded that any or all are feasible but that none can be specifically implicated. Moreover, since few studies were designed specifically to assess growth, the reported effects of n-3 PUFA on growth could represent chance findings secondary to the suboptimal design. Furthermore, although additional data are needed for a definitive conclusion, the observed effects on growth, regardless of mechanism, does not appear to be biologically significant.

Animals↗

Skeletal and total body volumes of human fetuses: assessment of reference data by spiral CT.

OBJECTIVE: To define reference data for skeletal and total body volumes of normal human fetuses. MATERIALS AND METHODS: Spiral CT was used to assess the skeletal and total body volumes of 31 normal human stillborn infants with gestational age (GA) and body weight (BW) ranging from 14 to 41.5 weeks and 22 to 3,760 g, respectively. CT scans (slice thickness 2.7 mm, pitch 0.7) were performed within the first 24 h after delivery. Precise bone and soft-tissue windows were defined from analysis of the density along the diaphysis of the fetal long bones and from the measurement of a phantom that mimics soft tissues. Lengths and volumes were obtained from 3D reconstructions. The femur lengths measured from CT images (FLct) were compared with those provided by US studies (FLus). RESULTS: Significant correlations ( r>0.9) were found between BW, measured volumes of the entire skeleton or head, long-bone lengths, biparietal diameter and GA. Strong linear correlations ( r>0.98) were observed between FLct and FLus. CONCLUSIONS: Skeletal and total body volume values obtained using spiral CT were significantly correlated with fetal biometric measurements. These data could complement those obtained in obstetric investigations with US.

Body Weight↗

Nitrogen utilization and bone mineralization in very low birth weight infants fed partially hydrolyzed preterm formula.

Partialy hydrolyzed formulas have been proposed for term and preterm infants, but decreased nitrogen and calcium intestinal absorption rates, together with plasma amino acid imbalances have been reported in preterm infants. We evaluated a new formula with modified nitrogen and calcium sources (glycerophosphate). During their second week of life, 16 preterm infants were randomly assigned to 1 of 2 groups: 9 were fed the new partially hydrolyzed formula and 7 a conventional formula. A nutrient balance was performed at the end of the first month of life. Amino acid concentrations and whole-body mineralization were measured at the end of study period (theoretical term). Birth weight and gestational age (mean +/- SD) were similar in the 2 groups (28.9 +/- 7.0 wks and 1,183 +/- 242 g v 27.7 +/- 1.0 wks and 1,139 +/- 162 g). Median nitrogen absorption rate (85% v 89%; P = .03) was lower in infants fed the new formula than in those fed the conventional one. After correction for difference in nitrogen intake, there was no significant difference in N retained between the 2 groups (P = .11). Plasma amino acid concentrations were also similar in the 2 groups. At theoretical term, median bone mineral content was not significantly different between the 2 groups (50 g/kg v 55 g/kg; P = .17) and it was close to the reference values obtained in term neonates just after birth. As long as nitrogen content is 10% higher in protein hydrolyzed formula than in entire protein formula, appropriate nitrogen retention, plasma amino acid profile can be achieved with the new partially hydrolyzed formula. In both groups, bone mineralization at theoretical term was close to the mineralization observed term neonates just after birth.

Amino Acids↗

The fatty acid profile of buccal cheek cell phospholipids is a noninvasive marker of long-chain polyunsaturated Fatty Acid status in piglets.

The fatty acid pattern of cheek cell phospholipids has been proposed as a noninvasive marker of long-chain polyunsaturated fatty acid (PUFA) status. However, the cheek cell phospholipid fatty acid pattern has been compared only with that of plasma and erythrocytes. The objective of this study was to assess the extent to which the fatty acid profile of cheek cell phospholipids reflects that of tissue phospholipids. Piglets (n = 31; 6 d old) were fed five formula diets differing in total fat and fatty acid composition. After 14 d of consuming the assigned diets, cheek cell plasma, erythrocyte, liver, muscle, adipose tissue, retina and brain samples were collected for determination of the phospholipid fatty acid patterns. There were significant correlations between the cheek cell phospholipid content of most PUFA and the content of these fatty acids in tissue phospholipids (r = 0.509-0.951, P < 0.01). The cheek cell phospholipid content of most of the PUFA, except 20:4(n-6), reflected that of other tissue phospholipids as well as, or nearly as well as the contents of plasma and/or erythrocyte phospholipids. The correlations between the 22:6(n-3) contents of cheek cell, plasma, or erythrocyte phospholipids and those of brain and retina phospholipids were relatively poor (r = 0.596-0.737, P < 0.001). We conclude that the fatty acid pattern of cheek cell phospholipid can be used as a noninvasive marker of PUFA status, but it is not a better index than the pattern of plasma or erythrocyte phospholipids, particularly for assessing the fatty acid pattern of organs with slow fatty acid incorporation and/or turnover rates.

