A ingestão de dieta deficiente em ferro pode causar alterações estruturais no Sistema Nervoso Central (SNC) bem como no nervo óptico por prejuízo no processo de mielinização. Essas alterações geradas pela anemia ferropriva pós-natal não são satisfatoriamente revertidas após a reposição de ferro. A estimulação tátil e o enriquecimento ambiental podem reduzir e/ou evitar os efeitos prejudiciais desta desnutrição sobre o SNC. O objetivo deste estudo foi avaliar estrutural e quantitativamente, o nervo óptico de ratos Wistar com anemia ferropriva submetidos à estimulação tátil e recuperação nutricional. Foram utilizados 4 grupos: Controle (C), Anêmico (A), Recuperado Não Estimulado (RN) e Recuperado Estimulado (E), compostos aleatoriamente por 1 rata mãe e 6 filhotes machos. Os grupos foram divididos de acordo com a variável dieta oferecida, pela quantidade de ferro/kg de dieta (com nível adequado em ferro (C), deficiente em ferro (A) e com recuperação do nível adequado de ferro (R)). O grupo C foi alimentado com dieta contendo 35 mg de ferro/kg de dieta, e o grupo A, com 4 mg de ferro/kg de dieta, e os grupos Recuperados (RN e RE), com 4 mg de ferro/kg de dieta do dia 0 ao 21º dia e, 35 mg de ferro/kg de dieta a partir do 22º dia. Os grupos Recuperados foram classificados de acordo com a variável estimulação: Estimulado (E), grupo submetido à estimulação tátil do dia 0 ao 32º dia, e Não Estimulado (N). Durante o período de amamentação, as ratas mães se alimentaram da dieta determinada para cada grupo, e no período pós lactação os filhotes receberam as mesmas dietas de suas respectivas mães. No 21º dia as ratas mães foram eutanasiadas e no 32º dia, todos os filhotes foram anestesiados e perfundidos via transcardíaca com uma solução de salina tamponada (PBS) 0,05M, pH 7,3, tendo seus nervos ópticos dissecados e os fragmentos selecionados refixados em tetróxido de ósmio a 1% em tampão fosfato 0,1 M, pH 7,3 e então processados para inclusão em araldite. Da área total da secção transversal do nervo óptico foram selecionadas 2 áreas que corresponderam aproximadamente 30% do nervo para a realização de análises morfológica e morfométrica. Na análise morfológica os animais do grupo RE mostraram um aspecto muito semelhante às características dos animais do grupo C, e com melhor aspecto em relação aos grupos A e RN, apresentando grande quantidade de fibras nervosas mielínicas, uniformemente distribuídas, bem agrupadas e compactadas, com espaço intersticial reduzido. Na análise morfométrica, em relação ao número de vasos sanguíneos, os fatores dieta, recuperação e estimulação não apresentaram interferência. Em relação ao número de astrócitos, a estimulação não interferiu, e em relação a dieta, o grupo A apresentou maior número que os grupos C e RN. Na avaliação do número de oligodendrócitos, em relação ao fator dieta, o grupo RN apresentou maior número que os grupos C e A, os quais não apresentaram diferença estatisticamente significante entre si. Já para o fator estimulação, o grupo RE apresentou menor número de oligodendrócitos quando comparado ao RN. Podemos concluir que: 1 - a dieta utilizada foi eficaz no desenvolvimento de anemia ferropriva leve nas ratas mães e severa nos filhotes; 2 - a associação das técnicas de estimulação tátil e recuperação nutricional resultou em uma reorganização estrutural do nervo óptico, semelhante ao grupo C e 3 - tal associação não interferiu no número de vasos sanguíneos, entretanto, resultou em uma normalização do número de astrócitos e de oligodendrócitos / Inadequate intake of dietary iron can cause structural changes in the Central Nervous System (CNS) and, thus, in the optic nerve with impaired myelination process. These changes generated by postnatal iron deficiency anemia are not satisfactorily reversed after replacement iron. The tactile stimulation and environmental enrichment can reduce and/or prevent the damaging effects of malnutrition on the CNS. The objective of this study was to evaluate structural and quantitatively the optic nerve of Wistar rats with iron deficiency anaemia submitted to tactile stimulation and nutritional recovery. We used 4 groups: Control (C), Anemic (A), Recovered Not Stimulated (RN) and Recovered Stimulated (R), randomly composed of 1 adult female rat and 6 male newborns. These groups were divided according to the variable diet provided, the amount of iron/kg in the diet (with appropriate levels of iron (C), deficient in iron (A) and with recovery of the appropriate level of iron (R)). The Control (C) group was fed with ration containing 35 mg iron/kg diet and the Anemic (A) group, with 4 mg iron/kg diet, and the Recovered groups (RN and RE) with 4 mg iron/kg diet from day 0 to day 21, and 35 mg iron/kg from day 22. The Recovered groups were classified according variable stimulation: Stimulated (E), group submitted to tactile stimulation from day 0 to day 32, and Not Stimulated (N). During the breastfeeding period, the mother rats fed the diet given to each group, and after lactation period the puppies received the same diets of their mothers. At day 21, the female rats were euthanized and at day 32 all juveniles were anesthetized and perfused transcardially with a buffered saline solution (PBS) 0,05M, pH 7,3, having their optic nerves dissected, and selected fragments were fixed in osmium tetroxide 1% and phosphate buffer 0,1 M, pH 7,3, and then processed for embedding in Araldite. Were selected 2 areas of the total area of optic nerve cross-section which approximately corresponded to 30% of the nerve to perform morphological and morphometric analysis. In the morphological analysis the optic nerve of the animals in RE group showed a very similar structural aspect to the characteristics of the optic nerves in group C, and looking better than in groups A and RN, with lot of myelinated nerve fibers well grouped and compacted and this organization was present uniformly across the nerve, resulting in reduced