Efeito da suplementação materna com palmitato de retinila sobre a concentração de retinol no colostro em condições de jejum e pós-prandial.

Vitamin A is important in many essential body processes and its deficiency results in serious consequences for human health. Breast milk is the only source of this vitamin for children that are exclusively breastfed. Analysis of vitamin A in mother s milk is important because its concentration is related to maternal vitamin A status and to its ingestion by the mother during pregnancy. The aim of the present study was to assess the effect of maternal supplementation with retynil palmitate on the concentration of colostrum retinol under fasting and postprandial conditions. A total of 149 nursing mothers were recruited at the Januário Cicco Maternity School (Natal, Brazil) and allocated to two groups: Comparison (n = 69) and Test (n = 80). Blood and colostrum (in fasting and postprandial conditions) samples were collected up to 24hs after delivery. Serum retinol and colostrum levels were analyzed by high-performance liquid chromatography. The serum retinol level of 41.6 ± 12.7μg/dL (mean ± standard deviation) indicates adequate biochemical nutritional status. Colostrum retinol level was not influenced by serum retinol levels under any of the conditions established. In the colostrum, the retinol concentration in the unsupplemented test group was 67.3 ± 37.7 μg/dL under fasting and 80.3 ± 35.1 μg/dL under postprandial conditions (p<0.05), showing an increase of 19.3%. In the supplemented test group the values were 102.6 ± 57.3 μg/dL and 133.4 ± 78.3 μg/dL under fasting and postprandial, respectively (p<0.05), representing an increase of 30%. Considering that under fasting conditions most of the vitamin A transported to the milk originates in the retinol binding protein (RBP), the postprandial increase in colostrum retinol suggests a different transport mechanism of retinol to maternal milk from that performed by RBP. This situation becomes more evident under supplementation conditions.

Influência da suplementação de retinol palmitato sobre os níveis de vitamina A no leite de puérperas saudáveis

The tendency towards reduction of serum retinol levels, an existing placental barrier and the increase of retinol demand, are factors that place puerperal and lactating women at risk for Vitamin A deficiency. This micronutrient is an essential component of vital processes such as differentiation, cellular proliferation, and apoptosis. The objective of this study is to evaluate the effect of palmitate retinol supplementation (100.000UI) upon the milk retinollevels in puerperal women at the Januário Cicco University Maternity Hospital. This intervention has been adopted by the Ministry of Health since 2002. The longitudinal experiment was conducted with 106 puerperal women (68 comprised the supplemented group and 38 the control group). The High Performance Liquid Chromatography (HPLC) method was used to dose the retinol of the milk and serum samples, and the creamtocrit method to determine the milk fat levels. The retinol means for the colostrums were 99.0 ± 64.4 ug/dL and 160.1 ± 94,4 ug/dl 6 hours afier supplementation; 68.9 ± 33.5 ug/dL for the transitional milk, and 30.6 ± 15.2 ug/dL for the mature milk of the supplemented group. Ali the difterences between means were statistically significant. The difterence between retinol means in the control group were also significant, with these being greater in the colostrum, 88.6 ± 62.1 ug/dL with 61.9 ± 30.1 ug/dl in the transition milk and 32.9 ±32.9 ± 17.6 ug/dL in the mature milk. No significant difference was observed in the retinol means of the three types ot milk in the supplemented group when compared to their respective means in the control group. The prevalence in serum (35.1 % and 81.1 % for the cutting point 20 ug/dL, respectively) and in milk (51.4%) revealed vitamin A deficiency as a public health problem. COlostrum, transition, and mature milk tats varied similarly in the supplemented group (1,92 ± 0,96; 3,25 ± 1,27 and 3,31 ± 1,36 grams) and in the control group (1,87 ± 1,14; 3,25 ± 1,31 and 3,36 ± 1,67 grams), with an observed difference between the colostrum/transition milk and the colostrum/mature milk fats. No difference was observed between the groups. The study showed that the 200.000UI supplementation was not sufficient to increase the milk retinol to the desired levels nor to meet the demands of the mothers with deprived hepatic reserves. It is suggested that another similar dose be offered within 30 days or less, and within 2 months post-partum, while continual/y monitoring for possible pregnancy

