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Biomedical subjects

R Uauy

Publications and source records attributed to R Uauy.

At least 19 recordsLinked to original sources
PubMed1998

Essentiality of copper in humans.

The biochemical basis for the essentiality of copper, the adequacy of the dietary copper supply, factors that condition deficiency, and the special conditions of copper nutriture in early infancy are reviewed. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. Mechanisms responsible for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support the existence of a copper-dependent gene regulatory element. Diets in Western countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption, elevated requirements induced by rapid growth, or increased copper losses. The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerance. A range of safe intakes should be defined for the general population, including a lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population.

Animals↗
PubMed1998

Copper in infant nutrition: safety of World Health Organization provisional guideline value for copper content of drinking water.

BACKGROUND: Copper is an essential nutrient for humans. Recently, a limit of 31.48 micromol/l (2 mg/l) was proposed by the World Health Organization as the provisional guideline value for copper content of drinking water. The objective of the study was to determine the tolerance of chronic exposure to drinking water with low or high copper content in infants. METHODS: Healthy infants (n = 128) were randomly assigned to receive drinking water with less than 1.57 micromol/l (<0.1 mg/l) (n = 48) or 31.48 micromol/l (2 mg/l) of copper (n = 80) from 3 to 12 months of age. At 6, 9, and 12 months of age, serum concentrations of copper, ceruloplasmin, and superoxide dismutase; erythrocyte metallothionein; bilirubin; transaminases; and gamma-glutamyl transferase were measured. RESULTS: Small differences in biochemical indexes of copper nutrition were observed between the groups, but there was no evidence of adverse or toxic effects. These findings may be explained by an adaptive response to the higher copper intake, limiting copper absorption, and increasing biliary secretion, as well as by an increase in copper storage. It is also possible that the sensitivity of the biochemical indicators employed to detect differences in copper status is limited. CONCLUSION: No acute or chronic adverse consequences of consuming water with copper content of 31.48 micromol/l (2 mg/l) were detected in infants during the first year of life. The results support the safety of the World Health Organization's provisional guideline value for copper in drinking water during infancy.

Alanine Transaminase↗
PubMed1998

Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants.

The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.

Arachidonic Acid↗
PubMed1997

Loss of the metal binding properties of metallothionein induced by hydrogen peroxide and free radicals.

The relationship between the metal-binding properties of metallothionein (MT) and its ability to interact with peroxides and free radicals was explored in vitro. The binding of 109Cd to MT and the thiol density of the protein were determined after incubation of a purified Zn/Cd-metallothionein preparation with either hydrogen peroxide alone, or with a number of free radical generating systems. Exposure of MT to H2O2, whether in the presence or absence of Fe2+, resulted in the progressive loss of the thiol residues of the protein and led to a parallel decrease of its 109Cd-binding capacity. These changes correlated with r values of 0.999 (P = 0.001) and 0.998 (P = 0.001), in the absence and presence of iron, respectively. The effects of H2O2, alone or plus Fe2+, on MT were completely prevented by catalase, but totally unaffected by superoxide dismutase or desferrioxamine. Exposure of MT to xanthine/xanthine oxidase also led to thiol oxidation and to a concomitant loss of the Cd-binding properties. In this system, both changes correlated with an r of 0.993 (P = 0.001) and were completely inhibited by superoxide dismutase. Exposure of MT to the peroxyl radical generator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), resulted in the progressive loss of its the metal-binding properties and its thiol residues, both changes correlating with an r of 0.986 (P = 0.002). The ability of MT to bind 109Cd, lost as a result of its prior exposure to either H2O2 alone, H2O2 plus Fe2+, xanthine/xanthine oxidase, or to AAPH was, in all cases, completely recovered after incubation of the modified protein with dithiothreitol. These results indicate that H2O2 alone, and/or the oxygen-derived species, superoxide anion and peroxyl radicals, can all directly interact in vitro with MT to modify the protein oxidatively, and suggest that, under in vivo conditions, these species may be implicated as modifying factors of the metal-binding capacity of metallothionein.

