Rozprawy doktorskie na temat „Vitamin E”

Background Vitamin supplements are commonly used in women of reproductive age. There is a range of vitamin supplements such as iron, folate, vitamin B and vitamin D that are used. Deficiencies in vitamin D can result in adverse health outcomes, such as exacerbation of asthma and fractures. Some studies suggest that vitamin D deficiency may be associated with increases in depressive symptoms and severity. These associations need further exploration to ascertain confirmation, with more vigorous research. Furthermore, there has been limited research on the reasons behind vitamin supplement use in women of reproductive age who originate from culturally and linguistically diverse (CALD) populations. These need further exploration to examine the beliefs, attitudes and practices of women regarding vitamin supplement use. Aims and Objectives Aims: To explore vitamin supplements use in women of reproductive age in terms of their beliefs, attitudes and practices particularly in CALD communities, with a focus on vitamin D and its potential role in depression in women of reproductive age. Objectives: 1) To investigate any association of vitamin D deficiency with depression in women of reproductive age. 2) To examine whether vitamin D supplementation results in a decrease depressive symptoms and severity. 3) To explore the beliefs, attitudes and practices of women of reproductive age, including those from CALD backgrounds, in relation to vitamin supplement use. 4) To explore the beliefs, attitudes and practices of CALD women regarding the Hijab and vitamin D. Content of this thesis This thesis is made up of four chapters. Chapter 1 contains the background. The challenges identified in Chapter 1 led to the exploration of the effect of vitamin D on depression in women of reproductive age via a systematic review in Chapter 2. The qualitative study in Chapter 3 describes the factors behind the beliefs, attitudes and practices of women of reproductive age in terms of vitamin supplement use. Lastly Chapter 4 presents general discussion and conclusions from the work described in this thesis. Methods A systematic review was conducted to investigate the effect of vitamin D on depression in women of reproductive age based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement checklist (Chapter 2). A systematic search strategy was deployed in ten databases including Medline, EMBASE, PsycINFO, CINAHL, AMED, International pharmaceutical abstracts, Maternal and infant care, EBM ALL, Global health, and PubMed to identify primary studies that met eligibility criteria. A qualitative study using semi-structured interviews was undertaken to explore the use of vitamin supplements in women of reproductive age. A semi-structured interview guide was developed and applied to facilitate the interview. Participants were recruited through advertisements in pharmacies, medical centres and community centres as well as via the distribution of flyers across a large university campus in Sydney, through social media, word of mouth and snowball sampling. Interviews were audio-recorded and transcribed. Interviews were conducted until thematic saturation was achieved and data was analysed. NVivo12 Plus Qualitative Data Analysis software (QSR International Pty Ltd. Version 12, 2019) was used to analyse the emerging themes. Initial codes were highlighted and organised into general themes and sub-themes, which were reviewed and refined. Results Chapter 2 Systematic review identified a total of 2377 studies through comprehensive search and search of cited references. After removing duplicates and based on title and abstract screening, 128 studies remained. Full text review yielded 21 observational studies (11 cohort studies and 10 cross-sectional studies) that assessed the association between vitamin D deficiency and depression and two intervention studies (two RCTs) that investigated women of reproductive age of 15-49 years in US, Australia, New Zealand, Asia, Europe, Middle East and South America. Two cohort studies that showed no difference in depression scores in relation to vitamin D, while 9 other cohort studies reported that after measuring participants’ depression scores and vitamin D level over time, lower vitamin D levels were associated with higher depression scores. Similarly, there were two cross sectional studies that did not find an association between vitamin D level and depression scores. However, eight other cross-sectional studies showed that low vitamin D levels were linked with higher depression scores. One RCT did not find any improvement in depression symptoms and severity based on the supplementation of vitamin D used. Another RCT showed a reduction in depression scores compared to controls. Chapter 3 Semi-structured interviews were conducted with 25 women aged 19-49 years old, all from CALD backgrounds. The beliefs, attitudes and practices regarding the use of vitamin supplements of women from CALD backgrounds were explored. Thematic analysis generated four main themes: 1) health literary 2) cultural factors that influence vitamin supplement use 3) life circumstances and 4) women’s perception of health outcomes. Health literacy and information sources were key factors that affected women’s decision-making about taking vitamin supplements; and sources such as Google were heavily relied upon. Moreover, cultural factors greatly influenced women’s initiation of vitamin supplement therapy. There were discrepancies regarding the impact of wearing the Hijab on vitamin D status and more research in this area is needed. Conclusion Prior to this research, there has been limited data on CALD women of reproductive age and their beliefs, attitudes and practices in terms of vitamin supplement usage. This body of research was the first to explore the use of vitamin supplements in women of reproductive age particularly from CALD backgrounds. Furthermore, it was also one of the few studies around the world that examined the effect of vitamin D on depression in women of reproductive age. Findings from this body of work demonstrated the reoccurring themes that shaped women’s beliefs, attitudes and practices towards vitamin supplement use specifically include health literacy, cultural factors, life circumstances and women’s perception of health outcomes. This study also ascertained that CALD women of reproductive age had differing levels of health literacy and use of a range of information sources. This study also highlighted differing views regarding the practice of Hijab and rate of vitamin D supplementation. In addition, this study provides a basis for further studies to explore whether the practice of Hijab affects vitamin D levels, which has consequences for recommendations around vitamin D supplementation in countries where the Hijab is commonly worn. There was an indication of an association between vitamin D deficiency and depression symptoms and severity from this research. However, the exact clinical association in terms of vitamin D being a causal factor in developing depression remains unclear. Supplementation with vitamin D that results in changing status from vitamin D deficient to vitamin D sufficient warrants further investigation, specifically to ascertain whether an optimal level is needed to achieve a reduction in depressive symptoms and severity. Thesis overview This thesis presents an analysis of previous research on the role of vitamin D deficiency in depression in women of reproductive age. It explores the role of supplementation with vitamin D on depression symptoms and severity. It also investigates the beliefs, attitudes and practices of women of reproductive age regarding their vitamin supplements usage. It examines the motivations behind usage in women particularly those from CALD backgrounds. Rationale for this study Vitamin D deficiency is common throughout the world, including Australia which has ample sunlight all year round. Low vitamin D status has been associated with multiple adverse health outcomes, one of which is depression (1). Consensus around the optimal level of vitamin D for women of reproductive age remains to be reached. It is critical to establish if a relationship between vitamin D levels and depression exists and what that relationship is in women of reproductive age. In order to evaluate this association, a systematic review of past studies was undertaken to examine the effect of vitamin D on depression in women of reproductive age. This is further discussed in Chapter 2 of this thesis. Similarly, vitamin supplementation use has grown in the last decade worldwide and in Australia (2). This may be due to increased advertising and availability, cultural influences, affordability and increase in the use of social media platforms. It is important to understand the beliefs, attitudes and cultural practices especially in women of reproductive age, around their use of vitamin supplements. In order to explore this research question, a qualitative study was undertaken to explore the use of vitamin supplements in women of reproductive age from CALD backgrounds. This is further discussed in Chapter 3 of this thesis. Research aim, objectives and research questions The overall aim of this project was to explore the use of vitamin supplements in women of reproductive age, with a focus on CALD communities as well as investigating vitamin D and its possible association with depression in women of reproductive age. The specific objectives of this research were to: • Evaluate the effect of vitamin D status on depression and depressive symptoms. • Explore the use of vitamin supplements in women of reproductive age, particularly in women of CALD backgrounds, with a particular focus on vitamin D • Describe the beliefs, attitudes, and practices of women of reproductive age, particularly women from CALD backgrounds, regarding vitamin supplement use. The research questions were: • Does vitamin D deficiency affect depression and depressive symptoms? • What level of vitamin D is needed to decrease depression severity and symptoms? • What level of vitamin D supplementation is required to increase level of vitamin D in order to decrease depression severity and symptoms? • What factors are involved when women of reproductive age initiate vitamin supplement use? • What are the beliefs, attitudes and practices of women of reproductive age around vitamin supplement use? • What are the beliefs and attitudes and practices of women from CALD backgrounds regarding vitamin supplement use? • What are the beliefs and practices of women from CALD backgrounds regarding the Hijab and its possible connection with vitamin D deficiency? Significance This research will contribute to the expanding body of knowledge related to vitamin D deficiency and depression as well as exploring vitamin supplement use in women of reproductive age particularly those from CALD backgrounds. It is the first study to systematically evaluate the effect of vitamin D on depression in women of reproductive age and explore the use of vitamin supplements in CALD women of reproductive age in Australia. This study complements current understanding of the links between vitamin D and depression as well as the differences in the beliefs, attitudes and practices of women from CALD backgrounds regarding vitamin supplement use. Considering existing evidence, public health interventions to decrease the prevalence of vitamin D deficiency in women of reproductive age in Australia are required, in addition to increasing awareness regarding the optimal vitamin D status in order to decrease the risk of depression and depressive symptoms. The identification of several motivating factors associated with vitamin supplement use in women of reproductive age and in particular those from CALD backgrounds is an important first step in future programs of public health research aimed at identifying and targeting culturally appropriate health related information that aides decision making when it comes to vitamin supplement use. This thesis investigates women’s use of vitamin supplements, vitamin D and its possible association with depression in women of reproductive age. The first chapter provides background information on vitamin supplements, vitamin D, depression and population characteristics. The second chapter examines the effect of vitamin D on depression in women of reproductive age in the form of a systematic review. The third chapter explores the use of vitamin supplements in women of reproductive age and in particular, women from CALD backgrounds through a qualitative study. The fourth chapter discusses the significance of all the findings, future research directions and conclusions.

La vitamine D (D3 ou cholécalciférol du règne animal et D2 ou ergostérol du règne végétal) est une hormone pléiotrope qui possède de nombreux effets biologiques incluant la régulation du métabolisme du calcium et du phosphate. Chez l’Homme, ce composé est synthétisé au niveau cutané sous forme inactive. On décrit ainsi le métabolisme de la vitamine D qui conduit à la production de métabolites actifs (par les vitamine D 25- et 1α-hydroxylases codées par les gènes CYP2R1 et CYP27B1) et à leur dégradation par la vitamine D 24-hydroxylase (gène CYP24A1). L’expression des vitamine 1α- et 24-hydroxylases est finement et inversement régulée afin de maintenir l’homéostasie phosphocalcique, grâce à plusieurs boucles de rétrocontrôle impliquant entre autres la forme 1,25-dihydroxylée de la vitamine D et son récepteur VDR, la calcémie et la parathormone, la phosphatémie et le FGF23. La carence en vitamine D et les défauts de son activation sont associés à un phénotype de rachitisme, tandis que les excès en vitamine D sont associés à un phénotype d’hypercalcémie-hypercalciurie par intoxication (surdosage) ou hypersensibilité à la vitamine D (excès d’activation ou défaut de dégradation).L’objectif de ce travail de thèse est d’identifier des causes génétiques de dérégulation du métabolisme de la vitamine D et de préciser leurs mécanismes physiopathologiques par une description précise du phénotype associé. Pour ce faire, nous avons utilisé de façon conjointe les outils de la génétique (séquençage nouvelle génération et Sanger) et de la biochimie (dosage des métabolites) dans une cohorte de patients recrutés grâce au centre de référence maladies rares du métabolisme du calcium et du phosphate.Ce travail a permis de préciser le rôle de deux gènes dans les maladies liées à la dérégulation métabolisme de la vitamine D, CYP2R1 et CYP24A1, par la mise en évidence de mutations perte de fonction chez des patients avec un phénotype de rachitisme à 25-hydroxyvitamine D basse et d’hypersensibilité à la vitamine D respectivement. Notre étude a permis aussi de préciser le phénotype de ces affections. Dans la cohorte des patients étudiés, l’identification de mutations de gènes impactant le métabolisme du phosphate (SLC34A1 et SLC34A3), souligne l’intérêt de l’étude des facteurs régulateurs des activités vitamine D 1α- et 24-hydroxylases.Aucune variation significative dans les régions promotrices proximales de CYP27B1 et CYP24A1 n’a été identifiée. Le peu de connaissances sur l’ensemble des éléments régulateurs chez l’Homme n’a pas permis d’approfondir notre étude. L’identification et l’étude de ces éléments régulateurs distaux permettra de déterminer leur implication dans les maladies rares du métabolisme de la vitamine D
The vitamin D (D3 or cholecalciferol from animal kingdom and D2 or ergosterol from plan kingdom) is a pleiotropic hormone who has numerous biological effects including the regulation of calcium and phosphate metabolism. In humans, this compound is synthetized in skin in an inactive form. Thus, we call vitamin D metabolism the biological process which leads to the production of active metabolites (by enzymes 25- and 1α-hydroxylases encoded by CYP2R1 and CYP27B1 genes) and its degradation by vitamin D 24-hydroxylase (gene CYP24A1). The expression of 1α- and 24-hydroxylases is tightly and inversely regulated to maintain calcium and phosphate homeostasis, thanks to several feedback loops including 1,25-dihydroxyvitamin D and its receptor VDR, serum calcium and parathormone, serum phosphate and FGF23. Vitamin D deficiency and vitamin D activation deficiency are associated with rickets, while vitamin D excess are associated with hypercalcemia-hypercalciuria due to vitamin D intoxication (overdose) or hypersensitivity to vitamin D (activation excess or degradation deficiency).Our aim is to identify genetic causes of vitamin D metabolism deregulation and to specify pathophysiologic mechanisms describing phenotype. Thus, we jointly used the tools of genetics (next-generation and Sanger sequencing) and biochemistry (vitamin D metabolites assay) in a cohort of human patients ascertained thanks to the national center for rare diseases of calcium and phosphate metabolism.This work allowed us to specify the role of two genes in diseases of vitamin D metabolism, CYP2R1 and CYP24A1, showing loss of function mutations in patients with rickets and low 25-hydroxyvitamin D and hypersensitivity to vitamin D, respectively. Our study brought new phenotypic elements in these affections. In our cohort of patients, the identification of mutations leading to phosphate deregulation (in SLC34A1 and SLC34A3) highlights the putative role of regulators of vitamin D 1α- and 24-hydroxylases activities in pathophysiology.No significant variation have been identified in the proximal promoting regions of CYP27B1 and CYP24A1. We could not go further considering the lack of knowledge in regulating regions and factors in humans. Identifying distal regulators will allow to study their implication in rare diseases of vitamin D metabolism

