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Biomedical subjects

R Uauy

Publications and source records attributed to R Uauy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regulation of copper uptake and transport in intestinal cell monolayers by acute and chronic copper exposure.

Adaptation to high and low copper intake in mammals depends on the cellular control of influx, efflux and storage mechanisms of cellular copper concentrations. In the present study, we used an intestinal cell line (Caco-2), grown in bicameral chambers to study the effect of equilibrium loading with copper. We analyzed (64)Cu uptake from the apical surface, intracellular metal (Cu, Zn, Fe) content, (64)Cu transport into the basal chamber, and total copper, zinc and iron in the basal chamber. We found that the (64)Cu uptake is saturable, shows a linear response phase up to 1.5 microM reaching a plateau at 4-6 microM extracellular Cu. Intracellular copper increased 21.6-fold, from 1.5 to 32.4 mM (at 0.2-20.2 microM extracellular copper respectively). The time course for (64)Cu uptake and transport was linear when the cells were incubated with different copper concentrations. Uptake increased 10-fold when intracellular copper concentration was raised. Fluxes were lowest at 1.5 mM and highest at 32.4 mM Cu intracellular copper (2.03 and 20. 98 pmole (64)Cu insert(-1) h(-1), respectively). The apical-to-basolateral copper transfer rate was lower at 32.4 mM as compared to 1.5 mM intracellular copper (0.55-1.95 pmole (64)Cu insert(-1) h(-1), respectively). The total copper in the basal chamber increased 4.2-fold (from 3.04 to 12.85 pmole Cu insert(-1) h(-1)) when the intracellular copper concentration was raised. If cells are preincubated in a low copper medium most of the newly incorporated copper (64%) is transferred to the basolateral compartment. In contrast, under preloading with high copper concentration, only 4% of the fresh copper is transferred to the basal chamber; however, the intracellular copper contribution to this chamber increases by 4.2-fold. Thus, the process results in an increase in both storage and intracellular-to-basolateral flux of copper. In summary, our results indicate that copper fluxes from apical-to-cell and apical-to-basolateral domains are affected by intracellular copper concentration suggesting that mechanisms of copper transport involved in cellular adaptation to low and high copper exposure are different.

Biological Transport↗
PubMed2000

Essential fatty acid metabolism in the micropremie.

Lipids are structural components of all tissues and are indispensable for cell membrane synthesis. The brain, retina, and other neural tissues are particularly rich in LCPUFAs, affecting neural structural development and function. LCPUFAs serve also as specific precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes, and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions, and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, uterine contraction). Dietary lipid intake affects cholesterol metabolism at an early age and is associated with cardiovascular morbidity and mortality in later life. Over recent years, the role of fatty acids in modulating signal transduction and regulating gene expression have been described, emphasizing the complex of fatty acid effects. Dietary fatty acids, especially LCPUFA, can have significant effects in the modulation of developmental processes affecting the clinical outcomes of extremely premature infants.

Fatty Acids, Essential↗
PubMed2000

A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants.

The effects of dietary docosahexaenoic acid (DHA) supply during infancy on later cognitive development of healthy term infants were evaluated in a randomized clinical trial of infant formula milk supplemented with 0.35% DHA or with 0.36% DHA and 0.72% arachidonic acid (AA), or control formula which provided no DHA or AA. Fifty-six 18-month-old children (26 male, 30 female) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development, 2nd edition (BSID-II) (Bayley 1993) at the Retina Foundation of the Southwest, Dallas, TX. These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition, sweep visual evoked potential (VEP) acuity, and forced-choice preferential looking (FPL) acuity (Birch et al. 1998). Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index (MDI) of the BSID-II. Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group. While a similar trend was found for the language subscale, it did not reach statistical significance. Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups, consistent with a specific advantage of DHA supplementation on mental development. Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI.

Analysis of Variance↗
PubMed2000

Essential fatty acids in early life: structural and functional role.

Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4alpha. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Animals↗
PubMed2000

Essential fat requirements of preterm infants.