Amidines↗
PubMed1996

Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants.

It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.

Arachidonic Acid↗
PubMed1996

Role of essential fatty acids in the function of the developing nervous system.

The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.

Animals↗
PubMed1996

Copper as an essential nutrient.

Animal and human studies have shown that copper is involved in the function of several enzymes. Studies have also shown that copper is required for infant growth, host defense mechanisms, bone strength, red and white cell maturation, iron transport, cholesterol and glucose metabolism, myocardial contractility, and brain development. Copper deficiency can result in the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly a pathology of infants; however, it has been diagnosed also in children and adults. Most cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia, neutropenia, and bone abnormalities. Other, less frequent manifestations are hypopigmentation of the hair, hypotonia, impaired growth, increased incidence of infections, alterations of phagocytic capacity of the neutrophils, abnormalities of cholesterol and glucose metabolism, and cardiovascular alterations. Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however, they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency.

Anemia↗
PubMed1996

Limits of metabolic tolerance to copper and biological basis for present recommendations and regulations.

Acute copper toxicity is infrequent in humans. The evidence for chronic toxicity is derived principally from patients with Wilson disease and cases of infantile cirrhosis that were related to excessive copper intakes. The evaluation of the safety of a nutrient requires toxicologic studies to determine the limits of safe exposure. The acceptable daily intake (ADI) is calculated by determining the highest no-observed-adverse-effect level (NOAEL). When it is not possible to identify the NOAEL, the lowest observed-adverse-effect level (LOAEL) may be used. For the calculation of human ADI, the NOAEL or LOAEL obtained is divided by an arbitrary safety factor to provide an adequate margin of security. Drinking water standards have been adopted by the United States, the European Community, the World Health Organization, and other countries. The upper limits of copper concentration in water are based on organoleptic considerations and on debatable toxicity information. Given the importance of copper as an essential mineral for human health, it is conceivable that this and other essential minerals with health significance should be approached differently from nonessential minerals.

Animals↗
PubMed1996

Protein quality and urea kinetics in prepubertal Chilean schoolboys.

Urea kinetics were measured non-invasively in 12 Chilean schoolboys aged 8-10 years who were receiving one of two diets, either predominantly animal protein or predominantly vegetable protein. Both the diets provided an equivalent level of gross protein, 1.2 g/kg/day. The study diets were given for 10 days to enable adaptation to take place. On the eighth day a single oral dose of 15N15N-urea, 100 mg, was given and the amount of label excreted as 15N15-urea in urine over the subsequent 48 hours was measured. There was little difference in any aspect of urea kinetics between the two diets with urea production (animal, 173 +/- 50 mgN/kg/day; vegetable 179 +/- 53 mgN/kg/day), urea excretion (animal, 86 +/- 19 mgN/kg/day; vegetable, 105 +/- 13 mgN/kg/day), urea nitrogen hydrolysis (animal, 87 +/- 49 mgN/kg/day; vegetable, 74 +/- 42 mgN/kg/day), and the salvaged urea-nitrogen derived from hydrolysis which returned to urea formation (animal, 12 +/- 5 mgN/kg/day; vegetable, 17 +/- 9 mgN/kg/day) all being similar. A very high proportion of the salvage nitrogen derived from urea hydrolysis was maintained within the metabolic pool, about 80%, which was equivalent to 0.4 g protein/kg/day. This is the first time urea kinetics have been measured in children of this age and shows that 57% of the ura produced is excreted in urine on average with about 43% of the urea-nitrogen being salvaged for further metabolic interaction. It is concluded that the vegetable based protein diet taken habitually by Chilean children is metabolically equivalent in terms of urea kinetics to a diet based upon animal protein at this level of intake, but that high rates of salvage of urea nitrogen are found on both diets.

Aging↗
PubMed1995

Metabolism of omega-3 fatty acids in patients with autosomal dominant retinitis pigmentosa.