interstitial space. In the morphometric analysis, the number of blood vessels, dietary factors, recovery and stimulation showed no interference, since all groups showed no statistically significant difference. Regarding to the number of astrocytes, the stimulation did not influence it and, regarding to diet, the group A presented a higher number of cells than groups C and RN. In assessing the number of oligodendrocytes, in relation to diet factor, RN group had a greater number of oligodendrocytes that C and A groups, which showed no significant statistically difference between them. As for the stimulation factor, the RE group had fewer oligodendrocytes than the RN. With the results can be concluded that: 1- the used diet was effective in the development of mild iron deficiency anaemia in mothers and severe in young rats; 2- the association of tactile stimulation and nutritional recovery techniques resulted in a structural reorganization of the optic nerve, similar to C group and 3- this association did not affect the number of blood vessels, however it resulted in a normalization of the number of astrocytes and oligodendrocytes

A biodisponibilidade de ferro de diferentes fontes foi avaliada pelo método de recuperação de hemoglobina em suínos anêmicos. O ensaio teve duração de 13 dias e os grupos foram homogeneizados de acordo com o produto do peso (kg) x hemoglobina (g/dL). As fontes de ferro estudadas foram: ferro microencapsulado com polímero de carboximetilcelulose sódica (NaCMC), ferro microencapsulado com polímero de alginato, ferro quelado com metionina e ferro reduzido eletrolíticamente. Com a finalidade de corrigir respostas devidas à variação na ingestão de ferro foram acrescentados três grupos chamados de grupos-padrão, cuja fonte dietética de ferro foi FeSO4.7H2O. A porcentagem média de absorção de ferro para os grupos experimentais variou de 12,8 (4,3) % (ferro eletrolítico) a 15,1 (3,8) % (ferro alginato), não sendo significativamente diferentes (P>0,05). A porcentagem média de absorção relativa ao FeSO4.7H2O variou de 89,5 (25,9)% (ferro NaCMC) a 105,9 (60,5)% (ferro quelado com metionina), sem diferenças significativas (p>0,05). Também não houve diferença significativa nos índices de conversão alimentar, eficiência alimentar e coeficiente de eficácia proteica (CEP). Não houve diferenças significativas (p>0,05) nas concentrações de ferro hepático entre as diferentes fontes estudadas. Nas condições deste ensaio, houve similaridade entre as fontes de ferro testadas quanto à biodisponibilidade. A microencapsulação proporcionou rneltlOr distribuição do produto na mistura quando comparada ao FeSO4.7H2O. / The iron availability from different sources was evaluated by the hemoglobin regeneration method in anemic pigs. The assay took 13 days and the animais were selected according to the weight (kg) x hemoglobina (g/dL) product. The iron sources studied were: microencapsulated iron with sodium carboximetilcelulose polymer (NaCMC), microencapsulated iron with alginato polymer, metionin-quelated iron and electrolytically reduced iron. To COITect answers due to iron ingestion variation three control groups were added, whose dietary iron source was FeSO4.7H2O. The average percentage of iron absorption for the experimental groups ranged from 12,8 (4,3) % (electrolytic iron) to 15,1 (3,8) % (iron alginato), without significant differences (p>0,05). The average percentage of FeSO4.7H2O relative absorption ranged from 89,5 (25.9)% (NaCMC iron) to 105,9 (60,5)% (metionin quelated-iron), without significant differences (p>O,OS). Also it did not have significant difference in the alimentary conversion and efficiency indexes and proteic effectiveness coefficient (CEP). No significant differences (p>0,05) were found in the hepatic iron concentrations among the different studied sources. Based on this assay\'s conditions, there were similarities among the tested iron sources regarding to their bioavailability. Microencapsulation provided better distribution of the product in the mixture when compared to the FeSO4.7H2O.

This parallel randomized control trial study assessed the effect of food-based strategies in improving the haemoglobin level; decreasing anaemia and thus the iron status of pregnant women. The study randomized 195 anaemic women enrolled from four randomly selected health centres in Dire Dawa while attending ANC into two intervention groups and control; and followed for 12weeks. The study intervened diet-based supplementation of 90mg/day vitamin C divided and consumed in three doses; combined with nutrition education intervention in intervention group 1; while only nutrition education intervention in group 2. Dietary diversity was assessed using past 24-hours and 7-days dietary recall approaches and haemoglobin levels were determined at baseline and end-line and compared to analyse treatment effects. By end of the study, intervention group 1 and 2 had significantly increased mean haemoglobin by 0.77 ± 0.11gm/dl and 0.398 ± 0.073gm/dl respectively; however, the control had significant decrease by -0.193 ± 0.05gm/dl. Anaemia prevalence also significantly decreased by 29% and 19.7% in intervention group 1 and 2 respectively. However, all women in the control were anaemic. Intervention group 1 and 2 also had significantly higher dietary diversity, consumption of vitamin C-rich fruits and vegetables, nutritional knowledge and modification practices. The researcher thus concludes that diet-based vitamin C supplementation integrated with nutrition education has a significant effect in improving haemoglobin, decreasing anaemia and thus improving the iron status of pregnant women in Dire Dawa. Based on the findings, the researcher developed a framework for an integrated food-based strategy for improving the iron status of pregnant women in Ethiopia. / Health Studies / D. Litt. et Phil. (Health Studies)

Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.

