24 research outputs found

    The Vitamin D Decrease in Children with Obesity Is Associated with the Development of Insulin Resistance during Puberty: The PUBMEP Study

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    This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563); CIBEROBN Network (CB15/00131, CB15/00043); Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). E.M.G.-G. holds a Juan de la Cierva-Formación grant (FJCI-2017-34967) from the Ministerio de Ciencia e Innovación (Spanish Government). L.V.P. acknowledges financial support of the Visiting Professor Program from the Coordination for the Improvement of Higher Education Personnel (CAPES—Grant 88881.337237/2019-01), Brazil.Obesity and cardiometabolic risk have been associated with vitamin D levels even in children. The objective of the present study was to evaluate the association between insulin resistance (IR), cardiometabolic risk factors, and vitamin D in children from prepubertal to pubertal stages. A total of 76 children from the PUBMEP study, aged 4-12 years at baseline, were included. Children were evaluated in prepubertal and pubertal stages. Anthropometric measurements and selected cardiometabolic risk biomarkers, such as plasma glucose, blood lipids, insulin, adiponectin, leptin, and blood pressure, and serum 25-hydroxyvitamin D (25(OH)D) were determined. Children were categorized by obesity degree and IR status combined before and after puberty. Paired t-test and multivariate linear regression analyses were conducted. During puberty, the increase in triacylglycerols, insulin, and HOMA-IR and the decrease in QUICKI were significantly associated with the reduction in 25(OH)D (B = -0.274, p = 0.032; B = -0.219, p = 0.019; B = -0.250, p = 0.013; B = 1.574, p = 0.013, respectively) after adjustment by BMI-z, sex, and pubertal stage. Otherwise, prepubertal non-IR children with overweight/obesity that became IR during puberty showed a significant decrease in 25(OH)D and HDL-c, and an increase in waist circumference and triacylglycerol concentrations (p < 0.05 for all) over time. These results suggest that changes in IR seem to be associated with an effect on 25(OH)D levels during puberty, especially in children with overweight.Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I)Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563)CIBEROBN Network (CB15/00131, CB15/00043)Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015)Instituto de Salud Carlos III (IFI17/00048)Juan de la Cierva-Formación grant (FJCI-2017-34967) Ministerio de Ciencia e Innovación (Spanish Government)Coordination for the Improvement of Higher Education Personnel (CAPES—Grant 88881.337237/2019-01), Brazi

    Vitamin D Food Fortification and Nutritional Status in Children: A Systematic Review of Randomized Controlled Trials

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    Children are in the risk group for developing hypovitaminosis D. Several strategies are used to reduce this risk. Among these, fortification of foods with vitamin D (25(OH)D) has contributed to the achievement of nutritional needs. This systematic review aims to discuss food fortification as a strategy for maintenance or recovery of nutritional status related to vitamin D in children. The work was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in the International prospective register of systematic reviews (PROSPERO) database (CRD42018052974). Randomized clinical trials with children up to 11 years old, who were offered vitamin D-fortified foods, and who presented 25(OH)D concentrations were used as eligibility criteria. After the selection stages, five studies were included, totaling 792 children of both sexes and aged between two and 11 years. Interventions offered 300–880 IU of vitamin D per day, for a period of 1.6–9 months, using fortified dairy products. In four of the five studies, there was an increase in the serum concentrations of 25(OH)D with the consumption of these foods; additionally, most children reached or maintained su ciency status. Moreover, the consumption of vitamin D-fortified foods proved to be safe, with no concentrations of 25(OH)D > 250 nmol/L. Based on the above, the fortification of foods with vitamin D can help maintain or recover the nutritional status of this vitamin in children aged 2–11 years. However, it is necessary to perform additional randomized clinical trials in order to establish optimal doses of fortification, according to the peculiarities of each region.This research was funded by the National Council for Scientific and Technological Development (CNPq/MS/SCTIE/DECIT/DAB/CGAN), grant number 440809/2017-7. In part by the Coordination of Improvement of Higher Education Personnel—Brazil (CAPES)—Finance Code 001. And by Unidad Científica de Excelencia Ejercicio y Salud (UCEES), University of Granada, Spain

    Fatores precoces para síndrome metabólica em sobreviventes de câncer pediátrico: resultados em adolescentes e adultos jovens tratados por meduloblastoma na infância