Adipose Tissue↗

Influence of dietary cholesterol on vitamin d metabolism in formula-fed preterm neonates.

OBJECTIVES: Supplementation of preterm formulas with cholesterol could help to mimic the fat composition of human milk. However, this could possibly influence vitamin D 25-hydroxylation because this reaction is catalyzed in part by the mitochondrial cytochrome P-450, the enzyme responsible for the 27-hydroxylation of cholesterol. The purpose of this study was to verify whether the addition of cholesterol to preterm formulas could interfere with vitamin D metabolism in preterm neonates. METHODS: In a prospective study, 30 preterm neonates were randomly assigned to a low (< 0.03 g/L), medium (0.15 g/L), or high (0.30 g/L) cholesterol-content preterm formula until theoretical term (i.e., 40 weeks post-conceptional age). Anthropometric data and serum hydroxy-vitamin D and 1,25 dihydroxy-vitamin D concentrations were measured at study entry and theoretical term. In a subgroup of 14 subjects, serum cholesterol and lymphocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA were also assessed. RESULTS: (median [25, 75 centiles]): At theoretical term, there were no significant differences in serum hydroxy-vitamin D concentrations among the three groups, even after adjustment for confounding variables (65 [50, 78] nmol/L, 79 [59, 86] nmol/L, and 67 [43, 103] nmol/L, respectively, = 0.65) or 1,25 dihydroxy-vitamin D ( = 0.88). Furthermore, there were no significant differences in 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA copy numbers. CONCLUSIONS: In preterm neonates fed formulas with a cholesterol content similar to or higher than that of human milk, we did not observe deleterious effects on vitamin D metabolism. However, long-term effects of cholesterol supplementation require further studies.

Bottle Feeding↗

Urinary excretion of cross-linked N-telopeptides of type 1 collagen to assess bone resorption in infants from birth to 1 year of age.

OBJECTIVES: To evaluate noninvasively bone resorption in infants and more specifically, to assess the accuracy of urinary collagen type 1 cross-linked N-telopeptide (NTX) excretion normalized to creatinine (NTX/Cr) in a spot urine sample as a reflection of daily NTX production in infants and to compute normative values for NTX excretion from birth to 1 year of age. METHODS: NTX/Cr values obtained from a single spot urine sample were compared with daily urinary NTX excretion and NTX/Cr obtained in 24-hour urine collected from 8 hospitalized infants. Normative values for NTX excretion were collated with a cross-sectional study in 70 healthy French infants (42 boys, 28 girls) aged 0 to 374 days (weight: 2700-11 340 g; length: 46-76.5 cm) and free of diseases or treatments that could influence growth, bone mineralization, or renal function. RESULTS: NTX/Cr values from single spot urine sample were significantly and linearly correlated with both daily NTX excretion (r = 0.783) and daily NTX/Cr (r = 0.952). In healthy infants, NTX excretion is low at birth, increases dramatically and significantly during the first 10 days of life, remains significantly elevated for approximately 3 months, and then decreases progressively to return to values similar to that observed at birth by 1 year of age. CONCLUSIONS: These data provide new insights regarding the use of spot urine analysis for assessing NTX excretion during the first year of life. The normative data demonstrate significant age-related variations in this marker, which probably reflect adaptation to extrauterine life and accelerated bone turnover in infancy and which should be considered for the interpretation of this noninvasive bone resorption marker in the clinical setting.

Biomarkers, Tumor↗

Fatty acid regulation of gene expression: a genomic explanation for the benefits of the mediterranean diet.

The development of obesity and associated insulin resistance involves a multitude of gene products, including proteins involved in lipid synthesis and oxidation, thermogenesis, and cell differentiation. The genes encoding these proteins are in essence the blueprints that we have inherited from our parents. However, what determines the way in which blueprints are interpreted is largely dictated by a collection of environmental factors. The nutrients we consume are among the most influential of these environmental factors. During the early stages of evolutionary development, nutrients functioned as primitive hormonal signals that allowed the early organisms to turn on pathways of synthesis or storage during periods of nutrient deprivation or excess. As single-cell organisms evolved into complex life forms, nutrients continued to be environmental factors that interacted with hormonal signals to govern the expression of genes encoding proteins involved in energy metabolism, cell differentiation, and cell growth. Nutrients govern the tissue content and activity of different proteins by functioning as regulators of gene transcription, nuclear RNA processing, mRNA degradation, and mRNA translation, as well as functioning as posttranslational modifiers of proteins. One dietary constituent that has a strong influence on cell differentiation, growth, and metabolism is fat. The fatty acid component of dietary lipid not only influences hormonal signaling events by modifying membrane lipid composition, but fatty acids have a very strong direct influence on the molecular events that govern gene expression. In this review, we discuss the influence that (n-9), (n-6), and (n-3) fatty acids exert on gene expression in the liver and skeletal muscle and the impact this has on intra- and interorgan partitioning of metabolic fuels.

Dietary Fats, Unsaturated↗