The etiology of anemia is characterized by abnormal hemoglobin synthesis. Iron deficiency is characterized by microcytic and hipochromic red cells and low serum ferritin, being the most prevalent nutritional deficiency worldwide, responsible for iron deficiency anemia (FA). Anemia of chronic disease (ACD) is considered a clinical syndrome associated with chronic inflammation, infectious disease, neoplastic or traumatic, being the second most frequent cause of anemia. The severity of anemia correlates with the degree of pathology. Both have functional iron deficiency. The objective of this study was to evaluate hematological and inflammatory, as well as the presence of oxidative stress in patients with anemia. The blood analyzer was done by the CBC, automated hematology analyzer processed, Sysmex® (Automated Hematology Analyzer). The quantitative determination of ferritin is serum was done in IMMULITE analyzer. Levels of CRP and AOPP were performed in serum by automated Cobas MIRA® (Roche Diagnostics). Statistical analysis was performed using GraphPad Prism 5. We analyzed 70 patients with microcytic and hypochromic anemia. Of these, 29 (41.43%) were diagnosed as iron deficiency anemia and 41 (58.57%) with anemia of chronic disease. As a control group, we used samples from 44 patients with hematological parameters, serum ferritin, CRP and AOPP normal. The values of MCV, MCH and MCHC significantly lower in iron deficiency anemia. Ferritin levels showed that it can be considered both a measure of iron store as an inflammatory marker. In ACD there is increased production of inflammatory cytokines, which, in turn, increases the concentration of C-reactive protein (CRP). The results indicate that AOPP in both groups with anemia showed increased levels of this marker, which indicates the presence of oxidative stress, probably caused by increased production of free radicals and decreases in enzyme activities of the antioxidant defense system of erythrocytes. / A etiologia das anemias caracteriza-se pela síntese anormal de hemoglobina. A deficiência de ferro é caracterizada por eritrócitos microcíticos e hipocrômicos e por ferritina sérica baixa, sendo a carência nutricional mais prevalente em todo o mundo, responsável pela Anemia Ferropriva (AF). A Anemia de Doença Crônica (ADC) é considerada uma síndrome clínica, associada à inflamação crônica, doença infecciosa, traumática ou neoplásica, sendo a segunda causa mais freqüente de anemia. Ambas apresentam deficiência funcional de ferro. O objetivo deste trabalho foi avaliar parâmetros hematológicos e inflamatórios, bem como a presença de estresse oxidativo em pacientes com anemia. A análise hematológica foi feita através do hemograma, processado em analisador hematológico automatizado, Sysmex® (Automated Hematology Analyzer). O doseamento quantitativo da ferritina no soro foi feito em analisador IMMULITE. A dosagem de Proteína C-Reativa (PCR) e de Produtos da Oxidação Avançada de Proteínas (AOPP) foram realizadas no soro através do sistema automatizado Cobas MIRA® (Roche Diagnostics). A análise estatística foi realizada através do programa GraphPad Prism 5. Foram analisados 70 pacientes portadores de anemia microcítica e hipocrômica. Destes, 29 (41,43%) foram diagnosticados como anemia ferropriva e 41 (58,57%) com anemia de doença crônica. Como grupo controle, foram utilizadas amostras de 44 indivíduos com parâmetros hematológicos, níveis de ferritina, PCR e AOPP dentro da normalidade. Os valores de VCM, HCM e CHCM foram significativamente menores na anemia ferropriva. Os níveis de ferritina revelaram que ela pode ser considerada tanto uma medida das reservas de ferro quanto um marcador inflamatório. Na ADC há aumento da produção de citocinas inflamatórias, que, por sua vez, aumenta também a concentração de PCR. Os resultados do AOPP indicam que ambos os grupos com anemia apresentaram níveis aumentados deste marcador, o que indica a presença de estresse oxidativo, provavelmente causado por aumento na produção de radicais livres e declínio das atividades das enzimas do sistema de defesa antioxidante dos eritrócitos.

