Introdução: O transplante de células tronco hematopoiéticas é reconhecidamente uma opção terapêutica para doenças neoplásicas hematológicas, tumores sólidos, deficiências imunológicas e doenças metabólicas. É um procedimento associado a uma alta freqüência de complicações agudas e crônicas, causadas pela toxicidade do regime de condicionamento, dentre elas a mucosite, Doença do Enxerto versus Hospedeiro - DECH e infecções. Essas complicações podem causar grandes mudanças na composição corporal através de mudanças no metabolismo, piorando o estado nutricional. Um adequado consumo de alguns micronutrientes como zinco, vitamina D e ferro, tem sido investigado como forma de evitar ou minimizar essas complicações. Objetivo: Avaliar em pacientes submetidos a transplante de células tronco hematopoiéticas os níveis séricos de zinco, vitamina D e ferritina e o seu impacto nos desfechos do TCTH alogênico e os níveis de ingestão de zinco, vitamina D e ferro. Métodos: Foram avaliadas as dosagens séricas de zinco, vitamina D e ferritina, e os níveis de ingestão de zinco, vitamina D e ferro, os tipos de condicionamento, o grau de DECH e mucosite, a presença de infecções e o estado nutricional. Resultado: Foram incluídos na análise 32 pacientes. Não foi encontrado associação significativa entre a deficiência sérica de Zinco e mucosite e os níveis elevados de ferritina sérica com a ocorrência de infecções. Deficiência sérica de vitamina D aos 45 dias pós transplante foi associado com o desenvolvimento de DECH. Conclusão: Os nossos resultados reforçam a importância dos pacientes manterem os níveis adequados de micronutrientes e reforçam o papel da vitamina D na prevenção de DECH durante o TCTH. / Introduction: The transplantation of hematopoietic stem cells is recognized as a treatment option for hematological neoplastic diseases, solid tumors, immune deficiencies and metabolic diseases. It is a procedure associated with a high frequency of acute and chronic complications caused by the toxicity of the conditioning regimen, among them mucositis, Graft-versus-Host Disease - GVHD and infections. These complications can cause major changes in body composition through changes in metabolism, worsening the nutritional status. An adequate intake of some micronutrients such as zinc, vitamin D and iron, has been investigated as a way to avoid or minimize these complications. Objective: To evaluate in patients undergoing hematopoietic stem cell transplantation serum levels of zinc, vitamin D and ferritin and its impact on the outcomes of allogeneic HSCT and zinc intake levels of vitamin D and iron. Method: The following aspects were evaluated: serum levels of zinc, vitamin D and ferritin, and zinc intake levels of vitamin D and iron, the conditioning types, the degree of GVHD and mucositis, the presence of infections, the nutritional status. Result: The analysis included 32 patients. No significant association has been found between zinc serum deficiency and mucositis and elevated levels of serum ferritin with the occurrence of infections. The serum deficiency of vitamin D at 45 days post-transplantation has been associated with the development of GVHD. Conclusion: Our results reinforce that it is important for the patients to maintain adequate levels of micronutrients and reinforce the role of vitamin D in the prevention of GVHD during the HSCT. Keywords: hematopoietic stem cell transplantation, GVHD, mucositis, infections, Vitamin D, ferritin, zinc, nutritional status.

