O ferro (Fe) é um oligoelemento capaz de aceitar e doar elétrons. Tal propriedade o torna extremamente útil em diversos componentes importantes ao bom funcionamento do organismo e da célula. O Fe está associado a algumas proteínas, está presente em citocromos, em moléculas que se ligam ao oxigênio (hemoglobina e mioglobina) e em uma grande variedade de enzimas. O aumento e a diminuição da sua oferta levam a alterações na expressão de RNAs mensageiros e proteínas responsáveis pela sua própria homeostase. Sabe-se que a expressão de vários genes envolvidos no metabolismo do Fe é regulada pós-transcricionalmente, por meio de mecanismo que é desencadeado por sua ligação em regiões não traduzíveis presentes em mRNAs específicos, o que interfere no seu grau de poliadenilação, e por conseguinte, na estabilidade e na tradução do transcrito. A Mb é uma heme-proteína de 18,8 kDa, altamente expressa no tecido muscular esquelético e cardíaco, e que pertence a mesma família da hemoglobina. Sabendo-se que cerca de 15% do Fe existente no organismo está presente nos músculos, no presente trabalho avaliamos se a suplementação e restrição de Fe, a curto e longo prazo, alteram a expressão gênica da Mb no músculo oxidativo Soleus (S), glicolítico Extensor Digital Longo (EDL) e no cardíaco. Observamos que a restrição de Fe, a longo prazo, provocou um aumento na expressão gênica e protéica da Mb, apenas no músculo Soleus, sem alterar o grau de poliadenilação do transcrito, enquanto a suplementação não alterou os parâmetros avaliados em nenhum dos tecidos. A administração aguda de Fe não alterou a expressão gênica e protéica da Mb, nem o grau de poliadenilação do transcrito em nenhum dos tecidos estudados. Estes resultados sugerem que a regulação da expressão da Mb pelo Fe se dá apenas transcricionalmente, e de maneira tecido específica. / Iron is a trace element that can accept and donate electrons. This property makes iron extremely important to several components involved with the proper functioning of the organism and cells. Iron is associated with some proteins, is present in cytochromes, molecules that bind to oxygen (hemoglobin and myoglobin) and a variety of enzymes. The increase and decrease of its offer lead to changes in the expression of mRNAs and proteins responsible for their own homeostasis. It is known that the expression of several genes involved in the metabolism of iron is regulated post-transcriptionally through a mechanism that is triggered by its binding in non-translatable regions of specific mRNAs, which interferes with their polyadenylation, and as a consequence, with the stability and translation of the transcripts. Mb is a heme-protein with 18,8 kDa, highly expressed in skeletal and cardiac muscle, and it belongs to the same family of hemoglobin. About 15% of iron in the body is present in muscle tissue. Thus, this study aimed to investigate if long- and short-term Fe supplementation and restriction affect Mb gene expression in the oxidative Soleus (S), glycolitic Extensorum Digitalis Longus (EDL), and cardiac muscles. It was shown that long- term Fe restriction increased Mb mRNA and protein expression only in S muscle, without interfering in the transcript polyadenylation, whereas Fe supplementation did not alter any parameter evaluated in the three tissues. The short-term iron administration did not change the Mb mRNA, polyadenylation and protein expression in any of the tissues studied. The present results indicate that the regulation of Mb gene expression by iron occurs only at transcriptional level and in a tissue specific manner.

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.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

La anemia en gestantes es un problema de salud pública importante a nivel mundial. Según la prevalencia registrada, en Perú persiste como un problema moderado. La pobre adherencia a la suplementación oral de hierro es una de las principales barreras para la efectividad de esta intervención. El objetivo del presente estudio fue determinar la variación de la adherencia a la suplementación oral de hierro en el tiempo y los factores asociados a esta. Para ello, se reanalizó la base de datos de la vigilancia centinela: “Estudio de adherencia a la suplementación con Hierro durante la gestación en las direcciones de salud de Apurímac y Ayacucho” de la Dirección General de Epidemiología (DGE), el cual tuvo un diseño de cohorte prospectiva longitudinal. Se realizó un análisis descriptivo de las 416 gestantes registradas y un análisis bivariado y multivariado en base a 376 gestantes. Se identificaron las variables sociodemográficas, gestacionales, relacionadas a la suplementación en el embarazo anterior y actual. Para el análisis de los factores asociados a la adherencia se usó el modelo GEE. En la segunda y tercera visita de seguimiento la adherencia incrementó en 4% y 8%, mientras que en la quinta y sexta, se redujo en 8% y 20,6%, respectivamente. Los factores que redujeron la adherencia fueron: falla en la dispensación (25, 3%), náuseas (9,5%), interacción de náuseas y vómitos (13,5%), y no le cae bien el suplemento (11%). En conclusión, la adherencia disminuye con el tiempo y los factores relacionados al suplemento y la falla en la distribución se relacionan a la reducción de esta / Anemia in pregnant women is a major public health problem worldwide. According to the registered prevalence, in Peru it persists as a moderate problem. Poor adherence to oral iron supplementation is one of the main barriers to the effectiveness of this intervention. The aim of this study was to determine the variation in adherence to oral iron supplements over time and the factors associated with it. To do this, the sentinel surveillance database of the "Study of Adherence to Iron Supplementation During Pregnancy in the Health Directions of Apurimac and Ayacucho", of general directorate of epidemiology (DGE), a longitudinal prospective cohort, was reanalyzed. A descriptive analysis of the 416 registered pregnant women and a bivariate and multivariate analysis based on 376 pregnant women was carried out. Sociodemographic, gestational, supplementation in the previous and current pregnancy variables were identified. For the analysis of the factors associated with adherence, the GEE model was used. At the second and third follow-up visit, adherence increased by 4% and 8%, while at the fifth and sixth, it decreased by 8% and 20,6%, respectively. The factors that reduced adherence were: dispensing failure (25,3%), nausea (9,5%), interaction of nausea and vomiting (13,5%), and did not like the supplement (11%). In conclusion, adherence decreases with time and the factors related to the supplement and the failure in the distribution are related to its reduction. / Tesis