L’obésité s’accompagne d’un état inflammatoire chronique qui joue un rôle délétère.Cet état associé à l’obésité été impliqué dans le développement de complications métaboliques:insulino-résistance et DT2.Chez les obèses,le TA est un site de production de médiateurs pro et/ou anti-inflammatoires, des adipokines.Les modifications et changements de style de vie et les approches thérapeutiques sont privilégiés pour lutter contre l’obésité.Toutefois,les approches préventives ne doivent pas être négligées,des études épidémiologiques ont mises en évidence une corrélation entre obésité et carence en micronutriments.Par ailleurs,il existe une corrélation inverse entre micronutriments lipophiles et caroténoïdes et la prévalence de l’obésité et du DT2.Le but de cette thèse est de comprendre le lien qui existe entre carence en micronutriments,obésité et complications associés.Une étude clinique transversale a été réalisée chez des obèses non diabétiques.Les résultats nous ont permis de montrer qu’il existe une association positive entre b-carotène et sensibilité à l'insuline chez l'obèse,effet pouvant être lié à une modulation de l'expression de certaines adipokines dont l'adiponectine qui est indépendamment associée à la concentration plasmatique en b-carotène.Une étude préclinique a été menée, dont l'objectif évaluer l'impact de la teneur en vitamines alimentaires sur la prise de poids et l'insulino-sensibilité.Des souris ont été soumises à un régime hypovitaminé.A 10 semaines,ce régime favorise la prise de masse grasse,modifie la sensibilité à l'insuline,en agissant au niveau du métabolisme lipidique hépatique,via une diminution des capacités oxydatives
Obesity is associated with chronic inflammatory condition that plays a deleterious role.This inflammatory state associated with obesity was involved in the development of metabolic complications : insulin resistance and T2DM.Obese, AT is a site for the production of pro and/or anti-inflammatory adipokines, and plays a major role in the development of chronic inflammation associated with obesity.Modifications and changes in lifestyle and therapeutic approaches are preferred to deal with obesity. However,preventive approaches should not be ignored,several epidemiological studies have shown a correlation between obesity and micronutrient deficiency.In addition,there is an inverse correlation between lipophilic micronutrients and carotenoids and the prevalence of obesity and T2DM.The purpose of this thesis is to understand the possible link between LM and carotenoids deficiency, obesity and associated physiological disorders.A cross-sectional study was performed in non-diabetic obese patients.The results allowed us to conclude the existence of a favorable effect of b-carotene on insulin sensitivity in obese patients.This effect may be related to modulation of inflammation or the expression of some adipokines(such as adiponectin), either directly or through its pro-vitamin A activity.A preclinical study was performed; the objective is to assess the impact of the vitamins on weight gain and insulin sensitivity.Mice were subjected to a hypovitaminic diet.After 10 weeks of regimen, we observed an increased adiposity and an altered insulin sensibility.This diet probably acts on the hepatic lipid metabolism via a decrease in oxidative capacity

The vitamin E, vitamin B-6, vitamin B-12, and folate status of 22 gastric bypass subjects ages 23 to 60 yr was evaluated before, 6 mo, and 12 mo post-surgery. Before surgery 77.3% of subjects had adequate vitamin E status; 36.3%, adequate vitamin B-6 status; 100.0%, adequate vitamin B-12 status; and 45.5%, adequate folate status. After surgery, subjects were classified into 3 vitamin supplement groups based on average daily vitamin supplement intake. Subjects taking higher levels of supplements containing these vitamins had significantly higher plasma concentrations of the vitamins than those taking low or moderate levels. The mean plasma vitamin values in the moderate supplement group were indicative of adequate status for all vitamins, but plasma vitamin B-12 levels at 12 mo post-surgery were significantly lower than pre-surgery levels. In the low supplement group, mean plasma vitamin levels were in or near marginal or deficient range. The majority of subjects consuming supplements of vitamin E, vitamin B-6, and folate near the US RDA maintained normal vitamin status. Subjects taking 100+ ug vitamin B-12 daily had adequate vitamin B-12 status. Significant correlations (r = .67 to .94) were observed between vitamin supplement levels and the respective plasma vitamin concentrations.
Ph. D.
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Orientador: Gabriel Hessel
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-10T23:58:17Z (GMT). No. of bitstreams: 1 Saron_MargarethLopesGalvao_D.pdf: 3406733 bytes, checksum: 734ea37c3690fa8925b87a9129e6019a (MD5) Previous issue date: 2008
Resumo: As doenças hepáticas crônicas podem induzir à má-absorção de lipídios e vitaminas lipossolúveis e levar ao comprometimento do estado nutricional. O objetivo da pesquisa foi determinar os níveis séricos de vitaminas lipossolúveis (A, D e E) em crianças e adolescentes com atresia biliar (AB) e hepatite auto-imune (HAI) e verificar a relação com o estado nutricional e indicadores laboratoriais e clínicos. O estudo foi transversal e controlado e foram avaliados os pacientes com HAI (n=25) e AB (n=24), e um grupo controle (n=53) pareado por sexo e idade. Os níveis séricos das vitaminas A, D e E foram determinados pela técnica de cromatografia líquida de alta eficiência. Além disso, foi realizada a avaliação antropométrica e a classificação dos pacientes na pontuação de Child-Pugh. Foram empregados os testes de Mann-Whitney, o coeficiente de correlação de Spearman e análise de variância, sendo considerada diferença significativa se p<0,05. Em relação às vitaminas, no grupo controle, constatou-se que os níveis séricos das vitaminas A e E variaram com a idade. Os níveis séricos das vitaminas A, D e E foram maiores no grupo controle em relação aos pacientes com AB e HAI, em conjunto ou separadamente. Em relação ao grupo AB, não foi observado diferença significativa nos níveis séricos das vitaminas A, D e E nos pacientes com ou sem colestase. Os pacientes com AB e HAI, em conjunto, classificados em Child C e Child B apresentaram os menores níveis séricos das vitaminas A e E comparados ao Child A. O déficit nutricional mais grave foi observado nos pacientes com AB com colestase. Verificou-se no grupo AB e HAI em conjunto a correlação do Peso/Idade (P/I), Prega Cutânea Triciptal (PCT), Prega Cutânea Subescapular (PCSE), Circunferência Braquial (CB), Área Adiposa Braquial (AAB) com as vitaminas A e E. Além destes indicadores a vitamina E também se correlacionou com Estatura/Idade (E/I), Índice de Massa Corporal (IMC), Área Muscular Braquial (AMB) e Soma das Pregas Cutâneas (SPG) nos pacientes com HAI e AB, em conjunto. Pode-se concluir que, foi observada deficiência das vitaminas A, D e E nos pacientes com AB e HAI. Quanto maior a gravidade da doença menores foram os níveis séricos das vitaminas A e E, nos pacientes com AB e HAI, em conjunto. Essa mesma relação da gravidade da doença ocorreu para as vitaminas A e D nos pacientes com HAI. Com relação ao estado nutricional, os pacientes com AB, principalmente com colestase, apresentaram maior comprometimento nutricional. Houve correlação diretamente proporcional, principalmente da vitamina E com todas as variáveis antropométricas do grupo de AB e HAI em conjunto
Abstract: The chronic liver diseases can cause malabsorption of lipids and fat-soluble vitamins, leading to a deficient nutritional status. The aim of research was: to evaluate the relation between serum levels of fat-soluble vitamins (A, D and E) on chidren and adolescents with biliary atresia (BA) and auto-immune hepatitis (AIH) with the nutritional status and with laboratorial and clinic indicators. The study was transversal controlled, which were evaluated patients with AIH (n=25) and BA (n=24) and a control group (n=53) lined up by sex and age. The determination of serum levels of vitamins A, D and E was carried out by high performance liquid chromatography. Anthropometrics evaluation and classification of patients on Child-Pugh scale were also used. It was used the Mann-Whitney test, the correlation coefficient of Spearman and variance analysis for data analysis, which was considered significant difference if p< 0.05. Have been evidenced that serum levels of vitamins A and E in healthful group were changed with age. The serum levels of vitamins A, D and E were higher in the healthful group when compared with the patients with BA and AIH together or isolated. No difference in the serum levels of vitamins A, D and E was noted in the BA group with or without cholestasis. The patients with BA and AIH together grouped and classified in Child C and Child B presented the lowest serum levels of vitamins A and E when compared to the patients classified in Child A. The nutritional deficit more intense was observed in the patients with BA and cholestasis. It was verified in the BA and AIH groups together a correlation weight/age (W/A), Triceps Skinfold Thickness (TST), Subscapular Skinfold Thickness (SST), Midarm Circunference (MC) and Midarm Fat Area (MFA), with the vitamins A and E. Besides indicators, the vitamin E was also correlated with Stature/Age (S/A), Body Mass Index (BMI), Midarm Muscle Area (MMA) and SKinfold Sum (SFS) for patients with AIH and BA together. In conclusion, have been observed deficiency of vitamins A, D and E in patients with AB and AIH. For higher serevity of disease, the serum levels of vitamins A e E are lower for patients with AB and AIH together. This same relation occurs for vitamins A and D for patients with AIH. When the nutrition status is evaluated, the patients with AB and cholestasis presented the highest nutritional deficiency. There is a correlation directly proportional, mainly of vitamin E with the anthropometric variables of the AB and AIH groups together
Doutorado
Saude da Criança e do Adolescente
Doutor em Saude da Criança e do Adolescente

A malária é uma das principais doenças parasitárias no mundo, e o aumento da resistência aos antimaláricos atualmente utilizados dificulta o controle dessa parasitose. Assim, é de interesse a descoberta de novas vias metabólicas que sirvam de alvos para o desenvolvimento de drogas para combater essa doença. Nosso laboratório, nos últimos anos, tem investido na caracterização de intermediários e produtos finais da via de isoprenóides. Baseando-se na presença das vias 2-C-metil-D-eritritol 4-fosfato e do chiquimato, decidimos verificar se ocorriam as biossínteses de retinóides e vitamina K no ciclo intraeritrocitário do P. falciparum, através da análise de produtos metabolicamente marcados com [1(n)-3H]-pirofosfato de geranilgranila por análises cromatográficas (HPLC e TLC), além da espectrometria de massas. Não identificamos a presença de retinal, retinol e ácido retinóico no ciclo intraeritrocitário do P. falciparum. Já a biossíntese de vitamina K precisa ser estudada com mais profundidade, pois há indícios de biossíntese, em especial da menaquinona-4.
Malaria is one of the most important parasitic diseases in the world. The spread of resistance to the antimalarials impairs the parasite\'s control. Therefore, is necessary the discovery of new metabolic routes to allow new antimalarials development. Our group has been studying the isoprenoid pathway, characterizing the intermediate and secondary products of this pathway. Based on the presence of 2-C-methyl-D-erythritol 4-phosphate and shikimate pathways, we decided to investigate the occurrence of retinoids and vitamin K biosynthesis in P. falciparum, through the chromatography of [1(n)-3H]Geranylgeranylpyrophosphate labeled products of intraerythrocytic stages of P. falciparum, and mass espectometry analysis. The retinal, retinol and retinoic acid were not identified in P. falciparum. The results indicate the menaquinone-4 biosynthesis, although deeper investigation is necessary.