Resumo: A beta talassemia é um dos mais freqüentes distúrbios genéticos no mundo. Estima-se que 1,5% a 3% da população mundial seja portadora do traço talassêmico. Esses portadores geralmente são oligo ou assintomáticos e têm uma expectativa de vida semelhante à dos não portadores. Entretanto, níveis elevados de ferritina sérica têm sido observados em alguns estudos comparativos entre beta talassemia heterozigota e não portadores e, alguns indivíduos, que nunca foram transfundidos, apresentam sinais clínicos e laboratoriais de sobrecarga de ferro. A fisiopatologia dessa complicação continua em discussão. Vários pesquisadores têm sugerido um efeito modulador da mutação do gene da beta globina e mutações em genes codificadores de proteínas relacionadas ao metabolismo do ferro. Mutações no gene HFE são as mais freqüentemente associadas à hemocromatose hereditária. O objetivo do presente trabalho foi avaliar a freqüência das mutações C282Y e H63D no gene HFE em portadores de beta talassemia heterozigota e analisar sua influência no metabolismo do ferro. Foram estudados 162 portadores de beta talassemia heterozigota, residentes na cidade de São Carlos ou região, caucasóides e, acompanhados no serviço de Hematologia. O diagnóstico de traço talassêmico foi confirmado em todos por meio do eritrograma e da quantificação da Hb A2 e Hb fetal por HPLC. O metabolismo do ferro foi avaliado pelas dosagens de ferro sérico, capacidade total de ligação do ferro, ferritina e saturação da transferrina e, a análise molecular das mutações no gene HFE, pela técnica de PCR-RLFP. Foram realizadas análises de correlação linear de Pearson por idade e gênero entre hemoglobina... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Beta thalassemia is one of the most frequent genetic disorder in the world. It is estimated that 1.5% to 3% of the world population is a thalassemia carrier. These individuals are generally slightly symptomatic or asymptomatic and they have a life expectancy similar to those who are non-carriers. However, high levels of serum ferritin have been observed in some comparative studies between heterozygous for beta thalassemia and non-carriers, and some individuals that were never transfused, present clinic and laboratories signs of iron overload. The physiopathology of this disease continues in discussion. Several researchers have suggested a modulator effect from the mutation of the beta globin gene and mutations in genes related with the iron metabolism. Mutations of the gene HFE are the most frequently associated to the hereditary hemochromatosis. The aim of this study was evaluate the frequency of C282Y and H63D mutations in the HFE gene in beta thalassemia carriers, and analyze its influence in the iron metabolism. 162 beta thalassemia carriers, Caucasoid, residing in the city of Sao Carlos or region and accompanied in the Hematology service were studied. The diagnostic of thalassemia trait was confirmed in every one through a complete erythrogram and quantification of Hb A2 and Hb fetal by HPLC. The iron metabolism was evaluated by serum iron, total iron-binding capacity, serum ferritin and percent saturation of transferring. The molecular analysis of the mutations in the HFE gene was made by PCR-RLFP. There were made analysis of linear Pearson' correlation, by age and gender, among hemoglobin, Hb A2, VCM and among reticulocytes count and the values of saturation of transferrin and serum ferritin. / Orientador: Claudia Regina Bonini Domingos / Coorientador: Antonio José Manzato / Banca: Celso Carlos de Campos Guerra / Banca: Paula Rahal Liberatore / Mestre

Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2009.

The aim of this thesis was to study maternal and infant effects of delayed cord clamping (≥180 seconds, DCC) compared to early (≤10 seconds, ECC) in a randomised controlled trial. Practice and guidelines regarding when to clamp the cord vary globally, and different meta-analyses have shown contradictory conclusions on benefits and disadvantages of DCC and ECC. The study population consisted of 382 term infants born after normal pregnancies and randomised to DCC or ECC after birth. The primary objective was iron stores and iron deficiency at 4 months of age, but the thesis was designed to investigate a wide range of suggested effects associated with cord clamping. Paper I showed that DCC was associated with improved iron stores at 4 months (45% higher ferritin) and that the incidence of iron deficiency was reduced from 5.7% to 0.6%. Neonatal anaemia at 2-3 days was less frequent in the DCC group, 1.2% vs. 6.3%. There were no differences between the groups in respiratory symptoms, polycythaemia, or hyperbilirubinaemia. In paper II we demonstrated that DCC versus ECC was not associated with higher risk for maternal post partum haemorrhage and rendered a comparable ratio of valid umbilical artery blood gas samples. In paper III, the Ages and Stages Questionnaire was used to assess neurodevelopment at 4 months. The total scores did not differ, but the DCC group had a higher score in the problem-solving domain and a lower score in the personal-social domain. Immunoglobulin G level was 0.7 g/L higher in the DCC group at 2–3 days, but did not differ at 4 months. Symptoms of infection up to 4 months were comparable between groups. Finally, in paper IV, iron stores and neurodevelopment were similar between groups at 12 months. Gender specific outcome on neurodevelopment at 12 months was discovered, implying positive effects from DCC on boys and negative on girls. We conclude that delaying umbilical cord clamping for 180 seconds is safe and associated with a significantly reduced risk for iron deficiency at 4 months, which may have neurodevelopmental effects at a later age.