Abnormalities in lipid metabolism have been reported in numerous patients with retinitis pigmentosa. As an initial step in evaluating these anomalies, two trials of fatty acid intervention were conducted with autosomal dominant retinitis pigmentosa (adRP) patients and controls. The first trial addressed absorption and incorporation of omega 3 long-chain fatty acids from a fish-oil concentrate into red blood cell (RBC) lipids. The utilization of omega 3 long-chain fatty acids by adRP patients was found to be equivalent to that of controls. The second trial addressed the conversion of precursor, eicosapentaenoic acid (EPA, 20:5 omega 3), to end-product, docosahexaenoic acid (DHA, 22:6 omega 3), following oral supplementation of EPA ethyl ester. Although the levels of EPA and the intermediate, docosapentaenoic acid (22:5 omega 3), were both elevated by EPA supplementation in RBCs of adRP patients with rhodopsin gene mutations and controls, DHA production was elevated only in controls. Based on these results, we suggest the presence of a metabolic defect in the final stages of DHA biosynthesis.

Adult↗
PubMed1995

Low-density lipoprotein apheresis as long-term treatment for children with homozygous familial hypercholesterolemia.

OBJECTIVE: To determine the safety and efficacy of long-term dextran sulfate-affinity column low-density lipoprotein (LDL) apheresis for the treatment of children with receptor-negative homozygous familial hypercholesterolemia (HFH). STUDY DESIGN: Two children with HFH (pretreatment cholesterol levels 22.1 to 24.7 mmol/L (ranges 850 to 950 mg/dl) began LDL apheresis treatments at ages 7 and 10 years, respectively. The LDL apheresis treatment interval was generally either 7 or 14 days; for the last 2 years of the study the treatment interval was 7 days. The patients had 167 and 188 LDL apheresis procedures during 64 and 70 months, respectively. RESULTS: Individual procedures decreased total blood cholesterol levels by 63% to 68%. When the treatment interval was 7 days, the patients' time-averaged mean total cholesterol levels decreased to 7.3 +/- 0.65 mmol/L (280 +/- 25 mg/dl) and 6.4 +/- 0.55 mmol/L (247 +/- 22 mg/dl), respectively. Both children remained clinically well with normal growth and development. There was significant regression of xanthomas in both patients. The older patient required heart surgery for preexisting aortic stenosis and coronary ostial stenosis, but neither patient had progression of hypercholesterolemia-related cardiovascular disease. With the exception of iron (deficiency in patient 1), there was no evidence of depletion of serum components. Adverse reactions to LDL apheresis were rare and never severe. CONCLUSIONS: Dextran sulfate-affinity column LDL apheresis is effective long-term treatment for children with receptor-negative HFH.

Apolipoproteins↗
PubMed1995

Effect of phosphorus supply on mineral balance at high calcium intakes in very low birth weight infants.

To evaluate the effect of varying phosphorus intake with constant high calcium intake (430 micrograms/kJ, or 180 mg/100 kcal), we randomly assigned 35 appropriate-for-gestational-age healthy male infants (birth weight, 715-1510 g) on day 21 postnatally to either standard-phosphorus (215 micrograms/kJ, or 90 mg/100 kcal), moderate-phosphorus (254 micrograms/kJ, or 106 mg/100 kcal), or high-phosphorus intake (287 micrograms/kJ, or 120 mg/100 kcal). Three-day mineral balances were determined after 7 d of the study diets. Weight and head circumference gain and intake of energy and vitamin D were not different for all groups. Calcium retentions were sufficient to meet intrauterine accretion in all groups. Phosphorus calculated to be available for soft tissue was significantly higher in the moderate- and high-phosphorus groups, and was sufficient to support soft tissue phosphorus accretion in these two groups. Total absorbed phosphorus and phosphorus tubular reabsorption were each affected by phosphorus intake. We conclude that very low birth weight infants fed high calcium may require greater phosphorus intake than that provided by formulas containing a ratio of calcium to phosphorus of 2:1. We suggest that the optimal mass ratio of calcium to phosphorus for formula for very low birth weight infants is from 1.6:1 to 1.8:1.