The interest in factors that modify early infant development has led investigators to focus on n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFAs) in the past 2 decades. The presence of docosahexaenoic acid (DHA) and arachidonic acid (AA) in breast milk, compared with their absence from infant formulas available in the United States, has prompted clinical trials designed to examine whether LCPUFA enrichment of infant formula has beneficial effects on maturational events of the visual system. These trials have shown significant functional advantages of LCPUFA supplementation for preterm infants, whereas benefits for full-term infants remain controversial. The growth and safety of preterm infants was not compromised by LCPUFA enrichment, although these issues remain to be resolved in clinical trials with full-term infants.

Adult↗
PubMed2000

Fat intake during childhood: metabolic responses and effects on growth.

Lipids are considered the most important energy source in the infant diet and are necessary for normal growth and physical activity. Human milk, in which most of the energy is present as fat, provides a relatively high cholesterol intake. Formula provides a much lower cholesterol intake. Infants fed human milk have higher total and LDL-cholesterol concentrations in plasma than do formula-fed infants (P: < 0.05), whereas plasma HDL- and LDL-cholesterol concentrations are lower in formula-fed infants if a formula high in linoleate is fed (P: < 0.05). Infants adapt to the high cholesterol content of human milk through a decrease in cholesterol synthesis; in contrast, the addition of cholesterol to formula does not suppress synthesis. Measurements of serum lipoproteins and LDL-receptor activity suggest that it is the fatty acid content, rather than the cholesterol content, of the diet that regulates cholesterol homeostasis. We studied the effect of total energy, source of energy, and fat on growth indexes of children <6 y of age in Latin America with use of food balance data. With respect to availability of animal fat, a negative relation was evident for being underweight (percentage weight-for-age <2 SDs of the World Health Organization-National Center for Health Statistics standards) and for having a low birth weight; the latter was also negatively related to energy. Wasting (percentage weight-for-height <2 SDs) was not related to dietary factors. These results suggest that diets that provide <22% of energy from fat and that are low in animal fats may restrict growth. The coexistence of early stunting with adult obesity in Latin America creates a dilemma for public nutrition intervention programs.

Child Development↗
PubMed2000

Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development.

BACKGROUND: In contrast to human milk, current infant formulas in the United States do not contain omega3 and omega6 long-chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind, randomized clinical trial. METHODS: Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid-enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid- (0.36%) and arachidonic acid- (0.72%) enriched formula. Eighty-seven infants completed the 17-week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age. RESULTS: Commercial formula-fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breastfed infants. Significant differences persisted at the 1-year follow-up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long-chain polyunsaturated fatty acid-enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age. Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age. Early (17-week) fatty acid profiles in blood lipids were correlated with later (52-week) visual function development in study infants. CONCLUSIONS: Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.

Arachidonic Acid↗
PubMed2000

Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.

Embryonic and Fetal Development↗
PubMed2000

[Molecular nutrition, role of the PPAR system in lipidic metabolism and its importance in obesity and diabetes mellitus].

PPARs are transcription factors belonging to the super family of hormonal receptors. Their activity is regulated by fibrates, thiazolidinediones, certain anti inflammatory drugs and fatty acid derivatives, present in food. PPAR isoforms play a central role in lipid homeostasis, regulating anabolic (PPAR gamma) and catabolic (PPAR alpha) pathways of lipid metabolism. Additionally, these receptors participate in glucose homeostasis, influence cellular proliferation and differentiation and participate in inflammatory processes. The effects of PPARs on oxidative substrate partitioning suggests that they have a relevant role in the development of obesity and insulin resistance.

Animals↗
PubMed1999

Fatty acid profile of buccal cheek cell phospholipids as an index for dietary intake of docosahexaenoic acid in preterm infants.

Cheek cells (buccal epithelia) were utilized as a noninvasive index of fatty acid status in a study of the effects of n-3 long chain polyunsaturated fatty acid supplementation on visual function in preterm infants. The fatty acid profile of cheek cell phospholipids was directly correlated with the dietary docosahexenoic acid (DHA) intake of infants receiving: (i) primarily human milk; (ii) n-3 fatty acid-deficient, corn oil-based, commercial formula (CO); (iii) alpha-linolenic acid-enriched, soy oil-based, commercial formula; or (iv) experimental formula enriched with soy and marine oils providing a DHA level equivalent to that in human milk. In a subset of infants with complete cheek cell fatty acid profiles and visual function assessments, preterm infants at both 36 wk (n = 63) and 57 wk (n = 45) postconceptional age had significantly (P < 0.0005) reduced cheek cell phospholipid DHA levels in the n-3-deficient, CO-fed group compared to the other diet groups. The DHA content in cheek cell phospholipids was highly correlated (P < 0.0005) with that of both red blood cell lipids and plasma phospholipids at the 36- and 57-wk time points. The DHA content in cheek cell lipids of infants at 36 wk was significantly correlated with electroretinographic responses (r = -0.29; P < 0.03) and visual acuity (r = -0.31; P < 0.02) as measured by visual-evoked potentials (VEP). Cheek cell DHA was highly correlated (r= -0.57; P < 0.0005) with VEP acuity at the 57-wk time point. These results suggest that the fatty acid profile of cheek cells is a valid index of essential fatty acid status, can be monitored frequently, and is associated with functional parameters in infants.