Introdução: Anemia por carência alimentar de ferro é a deficiência nutricional mais freqüente e preocupante do ponto de vista da saúde coletiva. Afeta principalmente crianças, gestantes e mulheres em idade fértil. Apesar das medidas de intervenção para prevenção e controle da anemia no Brasil, estudos mostram que as prevalências ainda continuam elevadas. Objetivo: Investigar a situação da anemia e seus determinantes em mães e filhos no Brasil, considerando o contexto familiar. Método: Pesquisa transversal de abordagem quantitativa, que utilizou o banco de dados da Pesquisa Nacional de Demografia e Saúde da Mulher e da Criança (PNDS) 2006. Foram utilizados dois questionários com informações básicas sobre o domicílio e seus moradores e informações detalhadas sobre o público-alvo, mulheres de 15 a 49 anos e seus filhos menores de 5 anos. Aproximadamente 40% dos domicílios foram selecionados para coleta de sangue das mulheres, porém todas as crianças nascidas a partir de janeiro de 2001 tiveram o sangue colhido, desde que filhos biológicos da entrevistada. Análise de hemoglobina foi realizada em 5.915 mulheres e 4.558 crianças. Este estudo analisou 1.476 pares, considerando a mãe e apenas uma criança. O programa Statistical Package for Social Science (SPSS versão 18.0) foi utilizado para análise dos dados, que analisou anemia em mães e/ou filhos, mães e filhos isoladamente e constou das etapas univariada e múltipla. Resultados: A ocorrência de anemia foi de 36,8% em mães e/ou filhos, 23,4% nas mães e 17,0% nos filhos. Mães apresentaram chance 1,49 vezes maior de ter anemia do que os filhos, e não se verificou associação entre anemia nas mães e nos filhos (p=0,478). Na análise múltipla, mães e/ou filhos que residiam nas regiões Nordeste e Centro-Oeste apresentaram chance 2,24 e 1,70 vezes maior, respectivamente, em relação às da região Sul; a chance também foi estatisticamente maior (1,78 vezes) para o par com insegurança alimentar (sentiu fome) e em que a mãe realizou consulta de puerpério (1,39 vezes); primiparidade mostrou-se como fator de proteção. Anemia nas mães também se associou com macrorregião de residência, com chance 2,39 vezes maior para as da região Nordeste em relação às da região Sul; mães com insegurança alimentar, que realizaram consulta de puerpério e tiveram pelo menos uma doença também apresentaram chance 50% maior para anemia. Nas crianças, anemia associou-se com insegurança e consumo alimentar, sendo que aquelas que ingeriram multimistura e leite fresco com água nas últimas 24 horas apresentaram chance 2,49 e 1,69 vezes maior para anemia, respectivamente, assim como crianças que não ingeriram lanche da tarde no dia anterior e que ingeriram arroz menos de 4 vezes na semana (chance 1,57 e 2,38 vezes maior, respectivamente); primiparidade materna revelou-se como fator de proteção. Conclusões: A ocorrência de anemia em mães e/ou filhos é maior nas macrorregiões menos desenvolvidas e em famílias com insegurança alimentar, o que evidencia a determinação social dessa carência nutricional. É mais freqüente nas mães e não se associa à ocorrência de anemia nos filhos. Nas mães, anemia associa-se com variáveis socioeconômicas, demográficas e insegurança alimentar. Nas crianças, anemia se associa apenas com insegurança e consumo alimentar. Os resultados indicam que embora mães e filhos estejam expostos aos mesmos determinantes sociais e ambientais que aumentam a suscetibilidade para anemia, as restrições alimentares ocasionadas por condições socioeconômicas e demográficas desfavoráveis têm maior impacto nas mães, em virtude da maior necessidade orgânica de ferro da mulher em idade fértil e provável proteção e cuidado das mães para com os filhos. Indica também que independente da condição socioeconômica, a alimentação inadequada da criança torna-a mais susceptível à anemia. Tais resultados podem estar atrelados também a um efeito positivo do Programa Nacional de Suplementação de Ferro, embora apenas um quarto das crianças de 6 a 24 meses tivesse recebido ferro nos últimos seis meses, o que indica a necessidade de melhorias na operacionalização do programa. / Introduction: Anemia an iron deficiency, is the most frequent and worrisome nutritional deficiency from the standpoint of public health. It mainly affects children, pregnant women and women of childbearing age. Despite the intervention measures for prevention and control of anemia in Brazil, studies shows that prevalence rates are high. Objective: Investigate the situation of anemia and its determinants in mothers and children in Brazil, considering the family context. Method: Quantitative cross-sectional survey, that used the database of the national survey of demography and health of women and children (PNDS) 2006. This information was collected through two questionnaires, with basic information about the home and its residents and also detailed information about the target audience women between 15 to 49 years and children under 5 years. The study evaluated approximately 15.000 women and 5.000 children, with a representative sample of five brazilian regions in urban and rural context. Approximately 40% of households had been selected for blood sampling of women, and all children born from January 2001 had the blood sampling taken provided they were biological children of the interviewees. Hemoglobin analysis was performed in 5.915 women and 4.558 children. This study looked at 1.476 pairs, considering the mother and only one children. The Statistical Package Program for Social Science (SPSS version 18.0) was used for data analysis, which examined anemia in mothers and/or children, mothers and children separately and consisted of univariate and multiple steps. Results: The occurrence of anemia was 36.8% in mothers and/or children, 23.4% of mothers and 17.0% in children. Mothers were 1.49 times more likely to have anemia than children, there was no association between anemia in mothers and children (p=0.478 ). In multiple regression analysis, mothers and/or children residing in the Northeast and Midwest had odds 2,24 and 1,70 times higher, respectively, in relation to the south; the chance was also statistically higher (1,78 times) for those with food insecurity and those in which the mother held a puerperal consultation (1,39 times); primiparity shown as protective factor. Anemia in mothers was also associated with the region of residence, with 2,39 times more chances for the Northeast than in mothers in the South; mothers with food insecurity, who performed a puerperal consultation and had at least one disease, also were 50% more likely to have anemia. In children, anemia was associated with insecurity and food consumption, and those who ate a mixture of water and fresh milk in the last 24 hours had a chance (2,49 and 1,69 times) to be more likely to develop anemia, respectively, as well as children who did not eat an afternoon snack on the last day and ate rice 4 times less in the week (odds 1,57 and 2,38 times higher for anemia, respectively), maternal primiparity proved to be a protector factor. Conclusions: The occurrence of anemia in mothers and/or children is higher in less develop macro-regions and among families with food insecurity, highlights the social causes of nutritional deficiency. It is more frequent in mothers and not associated with anemia in children. In mothers, anemia is associated with socioeconomic, demographic and food insecurity. In children, anemia is associated only with insecurity and food consumption. This result indicates that although there is evidence of mothers and children are exposed to the same social and environmental causes that increase susceptibility to anemia, dietary restrictions and their nutritional consequences caused by unfavorable demographic and socioeconomic conditions will have a greater impact on mothers, owing to the greater need for organic iron in women of childbearing age and protection and care of their mothers to the children. It also indicates that regardless of socioeconomic status, whether the childs diet is inadequate, it will be more susceptible to anemia. The results can be linked also to a positive effect of the National Iron Supplementation, although only one quarter of children aged 6 to 24 months had received iron in the last six months, which indicates the need for improvements in the operation of the program.