Calcium, Dietary↗
PubMed1995

Human milk and breast feeding for optimal mental development.

Human milk has been characterized as the optimal food for human growth and development because of its nutritional, antiinfective and biological properties. Research conducted over the past decades provides further evidence on the uniqueness of human milk feeding for optimal brain development. The recognition of specific functions for the long chain essential fatty acids present in human milk as key components of neural membranes necessary for optimal brain development has provided a biological basis for this phenomenon. In addition the act of breast feeding provides unique mother-infant interactions opportunities that may have important implications for infant growth and development. These findings may have special relevance to populations in developing countries because this provides yet other very strong reasons to favor human milk feeding.

Brain↗
PubMed1995

Lipoprotein-cholesterol responses in healthy infants fed defined diets from ages 1 to 12 months: comparison of diets predominant in oleic acid versus linoleic acid, with parallel observations in infants fed a human milk-based diet.

A prospective study in healthy infants predefining both diet fatty acid and cholesterol, from birth to age 1 year, compared response of cholesterol fractions in three groups: random assignment to 1) monounsaturated-(Hi-Mono) (n = 20), or 2) polyunsaturated-(Hi-Poly) (n = 22) fatty acid-enriched diets, or 3) non-randomized selection to breast feeding (Human Milk) (n = 25). In each group, designated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group's defined formulas, with long-term compliance confirmed by plasma phospholipid fatty acid concentrations. By 12 months, total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups (P < 0.05). Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group, compared to the Hi-Mono groups. However, at the earlier 4-month interval, total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other, although each was significantly lower than the parallel Human Milk-group (P < 0.05). The Hi-Mono group increased gradually in total and LDL-cholesterol such that, after 12 months' feedings, all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group. In independent group comparisons, there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets. Independent of diet, HDL-cholesterol showed a falling trend as an overall time-effect across all groups (P < 0.001). These data suggest that prolonged feeding of a diet enriched in polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates. These differences in total, LDL-, and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year.

Cholesterol, HDL↗
PubMed1995

[Biological quality of a milk substitute for school children based on refined flour subjected to enzymatic hydrolysis].

The biological quality of an experimental milk substitute based on a raw wheat flour subjected to enzymatic hydrolysis in comparison to a control product based on extruded flours and milk protein was studied in 35 < > female school age children. The girls were fed their customary diet during 2 consecutive 14 and 12 day periods, and randomized to the experimental and control products in a double blind crossover fashion. Apparent absorption of protein, energy, calcium and phosphorus was evaluated. Mean nitrogen intake from the experimental product was significantly lower (223 vs 244 mg/Kg/d p<0.0001). Absorbed nitrogen was also lower (187 vs 203 mg&kg/d p<0.0001). Energy intake and excretion were similar with both products; 96 and 95% of intake was absorbed for experimental and control products respectively. The mean calcium intake was significantly lower than the experimental product (39.7 vs 60.2 mg/kg/d p<0.0001). Absorbed calcium from the experimental product was 50% of control (20.7 vs. 39.5 mg/Kg/d p<0.0001). Phosphorus intake was also lower with the experimental product relative to control (22.0 vs 27.8 mg/Kg/d p<0.0001) and absorbed P was 13.1 vs 16.5 mg/Kg/d respectively. Both products were well tolerated. We conclude that the experimental product based on wheat flour does not differ significantly in protein and energy digestibility but calcium and phosphorus absorption and digestibility are significantly lower limiting its use in school feeding programs.

Animals↗
PubMed1994

Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula.

Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency, we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk. This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth, clinical tolerance, coagulation test results, changes in erythrocyte membrane fluidity, and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age. "Healthy" preterm infants were maternally selected to receive human milk or selected at random to receive commercial ready-to-feed liquid formula, which provided limited omega 3 fatty acid, or experimental formulas supplemented with soy oil or soy and marine oils. Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth, clotting function, erythrocyte membrane fluidity, or vitamin A or E levels in healthy very low birth weight preterm infants. Additional studies to evaluate safety in a representative preterm population are required.

Analysis of Variance↗