Cheek↗
PubMed1999

The effect of sleep state on electroretinographic (ERG) activity during early human development.

To assess the effects of sleep state on human retinal electric responses, full-field electroretinograms were obtained in a cross-sectional study from 123 preterm infants at 36, 40 and 56 weeks of post-gestational age. At each age, electroretinographic recordings were assigned to one of two groups according to whether the infants were in active sleep or quiet sleep. Both sleep states were determined behaviorally. Pure rod, maximal, 30 Hz flicker and light adapted single cone responses were evaluated when a sleep state was clearly established. Peak-to-peak amplitudes of most electroretinographic responses were significantly larger in active sleep relative to quiet sleep at 36 and 40 weeks of post-gestational age. We speculate that larger amplitudes during active sleep may play a role in the maturation of the visual system.

Age Factors↗
PubMed1999

Essential fatty acids as determinants of lipid requirements in infants, children and adults.

Essential fatty acids (EFA) are the indispensable component of the lipid supply beyond the provision of energy as a fuel for oxidation. They serve as dietary precursors for the formation of prostanoids and other eicosanoids thus are of great significance in health and modulation of disease conditions. Eicosanoids are powerful autocrine and paracrine regulators of cell and tissue functions: thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, and uterine contraction. Recent attention has focused on the effect of n-3 and n-6 long chain EFAs in normal fetal development. Results from human infant studies suggest that n-3 fatty acids are needed for optimal development of visual and brain function. Human milk is the best and only time proven source of fat and dietary essential fatty acids for infant feeding. International recommendations for n-3 and n-6 EFA dietary intake are reviewed and suggested intakes for long chain EFAs are provided.

Adult↗
PubMed1999

The role of industry in bringing foods for particular nutritional uses (PARNUTS) to the market.

The process of bringing new food products from innovation to implementation requires a high level of interaction between researchers, marketers, and consumers. Researchers from industry and academia have the task of developing products that are not only efficacious, but also have a high probability of consumer acceptance. For most foods, industry must provide the most leadership in finding new product concepts, determining which products will have the widest markets, and in funding research and development. To accomplish these tasks, industry has forged partnerships with academic centers and scientists who excel in research and development, and continues to search for the best ways to communicate with consumers. For some FSMPs, other considerations, such as medical and nutritional needs (e.g., products for inborn errors of metabolism), might change the pattern of industry leadership. The following article explores the ways in which industry can facilitate the development and acceptance of beneficial and marketable food products.

Academic Medical Centers↗
PubMed1999

Consumption pattern of dietary fats in Chile: n-6 and n-3 fatty acids.

Chile consumes both vegetable and animal fats. Vegetable oils are almost totally imported but animal fats, mainly from marine origin, are locally produced. The country is the second world producer of fish meal and fish oil, and fish oil has been incorporated into the human nutrition through the manufacture of blends of vegetable oil with fractions of deodorized fish oil. Consumption of such oils contributes as a significant source of n-6 and n-3 fatty acids, mainly for the low-income consumers. The use of fish meal and fish oil for animal nutrition is also an additional source of n-3 fatty acids for the Chilean population. Pork, poultry and eggs are important sources of essential fatty acids, especially long-chain n-3 fatty acids. As result of the consumption of these products, milk from low-income Chilean mothers shows significantly higher total n-3 fatty acids relative to mothers from the USA and Germany. Safety concerns about fats consumption in Chile are regulated by a Food Safety Codex recently promulgated which follows FAO/WHO Codex Alimentarius directives.

Animals↗