A biodisponibilidade de ferro de diferentes fontes foi avaliada pelo método de recuperação de hemoglobina em suínos anêmicos. O ensaio teve duração de 13 dias e os grupos foram homogeneizados de acordo com o produto do peso (kg) x hemoglobina (g/dL). As fontes de ferro estudadas foram: ferro microencapsulado com polímero de carboximetilcelulose sódica (NaCMC), ferro microencapsulado com polímero de alginato, ferro quelado com metionina e ferro reduzido eletrolíticamente. Com a finalidade de corrigir respostas devidas à variação na ingestão de ferro foram acrescentados três grupos chamados de grupos-padrão, cuja fonte dietética de ferro foi FeSO4.7H2O. A porcentagem média de absorção de ferro para os grupos experimentais variou de 12,8 (4,3) % (ferro eletrolítico) a 15,1 (3,8) % (ferro alginato), não sendo significativamente diferentes (P>0,05). A porcentagem média de absorção relativa ao FeSO4.7H2O variou de 89,5 (25,9)% (ferro NaCMC) a 105,9 (60,5)% (ferro quelado com metionina), sem diferenças significativas (p>0,05). Também não houve diferença significativa nos índices de conversão alimentar, eficiência alimentar e coeficiente de eficácia proteica (CEP). Não houve diferenças significativas (p>0,05) nas concentrações de ferro hepático entre as diferentes fontes estudadas. Nas condições deste ensaio, houve similaridade entre as fontes de ferro testadas quanto à biodisponibilidade. A microencapsulação proporcionou rneltlOr distribuição do produto na mistura quando comparada ao FeSO4.7H2O. / The iron availability from different sources was evaluated by the hemoglobin regeneration method in anemic pigs. The assay took 13 days and the animais were selected according to the weight (kg) x hemoglobina (g/dL) product. The iron sources studied were: microencapsulated iron with sodium carboximetilcelulose polymer (NaCMC), microencapsulated iron with alginato polymer, metionin-quelated iron and electrolytically reduced iron. To COITect answers due to iron ingestion variation three control groups were added, whose dietary iron source was FeSO4.7H2O. The average percentage of iron absorption for the experimental groups ranged from 12,8 (4,3) % (electrolytic iron) to 15,1 (3,8) % (iron alginato), without significant differences (p>0,05). The average percentage of FeSO4.7H2O relative absorption ranged from 89,5 (25.9)% (NaCMC iron) to 105,9 (60,5)% (metionin quelated-iron), without significant differences (p>O,OS). Also it did not have significant difference in the alimentary conversion and efficiency indexes and proteic effectiveness coefficient (CEP). No significant differences (p>0,05) were found in the hepatic iron concentrations among the different studied sources. Based on this assay\'s conditions, there were similarities among the tested iron sources regarding to their bioavailability. Microencapsulation provided better distribution of the product in the mixture when compared to the FeSO4.7H2O.

Introdução. A Anemia das Doenças Crônicas (ADC) é uma desordem comum em idosos, freqüentemente multifatorial, e exacerbada por citocinas pró-inflamatórias. Nesta população, o diagnóstico de anemia por deficiência de ferro (ADF) é difícil utilizando-se os testes laboratoriais convencionais, devido à prevalência destes estados crônicos. Espécies reativas de oxigênio (ERO) são produzidas por fagócitos durante o burst oxidativo em defesa do hospedeiro, mas são também implicadas como agentes deletérios em um grande número de desordens inflamatórias. Objetivos. Verificar a eficiência do receptor de transferrina sérico (sTfR) e índice sTfR-log ferritina (sTfR-F) no diagnóstico da ADF e ADC; determinar os efeitos das anemias e de estados inflamatórios crônicos sem anemia no burst oxidativo, fagocitose, produção de óxido nítrico (NO) por monócitos, e produção de ácido hipocloroso (HOCl) por neutrófilos. Métodos. Participaram do estudo cinqüenta e três indivíduos (42 mulheres e 11 homens) idosos recrutados do departamento de Cardio-Geriatria da Rede Pública de Saúde de Ribeirão Preto-SP. A proteína C reativa (PCR), utilizada como marcador inflamatório foi analisada pela metodologia ultra-sensível. O status férrico foi estabelecido pelos níveis do sTfR (enzimaimunoensaio, kit Quantikine soluble transferrin receptor, R&D Systems, USA), ferritina sérica (ensaio quimioluminescente, kit Ferritin Immulite®- DPC, England) e índice sTfR-F. Foram compostos os seguintes grupos, com base nos valores de normalidade dos parâmetros PCR, concentração de hemoglobina, ferritina e sTfR: controle (n=15), ADC (n=12), inflamação (n=08), anemia inexplicável (n=06) e grupo ADF (n=12). Nenhum paciente apresentou função renal prejudicada, hemoglobinopatias, diabetes mellitus descompensada, doenças infecciosas ou malignas. Estudou-se o efeito da ADC, ADF, anemia inexplicável e inflamação no burst oxidativo, fagocitose de neutrófilos e monócitos por citometria de fluxo, produção de HOCl por