Introdução - A concentração sérica de vitamina D pode variar em indivíduos de diferentes grupos etários e de diversas regiões geográficas e pode ser influenciada pela exposição solar, estação do ano, bem como pelos valores de IMC e paratormônio (PTH). A classificação utilizada para definir concentração sérica adequada de vitamina D refere valores de 25(OH)D acima de 30 ng/mL. Porém, essa classificação pode estar inapropriada para a população brasileira, devido às particularidades climáticas e alimentares. Objetivo - Verificar as concentrações séricas médias de 25(OH)D e PTH e sua relação com IMC, exposição solar e estação do ano e identificar os valores de corte da 25(OH)D associados à elevação do paratormônio (PTH) em adultos e idosos de amostra representativa da população do município de São Paulo. Métodos - Para esta dissertação foi desenvolvido um artigo original. O artigo original descreve o estudo transversal realizado com indivíduos do estudo ISA-Capital, estudo multicêntrico e de base populacional, onde foram investigados 589 indivíduos, de ambos os sexos, dos grupos etários: 20 a 59 (adultos) e 60 e mais (idosos). Foram coletadas amostras de sangue, para dosagens de 25(OH)D e PTH. Os indivíduos que aceitaram participar da coleta de sangue, também responderam um questionário sobre exposição solar. A análise estatística incluiu a curva ROC, testes t de Student, correlação e ANOVA. Os cálculos foram realizados pelo software SPSS versão 17.0. e p 0,05 foi considerado significante. Resultados - No artigo original observou-se idade média de 54,83 (19,21) anos, sendo 61,3 por cento do sexo feminino e 38,7 por cento do sexo masculino. A concentração sérica média de 25(OH)D foi 50,02 (22,69) ng/mL, já entre os grupos foi de 47,48 (23,03) (adultos) e 52,68 (22,06) ng/mL (idosos) havendo diferença significativa entre eles (p=0,005). Observou-se variação sazonal da concentração sérica de 25(OH)D e correlação positiva entre 25(OH)D e IMC (r = 0,114, p = 0,006). O novo valor de corte 55.8 ng/mL, determinado pela análise da curva ROC, encontrou 67,6 por cento dos indivíduos insuficientes de 25(OH)D e entre os grupos 72,1 por cento (adultos) e 62,8 por cento (idosos). Conclusão - Os resultados demonstram a presença de variação sazonal nas concentrações séricas de 25(OH)D no municipio de São Paulo. O ponto de corte proposto para nossa população indicou elevada prevalência de insuficiência de vitamina D. Portanto, se faz necessário políticas públicas de prevenção de insuficiência de vitamina D visando os efeitos benéficos na saúde e qualidade de vida desta população.
Introduction - The serum concentration of vitamin D may vary in individuals of different age groups and geographic regions and may be influenced by sun exposure, season and by BMI and parathyroid hormone (PTH). The classification widely used as a cut-off for appropriate vitamin D status refers serum 25 (OH) D above 30 ng/mL. However, this classification may be inappropriate for the Brazilian population, due to the particular food and the climate of our population. Objective - To determine the mean serum concentrations of 25(OH)D and PTH and correlate them with BMI, sunlight exposure and season and to identify the cutoff values of 25 (OH) D associated with elevation in PTH. Methods For this dissertation, one original article were developed. Original article describe cross-sectional study performed with subjects from the ISA Capital, multicenter population-based. We investigated 589 individuals were of both sexes, age groups: 20-59 (adults) and 60 (elderly). Blood samples for laboratory measurements of 25(OH)D and PTH were collected. Individuals, who agreed to participate in blood collection, also answered a questionnaire on sunlight exposure. Statistical analysis included ROC curve, Student t test, correlation tests, ANOVA. The calculations were performed by the software SPSS version 17.0. and p 0.05 was considered significant. Results - In the original article, the mean age of participants was 54.83 (19.21) years, 61.3 per cent female and 38.7 per cent were male. The mean serum 25 (OH) D was 50.02 (22.69) ng/mL, between the groups was 47.48 (23.03) (adults) and 52.68 (22.06) ng/ mL (elderly) and significant difference between them (p = 0.005). A seasonal variation in serum 25 (OH) D was observed and positive correlation between 25(OH)D and BMI (r = 0.114, p = 0.006). The new cutoff value 55.8 ng / mL, determined by ROC curve analysis found 67.6 per cent of subjects insufficient 25 (OH) D and between groups 72.1 per cent (adults) and 62.8 per cent (elderly). Conclusion - The results demonstrate the presence of seasonal variation in serum 25 (OH) D in the municipality of Sao Paulo. The cutoff point proposed for our population showed a high prevalence of insufficient vitamin D. Therefore, public policy is needed to prevent vitamin D insufficiency in order to beneficial effects on health and quality of life in this population.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Na produÃÃo in vitro (PIV) de embriÃes bovinos vÃrios fatores contribuem para as variÃveis na produÃÃo e qualidade dos oÃcitos e embriÃes. Avaliou-se o uso parenteral de vitamina A (VA) e vitamina E (VE) na produÃÃo de oÃcitos colhidos por aspiraÃÃo folicular (OPU) e embriÃes por produÃÃo in vitro (PIV) em de vacas (n=22), sendo: Simental (S) (n=2); Nelore (N) (n=4); Brahma (B) (n=5) e Gir (G) (n=11). Todos os animais foram alocados na fase prÃ-tratamento (F1) (n=22) (nÃo receberam vitaminas) e os mesmos animais utilizados para a fase pÃs-tratamento (F2) (receberam 1.000.000 UI de vitamina A e 1g de vitamina E). A primeira OPU foi na F1, logo em seguida foi aplicado 1.000.000 UI de VA e 1g de VE, e apÃs 12 dias realizou-se nova OPU para fazer a F2. Os oÃcitos (CCO) foram maturados, fecundados e cultivados in vitro. As 44 OPU produziram 520 oÃcitos, 217 (F1) e 303 (F2), havendo efeito significativo, com acrÃscimo de 86 oÃcitos, obtendo mÃdia e desvio padrÃo 9,86Â5,53 F1 e 13,77Â2,0 F2, (*p<0,0219). Quando separada as raÃas NBG (Nelore, Brahma e Gir) (n=20) houve acrÃscimo de 95 oÃcitos, obtendo mÃdia e desvio padrÃo 9,90Â5,81 F1-NBG e 14,65Â9,44 F2-NBG, (*p<0,0085). As 44 PIV produziram 224 embriÃes, sendo 93 F1 e 131 F2, obtendo mÃdia e desvio padrÃo 4,23Â3,09 F1 e 5,95Â4,05 F2, (*p<0,0228). Quando separada as NBG a produÃÃo foi de 214 embriÃes, havendo acrÃscimo de 38 embriÃes, obtendo valores de 4,45Â3,15 F1 e 6,25Â4,09 F2, (*p<0,0285). Houve um efeito significativo na quantidade produzida de oÃcitos (n=22) e oÃcitos NBG (n=20). Houve efeito na produÃÃo de embriÃes de todas as raÃas (n=22) e embriÃes NBG (n=20). A suplementaÃÃo com VA e VE aumentou o nÃmero de oÃcitos totais (1,7Â0,7); oÃcitos NBG (1,8Â0,8); embriÃes totais (3,9Â1,6) e embriÃes NBG (4,7Â1,6). A resposta da F2 comparado com a F1 na produÃÃo de oÃcitos e embriÃes foi significativa quando todas as raÃas estavam agrupadas e tambÃm quando foi agrupado apenas as Bos taurus indicus (NBG). O uso das vitaminas A e E pode ser usada para maior recuperaÃÃo oÃcitÃria e embrionÃria em raÃas ZebuÃnas.
The in vitro (IVP) bovine embryos production has several factors that contribute to the variables in the production and quality of oocytes and embryos. We evaluated the parenteral use of vitamin A (VA) and vitamin E (VE) in the production of oocytes collected by follicular aspiration (OPU) and embryos by in vitro production (IVP) in cows (n = 22), where: Simmental (S) (n = 2), Nelore (N) (n = 4), Brahma (B) (n = 5) and Gir (G) (n = 11). All animals were allocated in the pre-treatment (F1) (n = 22) (not receiving vitamins) and the same animals used for post-treatment (F2) (received 1,000,000 IU of vitamin A and vitamin 1g E). The first OPU was in F1, soon after 1,000,000 IU was administered 1 g of VE and VA, and after 12 days was held to make the new OPU F2. Oocytes (COC) were matured, fertilized and cultured in vitro. The OPU 44 yielded 520 oocytes, 217 (F1) and 303 (F2), with significant effect, an increase of 86 oocytes, obtaining mean and standard deviation 9.86 Â 5.53 13.77 Â 2.0 F1 and F2, (*p <0.0219). When separate races NBG (Nelore, Brahman and Gir) (n = 20) there was an increase of 95 oocytes, obtaining mean and standard deviation 9.90 Â 5.81 and 14.65 NBG F1-F2-NBG Â 9.44, (*p <0.0085). The 44 IVP embryos produced 224, 93 F1 and 131 F2, getting mean and standard deviation 4.23 Â 3.09 5.95 Â 4.05 F1 and F2, (*p <0.0228). When separated from the NBG production was 214 embryos, with an increase of 38 embryos, obtaining values of 4.45 Â 3.15 6.25 Â 4.09 F1 and F2, (*p <0.0285). There was a significant effect on the quantity produced of oocytes (n = 22) and NBG oocytes (n = 20). It was an increased in all breeds embryos production (n = 22) and NBG embryos (n = 20). Supplementation with VE and VA increased the total number of oocytes (1.7 Â 0.7); NBG oocytes (1.8 Â 0.8); total embryos (3.9 Â 1.6) and embryos NBG (4 7 Â 1.6). The response of the F2 compared to F1 in the production of oocytes and embryos was significant when all races were grouped together and also when it was grouped only Bos taurus indicus (NBG). The use of vitamins A and E can be used to greater oocyte recovery and embryo in Zebu breeds.

As vitaminas do complexo B e o ferro estão presentes em farinhas de cereais, alimentos amplamente consumidos pela população brasileira. O teor natural desses compostos em farinhas de cereais pode ser significativo no cálculo de uma dieta bem balanceada e o consumo de produtos industrializados enriquecidos com vitaminas do complexo B e ferro ajuda a contribuir na ingestão diária recomendada desses micronutrientes. Tabelas Mundiais de Composição de Alimentos apresentam dados incompletos das vitaminas do complexo B e do ferro em farinhas de cereais. No Brasil, a adição de ácido fólico e ferro em farinhas de milho e trigo produzidas para fins industriais é obrigatória desde 2002. Deste modo, para a adequação dos teores de rotulagem de produtos enriquecidos com vitaminas e ferro se fazem necessários o desenvolvimento e a validação de metodologias analíticas confiáveis e sensíveis para análise de vitaminas do complexo B e ferro em alimentos que apresentam tais micronutrientes em quantidades baixas, porém significativas, que correspondem aos teores naturalmente presentes. O objetivo do presente trabalho é a avaliação dos teores de sete vitaminas do complexo B (B1, B2, B6, ácido pantotênico, ácido fólico, niacina e biotina) e ferro em cinco farinhas de cereais (aveia, arroz, cevada, milho e trigo) utilizadas como matéria prima de produtos enriquecidos na indústria alimentícia, utilizando métodos validados.
Complex B vitamins and iron are present in some cereal foods, a kind of food largely consumed by Brazilian people. The total of these micronutrients can be significant at the dairy ingestion portion and in the consume of industrialized products enriched with complex B vitamins and iron contribute in the recommended dietary intake of these micronutrients. Table of food composition do not report complete data of complex B vitamins and iron in cereal flours. In Brazil, since 2002 the addition of folic acid and iron in com and wheat flours is compulsory. Therefore, to adapt the label of some products enriched with vitamins and iron, there is necessary the development and validation of analytical methods. These methods must be reliable and with enough sensitivity to analyse complex B vitamins and iron, in low concentration, wich are natural content in food. The purpose of this work is the evaluation, with validated methods, of the content of seven complex B vitamíns (B1, B2, B6, niacin, folic acid, pantothenic acid and biotin) and iron in five kinds of cereal flours (oat, rice, barley, com and wheat). These raw materiais are used in food industry in order to enrich the industrialized products.