Background: Clinical studies have shown that tea consumption leads to decreased iron absorption. This finding is however, not supported by epidemiological studies, where no relationship between an increased tea consumption and a lower iron status in a population at risk of iron depletion has been found. Objectives: The main aim of this study was to compare the effects of black tea and Rooibos consumption on the iron status of primary school children in a rural setting in Potchefstroom, South Africa. Methods: One hundred and seventy five children, aged six to fifteen years, participated in this single blind, randomised, parallel intervention trial. Subjects were randomly allocated to receive two 200ml servings of either black tea or Rooibos with milk and sugar. These beverages were consumed during breaks and at the same time as the food h m the school-feeding scheme. The trial proceeded for sixteen weeks. The children received antihelminthic treatment (500mg mebendazole) at baseline. Haemoglobii haematocrit, serum iron, ferritin and transferfin were measured and total iron binding capacity and transferrin saturation were calculated. Trained fieldworkers measured dietary intakes by means of 24-hour dietary recalls and anthropometrists took anthropometric measurements. All the above mentioned data were gathered at the beginning and at the end of the intervention period. Results: Measurements indicated a study population that is malnourished in terms of anthropometrical indices and nutrient intakes. Biochemical markers of iron status also indicated that the population could be at risk of iron depletion. Changes in red blood cell count, haemoglobin, haematocrit, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), serum iron, transferrin, transferrin saturation, ferritin and total iron binding capacity (TIBC) did not differ significantly between the two groups. Mean red blood cell count, haematocrit, MCV, transferrin and TIBC increased significantly h m baseline to end in both groups (all p<0.0001) and MCH decreased significantly (p<.0001). Mean haemoglobin increased significantly with black tea consumption (p=0.002), although not with the consumption of Rooibos (p=0.073). Conclusion: Black tea or Rooibos consumption has similar effects on the iron status of primary school children. Iron status was not compromised by black tea in comparison with Rooibos. This questions the proposed limitation of black tea consumption as a public health strategy in order to combat iron deficiency in a population with marginal iron status. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Atherosclerotic cardiovascular diseases (CVD), particularly coronary heart disease (CHD) and cerebrovascular disease, are today major causes of death in the industrialised parts of the world. There are evidence to suggest that the atherosclerotic process starts in childhood, implying that preventive measures should be implemented already in children and adolescents. The aim of this study was to examine CVD risk indicators and their determinants in healthy Swedish adolescents. The study population comprised 14- and 17-year-old boys and girls (n=1032), in the dty and surroundings of Umeå in northern Sweden. Biochemical, anthropometric, and physiological parameters associated to CVD (s- lipoproteins and s-apolipoproteins, s-insulin, s-ferritin, anthropometric measurements, blood pressure, and physical fitness) were evaluated in relation to family history of CVD, weight and length at birth, infant feeding regimen, physical growth during infancy and childhood, current diet, physical activity, smoking, and educational level and occupation of the parents. The main findings of the study were that, on average, total serum cholesterol (TC) values in boys and girls were at the same level as reported from other European countries. A family history of CVD, short duration of breast feeding, low attained height during infancy and childhood, high body mass index (BMI), and low physical fitness were all associated with an unfavourable serum lipid profile. The findings also showed that features typical of the insulin resistance syndrome are present already in adolescents. In boys, iron stores, estimated by serum ferritin, were related to BMI and physical fitness, in a similar way as well established CVD risk indicators. Compared to previous dietary studies in Sweden, mean relative (energy %) fat intake had decreased substantially although the mean relative intake of saturated fat was still rather high. For both boys and girls, reported relative energy intake (energy intake/estimated energy expenditure) decreased with increasing level of BMI. Furthermore, daily smoking was more common among adolescents from families with low socio-economic status (SES) but was most strongly associated to smoking in peers. Tobacco use was considerably higher among adolescents attending vocational programs at secondary high school as compared to theoretical programs. Daily smokers had a more unfavourable serum lipid profile compared to non-smokers. Low socio-economic status of the parents was related to higher BMI and low educational level to higher dietary fat intake in both boys and girls. In conclusion, the findings of the study show that parameters linked to adult CVD when examined in adolescents, are related to family history, infant nutrition, previous physical growth, current body composition, physical fitness, physical activity, smoking, and social status and educational level of the parents. / digitalisering@umu