neutrófilos purificados e de NO produzido em cultura de monócitos em meio RPMI 1640, estimulados por lipopolissacáride (LPS). Resultados. Os níveis de sTfR foram capazes de diagnosticar ADF em sete (58,34%) dos doze pacientes do grupo ADF. A intensidade de fluorescência (IF) do burst oxidativo de neutrófilos, que reflete a atividade celular, no grupo ADF foi significativamente menor que a do grupo controle (p<0,05), mas a IF de monócitos não foi estatisticamente diferente. As percentagens de monócitos e neutrófilos realizando burst oxidativo e fagocitose dos grupos ADF, anemia inexplicável e inflamação não foram estatisticamente diferentes do grupo controle. As percentagens de monócitos e neutrófilos realizando fagocitose do grupo ADC foram estatisticamente maiores que as do grupo controle (p<0,05). A produção de HOCl nos grupos ADC e inflamação foram estatisticamente menores comparadas ao grupo controle (p<0,05), enquanto houve uma superprodução de NO por monócitos no grupo ADC (p<0,05). Conclusão. No presente estudo, o sTfR foi uma ferramenta diagnóstica adicional à ferritina no diagnóstico da ADF, mas o valor do índice sTfR-F não aumentou a utilidade diagnóstica do sTfR em indivíduos idosos. NO parece modular a produção de HOCl, provavelmente por regular a atividade enzimática da mieloperoxidase (MPO). Estes resultados mostraram o papel importante do ferro na ADC e ADF em manter a resposta imunológica de fagócitos durante o processo de envelhecimento. / Background: Anemia of Chronic Disease (ACD) is a very common disorder in elderly and it is often multifatorial, exacerbated by pro-inflammatory cytokines. In these people, the diagnostic of iron deficiency anemia (IDA) or iron deficiency is difficult in these patients using the conventional iron status tests, because of the prevalence of these chronic states. Reactive oxygen species (ROS) are produced by phagocytic cells during the oxidative burst in defense of the host, but it has also been implicated as a very harmful agent in an increasing number of inflammatory-mediated disorders. Objectives: to elucidate the use of serum transferrin receptor (sTfR) and sTfR-log ferritin index (TfR-F index) to diagnose IDA and ACD; to determinate the effects of anemia and chronic inflammatory states without anemia in some function of oxidative stress, such as oxidative burst, phagocytosis, nitric oxide (NO) production by monocytes and the hypochlorous acid (HOCl) production by purified neutrophils. Methods: Fifty three (42 women and 11 men) elderly subjects recruited from geriatric department of healthy public system of Ribeirão Preto city were selected. The high sensitivity C-Reactive Protein (CRP) was analyzed as an inflammatory marker. The iron status was confirmed by sTfR (enzyme-linked immunosorbent assay, ELISA, kit Quantikine soluble transferrin receptor R&D Systems, USA), serum ferritin levels (chemiluminescence assay, kit Ferritin Immulite®- DPC, England) and TfR-F index. The groups were established according to the criteria CRP assay, hemoglobin analysis, ferritin and sTfR: control (n =15), ACD (n =12), inflammation (n =08), unexplained anemia (n=06), and IDA (n=12). Patients with impaired kidney function, hemoglobinopathy, decompensate diabetes mellitus or infectious and malignancies diseases were excluded. We also studied the effect of ACD, IDA, unexplained anemia and inflammation on oxidative burst, phogocytosis of neutrophils and monocytes by flow cytometry and HOCl generation of neutrophils and NO produced by the monocytic cell culture, cultured in RPMI 1640 medium, stimulated by lipopolysaccharide (LPS). Results: Our results showed that sTfR could diagnose IDA in seven (58.34%) of twelve patients in IDA group. Oxidative burst fluorescence intensity of neutrophil in IDA group was lower statistically compared to control group, p<0.05. Oxidative burst fluorescence intensity of monocytes did not differ significantly. The percentages of monocytes and neutrophils expressing oxidative burst and the phagocytosis did not differ significantly amongst control, IDA, unexplained anemia and inflammatory groups. However, the percentages of neutrophils and monocytes expressing phagocytosis in ACD group were statistically higher when compared to control group (p<0.05). The HOCl generation in ACD, and inflammation groups were lower significant statistically than control group, p<0.05, while there was an overproduction of NO by monocyte in ACD group (p<0.05). Conclusion: In the present study, the sTfR was an additional diagnostic tool to ferritin for the diagnosis of IDA, but the value of the sTfR-F index did not increase the utility diagnostic of sTfR in elderly patients. NO seems modulate the HOCl production, perhaps by regulates the myeloperoxidase (MPO) enzyme activity. These results showed the important role of iron in ACD and IDA to maintaining phagocyte immune defense of organism during the aging process.