FundaÃÃo de Amparo à Pesquisa do Estado do CearÃ
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O objetivo do presente trabalho foi investigar a existÃncia de variaÃÃo sazonal nos conteÃdos de carotenÃides provitamina A ( e caroteno) e vitamina E ( e tocoferol) em duas espÃcies de macroalgas marinhas vermelhas, Cryptonemia luxurians e C. crenulata. As algas foram coletadas mensalmente de janeiro a dezembro de 2007, durante as marÃs baixas na Praia do Pacheco, Caucaia, CearÃ. Em laboratÃrio as algas foram desidratadas em estufa a 40ÂC por 15 horas. O material desidratado foi triturado atà a obtenÃÃo de um pà fino e, em seguida, submetido aos procedimentos de extraÃÃo com metanol, saponificaÃÃo com hidrÃxido de potÃssio e partiÃÃo em n-hexano. Para a anÃlise simultÃnea de carotenÃides e tocoferÃis, por cromatografia lÃquida de alta eficiÃncia, uma coluna Waters Spherisorb-Hichrom S5 ODS-2 (4,6 x 250 mm) e fase mÃvel de MeOH: THF (95:5, v/v), com fluxo de 1,5 mL min -1 foram utilizadas, com detecÃÃo em 450 nm e 292 nm, respectivamente. Em ambas as espÃcies pertencentes ao gÃnero Cryptonemia foram detectados e caroteno ao longo dos meses de coleta. De uma maneira geral, as duas espÃcies apresentaram maiores teores de caroteno que caroteno. Apesar de as macroalgas analisadas pertencerem ao mesmo gÃnero, foi possÃvel verificar uma variaÃÃo nos teores de carotenÃides provitamina A ao longo do ano entre as espÃcies. C. luxurians pode ser eleita como melhor fonte de vitamina A que C. crenulata. Dentre os isÃmeros da vitamina E, tocoferol apresentou as maiores concentraÃÃes. C. luxurians exibiu os maiores teores de ambos os tocoferÃis. De acordo com os resultados obtidos no presente estudo, as macroalgas marinhas C. luxurians e C. crenulata desidratadas em estufa a 40ÂC por 15 horas possivelmente sÃo melhores fontes de vitamina E do que de vitamina A. Para avaliar o comportamento sazonal dos teores de  e caroteno e  e tocoferol, foi utilizada a anÃlise de agrupamentos. A partir dessa anÃlise constatou-se que os teores de tocoferÃis apresentaram variaÃÃo mais proeminente, tanto entre as estaÃÃes do ano como entre as espÃcies, quando comparados com os carotenÃides provitamina A, os quais demonstraram maior estabilidade nos teores por espÃcie e por estaÃÃo do ano. Entretanto, somente a partir de estudos posteriores serà possÃvel determinar quais fatores e sua influÃncia na variaÃÃo dos teores de carotenÃides provitamina A e vitamina E das espÃcies analisadas.
The objective of this research project was to investigate the existence of seasonal variation of both provitamin A carotenoids ( and carotene) and vitamin E ( and tocopherol) in two species of red marine macroalgae, Cryptonemia luxurians and C. crenulata. The alga samples were collected monthly from January to December of 2007, during the low tides of Pacheco Beach, Caucaia, CearÃ. The alga samples were dehydrated at 40ÂC for 15 h. The dried alga material was crushed into a fine powder and then submitted into the procedures of extraction with methanol, saponification with potassium hydroxide and partition with n-hexane. For simultaneous analyses of carotenoids and tocopherols the HPLC system consisted of a Waters Spherisorb-Hichrom S5 ODS-2 (4.6 x 250 mm) column and a mobile phase of MeOH: THF (95:5, v/v), delivered at 1.5 mL min -1 , with detection at 450 nm and 292 nm, respectively. In both species belonging to the genre Cryptonemia were detected  and carotene throughout all the sampling months. In general, both species contained larger concentrations of carotene than carotene. Despite the macroalgae analyzed belonged to the same genre, it was possible to verify a variation in the concentrations of provitamin A carotenoids throughout the year. C. luxurians was elected as a better source of vitamin A than C. crenulata. Among the isomers of vitamin E, tocopherol showed the higher concentrations. C. luxurians showed the highest levels of both tocopherols. According to these results, C. luxurians and C. crenulata oven-dried at 40ÂC for 15 h are possibly better sources of vitamin E than vitamin A. To verify the seasonal behavior of the concentrations of provitamin A carotenoids and vitamin E, grouping analysis was utilized. Based upon the results of this analysis it was established that tocopherol concentrations showed a more substantiated variation in the macroalgae within the seasons of the year as well as among the two species. On the other hand, the provitamin A carotenoids, exhibited more stable concentrations considering the species and the seasons. Nevertheless, only with subsequent studies it will be possible to determine the factors and its influence on the variation of provitamin A carotenoids and vitamin E contents of the analyzed species.

[Truncated abstract] Vitamin E is comprised of a family of tocopherols (TOH) and tocotrienols. The most studied of these is [alpha]-tocopherol ([alpha]-TOH), as this form is retained within the body and any deficiency of vitamin E is corrected with this supplement. [alpha]-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes and potentially acts as a defense against oxidative stress. Individuals who have a primary vitamin E deficiency such as low birth weight infants, secondary vitamin E deficiency due to fat malabsorption such as in abetalipoproteinaemia, or a genetic defect in TOH transport require supplementation. There is debate as to whether vitamin E supplementation in other patient groups is required. Vitamin E supplementation has been recommended for persons with FHBL, a rare disorder of lipoprotein metabolism that leads to low serum [alpha]-TOH and decreased LDL cholesterol and apolipoprotein B concentrations. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with heterozygous FHBL. We used HPLC with electrochemical detection to measure [alpha]- and [gamma]-TOH in serum, erythrocytes, and platelets, and GC-MS to measure urinary F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. Erythrocyte [alpha]-TOH was decreased, but we observed no differences in lipid-adjusted serum TOHs, erythrocyte [gamma]-TOH, platelet [alpha]- or [gamma]-TOH, urinary F2-isoprostanes, or TOH metabolites. Taken together, our findings do not support the recommendation that persons with heterozygous FHBL should receive vitamin E supplementation. ... Sesame lignans are natural components of sesame seed oil and there is evidence that these lignans can inhibit CYP450 enzymes, in particular, those responsible for vitamin E metabolism. We hypothesised that sesame seed ingestion would increase serum [gamma]-TOH, lower plasma lipids and inhibit platelet function in human subjects with at least one cardiovascular risk factor. We used HPLC with electrochemical detection to measure [alpha]- and -TOH in serum and GC-MS to measure F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. We used high-sensitive C-reactive protein as a measure of systemic inflammation. Platelet function was assessed using the PFA-100 platelet aggregation assay. Although serum [gamma]-TOH increased by 17%, we observed no effect on lipid metabolism, markers of inflammation, oxidative stress or platelet function following treatment with ~25 g/day sesame seeds for five weeks. Our findings challenge the hypothesis that sesame seed ingestion provides beneficial cardiovascular effects. In summary, we have studied the metabolism and transport of both [alpha]- and [gamma]-TOH in humans to evaluate the requirements for supplementation and the effects of vitamin E on platelet function and CYP3A4 activity. Specialised techniques using HPLC were developed to measure serum and cellular TOH concentrations both in supplemented and un-supplemented individuals. We also used GCMS to provide a sensitive, accurate assessment of TOH metabolites and midazolam pharmacokinetics in humans after vitamin E supplementation. We have examined the role vitamin E has on important biochemical endpoints, with emphasis on the implications for TOH supplementation in subjects at risk of CVD.

Orientador: Wilma De Grava Kempinas
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-15T09:54:25Z (GMT). No. of bitstreams: 1 Fernandes_GlauraScantamburloAlves_D.pdf: 1055644 bytes, checksum: ab0438c5919291591e8712767f1827c9 (MD5) Previous issue date: 2009
Resumo: A hiperglicemia está relacionada com desordens no sistema reprodutor masculino. Quando induzida quimicamente, ela pode causar diminuição nos níveis dos hormônios sexuais, no peso dos órgãos reprodutores, na concentração espermática, na fertilidade bem como alteração no comportamento sexual de ratos machos. No homem, a hiperglicemia pode levar a impotência sexual, diminuição da libido e da espermatogênese. Contudo, os principais fatores que ocasionam essas alterações ainda são discutíveis. Uma das hipóteses seria o aumento do estresse oxidativo, o qual pode causar peroxidação lipídica nas membranas biológicas, neuropatias hiperglicêmicas, danificar a molécula de DNA e comprometer a comunicação celular. No entanto, há escassez de informações que relacionem o efeito do estresse oxidativo aumentado com a morfofisiologia do sistema reprodutor masculino em indivíduos hiperglicêmicos. Diante disso, o objetivo deste estudo foi avaliar se o tratamento com antioxidantes (vitaminas C e/ou E), ao diminuir o estresse oxidativo, poderia diminuir os danos causados pela hiperglicemia no sistema reprodutor masculino de ratos. Para tanto, a hiperglicemia foi induzida quimicamente utilizando dose única do antibiótico streptozotocin em ratos machos adultos (90 dias de idade; 9 ou 10/grupo experimental). Esses animais foram divididos em grupos experimentais que receberam vitamina C e E (sozinhas ou associadas), ou apenas os veículos (grupo normoglicêmico) durante trinta dias consecutivos por via oral. No 31º dia do período experimental, após a eutanásia dos animais, foi coletado sangue para avaliação dos biomarcadores do estresse oxidativo e dos níveis hormonais, e órgãos reprodutores para avaliação dos parâmetros espermáticos e resposta noradrenérgica do ducto deferente. O delineamento experimental acima descrito foi empregado a um outro lote de animais para realização das análises histopatológicas e morfométricas do testículo e epidídimo. Os resultados mostraram que a hiperglicemia causou significativo aumento do estresse oxidativo e da sensibilidade dos receptores a1 noradrenérgicos, diminuição no peso corporal e dos órgãos reprodutores, redução na motilidade espermática, no nível de testosterona, aumento no número de espermatozóides malformados e um rearranjo nos componentes do tecido epididimário. As vitaminas reduziram significativamente o nível do estresse oxidativo e o número de espermatozóides malformados, mas em ambos os casos a vitamina C foi mais efetiva. As vitaminas também reduziram parcialmente a sensibilidade dos receptores a à noradrenalina. Com relação aos prejuízos da motilidade espermática a vitamina C sozinha amenizou parcialmente essas alterações. Também, a administração da vitamina C sozinha preveniu a redução da proporção dos componentes epididimários. Além disso, a vitamina C sozinha e associada com a vitamina E restabeleceram parcialmente os níveis de testosterona. Entretanto, a associação das vitaminas causou uma redução significativa nos níveis de LH. Contudo, a produção espermática diária, o tempo de trânsito espermático pelo epidídimo, o aspecto histológico dos testículos e epidídimos, o diâmetro dos túbulos seminíferos, os níveis de FSH e a resposta máxima noradrenérgica foram estatisticamente semelhantes entre os grupos experimentais. Em conclusão, essas vitaminas, atuando como antioxidantes, podem diminuir algumas alterações no sistema reprodutor masculino de ratos causados pela hiperglicemia.
Abstract: The hyperglycemia is related to disorders in the male reproductive system. When induced chemically, it can reduce the sexual hormones' level, reproductive organs' weight, sperm concentration, and fertility as well as the male rat sexual behavior. In men, the hyperglycemia can lead to sexual impotence, libido and spermatogenesis reduction. However, the main factors that are responsible for these alterations are still controversial. One of the possible causes for this would be the increase of the oxidative stress, which can cause lipid peroxidation in the biological membranes, hyperglycemic neuropathies, injury in the DNA molecule and to compromise the cellular communication. However, there is a lack of information related to the increased oxidative stress effect with the morphophysiology from the male reproductive system in hyperglycemic subjects. In this sense, the aim of the present study was to evaluate if the treatment with antioxidants (vitamins C and/or E), lowering the oxidative stress, could somehow attenuate the damages caused by hyperglycemia in the male rat reproductive system. Therefore the hyperglycemia was induced chemically using a single dose of streptozotocin antibiotic in male adult rats (90 days old; 9 or 10/experimental group). These animals were divided into experimental groups that received vitamin C or E (isolated or in association), or only the vehicles (normoglycemic group) during thirty consecutive days orally. At the 31st day from the experimental period, after the euthanasia of the rats, blood was collected to evaluate biomarkers of oxidative stress and hormonal levels, and reproductive organs to evaluate the permatic parameters and the noradrenergic response of vas deferens. The experimental design described above was applied in another amount of animals for the accomplishment of histopathological and morphometric analysis from testis and epididymis. The results showed that hyperglycemia caused significant increase in the oxidative stress and in the sensibility of noradrenergic a1 receptors, decrease in the body mass and in the reproductive organs' weights, reduction on the sperm motility, on epididymal tissue, in the testosterone level, an increase in the malformed sperm number and a rearrangement in the epididymal tissue components. The vitamins reduced significantly the level of oxidative stress and the number of malformed sperm, but in both cases vitamin C was more effective. These vitamins also reduced partly the sensibility to noradrenalin in the a receptors. In relation to the injuries in the sperm motility, the vitamin C alone attenuated partly these alterations. In addition, the vitamin C alone also prevented the reduction of the epididymal compartimental. Besides that, the vitamin C alone and in association to vitamin E reestablished partly the testosterone levels. Meanwhile, the association of the vitamins caused a significant reduction in the LH levels. Nonetheless, the daily sperm production, the transit time by epididymis, the histological aspect of the testes and epididymides, the seminiferous tubular diameter, the FSH levels and the maximum noradrenergic response were statistically equal among the groups. In summary, these vitamins, acting as antioxidants, may reduce some changes in the rat male reproductive system caused by hyperglycemia.
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural

Les leishmaniosis són un grup de malalties causades per protozous del gènere Leishmania que es transmeten per vectors. La leishmaniosi visceral (LV) humana pot ser mortal si no es tracta, resultant en 26 000-65 000 morts a l’any. Els cànids són el principal reservori i hostes de Leishmania infantum, l’agent causant de la LV zoonòtica a la conca mediterrània. Es desconeixen els mecanismes que regulen el resultat final de la infecció, però és sabut que el sistema immunitari juga un paper clau en el control de la malaltia. Diversos estudis han demostrat que la vitamina D té un rol important en la resposta immune, activant el sistema immunitari innat i modulant la resposta adaptativa. A més, s’ha descrit la relació entre la deficiència de vitamina D i el risc de patir diverses malalties. L’objectiu de la tesis va ser estudiar si la vitamina D té una contribució rellevant en la leishmaniosi canina (LCan). Per això, es va mesurar la concentració de vitamina D en mostres de sèrum d’una població de gossos sans i malalts residents en zona altament endèmica i se’n va estudiar la relació amb paràmetres parasitològics i immunològics. Els gossos malalts presentaven nivells de vitamina D significativament més baixos que els no infectats i que els infectats asimptomàtics. A més, la deficiència de vitamina D es correlacionava amb paràmetres relacionats amb la progressió de la LCan. També vam investigar si variacions genètiques en el locus del gen del receptor de la vitamina D s’associa amb la progressió de la LCan, però les freqüències al·lèliques dels polimorfismes (SNPs) trobats no van resultar ser estadísticament diferents entre grups. Llavors, vam analitzar la concentració de vitamina D en mostres de sèrum preses en diferents períodes de l’any en una cohort de gossos sans. Els resultats van mostrar que no hi ha variació estacional dels nivells de vitamina D en gossos. També es va analitzar retrospectivament la concentració de vitamina D en gossos amb leishmaniosi clínica i gossos no-infectats a l’inici de l’estudi, quan tots els animals eren negatius a Leishmania, i un any després. Mentre que els gossos sans no van mostrar canvis en els nivells de vitamina D durant l’estudi, els que van desenvolupar leishmaniosi van mostrar una reducció significativa al final de l’estudi. Per tant, la concentració de vitamina D no és un factor de risc per desenvolupar LCan, sinó que disminueix amb el curs de la malaltia. Un model in vitro va demostrar que afegir vitamina D activa (1,25(OH)2D3) comporta una reducció significativa de la càrrega de L. infantum en macròfags canins. Analitzant l’expressió de gens relacionats amb la via de la vitamina D en monòcits canins primaris vam demostrar que l’expressió de la β-defensina CBD103 augmenta significativament amb l’addició de 1,25(OH)2D3. Els resultats van corroborar que la vitamina D juga un paper en el control del paràsit. Per últim, es va estudiar la viabilitat de la vitamina D com a adjuvant per potenciar l’efecte d’una vacuna enfront la leishmaniosi. Es va administrar vitamina D conjuntament amb una vacuna d’ADN encapsulada en liposomes a ratolins BALB/c. Dues setmanes després de la vacunació els animals van ser infectats amb L. infantum. Es va mesurar la càrrega parasitària en òrgans diana i es va avaluar la resposta immune abans de la infecció i sis setmanes després. La vacuna no va reduir significativament la càrrega parasitària, però amb la co-administració de vitamina D es va apreciar una tendència a disminuir-la. L’estudi de la resposta immunològica va suggerir que l’augment de limfòcits T CD4+ i CD8+ podrien haver contribuït en la protecció parcial aconseguida per la vacuna amb la vitamina D com a potenciador.
Las leishmaniosis son un grupo de enfermedades causadas por protozoos del género Leishmania que se transmiten por vectores. La leishmaniosi visceral (LV) humana puede ser mortal si no se trata, resultando en 26 000-65 000 muertes por año. Los cánidos son el principal reservorio y huéspedes de Leishmania infantum, el agente causante de la LV zoonótica en la cuenca mediterránea. Se desconoce el mecanismo que regula el resultado final de la infección, pero se sabe que el sistema inmunitario juega un papel clave en el control de la enfermedad. Varios estudios han demostrado que la vitamina D tiene un rol importante en la respuesta inmune, activando el sistema inmunitario innato y modulando la respuesta adaptativa. Además, se ha descrito la relación entre la deficiencia de vitamina D y el riesgo de sufrir algunas enfermedades. El objetivo de la tesis fue estudiar si la vitamina D tiene una contribución relevante en la leishmaniosis canina (LCan). Para ello se determinó la concentración de vitamina D en muestras de suero de una población de perros sanos y enfermos de leishmaniosis residentes en una zona altamente endémica y se estudió la relación de ésta con parámetros parasitológicos e inmunológicos. Los perros enfermos mostraron niveles de vitamina D significativamente más bajos que los no infectados y que los infectados asintomáticos. Además, la deficiencia de vitamina D se correlacionó con parámetros relacionados con la progresión de la enfermedad. También investigamos si las variaciones genéticas en el locus del gen del receptor de la vitamina D se asocia con la progresión de LCan, pero las frecuencias alélicas de los polimorfismos (SNPs) encontrados no resultaron ser estadísticamente diferentes entre grupos. Posteriormente se analizó la concentración de vitamina D en muestras de suero tomadas en diferentes periodos del año en una cohorte de perros sanos. Los resultados mostraron que no hay una variación estacional de los niveles de vitamina D en perros. También se analizó retrospectivamente la concentración de vitamina D en perros con leishmaniosis clínica y perros no infectados al inicio del estudio, cuando todos los animales eran negativos a Leishmania, y un año después. Mientras que los perros sanos no mostraron cambios en los niveles de vitamina D durante el estudio, los que desarrollaron leishmaniosis mostraron una reducción significativa al final del estudio. Por lo tanto, la concentración de vitamina D no es un factor de riesgo para desarrollar LCan, sino que disminuye con el curso de la enfermedad. Un modelo in vitro demostró que añadir vitamina D activa (1,25(OH)2D3) conlleva una reducción significativa de la carga de L. infantum en macrófagos caninos. Analizando la expresión de genes relacionados con la vía de la vitamina D en monocitos caninos primarios demostramos que la expresión de la β-defensina CBD103 aumenta significativamente con la adición de 1,25(OH)2D3. Los resultados corroboraron que la vitamina D juega un papel en el control del parásito. Por últimos, se estudió la viabilidad de la vitamina D como adyuvante para potenciar el efecto de una vacuna frente la leishmaniosis. Se administró vitamina D junto a una vacuna de ADN encapsulada en liposomas a ratones BALB/c. Dos semanas después de la vacunación los animales se infectaron con L. infantum. Se determinó la carga parasitaria en órganos diana y se evaluó la respuesta inmune antes de la infección y seis semanas después. La vacuna no redujo significativamente la carga parasitaria, pero con la coadministración de vitamina D se apreció una tendencia a reducirla. El estudio de la respuesta inmunológica sugirió que el aumento de linfocitos T CD4+ y CD8+ podrían haber contribuido a la protección parcial conseguida cuando se administró vitamina D como potenciador junto a la vacuna.
Leishmaniasis are a group of neglected vector-borne diseases caused by obligate intracellular protozoan parasites of the genus Leishmania. Human visceral leishmaniasis (VL) can be fatal if left untreated, resulting in 26 000-65 000 deaths per year. Canids are the main reservoir and hosts of L. infantum, the causative agent of zoonotic VL in the Mediterranean Basin. The mechanisms that regulate the outcome of the infection are undisclosed, although it is well known that immune system plays a key role in leishmaniasis disease control. Several studies have shown that vitamin D plays an important immunomodulatory role by activating innate immune system and modulating the adaptive immune response. Furthermore, the relationship between vitamin D deficiency and the risk of suffering from a plethora of health disorders has been described. The aim of the thesis was to study if vitamin D have a relevant contribution in canine leishmaniasis (CanL). Because of that, we measured vitamin D concentration in serum samples from a cohort of healthy and ill dogs from a highly endemic area and we have also studied the relationship of vitamin D concentration with parasitological and immunological parameters. The sick dogs presented significantly lower vitamin D levels than their non-infected and the asymptomatic counterparts. In addition, vitamin D deficiency correlated with several parameters linked to leishmaniasis progression. We also aimed to investigate whether genetic variation within the vitamin D receptor gene locus is associated with the progression of CanL, but the allelic frequencies of the four single nucleotide polymorphisms (SNPs) found were not statistically different between groups. Afterwards, we analysed retrospectively vitamin D concentration in serum samples from a cohort of healthy dogs collected in different periods of the year. The results showed that there is not a seasonal variation of vitamin D concentration in dogs. We also analysed retrospectively vitamin D concentration in serum samples from dogs with clinical leishmaniasis and non-infected healthy dogs, in which we measured vitamin D levels at the beginning of the study, when all dogs were negative for Leishmania, and 1 year later. Whereas non-infected dogs showed no changes in vitamin D levels along the study, those developing clinical leishmaniasis showed a significant vitamin D reduction at the end of the study. Therefore, vitamin D concentration is not a risk factor for developing canine leishmaniasis, but it diminishes with the onset of clinical disease. An in vitro model using a canine macrophage cell line proved that adding active vitamin D (1,25(OH)2D3) leads to a significant reduction in L. infantum load. Analyzing expression of genes related to vitamin D pathway on primary canine monocytes, we showed that defensin CBD103 expression was significantly enhanced after active vitamin D addition. The in vitro results corroborated that vitamin D plays a role in parasitic control. Finally, we studied the suitability of vitamin D as an adjuvant to enhance the effect of a DNA vaccine against VL. BALB/c mice were treated with vitamin D concomitantly with a DNA vaccine encapsulated in liposomes. Two weeks after vaccination, the animals were infected with L. infantum parasites. Parasite load was measured in target tissues and immune response was evaluated before challenge and six weeks post-infection. Our DNA vaccine did not significantly reduce parasite load in liver nor spleen, but vitamin D coadministration showed a tendency to diminish parasite load in target organs. The study of cell response in splenocytes suggested that higher levels of CD4+ and CD8+ T cells may be responsible for the partial protection mediated by the DNA vaccine with vitamin D as enhancer.
Universitat Autònoma de Barcelona. Programa de Doctorat en Farmacologia