Background: Clinical studies have shown that tea consumption leads to decreased iron absorption. This finding is however, not supported by epidemiological studies, where no relationship between an increased tea consumption and a lower iron status in a population at risk of iron depletion has been found. Objectives: The main aim of this study was to compare the effects of black tea and Rooibos consumption on the iron status of primary school children in a rural setting in Potchefstroom, South Africa. Methods: One hundred and seventy five children, aged six to fifteen years, participated in this single blind, randomised, parallel intervention trial. Subjects were randomly allocated to receive two 200ml servings of either black tea or Rooibos with milk and sugar. These beverages were consumed during breaks and at the same time as the food h m the school-feeding scheme. The trial proceeded for sixteen weeks. The children received antihelminthic treatment (500mg mebendazole) at baseline. Haemoglobii haematocrit, serum iron, ferritin and transferfin were measured and total iron binding capacity and transferrin saturation were calculated. Trained fieldworkers measured dietary intakes by means of 24-hour dietary recalls and anthropometrists took anthropometric measurements. All the above mentioned data were gathered at the beginning and at the end of the intervention period. Results: Measurements indicated a study population that is malnourished in terms of anthropometrical indices and nutrient intakes. Biochemical markers of iron status also indicated that the population could be at risk of iron depletion. Changes in red blood cell count, haemoglobin, haematocrit, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), serum iron, transferrin, transferrin saturation, ferritin and total iron binding capacity (TIBC) did not differ significantly between the two groups. Mean red blood cell count, haematocrit, MCV, transferrin and TIBC increased significantly h m baseline to end in both groups (all p<0.0001) and MCH decreased significantly (p<.0001). Mean haemoglobin increased significantly with black tea consumption (p=0.002), although not with the consumption of Rooibos (p=0.073). Conclusion: Black tea or Rooibos consumption has similar effects on the iron status of primary school children. Iron status was not compromised by black tea in comparison with Rooibos. This questions the proposed limitation of black tea consumption as a public health strategy in order to combat iron deficiency in a population with marginal iron status. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2009.

Background: In South Africa, as in many other developing countries, iron deficiency (the most common micronutrient deficiency) still remains unresolved; while obesity has emerged as a public health challenge causing increases in the incidence and prevalence of cardiovascular diseases (CVDs). Research has shown that certain iron indices are associated with both anthropometric and biological markers of CVDs. Adiposity is thought to modulate the pathway linking iron status to CVDs. Objective: To examine the associations between iron indices, anthropometric and biological markers of CVDs in an African population undergoing transition. Methods: This thesis was based on secondary analysis of data generated during the Transition and Health during Urbanisation of South Africans (THUSA) study; and primary and secondary analysis of the baseline Prospective Urban and Rural Epidemiological (PURE) study. Both studies were cross–sectional in design and were conducted between 1996–1998 and in 2005 respectively in the North West Province of South Africa. The 1854 men and women participants in the THUSA study (>15years) and 1262 women participants in the PURE study (>35years) were included in the analysis. The relationship between iron and anthropometric indicators of CVD risk was examined in the THUSA study while that of iron status, anthropometric and biological markers of CVD risk was examined in the PURE study. Results: In the THUSA study, ferritin was positively associated with body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), body fat and subscapular skinfold (r=0.141, 0.359, 0.396, 0.308, 0.141 respectively for men and 0.126, 0.232, 0.319, 0.126, 0.105 respectively for women; p<0.01). Only the women showed decreased serum iron concentration with increasing BMI (p<0.05). WC and WHR increased with increasing serum ferritin concentration for both genders (p<0.05). As for the PURE study, associations between iron status parameters and CVD risk factors were generally weak (r<0.3, p<0.01) and were not retained after adjusting for valid confounders. WC and WHR increased with increasing ferritin concentration (p<0.05). Conclusion: Although these results do not indicate any significant association between iron indices and biological markers of CVD, its association with anthropometric indices gives an indication of the possible contribution of iron in the aetiology of CVDs. Thus, it may be necessary to exercise caution on the emphasis placed on iron as a nutrient and iron intervention programmes because of the suggestive role of iron in CVD development. / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2011.