Introdução. A Anemia das Doenças Crônicas (ADC) é uma desordem comum em idosos, freqüentemente multifatorial, e exacerbada por citocinas pró-inflamatórias. Nesta população, o diagnóstico de anemia por deficiência de ferro (ADF) é difícil utilizando-se os testes laboratoriais convencionais, devido à prevalência destes estados crônicos. Espécies reativas de oxigênio (ERO) são produzidas por fagócitos durante o burst oxidativo em defesa do hospedeiro, mas são também implicadas como agentes deletérios em um grande número de desordens inflamatórias. Objetivos. Verificar a eficiência do receptor de transferrina sérico (sTfR) e índice sTfR-log ferritina (sTfR-F) no diagnóstico da ADF e ADC; determinar os efeitos das anemias e de estados inflamatórios crônicos sem anemia no burst oxidativo, fagocitose, produção de óxido nítrico (NO) por monócitos, e produção de ácido hipocloroso (HOCl) por neutrófilos. Métodos. Participaram do estudo cinqüenta e três indivíduos (42 mulheres e 11 homens) idosos recrutados do departamento de Cardio-Geriatria da Rede Pública de Saúde de Ribeirão Preto-SP. A proteína C reativa (PCR), utilizada como marcador inflamatório foi analisada pela metodologia ultra-sensível. O status férrico foi estabelecido pelos níveis do sTfR (enzimaimunoensaio, kit Quantikine soluble transferrin receptor, R&D Systems, USA), ferritina sérica (ensaio quimioluminescente, kit Ferritin Immulite®- DPC, England) e índice sTfR-F. Foram compostos os seguintes grupos, com base nos valores de normalidade dos parâmetros PCR, concentração de hemoglobina, ferritina e sTfR: controle (n=15), ADC (n=12), inflamação (n=08), anemia inexplicável (n=06) e grupo ADF (n=12). Nenhum paciente apresentou função renal prejudicada, hemoglobinopatias, diabetes mellitus descompensada, doenças infecciosas ou malignas. Estudou-se o efeito da ADC, ADF, anemia inexplicável e inflamação no burst oxidativo, fagocitose de neutrófilos e monócitos por citometria de fluxo, produção de HOCl por neutrófilos purificados e de NO produzido em cultura de monócitos em meio RPMI 1640, estimulados por lipopolissacáride (LPS). Resultados. Os níveis de sTfR foram capazes de diagnosticar ADF em sete (58,34%) dos doze pacientes do grupo ADF. A intensidade de fluorescência (IF) do burst oxidativo de neutrófilos, que reflete a atividade celular, no grupo ADF foi significativamente menor que a do grupo controle (p<0,05), mas a IF de monócitos não foi estatisticamente diferente. As percentagens de monócitos e neutrófilos realizando burst oxidativo e fagocitose dos grupos ADF, anemia inexplicável e inflamação não foram estatisticamente diferentes do grupo controle. As percentagens de monócitos e neutrófilos realizando fagocitose do grupo ADC foram estatisticamente maiores que as do grupo controle (p<0,05). A produção de HOCl nos grupos ADC e inflamação foram estatisticamente menores comparadas ao grupo controle (p<0,05), enquanto houve uma superprodução de NO por monócitos no grupo ADC (p<0,05). Conclusão. No presente estudo, o sTfR foi uma ferramenta diagnóstica adicional à ferritina no diagnóstico da ADF, mas o valor do índice sTfR-F não aumentou a utilidade diagnóstica do sTfR em indivíduos idosos. NO parece modular a produção de HOCl, provavelmente por regular a atividade enzimática da mieloperoxidase (MPO). Estes resultados mostraram o papel importante do ferro na ADC e ADF em manter a resposta imunológica de fagócitos durante o processo de envelhecimento. / Background: Anemia of Chronic Disease (ACD) is a very common disorder in elderly and it is often multifatorial, exacerbated by pro-inflammatory cytokines. In these people, the diagnostic of iron deficiency anemia (IDA) or iron deficiency is difficult in these patients using the conventional iron status tests, because of the prevalence of these chronic states. Reactive oxygen species (ROS) are produced by phagocytic cells during the oxidative burst in defense of the host, but it has also been implicated as a very harmful agent in an increasing number of inflammatory-mediated disorders. Objectives: to elucidate the use of serum transferrin receptor (sTfR) and sTfR-log ferritin index (TfR-F index) to diagnose IDA and ACD; to determinate the effects of anemia and chronic inflammatory states without anemia in some function of oxidative stress, such as oxidative burst, phagocytosis, nitric oxide (NO) production by monocytes and the hypochlorous acid (HOCl) production by purified neutrophils. Methods: Fifty three (42 women and 11 men) elderly subjects recruited from geriatric department of healthy public system of Ribeirão Preto city were selected. The high sensitivity C-Reactive Protein (CRP) was analyzed as an inflammatory marker. The iron status was confirmed by sTfR (enzyme-linked immunosorbent assay, ELISA, kit Quantikine soluble transferrin receptor R&D Systems, USA), serum ferritin levels (chemiluminescence assay, kit Ferritin Immulite®- DPC, England) and TfR-F index. The groups were established according to the criteria CRP assay, hemoglobin analysis, ferritin and sTfR: control (n =15), ACD (n =12), inflammation (n =08), unexplained anemia (n=06), and IDA (n=12). Patients with impaired kidney function, hemoglobinopathy, decompensate diabetes mellitus or infectious and malignancies diseases were excluded. We also studied the effect of ACD, IDA, unexplained anemia and inflammation on oxidative burst, phogocytosis of neutrophils and monocytes by flow cytometry and HOCl generation of neutrophils and NO produced by the monocytic cell culture, cultured in RPMI 1640 medium, stimulated by lipopolysaccharide (LPS). Results: Our results showed that sTfR could diagnose IDA in seven (58.34%) of twelve patients in IDA group. Oxidative burst fluorescence intensity of neutrophil in IDA group was lower statistically compared to control group, p<0.05. Oxidative burst fluorescence intensity of monocytes did not differ significantly. The percentages of monocytes and neutrophils expressing oxidative burst and the phagocytosis did not differ significantly amongst control, IDA, unexplained anemia and inflammatory groups. However, the percentages of neutrophils and monocytes expressing phagocytosis in ACD group were statistically higher when compared to control group (p<0.05). The HOCl generation in ACD, and inflammation groups were lower significant statistically than control group, p<0.05, while there was an overproduction of NO by monocyte in ACD group (p<0.05). Conclusion: In the present study, the sTfR was an additional diagnostic tool to ferritin for the diagnosis of IDA, but the value of the sTfR-F index did not increase the utility diagnostic of sTfR in elderly patients. NO seems modulate the HOCl production, perhaps by regulates the myeloperoxidase (MPO) enzyme activity. These results showed the important role of iron in ACD and IDA to maintaining phagocyte immune defense of organism during the aging process.