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Universidade Estadual Paulista (UNESP)
O excesso na geração de espécies reativas como os radicais livres pode resultar num desequilíbrio que, embora benéfico em casos específicos como no combate a microrganismos patógenos, está implicado na etiologia de diversas patologias crônicas e com o envelhecimento precoce. Muitos pesquisadores indicam o uso de antioxidantes como potenciais para a prevenção destas patologias e inclusive, algumas pesquisas com antioxidantes como a curcumina estão em etapas finais do desenvolvimento de novos medicamentos. Embora atividades biológicas como a antimicrobiana e antioxidante sejam bastante exploradas para várias substâncias, há um grande potencial para a investigação em relação às atividades de duas ou mais substâncias associadas. O ácido ascórbico, por exemplo, possui algumas atividades biológicas semelhantes às da curcumina, entretanto seu uso e custo são mais acessíveis. Deste modo, há perspectivas para investigações sobre os efeitos resultantes da associação entre a curcumina e o ácido ascórbico em relação a algumas atividades biológicas, com destaque para a curcumina. Assim, este trabalho objetivou determinar os efeitos resultantes desta associação em relação ao perfil de atividades antimicrobiana, antioxidante, hemolítica e na estabilidade da curcumina. Foram utilizadas metodologias de análise de atividade antioxidante como os ensaios de ação scavenger do DPPH·, ABTS·+, O2 ·-, HOCl e também por análise do sistema oxidativo catalisado por peroxidase. Em relação às análises celulares e antimicrobianas, foi determinada a toxicidade sobre eritrócitos e a atividade em relação à Sthaphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans e Candida krusei. A estabilidade da curcumina foi determinada por espectrofotometria...
The excessive generation of reactive species such as free radicals can result in an imbalance which is implicated in the etiology of various chronic diseases and premature aging, although it is beneficial in specific cases, such as in against microbial pathogens. Many researchers suggest the antioxidants usage to prevent these diseases. Some researches about curcumin and others antioxidants are even in final stages of developing new medicines. Although some biological activities are fully explored for various substances, there is great potential of research about the activities of two or more associated substances. Ascorbic acid, for example, has some biological activities similar to those of curcumin, but its use and cost are more accessible. Thus, there are prospects for research on the effects of the association between these molecules, especially curcumin, in relation to some biological activities. This study aimed to determine the effects of this association on antioxidant, antimicrobial and hemolytic activities of curcumin. Since this association can prevent the oxidative degradation of curcumin, it was also aimed to analyze the effects of ascorbic acid on the curcumin stability. Antioxidant activities were evaluated through DPPH , ABTS +, O2 - and HOCl scavenging assays and guaiacol oxidation catalyzed by peroxidase. Regarding the cellular and microbial analysis, the toxicity was determined on erythrocytes and the antimicrobial activity was studied to Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Candida krusei. The stability of curcumin was determined spectrophotometrically. The combination resulted in a increase in antioxidant activity of curcumin against DPPH , ABTS + and HOCl. We were unable to determine the effect of the association against... (Complete abstract click electronic access below)

A 700bp portion of the promoter of CYP2D25, the porcine microsomal vitamin D 25-hydroxylase was isolated and sequenced. The computer analysis of the sequence revealed the existence of a putative VDRE at 220 bp upstream of the transcription start site. A CYP2D25 promoter-luciferase reporter plasmid was constructed in order to study the transcriptional regulation of the gene. Treatment with the vitamin D metabolites calcidiol and calcitriol suppressed the promoter, provided that the nuclear receptors VDR and RXR were overexpressed. Phenobarbital was also capable of suppressing the promoter if the nuclear receptors PXR or CAR were overexpressed. The 25-hydroxylases are not expressed solely in liver but in a wide array of other organs as well. It is therefore possible at least in theory to study the vitamin D 25-hydroxylation in human subjects using cells from extrahepatic organs, from which biopsy retrieval is easier than from the liver. Dermal fibroblasts are frequently used to study different pathological conditions in human subjects and they are easy to come by. Dermal fibroblasts were shown to express two vitamin D 25-hydroxylases: CYP27A1 and CYP2R1. The expression pattern of CYP2R1 displayed considerable interindividual variation. The fibroblasts were also capable of measurable vitamin D 25-hydroxylation, which makes dermal fibroblasts a possible tool in studying vitamin D 25-hydroxylation in human subjects. Little is known about the regulation of expression and activity of the human vitamin D 25-hydroxylases. Therefore dermal fibroblasts – expressing CYP2R1 and CYP27A1 – and human prostate cancer LNCaP cells, that express CYP2R1 and CYP2J2, were treated with calcitriol and phenobarbital and efavirenz, two drugs that give rise to vitamin D deficiency. Treatment decreased the mRNA levels of CYP2R1 and CYP2J2 provided that the treated cells also expressed the necessary nuclear receptors. CYP27A1 did not respond to any of the treatments. The treatments also managed to decrease the 25-hydroxylating activity of the cells. The results show that vitamin D 25-hydroxylases can be regulated by both endogenous and xenobiotic compounds.

Introdução: Uma elevada prevalência de deficiência de vitamina D (DVD) em crianças tem sido observada em todo o mundo, mas poucos são os estudos com relação ao estado nutricional da vitamina D (VD) em lactentes saudáveis. A principal causa da deficiência em crianças saudáveis é o aleitamento materno sem suplementação e a falta ou insuficiência de exposição solar. Objetivos: Determinar as concentrações séricas de VD e verificar sua associação com concentrações de paratormônio (PTH), fosfatase alcalina (FA), cálcio (Ca), fósforo (P) e albumina e uso da suplementação de VD em lactentes saudáveis com idades entre >= 6 e <= 24 meses atendidos em duas Unidades Básicas de Saúde do município de Ribeirão Preto, SP, Brasil. Métodos: Estudo transversal, observacional e analítico em que foram determinadas as concentrações séricas de 25 (OH)D, PTH, FA, Ca, P e albumina de 155 lactentes saudáveis. Informações sobre exposição solar, aspectos sociodemográficos das mães e características clínico-nutricionais dos lactentes foram obtidas por entrevistas com os responsáveis dos lactentes. Concentrações séricas de 25(OH)D maiores que 20ng/ml foram consideradas adequadas, entre 12 a 20ng/ml insuficientes e < 12ng/ml deficientes. Resultados: Dez lactentes (6,5%, Intervalo de Confiança 95% 3,5-11,4) apresentaram insuficiência de VD e nenhum apresentou DVD. Nenhuma alteração nas concentrações séricas de P, Ca e albumina foram detectadas. Apenas um lactente apresentou aumento nas concentrações séricas de PTH e 35,5% dos lactentes apresentaram FA elevada, porém nenhum apresentou DVD ou insuficiência de VD. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e as de FA, Ca e albumina. Houve associação entre concentrações séricas de 25(OH)D e PTH mesmo após ajuste para sexo, idade e Índice de Massa Corporal; também foi observada associação entre concentrações séricas de 25(OH)D e P apenas após o ajuste pelas covariáveis. Não foram verificadas associações entre insuficiência de VD, exposição solar e suplementação de VD. Conclusões: Uma baixa prevalência de concentrações insuficientes de 25(OH)D foi observada. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e PTH, FA, Ca, P e albumina. Da mesma forma, não foram encontradas associações entre de concentrações séricas de 25(OH)D, exposição solar e suplementação de VD.
Introduction: A high prevalence of vitamin D deficiency (VDD) in children has been observed worldwide, but there are few studies on the nutritional status of vitamin D (VD) in healthy infants. The main cause of deficiency in healthy children is breastfeeding without supplementation and lack or insufficiency of sun exposure. Objective: To determine serum concentrations of VD and verify its association with parathyroid hormone (PTH) levels and use of VD supplementation in healthy infants aged >= 6 to <= 24 months attended at two Basic Health Units in Ribeirão Preto city, São Paulo, Brazil. Methods: A cross-sectional, observational and analytical study was performed in which were determined serum concentrations of 25 (OH) D, PTH, alkaline phosphatase (AP), calcium (Ca), phosphorus (P) and albumin of 155 healthy infants. Information of sun exposure, sociodemographic aspects of mothers and clinical and nutritional characteristics of infants were obtained through interviews with responsible for infants. Serum concentrations of 25(OH)D greater than 20ng / ml were considered adequate, between 12 to 20ng / ml insufficient and <12ng/ml, deficient. Results: Ten infants (6.5%, 95% Confidence Interval 3.5-11.4) presented VD insufficiency and none presented DVD. Only one infant had an increase in PTH serum concentrations and 35.5% of infants had high AP but none presented DVD or VD insufficiency. No changes in serum P, Ca and albumin concentrations were detected. No associations were found between serum concentrations of 25 (OH) D and AP, Ca and albumin. There was an association between serum concentrations of 25(OH)D and PTH even after adjusting for sex, age and body mass index; an association between serum concentrations of 25(OH)D and P was observed only after adjustment for covariates. There were no associations between VD insufficiency, sun exposure and VD supplementation. Conclusions: A low prevalence of insufficient concentrations of 25 (OH)D was observed. No associations were found between serum concentrations of 25 (OH)D and PTH, FA, Ca, P and albumin. Likewise, no associations were found between serum concentrations of 25 (OH)D, sun exposure and VD supplementation.

Les vitamines D et K sont des micronutriments liposolubles qui participent au bon fonctionnement de l’organisme. Elles jouent des rôles clés dans la prévention de trouble de l'hémostase et de la coagulation, des pathologies osseuses, métaboliques et cardiovasculaires. Cependant, même si ces vitamines sont apportées en quantités suffisantes par notre alimentation, leurs effets bénéfiques sont étroitement conditionnés par leur biodisponibilité. Or, mieux connaitre les mécanismes d’absorption permettrait d’appréhender leur biodisponibilité. Nous avons tout d’abord montré que l’absorption de la vitamine K implique des transporteurs du cholestérol, SR-B1 et CD36. Nous avons également montré que l’entérocyte est non seulement capable d’effluer les vitamines D et K néo-absorbées mais également d’excréter ces vitamines du compartiment sanguin vers la lumière intestinale. Ce phénomène bien connu pour le cholestérol (excrétion transintestinale du cholestérol) implique des transporteurs communs, dont ABCB1 et ABCG5/G8. Dans un second temps, dans le cadre de la relance de la consommation des légumineuses, nous avons mis en évidence que la présence de légumineuses dans un repas limite la biodisponibilité de ces vitamines. En effet, les fibres, phytates, saponines et tanins diminuent leur bioaccessibilité et/ou leur captage. La méthode de cuisson des légumineuses, en affectant leur composition nutritionnelle, peut moduler l’incorporation des vitamines D et K au sein des micelles mixtes et donc affecter leur biodisponibilité. Ces données soulignent ainsi le fait que les légumineuses doivent être cuites de manière appropriée et consommés dans des repas riches en micronutriments
Vitamin D and K are fat-soluble micronutrients that participate to the proper functioning of the organism. They are essential to prevent bleeding, bone, metabolic and cardiovascular disorders. However, even if those vitamins are provided in sufficient quantities in our diet, their health effects are closely linked to their bioavailability. A better knowledge of their absorption mechanisms would help to optimize their bioavailability.Firstly, we showed that vitamin K absorption involves the cholesterol transporters SR-B1 and CD36. We also showed that enterocytes can not only efflux newly absorbed vitamins D and K but also excrete vitamin D and K from the blood compartment to the intestinal lumen. This phenomenon of transintestinal excretioninvolves the cholesterol membrane transporters ABCB1 and ABCG5/G8.Secondly, we showed that the presence of pulses within a meal limits vitamin D and K bioavailability. Indeed, fibers, phytates, saponins and tannins can decrease bioaccessibility and/or uptake of vitamin K. By modulating the nutritional profile of pulses, the cooking method can impact on fat-soluble vitamin transfer to mixed micelles, and in turn affect their bioavailability. These data suggest that pulses must be cooked in an appropriate manner and consumed in micronutrient-rich meals.Keywords: vitamin D, vitamin K, bioaccessibility, intestinal absorption, pulses

Sammanfattning Vitamin E är en substans med antioxidanta egenskaper, ett fettlösligt vitamin som kan finnas i naturliga källor såsom vegetabiliska oljor, ägg, grönsaker, spannmål, frukter,kött men också i syntetisk form. I dagsläget är vitamin E också tillgängligt som kosttillskott och används förebyggande och/eller vid behandling av sjukdomar som kardiovaskulära sjukdomar, arterioskleros, diabetes mellitius samt olika former av cancer. Vid intag av vitamin E kan oxidativ stress minskas vilket produceras av fria radikaler (t.ex. joniserande strålning, giftiga föreningar från luft, vatten, mat) som drabbar celler och på det sättet förebyggs och fördröjs uppkomst av sjukdomar. Utöver sin antioxidant effekt och är vitamin E involverat i immunförsvaret, cellsignalering,genreglering samt andra metaboliska processer. Dessa egenskaper har gjort av vitaminE är en intressant kandidat till utredning vid prostatacancer (adenocarcinom), som är den vanligaste tumörformen i Sverige hos män över 50-års ålder. Denna litteraturstudie har för syfte att undersöka det empiriska stödet för tesen omvitamin E kan ha en förebyggande effekt mot prostatacancer och vilka risker som finns vid intag av vitamin E vid prostatacancer. Tidigare forskning har visat att det har enantioxidativ inverkan på kroppens organ och det har därför funnits en tro på att den kan hjälpa förebygga prostatacancer. Litteraturstudien bygger på originalartiklar framförallt från PubMed, Socialstyrelse hemsidan, WebMd, olika medicinska böcker och i Google med sökord som: vitamin E, prostatacancer, tokoferol och prostatacancer,oxidative stress, antioxidant, androgen metabolism och vitamin E, prostatacancer ocharv, androgen och vitamin E. Resultatet av studierna visar att det inte finns ett entydigt empiriskt stöd för att vitaminE (tokoferol) har en förebyggande effekt mot prostatacancer. Vissa studier visar ett stöd för att det finns en förebyggande effekt, andra visar att det inte finns ett stöd och en visar en signifikant ökad risk för prostatacancer vid intag av tokoferol. Prostatacancer kan inte förebyggas med vitamin E (tokoferol) enligt forskningsresultaten i denna studie. Vidare forskning krävs för att se om det kan finnas kombinationer med t.ex. selen för att öka effektiviteten för att förebygga prostatacancer.