Concentrações de retinol e de beta-caroteno séricos e perfil nutricional de crianças em Teresina, Piauí, Brasil

OBJETIVO: Avaliar as concentrações séricas de retinol e beta-caroteno de pré-escolares em Teresina, Piauí, com caracterização do perfil antropométrico e do consumo alimentar. MATERIAL E MÉTODOS: Estudo transversal envolvendo 135 crianças em creche municipal, com avaliação do estado nutricional pelos métodos: bioquímico (concentração sérica de retinol e beta-caroteno), antropométrico (índices de peso para estatura - P/E e estatura para idade - E/I) e dietético (freqüência de consumo alimentar). RESULTADOS: Observou-se prevalência de deficiência de vitamina A (DVA) de 8,9% (IC95%: 4,7 - 15,0%) e existência de associação entre suplementação anterior e concentrações de retinol, com maior proporção de crianças com níveis normais de retinol entre as suplementadas (p = 0,025). As concentrações de retinol e de beta-caroteno mostraram-se correlacionadas, porém com força leve a moderada (p < 0,021). Os percentuais de crianças com baixo P/E e de baixa E/I foram de 1,9% (IC95%: 0,2 - 6,8%) e 9,7% (IC95%: 4,8 - 17,1%), respectivamente. Na avaliação dietética verificou-se baixo consumo de alimentos ricos em vitamina A. CONCLUSÕES: A elevada prevalência de DVA nas crianças, combinada com a alta percentagem de crianças com valores aceitáveis de retinol, os baixos valores medianos de beta-caroteno, a alta percentagem de déficit estatural e a inadequação do consumo de alimentos ricos em vitamina A, indicam a necessidade de se aprimorar as estratégias de educação em saúde e nutrição da população, incentivando o consumo de alimentos fontes de vitamina A, como medidas auto-sustentáveis importantes no combate ao problema. Além disso, deve ser considerado o incentivo à fortificação dos alimentos e ao fortalecimento de Programas de suplementação.

Stability of vitamin A during storage of enteral feeding formulas

Vitamin A (13-cis-retinol, all-trans-retinol and total carotenes) content was evaluated in 15 samples of enteral feeding formulas during 3-6,9 and 12 months of storage in closed containers, protected from light and at room temperature (22-30 degrees C). All formulas were nutritionally complete and/or recommended for different diseases. Equivalent batches were also evaluated after preparation and refrigerated storage for 24 h. Nutrient content did not decrease during both storage scenarios. Stability of vitamin A in the enteral feeding formulas, as determined in this study, is probably due to production and storage conditions, e.g. absence of oxygen in contact with the packaged product, the technological process used in the microencapsulation of vitamins, and protected storage in the absence of light and at a temperature maximum of 30 degrees C. (C) 2010 Elsevier Ltd. All rights reserved.

Both human immunodeficiency virus-infected and human immunodeficiency virus-exposed, uninfected children living in Brazil, Argentina, and Mexico have similar rates of low concentrations of retinol, beta-carotene, and vitamin E

Our objective was to describe the prevalence of low concentrations of retinol, beta-carotene, and vitamin E in a group of human immunodeficiency virus (HIV)-infected Latin American children and a comparison group of HIV-exposed, uninfected children. Our hypothesis was that the rates of low concentrations of these micronutrients would be higher in the HIV-infected group than those in the HIV-exposed, uninfected group. This was a cross-sectional substudy of a larger cohort study at clinical pediatric HIV centers in Latin America. Serum levels of micronutrients were measured in the first stored sample obtained after each child`s first birthday by high-performance liquid chromatography. Low concentrations of retinol, beta-carotene, and vitamin E were defined as serum levels below 0.70, 0.35, and 18.0 mu mol/L, respectively. The Population for this analysis was 336 children (124 HIV-infected, 212 HIV-exposed, uninfected) aged I year or older to younger than 4 years. Rates of low concentrations were 74% for retinol, 27% for beta-carotene, and 89% for vitamin E. These rates were not affected by HIV status. Among the HIV-infected children, those treated with anti retrovirals were less likely to have retinol deficiency, but no other HIV-related factors correlated with micronutrient low serum levels. Low concentrations of retinol, beta-carotene, and vitamin E are very common in children exposed to HIV living in Brazil, Argentina, and Mexico, regardless of HIV-infection status. Published by Elsevier Inc.