Background Iron deficiency (ID) is the world‟s most prevalent micronutrient deficiency and predominantly affects developing countries, also South Africa. In areas with low fish consumption and high n-6 PUFA vegetable oil intake, there is a risk for having inadequate n-3 PUFA status. Both iron and n-3 PUFA play important roles in the immune response, and supplementation is a strategy to alleviate deficiencies. However, little is known about potential interactive effects between concurrent iron and n-3 PUFA supplementation on the immune system. This is also important in the context that iron supplementation may be unsafe and may increase morbidity and mortality. Aim The overall aim of this thesis was to assess the effects of iron and docosahexaenoic (DHA)/eicosapentaenoic acid (EPA) supplementation, alone and in combination, on the immune system of ID children. More specifically, these effects were investigated on the occurrence and duration of illness and school-absenteeism due to illness, peripheral blood mononuclear cell (PBMC), red blood cell (RBC) and plasma total phospholipid fatty acid composition, iron status, fatty acid-derived immune modulators and targeted PBMC gene expression. Furthermore, association of PBMC, RBC and plasma total phospholipid fatty acid composition with allergic disease, were also examined. Design In a 2-by-2 factorial, randomised, double-blind, placebo-controlled trial, South African children (n = 321, aged 6–11 y) were randomly assigned to receive oral supplements of either 1) iron (50 mg as ferrous sulphate) plus placebo; 2) DHA/EPA (420/80 mg) plus placebo; 3) iron plus DHA/EPA (420/80 mg); or 4) placebo plus placebo for 8.5 mo, four times per week. Absenteeism and illness symptoms were recorded and biochemical parameters for compliance as well as parameters fundamental to immune function were assessed at baseline and endpoint. Furthermore, in a cross-sectional design, associations of allergic disease with baseline fatty acid composition of PBMC, RBC and plasma were examined. Results The combination of iron and DHA/EPA significantly attenuated respiratory illness caused by iron supplementation. DHA/EPA supplementation alone improved respiratory symptoms at school, but increased headache-related absenteeism. DHA/EPA and iron supplementation individually tended to increase and decrease anti-inflammatory DHA and EPA-derived mediators, respectively. Furthermore the anti-inflammatory DHA-derived immune mediator, 17HDHA was higher in the DHA/EPA plus placebo and iron plus DHA/EPA groups than in the iron plus placebo group. Also, the pro-inflammatory arachidonic acid (AA)-derived modulators (5- and 15-hydroxyeicosapentaenoic acid) were significantly lower in the iron plus DHA/EPA group compared to the placebo plus placebo groups. In the study population, 27.2% of the children had allergic disease and AA in PBMC phospholipids was significantly lower in the allergic children than in the non-allergic children. In RBC phospholipids dihomo-gamma-linolenic acid (DGLA) and the ratio of DGLA: linoleic acid (LA) correlated negatively and the n-6:n-3 PUFA ratio positively with total immunoglobulin E (tIgE). Furthermore, trans-C18:1n-9, tended to be higher in the allergic group. Conclusion DHA/EPA prevented respiratory illness caused by iron supplementation and although DHA/EPA on its own reduced respiratory morbidity when the children were present at school, surprisingly it increased the likelihood of being absent with headache and fever. The biochemical findings compliment the clinical results and support previous observations about DHA/EPA supplementation to reduce inflammation, but add to the current knowledge base that a relatively high oral dose of non-haem iron modulates circulating lipid-derived immune modulators and related gene expression. Furthermore, when supplementing with iron and DHA/EPA combined, in this ID population with low fish intake, the anti-inflammatory effect of DHA/EPA is maintained concurrently with attenuation of respiratory morbidity. This finding support the notion that excess iron (probably as non-transferrin bound iron) becomes available for pathogens and is probably why we found that iron increased respiratory infectious morbidity. The improved clinical outcome with combined supplementation seems to be related to increased lipid-mediator synthesis gene expression and the availability of DHA/EPA, leading to a more pro-resolving profile and enhanced immune competence. Overall these results give better insight into immune function and infectious morbidity in relation to n-3 PUFA and iron status and treatment, as well as the possible association of fatty acid status with allergic disease in young South-African school children. / PhD (Nutrition), North-West University, Potchefstroom Campus, 2015