Doctor of Philosophy
Department of Animal Sciences and Industry
Jim Nelssen
A total of 701 pigs were used to evaluate effects of natural vitamin E relative to synthetic vitamin E in sow diets, late gestation feeding level on sow reproductive performance, dietary L-carnitine and chromium on sow reproductive performance, and experimental design on nursery pig trial interpretation. As D-α-tocopheryl acetate increased in the sow’s diet, concentrations of α-tocopherol increased (P < 0.03) in sow plasma, colostrum, milk, pig plasma, and pig heart. Regression analysis indicated that the bioavailability coefficients for D-α-tocopheryl acetate relative to DL-α-tocopheryl acetate ranged from 2.1 to 4.2 for sow and pig plasma α-tocopherol, 2.9 to 3.0 for colostrum α-tocopherol, 1.6 for milk α-tocopherol, 1.8 for heart α-tocopherol, and 2.0 for liver α-tocopherol. Overall, this study indicates that the relative bioavailability for D-α-tocopheryl acetate relative to DL-α-tocopheryl acetate varies depending on the response criteria but is greater than the standard potency value of 1.36. Increasing sow gestation feeding level by 0.9 kg from d 90 of gestation through farrowing reduced (P = 0.001) daily lactation feed intake in gilts, but also resulted in improved conception rate in gilts, whereas increasing late gestation feeding level decreased conception rate in sows (interaction; P = 0.03). Increasing late gestation feed intake in gilts also increased (P < 0.02) pig weaning weights during the second parity. Increasing late gestation feeding levels did not improve performance of older sows. Adding L-carnitine and chromium from chromium picolinate to sow gestation and lactation diets reduced (P = 0.01) the amount of sow weight loss during lactation, however, did not improve (P > 0.05) litter size, pig birth weight, or the variation in pig birth weight. Blocking pens of nursery pigs by BW in a randomized complete block design (RCBD) did not improve the estimates for σ2error compared to a completely randomized design (CRD) where all pens were allotted to have similar means and variations of body weight. Therefore, the added degrees of freedom for the error term in the CRD allowed more power to detect treatment differences for the CRD compared to the RCBD.

Vitamin B₁₂-dependent algae are unable to grow in medium made with natural filter-sterilized seawater or freshwater unless a vitamin B₁₂ supplement is added to the culture, suggesting that the concentration of free vitamin B₁₂ in the natural environment in generally too low to support the growth of vitamin B₁₂-dependent algae.  The source of cobalamin for algae appears to be vitamin B₁₂-synthesizing bacteria, because when these organisms are grown in co-culture, the algae no longer require the vitamin. In return for vitamin B₁₂, the bacteria are able to use the products of algal photosynthesis to grow, indicating an important and unsuspected symbiosis. Using the green alga Chlamydomonas reinhardtii as a model organism, RT-PCR analysis has demonstrated that vitamin B₁₂ regulates the expression of the gene encoding the vitamin B₁₂-independent methionine synthase. Cobalamin is likely to regulate the expression of this gene by binding directly to the mRNA and influencing its secondary structure, since affinity binding studies suggest that the mRNAs that encode for the methionine synthase proteins have a high affinity for cobalamin. Further work in C. reinhardtii and Euglena gracilis has shown that a cell wall protein is involved in the high affinity uptake of vitamin B₁₂, since mutants deficient in cell wall biosynthesis are impaired in their ability to take up the vitamin. The C. reinhardtii protein has been purified by affinity chromatography, and identified by mass spectrometry. The complete cDNA encoding the C. reinhardtii vitamin B₁₂ binding protein has been cloned, and the protein shown to be a member of the pherophorin family, a well-known group of green algal cell wall proteins. A combination of techniques has indicated that the protein is glycosylated, and that the sugar moieties are attached to a central domain that contains a significant number of hydroxyproline residues.

The aim of this research was to apply analytical epidemiology to examine associations between hypertension and vitamin D status (serum 25-hydroxyvitamin D (25OHD)). The first objective was to appraise and synthesize the research evidence on the relationship between hypertension and 25OHD. The follow-up objective was to complete a sequence of studies exploring the association between hypertension and 25OHD in two populations with high hypertension and vitamin D deficiency rates, Finland and China. The results of the meta-analysis were that higher vitamin D levels were associated with lower hypertension rates. In a prospective study from Finland higher 25OHD levels at baseline were found to associate with less hypertension and a lower pulse rate. On follow-up only low pulse rate remained associated with higher 25OHD. A hypertension prevalence rate of 34% was reported from a cross-sectional survey in Macau 2012. Potentially modifiable predictors of hypertension were found to be smoking, obesity and lack of exercise, sunlight exposure and low intake of fish. Only 45% of this population on whom blood was collected were found to have sufficient vitamin D status (≥50 nmol/L). Young highly educated women were at greatest risk of not being sufficient. Higher sun exposure, fish intake and more physical activity and less sitting were associated with higher 25OHD levels. In the older population (≥55 years) higher 25OHD levels significantly predicted having either lower hypertension or lower pulse rates. The evidence from these series of studies indicates a small consistent association between vitamin D sufficiency and reduction in hypertension risk. These results are consistent with recent meta-analyses of observational studies. The unique finding from this study is that there is an age cohort differential with younger Chinese having lower vitamin D status and in a population with increasing hypertension this fact may have public health consequences in the future.

O pólen apícola é o resultado da aglutinação do pólen das flores efetuada pelas abelhas, mediante acréscimo de substâncias salivares e pequenas quantidades de néctar ou mel. Trata-se de um produto consumido devido a seus benefícios nutricionais e terapêuticos. Sua importância nutricional é reconhecida por ser uma fonte protéica de elevado valor biológico, apresentando ainda carboidratos, lipídeos e minerais em sua composição, além das vitaminas do complexo B, C, E, β-caroteno (como pró-vitamina A) e D; características estas que variam de acordo com sua origem botânica. Este trabalho teve como objetivos: caracterizar o pólen apícola produzido em diferentes épocas de coleta; obter dados científicos nacionais sobre o valor vitamínico de pólen apícola, relacionando-o com sua origem botânica e avaliar o efeito de dois tipos de processos de secagem do pólen apícola nos teores das vitaminas antioxidantes (β-caroteno, como pró-vitamina A, vitamina C e E), considerando-se que estas vitaminas podem ser degradadas durante o processamento. Foram analisados os teores de vitaminas em 10 lotes de pólen apícola fresco, sendo 5 coletados em abril e 5 em outubro de 2005. Os lotes frescos de pólen apícola foram desidratados por um método convencional (desidratação à 42° C) e por um método alternativo (desidratação a 30-35° C). Além disso, foi realizada a identificação dos tipos polínicos encontrados nas amostras frescas de pólen apícola e a associação com o teor de vitaminas encontradas. Os valores das vitaminas determinados nas amostras frescas de pólen apícola variaram entre 13,5 e 42,5 µg/g para vitamina E; 56,3 e 198,9 (µg/g) para β-caroteno e entre 273,9 e 560,3 µg/g para vitamina C. De acordo com os resultados concluiu-se que a origem botânica e a época de coleta influenciaram no teor das vitaminas encontradas, interferindo inclusive na classificação da amostra como fonte ou não de determinada vitamina. Além disso, foi observado que o processamento alternativo foi mais eficaz que o processamento convencional na manutenção dos teores de todas as vitaminas em estudo.
Bee-collected pollen (bee pollen) is highly consumed around the world due its nutritive and therapeutic value. It contains proteins, carbohydrates, lipids, minerals and vitamins of complex B, vitamin C, D, E and totals carotenoids. However there are few literature data correlating nutritional composition with botanical origin and thermal process. The aim of this study was to quantify vitamins C, E and beta-carotene (provitamin A) in fresh and processed samples of bee pollen, correlating them with botanical origin. In addition, to evaluate the effect of drying process in the vitamin content. Ten samples of fresh bee pollen were collected, five in April and five in October of 2005. Samples of fresh bee pollen were dried by conventional method (drying at 42° C) and by an alternative method (drying at 30-35° C). The fresh bee pollen and the processed ones were assayed regarding their vitamin contents (n=30). Vitamin C was quantified by potentiometric titration, vitamin E by HPLC-normal phase and beta-carotene by open column chromatography. The date from botanical characterization of the bee pollen were obtained and correlated to the vitamins content. Vitamin content in fresh samples varied between 13,5 and 42,5 µg/g for vitamin E; 56,3 and 198,9 (µg/g) for β-carotene and 273,9 and 560,3 µg/g for vitamin C. The alternative drying method was more efficient that conventional one in retaining the vitamins. It was also concluded that the botanical origin and collecting season influenced the vitamin contents. Being important factor to predict if bee pollen was source or not of each vitamin.

O pólen apícola apresenta elevadas porcentagens de nutrientes e pode ser utilizado como suplemento nutricional na alimentação humana. Este trabalho teve por objetivo principal avaliar a estabilidade das vitaminas antioxidantes (vitamina C, E e β-caroteno) em pólen apícola durante um ano de estocagem. Foram adquiridos entre os meses de março e abril 2007 seis lotes de pólen apícola in natura e desidratado, diretamente de entrepostos de comercialização de produtos apícolas. Foram analisadas as concentrações das três vitaminas no tempo zero e em seguida amostras foram armazenadas, em embalagens fornecidas pelo produtor, sob três formas: a temperatura ambiente; a temperatura ambiente, porém protegida da luz; em freezer. Foi utilizado o método títulométrico para análise de vitamina C. Para β-caroteno utilizou-se a cromatografia em coluna aberta no tempo zero e cromatografia líquida de alta eficiência após 6 e 12 meses de estocagem. Esta última foi utilizada para as análises da vitamina E. Foram realizadas ainda análises polínica e de composição centesimal. Foram encontradas as seguintes variações: 14±0,25 a 119±1,961 µg/g para vitamina C, 19,43±1,70 a 45,00±3,61µg/g para vitamina E 3,77±0,10 a 99,27±2,45 µg/g para β-caroteno em amostras frescas. Após processo de desidratação, houve uma alteração de 67,1% para mais na vitamina C (diferença significativa p<0,05), uma perda de 18,7% para vitamina E e de 15,6% para β-caroteno. O valor pró-vitamínico A das amostras desidratadas variou de 0,26 a 6,48 µg/g. A composição centesimal das amostras estudadas está de acordo com as especificações estabelecidas pela legislação brasileira em vigor (Instrução Normativa N° 3, de 19/01/2001). Houve grande variabilidade dos tipos polínicos encontrados nas amostras e alguns deles estiveram fortemente correlacionados com os teores de vitamina C (Myrtaceae), de β-caroteno (Arecaceae, Cecropia e Fabaceae) e de lipídeos (Arecaceae e Fabaceae). Outros estiveram correlacionados de forma negativa, como é o caso dos Mimosa caesalpineafolia e Poacease com os níveis de β-caroteno, do tipo Arecaceae com as proteínas e do tipo Mimosa caesalpineafolia com os lipídeos. A estocagem em freezer foi a condição mais eficiente na conservação das três vitaminas e a perda na estocagem a temperatura ambiente exposto a luz e protegido da luz foram semelhantes. Considerando-se as três condições estudadas, a vitamina E parece ser mais preservada durante estocagem quando comparada à vitamina C e ao β-caroteno. Entretanto, conforme teste estatístico realizado, houve perdas significativas (p<0,05) apenas para vitamina C em todas as condições estudadas quando comparadas a sua concentração inicial (tempo 0).
Bee pollen contains high percentages of nutrients and it can be used as a nutritional supplement for human feeding. The aim of this work was to evaluate the stability the antioxidant vitamins (vitamin C, E and β-carotene) in bee pollen during one year of storage. Six batches of fresh and dried bee pollen pellets were acquired in 2007 March and April from bee products warehouses. The three vitamins were quantified and then stored under three forms in packages supplied by the producer: in room temperature, in room temperature protected from light and frozen. Vitamin C was quantified by potentiometric titration. The open column chromatography was used for β-carotene analyses in the zero time and the high performance liquid chromatography after 6 and 12 months storage. This last one was used for the vitamin E analyses. The centesimal composition and botanical characterization of the bee pollen were obtained. Vitamin content in fresh samples varied between 14±0.25 and 119±1.96µg/g for vitamin C; 19.43±1.70 and 45.00±3.61µg/g for vitamin E and 3.77±0.10 and 99.27±2.45µg/g for β-carotene. After the drying process a significant alteration 67.1 % for more in the vitamin C (p<0.05), a losses of 18.7% for vitamin E and 15.6% for β-carotene were observed. The provitamin A value was between 0.26 and 6.48µg/g. The proximal composition of the samples studied presented results which were ali accordance to the specifications established for the Brazilian regulation (Normative Instruction N° 3, 19/01/2001). A great variability of the pollen types was found in the samples and some of them were strongly correlated with the vitamin C (Myrtaceae), β-carotene (Arecaceae, Cecropia and Fabaceae) and lipids (Arecaceae and Fabaceae). Other ones were negatively correlated, such as Mimosa caesalpineafolia and Poaceae types with β-carotene, Arecaceae type with proteins and Mimosa caesalpineafolia type with lipids. Storage in freezer was more efficient to keep the vitamins and the losses at room temperature storage when exposed to light and in the dark were similar. Vitamin E was more preserved during the storage when compared to vitamin C and β-carotene. However, only vitamin C presented significant statistical losses (p<0.05) in ali of the studied conditions when compared to its initial content.