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    OBJECTIVE: To analyze traits of metabolic syndrome (MetS) in medulloblastoma survivors. SUBJECTS AND METHODS: Sixteen childhood medulloblastoma survivors aged 18.0 (4.4) years, with history of craniospinal radiation therapy (RT) were compared with nine control subjects matched by age, gender, and body mass index, according to fat distribution, metabolic and cardiovascular variables. RESULTS: Medulloblastoma patients showed increases in waist circum-ference and its relationships (all p < 0.05), and HOMA1-IR (p = 0.006), which were modified by growth hormone (GH) secretion status. However, these increases were within normal range. CONCLUSIONS: Adolescent and young adult survivors of medulloblastoma showed centripetal fat deposition and decreased insulin sensitivity, associated with GH status. Pediatric brain tumor survivors following RT should be monitored for the diagnosis of MetS traits predisposing to cardiovascular disease.OBJETIVO: Analisar características que predispõem para síndrome metabólica (SM) em sobreviventes de meduloblastoma. SUJEITOS E MÉTODOS: Dezesseis sobreviventes de meduloblastoma pediátrico, 18,0 (4,4) anos, história de radioterapia (RT) cranioespinhal, comparados a nove controles pareados por idade, sexo e índice de massa corporal, de acordo com distribuição de gordura, variáveis metabólicas e cardiovasculares. RESULTADOS: Pacientes com meduloblastoma mostraram aumento da cintura e relações (todos p < 0,05) e HOMA1-IR (p = 0,006), modificados pela secreção do hormônio de crescimento (GH), mas dentro dos limites de normalidade. CONCLUSÕES: Sobreviventes adolescentes e adultos jovens de meduloblastoma apresentaram deposição centrípeta de gordura e diminuição da sensibilidade à insulina, associados ao estado do GH. Sobreviventes de tumor cerebral pediátrico que receberam RT devem ser monitorados para diagnosticar fatores para SM predispondo à doença cardiovascular.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of PediatricsUNIFESP-EPM Department of MedicineUniversidade de São Paulo Department of Food Science and Experimental Nutrition Pharmaceutical Science SchoolUNIFESP-EPM Department of PediatricsUNIFESP, EPM, Department of PediatricsUNIFESP, EPM Department of MedicineUNIFESP, EPM Department of PediatricsSciEL

    Instrumento para análise de consumo de alimentos com alto teor de sódio

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    Diante da importância para estudos epidemiológicos objetivou-se elaborar um instrumento para avaliar o consumo de alimentos com alto teor de sódio. Recordatório de 24 horas (R24) foi aplicado em 50 indivíduos ?18 anos, de ambos os sexos, para identificar alimentos e preparações consumidas. Para a elaboração do questionário de frequência alimentar de alimentos com alto teor de sódio (QFA-ATS) foram selecionados alimentos com quantidade de sódio ?400mg por 100g/mL de alimento. A lista inicial foi composta de 44 itens, distribuídos em seis grupos alimentares. Em estudo piloto o QFA-ATS inicial foi aplicado em 32 hipertensos ?40 anos, selecionados aleatoriamente de amostra probabilística de estudo de base populacional. A reestruturação do QFA-ATS foi necessária para incluir alimentos que contribuem com a ingestão de sódio, por representar consumo habitual da população-alvo.  QFA-ATS desenvolvido é do tipo semiquantitativo, constituído de 55 itens, distribuídos em sete grupos alimentares. A porção padrão de cada item foi definida a partir da tabela de medidas referidas para alimentos consumidos no Brasil. Estabeleceram-se quatro opções para a quantidade consumida e oito categorias de frequência de ingestão. Aplicou-se estatística descritiva para estimativa da ingestão de sódio. Foi observada ingestão inadequada de sódio na população saudável (76%) e na população hipertensa (84,4%). No estudo piloto, o QFA-ATS inicial mostrou que 40,4% do sódio consumido provém dos alimentos com alto teor de sódio. O QFA-ATS atendeu aos aspectos metodológicos para a quantificação de sódio. Estudos para validação e reprodutibilidade deste instrumento estão em andamento

    Food and nutritional education in reducing cardiovascular risks in individuals with type 2 diabetes / Educação alimentar e nutricional na redução do risco cardiovascular em indivíduos com diabetes tipo 2