Hepatocyte [H-3]-palmitate uptake: effect of albumin surface charge modification

The role of plasma proteins on the cellular uptake of lipophilic substrates has perplexed investigators for many years. We tested the hypothesis that an ionic interaction between the protein-ligand complex and hepatocyte surface may be responsible for supplying more ligand to the cell for uptake. The surface-charged groups on albumin were modified to yield proteins having a range of isoelectric points (ALB, ALBs, ALBm, ALBe had values of 4.8-5.0, 4.5-4.7, 3.0-3.5, 8.4-8.6, respectively). [H-3]-Palmitate uptake studies were performed with adult rat hepatocyte suspensions using similar unbound ligand fractions in the presence of the different binding proteins. Mass spectrometry, isoelectric focusing (pI), and heptane : water partitioning were used to determine protein molecular weight, pI, and protein-palmitate equilibrium binding constant, respectively. Hepatocyte [H-3]-palmitate clearance in the presence of ALBs and ALBm were significantly lower (p < 0.05) than ALB, whereas [H-3]-palmitate clearance in the presence of ALBe was significantly higher (p < 0.05) than ALB. The data were consistent with the notion that ionic interactions between extracellular protein-ligand complexes and the hepatocyte surface facilitate the uptake of long-chain fatty acids.

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites

Disposition kinetics of [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [H-3] palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [H-3] palmitate and metabolites were measured in four experimentalgroups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [H-3] palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [H-3] palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Níveis plasmáticos de vitamina A, carotenóides e proteína ligadora de retinol em crianças com infecções respiratórias agudas e doenças diarréicas

Planejou-se um estudo com o objetivo de se avaliar os níveis plasmáticos de vitamina A, carotenóides e proteína ligadora de retinol (RBP) em 311 crianças, de 7 meses a onze anos de idade, com história de infecções das vias aéreas superiores (IVAS), pneumonia e diarréia, residentes na área urbana da Cidade de São Paulo, Brasil, e atendidas no serviço de pediatria de um hospital-escola. As dosagens de vitamina A e carotenóides realizaram-se pelo método de Neeld-Pearson e o RBP pelo método de Mancini. Os níveis plasmáticos de vitamina A (µg/dl) e RBP (mg/dl) foram mais baixos (p<0,05) nos grupos diarréia e pneumonia (15,2 µg/dl e 1,7 µg/dl; 15,2 µg/dl; 2,6 mg/dl, respectivamente), quando comparados com os grupos IVAS e testemunha (19,0 µg/dl; 2,4µg/dl e 18,8µg/dl; 2,6mg/dl, respectivamente. Os níveis de carotenóides foram mais baixos nos três grupos de estudo em relação ao grupo testemunha (p<0,05). Os baixos níveis de vitamina A verificados nas crianças estudadas estão em concordância com outras pesquisas que encontraram diminuição dos níveis de vitamina A durante as infecções.

Interrelation between parasitic infections and hypovitaminosis A: Schistosoma mansoni infection and the retinol blood levels in an endemic area of State of Minas Gerais (Brazil)

The interrelation between schistosomiasis and the retinol blood levels was studied in a double blind method, by comparing the serum vitamin A of the infected and non-infected group of an endemic area of Schistosoma mansoni infection. The infected group was characterized by 106 parasitized persons in the intestinal and hepatointestinal forms, who eliminated less than 500 eggs/gram of feces (Modified Kato's method); the non-infected group was characterized by 112 inhabitants of this endemic area without eggs in the stools and presenting negative intradermal reactions, and absence of previous specific treatment. The blood levels of retinol was determinated using trifluoracetic acid method, regarding the normal levels > 20,0mg/100ml. The results of this study point out the absence of correlation between S. mansoni infection and blood levels of vitamin A.