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    The objective of this study was to evaluate the effect of food and nutritional education on eating habits and cardiovascular risk in individuals with type 2 diabetes. In this longitudinal intervention study, participants with type 2 diabetes mellitus were evaluated before and after the intervention with food and nutritional education actions, which were performed every fifteen days for five months. Individuals were evaluated for anthropometry, systemic arterial pressure, food intake, and serum concentrations of fasting glucose and lipid control markers. The Castelli risk indexes I e II were calculated by the total cholesterol/HDL-c ratio and by the LDL-c/HDL-c ratio, respectively. Non-parametric Wilcoxon test for comparison of results between times was performed, with p-value &lt; 0.05 considered significantly different and p-values between 0.05 and 0.10 as marginally significant. The intervention was able to promote improvement in markers related to cardiovascular risk, reducing significantly waist (p=0.015) and hip circumference (p=0.021), triciptal cutaneous (p=0.011) and subscapular cutaneous folds (p=0.005), dietary lipids (p=0.071), total cholesterol (p=0.003), LDL-c (p=0.004) and Castelli I (p=0.033) and II (p=0.002) indexes. Food and nutritional education actions were able to improve markers associated with cardiovascular risks since they the leading causes of morbidity and mortality in individuals with diabetes

    Pervasive gaps in Amazonian ecological research

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    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

    Effect of supplementation with Brazil nuts (Bertholletia excelsa H.B.K.) on gene expression of inflammatory cytokines and its relationship to oxidative stress in patients with type 1 diabetes mellitus