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

The objective of this study was to assess vitamin A status and association between acute diarrhoea and plasma levels of vitamin A through cross-sectional comparison in children. Plasma vitamin A was measured by colorimetric method of Neeld & Pearson and RBP by radial immunodiffusion technique. Seventy eight children (aged 18-119 months), 26 with current history of diarrhoea and 52 children as controls (outpatient from the Santa Casa de Misericórdia Hospital in metropolitan area of São Paulo City, Brazil) were studied. Children with history of diarrhoea showed significant low levels (mean ± s.e.) as compared to controls, vitamin A (15.87 ± 1.4 µg/dl vs. 21.14 ± 1.15 µg/dl, p < 0.007) and RBP (1.70 ± 0.2 mg/dl vs. 2.52 ±0.11 mg/dl). Multivariate logistic regression adjusted by sex, age, nutritional status and mother education revealed association between diarrhoea and inadequate levels of vitamin A and RBP.

Influência da resposta inflamatória de fase aguda nos níveis séricos de retinol e da proteína de ligação do retinol em pacientes com AIDS

INTRODUÇÃO: a hiporretinolemia constitui fator prognóstico independente em pacientes com AIDS, e a atividade inflamatória causa redução dos níveis séricos deste nutriente na população em geral. Entretanto, faltam estudos que avaliem o impacto da atividade inflamatória sobre o nível sérico do retinol em pacientes com AIDS. MÉTODOS: foram avaliados transversalmente 41 pacientes internados por complicações da AIDS, que tiveram quantificados alguns marcadores de inflamação (proteína C reativa e fator de necrose tumoral alfa) e concentrações séricas de retinol e da proteína de ligação do retinol. RESULTADOS: apesar da baixa (14,6%) prevalência de hiporretinolemia evidenciou-se correlação negativa dos marcadores de inflamação com os níveis séricos de retinol e de sua proteína de ligação nos pacientes com AIDS. CONCLUSÕES: a atividade inflamatória de fase aguda está associada a baixos níveis séricos de retinol em indivíduos com AIDS.

PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.

BACKGROUND: Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells. METHODS AND RESULTS: Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers. CONCLUSION: Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.

Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment

Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impact

Avaliação da concentração de retinol em leite UHT ("Ultra High Temperature") comercializado em Natal, Rio Grande do Norte

Deficiency of micronutrients is a public health problem. Cow milk is a source of retinol. The objective of this study is to evaluate the retinol concentration in milk commercialized in Natal/RN. Ten samples were taken of each brand of UHT milk. Vitamin content was determined by HPLC using the Shimadzu LC-10 AD Chromatograph, coupled to the Shimadzu SPD 10 A UV-VIS Detector and the Shimadzu C-R6A Chromatopac Integrator with Shim-pack CLC-ODS (M) column, measuring 4.6 mm x 25 cm. The mobile phase was 100% methanol, with a flow of 1 mL/min. The mean retinol concentration varied between 22.7 ± 4.9 µg/100 mL and 44.1 ± 4.1 µg/100 mL, with the differences statistically significant (p<0.001). Only one of the 7 brands had retinol concentration below the normal requirements for human consumption.

Effects of ethanol intake on retinol concentration in the milk of lactating rats

The effect of the consumption of ethanol (5%) on retinol concentration in milk was studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5%) in drinking water during lactation (N = 7) were compared to normal controls fed ad libitum (N = 6). The mean maternal alcohol intake was 3.96 ± 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores ((1978) Clinical Chemistry, 24: 386-392). The pups were separated from dams for a 2-4-h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 ± 10.60 µg/dl in the control group and 60.02 ± 8.22 µg/dl in the ethanol group (P<0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 ± 0.43, 16.12 ± 0.48 and 18.60 ± 0.91 g, respectively) were significantly lower (P<0.05) than the weight of pups from controls (15.2 ± 0.44, 18.36 ± 0.54, 20.77 ± 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.