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    Diversas hipóteses têm sido sugeridas para atividade anti-inflamatória do mineral selênio, tais como, efeito inibitório da enzima óxido nítrico sintase induzível e inibição da via de ativação do NF&#954;B. Associado a esse aspecto, o selênio faz parte do sistema de defesa antioxidante como parte da enzima glutationa peroxidase (GPx), reduzindo as concentrações de espécies reativas, e consequentemente, atenuando o estresse oxidativo. Assim, este trabalho teve como objetivo avaliar o efeito da suplementação com castanha-do-brasil (Bertholletia excelsa H.B.K.), fonte dietética de selênio, na expressão gênica de citocinas inflamatórias e sua relação com o estresse oxidativo em pacientes com diabetes mellitus tipo 1. Inicialmente foi realizada a caracterização da composição de macronutrientes, teor de selênio e de fenólicos totais presentes nas castanhas-do-brasil utilizadas neste estudo. A atividade antioxidante in vitro foi realizada nas frações ricas em ácidos fenólicos (ácidos fenólicos livres-AFL, ácidos fenólicos solúveis-AFS e ácidos fenólicos insolúveis-AFI) extraídas das castanhas desengorduradas pelos métodos de DPPH, capacidade redutora, &#946;-caroteno/ácido linoléico e inibição da peroxidação espontânea. O estudo com pacientes diabéticos foi de natureza longitudinal. Foram avaliados 70 pacientes com diabetes mellitus tipo 1, com idade média de 15 anos, atendidos no Setor de Endocrinologia Pediátrica da Universidade Federal de São Paulo. Foram constituídos dois grupos experimentais, um (35 pacientes - grupo suplementado - SDM) que recebeu a suplementação de 2,5 g de castanha-do-brasil por dia, durante sessenta dias, e o outro (35 pacientes - grupo controle - CDM) que não recebeu a suplementação. Foi realizada avaliação da composição corporal e do consumo alimentar. Além disso, foram avaliados os parâmetros bioquímicos relativos ao status de selênio, perfil lipídico, controle glicêmico (glicose e HbA1C), atividade da GPx e SOD, MDA, LDL(-), 8-isoprostanos e os níveis circulantes de IL-6, TNF-&#945;, PCR, fibrinogênio, VCAM, ICAM, PAI-1 e MCP-1. A expressão gênica da GPx1, ICAM, COX-2, MCP-1, IL-7 e TNF- &#945; foi determinada por PCR em tempo real. Verificou-se alta concentração de selênio na castanha in natura (115,53 &#181;g/g) e alto conteúdo de lipídios. Entre as frações, a AFL apresentou a maior quantidade de compostos fenólicos, seguida da AFS e AFI. Esses compostos estão relacionados com a capacidade antioxidante observada nessas amostras por mecanismos distintos. Os pacientes com diabetes mellitus tipo 1 apresentaram baixo consumo de selênio, e após a intervenção com a castanha-do-brasil, o consumo aumentou significativamente. Em relação ao status de selênio, houve aumento estatisticamente significativo (p<0,05) na concentração de selênio no plasma, eritrócitos e urina após a intervenção com a castanha-do-brasil. A suplementação não foi capaz de modificar positivamente os marcadores de estresse oxidativo, com exceção da atividade da GPx no sangue total, a qual teve sua atividade aumentada em ambos os grupos após o período de intervenção. Após o consumo da castanha-do-brasil, houve redução nas concentrações de ICAM e PAI-1, no entanto, os demais marcadores inflamatórios, tanto os bioquímicos quanto os de expressão gênica, não foram alterados com a suplementação. A castanha-do-brasil, além de ser uma boa fonte de selênio, apresenta quantidades elevadas de compostos fenólicos e expressiva atividade antioxidante in vitro. A suplementação com a castanha-do-brasil mostrou-se efetiva em melhorar o estado nutricional relativo ao selênio dos pacientes com diabetes mellitus tipo 1, sem no entanto, reduzir as concentrações dos marcadores de estresse oxidativo e de inflamação (com exceção da ICAM e PAI-1) nas condições estudadas.Several mechanisms have been suggested for the anti-inflammatory activity of selenium, including inhibition of inducible nitric oxide synthase and inhibition of NFkB activation. In this regard, selenium, as an integral constituent of glutathione peroxidase (GPx), a key enzyme in antioxidant defense systems, plays an important role in reducing the concentrations of reactive species, and, consequently, in attenuating oxidative stress. This work aimed to evaluate the effect of supplementation with Brazil nuts (Bertholletia excels HBK), dietary sources of selenium, over gene expression of inflammatory cytokines and its relationship to oxidative stress in patients with type 1 diabetes mellitus. Initially, the composition of macronutrients and the contents of selenium and phenolic compounds in the Brazil nuts used in this study were characterized. In vitro antioxidant activity of three phenolic acid-rich fractions from the defatted nuts (free phenolic acids - FPA, soluble phenolic acids - SPA and insoluble phenolic acids - IPA) was assessed by the following methods: DPPH, reducing power, &#946;-carotene/linoleic acid and inhibition of spontaneous peroxidation. Seventy type 1 diabetic individuals, at an average age of 15 years old, either patients attending the Division of Pediatric Endocrinology of the Federal University of Sao Paulo or patients being assisted by local non-governmental organizations (NGOs) for diabetes, were followed longitudinally for two months. They were divided into two experimental groups: group 1 (n=35, supplemented with 2.5 g Brazil nuts a day for sixty days, SDM) and control group (n=35, non-supplemented, CDM). Body composition and dietary intake were monitored. The biochemical parameters related to selenium status, lipid profile, glycemic control (glucose and HbA1C), activities of GPx and SOD, MDA, LDL(-), 8-isoprostanes and circulating levels of IL-6, TNF-&#945;, CRP, fibrinogen, VCAM-1, ICAM-1, PAI-1 and MCP-1 were also evaluated. Gene expression of GPx1, ICAM, COX-2, MCP-1, IL-6 and TNF-&#945; was determined by real time PCR. Non-processed Brazil nuts were found to be rich in selenium (115.5 &#181;g.g-1) and to have high lipid content. Of the phenolic fractions studied, the FPA fraction showed the highest levels of phenolic compounds, followed by SPA and IPA. The phenolic content of the fractions was related to the antioxidant capacity, regardless of the method used for determination. The previously low intake of selenium by the type 1 diabetic patients studied increased significantly following supplementation with Brazil nuts. Selenium concentration in plasma, erythrocytes and urine showed a statistically significant increase (p<0.05) after intervention. Apart from a greater GPx activity in whole blood, observed in both groups, no other positive changes in oxidative stress markers were noted after the 2 month-supplementation. The consumption of Brazil nuts led to reductions in ICAM-1 and PAI-1 levels. However, other inflammatory markers were not affected by supplementation. As well as being rich sources of selenium, Brazil nuts also have great quantities of phenolic compounds and display significant in vitro antioxidant activity. Supplementation with Brazil nuts was shown to be effective in improving the nutritional status of selenium in patients with type 1 diabetes; however, it did not succeed in reducing any oxidative stress and inflammation marker levels, other than ICAM and PAI-1 levels, under the conditions studied

    Assessment of nutritional status on the zinc and selenium of patients with Turner syndrome in different stages of development

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    Estudos relacionando a síndrome de Turner com o estado nutricional relativo aos micronutrientes, em especial o zinco e selênio, são praticamente inexistentes. Portanto, o presente estudo teve como objetivo avaliar o estado nutricional relativo ao zinco e ao selênio dessa população, considerando as diferentes fases de vida. A avaliação antropométrica das crianças mostrou que 55,6% estavam eutróficas e 44,4% com sobrepeso, de acordo com o índice de peso/estatura. As adolescentes foram classificadas segundo o percentil de IMC ajustado para a idade, onde 73,7% estavam eutróficas e 26,3% com sobrepeso. Em relação ao grupo das adultas, 42,9% estavam com sobrepeso e 14,3% com obesidade, considerando o IMC (kg/(m)2). A avaliação do consumo alimentar foi realizada por meio do software Nutwin, mostrando que a ingestão de zinco dietético de 35,7% das participantes do estudo estava abaixo da EAR. Em relação à ingestão de selênio, observou-se que 100% das pacientes consumiram quantidades deste mineral acima da EAR. Na avaliação da concentração de zinco plasmático foi demonstrado que 22,2%, 68,4% e 14,3% das crianças, adolescentes e adultas estavam deficientes em zinco. A concentração de zinco eritrocitário apresentou-se deficiente em 66,7% das crianças, 57,9% das adolescentes e 28,6% das adultas. Na avaliação da excreção urinária de zinco observou-se que mais de 50% da população estudada estavam eliminando baixas concentrações desse mineral. Em relação ao estado nutricional de selênio, 77,8% das crianças, 78,9% das adolescentes e 85,7% das adultas encontravam-se deficientes em selênio plasmático e 55,6%, 52,6% e 57,1% das crianças, adolescentes e adultas, respectivamente, estavam deficientes em selênio eritrocitário. Opercentual de crianças, adolescentes e adultas com baixas concentrações de selênio na urina foi de 100%, 94,7% e 100%, respectivamente. A determinação da concentração de selênio nas unhas mostrou que 100% das crianças, 93,8% das adolescentes e 66,7% das adultas se encontravam com valores reduzidos neste compartimento. Os resultados da atividade da glutationa peroxidase se mostraram dentro dos limites de normalidade nas três fases de desenvolvimento. Assim, pode se concluir que o estado nutricional relativo ao zinco e ao selênio está deficiente para grande parte das pacientes, visto que as concentrações desses micronutrientes encontram-se reduzidos para a maioria dos parâmetros utilizados.Studies relating to Turner Syndrome with the nutritional status on micronutrients, in particular zinc and selenium are practically non-existent. This study aimed to assess the nutritional status on zinc and selenium in this population, considering the different stages of life. Anthropometric evaluation of the children showed that 55.6% were eutrophic and 44.4% with overweight, according to the rate of weight/height. The adolescents were c1assified according to the percentile of BMI adjusted for age, where 73.7% were eutrophic and 26.3% with overweight. Regarding the group of adults, 42.9% were overweight and 14.3% with obesity, according BMI (kg/m2). The assessment of food consumption was made through the software Nutwin, demonstrating that the intake of dietary zinc, 35.7% of participants in the study were below the EAR. Regarding the intake of selenium, it was observed that 100% of patients consumed quantities of this mineral above the EAR. In assessing the plasma concentration of zinc has been shown that 22.2%, 68.4% e 14.3% of children, adolescents and adults were deficient in zinco The concentrations of zinc in erythrocyte were deficient 66.7% of children, 57.9% of adolescents and 28.6% of adults. In assessing the urinary excretion of zinc observed that 55.6%,57.9% and 66.7% of children, adolescents and adults, respectively, eliminate low concentrations of this mineral. The nutritional status of selenium, 77.8% of children, 78.9% of adolescents and 85.7% of adults were found deficient in plasmatic selenium and 55.6%, 52.6% and 57.1% of children, adolescents and adults, respectively, were deficient for selenium in erythrocyte. The percentage of children, adolescents and adults with low concentrations of selenium in urine was 100%, 94.7% and 100% respectively. The determination of the concentration of selenium Nail showed that 100% of children, adolescents and 93.8% from 66.7% of adults with values were reduced in this compartment. The results of the activity of glutathione peroxidase were within the limits of normality in the three stages of development. Thus, it can be concluded that the nutritional status on the zinc and selenium is deficient for most patients, because the concentrations of these micronutrients, are reduced for most of the parameters used
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