La transició demogràfica cap a una societat més envellida ha esdevingut un desafiament per l’economia social global, especialment pels sistemes de salut públics. Per tal de millorar la qualitat de vida fins un procés d’envelliment més saludable, son necessàries evidències que suportin diferents promotors de salut en condicions relacionades amb l’edat. Prèviament, s’ha suggerit que la vitamina K podria desenvolupar un paper modulador en el procés de l’envelliment i els mecanismes relacionats amb l’edat, com l’estrès oxidatiu, la inflamació i la resistència a la insulina. No obstant, l’evidència actual sobre l’associació de la ingesta de vitamina K i el risc de malalties associades a l’envelliment és escassa. L’objectiu principal d’aquest treball va ser avaluar l’associació entre la ingesta dietètica de vitamina K1 i el risc de cataractes, nefropatia i retinopatia diabètica, el deteriorament de la funció cognitiva i la demència. La present tesi doctoral s’ha realitzat en el marc dels estudis PREDIMED i PREDIMED-plus, ambdós grans assajos clínics aleatoritzats, multicèntrics i paral·lels, realitzats en poblacions mediterrànies d’edat avançada amb elevat risc cardiovascular. Els resultats derivats del present treball van mostrar associacions positives significatives entre el consum dietètic de vitamina K1 i el risc de cataractes, nefropatia diabètica i demència. Tanmateix, un increment en la ingesta de la vitamina K1 es va associar amb una millor puntuació en índexs de funció cognitiva. La conclusió principal obtinguda d’aquesta tesi doctoral és que, en comparació amb una ingesta baixa, un consum dietètic elevat de vitamina K1 s’associa amb un envelliment saludable al disminuir el risc de diferents patologies associades a l’envelliment d’una població mediterrània d’edat avançada amb elevat risc cardiovascular.
La transición demográfica hacia una sociedad más envejecida se ha convertido en un desafío para la economía social global, especialmente para los sistemas públicos de salud. Evidencia que soporte diferentes promotores de salud en condiciones relacionadas con la edad son necesarias para mejorar la calidad de vida hacia un proceso de envejecimiento más saludable. Se ha sugerido previamente que la vitamina K podría desempeñar un papel modulador en el proceso de envejecimiento y los mecanismos relacionados con la edad, como el estrés oxidativo, la inflamación y la resistencia a la insulina. Sin embargo, la evidencia actual sobre la asociación del consumo de vitamina K y el riesgo de enfermedades asociadas al envejecimiento es aún escasa. El objetivo principal de este trabajo fue evaluar la asociación entre la ingesta dietética de vitamina K1 y el riesgo de cataratas, nefropatía y retinopatía diabética, el deterioro de la función cognitiva y la demencia. El presente trabajo se realizó en el marco de los estudios PREDIMED y PREDIMED-plus, ambos grandes ensayos clínicos aleatorizados, multicéntricos, paralelos realizados en poblaciones Mediterráneas de edad avanzada con alto riesgo cardiovascular. Los resultados derivados del presente trabajo mostraron asociaciones positivas significativas entre el consumo dietético de vitamina K1 y el riesgo de cataratas, nefropatía diabética y demencia. Asimismo, un incremento en el consumo de vitamina K1 se asoció con un mejor desempeño en los scores de función cognitiva. La conclusión principal derivada de esta Tesis Doctoral es que, en comparación con una ingesta baja, un alto consumo dietético de vitamina K1 se asocia con un envejecimiento saludable al disminuir el riesgo de diferentes patologías asociadas al envejecimiento en una población Mediterránea de edad avanzada con alto riesgo cardiovascular.
The demographic transition headed for an older society is becoming a challenge for the global social economy, especially for the public health care systems. Evidence, supporting different promoters of health on age-related conditions is necessary in order to improve the quality of life towards a heathier ageing process. Vitamin K has been suggested to play a modulatory role in ageing and age-related mechanisms such as oxidative stress, inflammation and insulin resistance. However, the current evidence regarding vitamin K’s association with the risk of age-related diseases is still scarce. The main objective of this work was to evaluate, the association between the dietary vitamin K1 intake and the risk of cataracts, diabetic nephropathy and retinopathy, cognitive function decline and dementia. The present work was conducted in the framework of the PREDIMED and the PREDIMED-plus studies, both large multicentre, parallel, randomized clinical trials carried out on elderly Mediterranean populations at high cardiovascular risk. Results derived from the present work showed significant positive associations between dietary vitamin K1 intake and the risk of cataracts, diabetic nephropathy and dementia. Likewise, an increment in the consumption of vitamin K1 was associated with better performance in cognitive functioning scores. The main conclusion derived from this Doctoral Thesis is that compared to a low intake, a high dietary vitamin K1 intake is associated with healthy ageing through decreasing the risk of different age-related diseases among an elderly Mediterranean population at high cardiovascular risk.

NASCIMENTO, Rômulo Malta. Avaliação sazonal de Carotenóides provitamina A (alfa- e beta caroteno) e vitamina E ( alfa- tocoferol) em macroalgas marinhas pertencentes ao gênero Cryptonemia. 2009. 77 f. : Dissertação (mestrado) - Universidade Federal do Ceará, Centro de Ciências Agrárias, Departamento de Engenharia de Pesca, Fortaleza-CE, 2009
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The objective of this research project was to investigate the existence of seasonal variation of both provitamin A carotenoids ( and carotene) and vitamin E ( and tocopherol) in two species of red marine macroalgae, Cryptonemia luxurians and C. crenulata. The alga samples were collected monthly from January to December of 2007, during the low tides of Pacheco Beach, Caucaia, Ceará. The alga samples were dehydrated at 40°C for 15 h. The dried alga material was crushed into a fine powder and then submitted into the procedures of extraction with methanol, saponification with potassium hydroxide and partition with n-hexane. For simultaneous analyses of carotenoids and tocopherols the HPLC system consisted of a Waters Spherisorb-Hichrom S5 ODS-2 (4.6 x 250 mm) column and a mobile phase of MeOH: THF (95:5, v/v), delivered at 1.5 mL min -1 , with detection at 450 nm and 292 nm, respectively. In both species belonging to the genre Cryptonemia were detected  and carotene throughout all the sampling months. In general, both species contained larger concentrations of carotene than carotene. Despite the macroalgae analyzed belonged to the same genre, it was possible to verify a variation in the concentrations of provitamin A carotenoids throughout the year. C. luxurians was elected as a better source of vitamin A than C. crenulata. Among the isomers of vitamin E, tocopherol showed the higher concentrations. C. luxurians showed the highest levels of both tocopherols. According to these results, C. luxurians and C. crenulata oven-dried at 40°C for 15 h are possibly better sources of vitamin E than vitamin A. To verify the seasonal behavior of the concentrations of provitamin A carotenoids and vitamin E, grouping analysis was utilized. Based upon the results of this analysis it was established that tocopherol concentrations showed a more substantiated variation in the macroalgae within the seasons of the year as well as among the two species. On the other hand, the provitamin A carotenoids, exhibited more stable concentrations considering the species and the seasons. Nevertheless, only with subsequent studies it will be possible to determine the factors and its influence on the variation of provitamin A carotenoids and vitamin E contents of the analyzed species.
O objetivo do presente trabalho foi investigar a existência de variação sazonal nos conteúdos de carotenóides provitamina A ( e caroteno) e vitamina E ( e tocoferol) em duas espécies de macroalgas marinhas vermelhas, Cryptonemia luxurians e C. crenulata. As algas foram coletadas mensalmente de janeiro a dezembro de 2007, durante as marés baixas na Praia do Pacheco, Caucaia, Ceará. Em laboratório as algas foram desidratadas em estufa a 40°C por 15 horas. O material desidratado foi triturado até a obtenção de um pó fino e, em seguida, submetido aos procedimentos de extração com metanol, saponificação com hidróxido de potássio e partição em n-hexano. Para a análise simultânea de carotenóides e tocoferóis, por cromatografia líquida de alta eficiência, uma coluna Waters Spherisorb-Hichrom S5 ODS-2 (4,6 x 250 mm) e fase móvel de MeOH: THF (95:5, v/v), com fluxo de 1,5 mL min -1 foram utilizadas, com detecção em 450 nm e 292 nm, respectivamente. Em ambas as espécies pertencentes ao gênero Cryptonemia foram detectados e caroteno ao longo dos meses de coleta. De uma maneira geral, as duas espécies apresentaram maiores teores de caroteno que caroteno. Apesar de as macroalgas analisadas pertencerem ao mesmo gênero, foi possível verificar uma variação nos teores de carotenóides provitamina A ao longo do ano entre as espécies. C. luxurians pode ser eleita como melhor fonte de vitamina A que C. crenulata. Dentre os isômeros da vitamina E, tocoferol apresentou as maiores concentrações. C. luxurians exibiu os maiores teores de ambos os tocoferóis. De acordo com os resultados obtidos no presente estudo, as macroalgas marinhas C. luxurians e C. crenulata desidratadas em estufa a 40°C por 15 horas possivelmente são melhores fontes de vitamina E do que de vitamina A. Para avaliar o comportamento sazonal dos teores de  e caroteno e  e tocoferol, foi utilizada a análise de agrupamentos. A partir dessa análise constatou-se que os teores de tocoferóis apresentaram variação mais proeminente, tanto entre as estações do ano como entre as espécies, quando comparados com os carotenóides provitamina A, os quais demonstraram maior estabilidade nos teores por espécie e por estação do ano. Entretanto, somente a partir de estudos posteriores será possível determinar quais fatores e sua influência na variação dos teores de carotenóides provitamina A e vitamina E das espécies analisadas.

Little is known regarding the vitamin D status of Canadian youth. Our objectives were: (i) to describe the vitamin D status of Québec youth using a representative sample; (ii) examine the relative contributions of diet, physical activity and fat mass to the variance in plasma 25-hydroxyvitamin D{25(OH)D}, the best biomarker of vitamin D status; and (iii) examine the influence of household income and food insecurity on the intakes of dietary vitamin D, calcium and dairy foods.
To describe vitamin D status, we used data from a cross-sectional survey representative of Québec youth aged 9, 13 and 16, the Québec Child and Adolescent Health and Social Survey (QCAHS). For the second objective, 159 youth, aged 8-11 whose parents (at least one) were obese or had the metabolic syndrome were used for cross-sectional analysis in the Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Fat mass was measured using Dual X-ray Absorptiometry (DXA) and physical activity was assessed by accelerometer. Finally, we analyzed data from the Canadian Community Health Survey (CCHS), a sample of 8960, 9-18-year-olds representative of Canadian youth for whom a single 24 hour dietary recall, measured height and weight, sociodemographic and information on food insecurity were available.
Greater than 90% of youth had sub-optimal vitamin D levels {plasma 25(OH)D < 75 nmol} at the end of winter and beginning of spring in both the QUALITY and QCAHS study. In the QCAHS study, older youth had a higher prevalence of vitamin D deficiency {25(OH)D < 27.5 nmol} (> 10%) than younger youth and girls from low income households had lower plasma 25(OH)D concentrations. In the QUALITY study, milk consumption and physical activity had modest associations with plasma 25(OH)D corresponding to 2.9 nmol/L and 2.1 nmol/L higher plasma 25(OH)D per standard deviation increase in these exposures, respectively. In the CCHS study, we found evidence that milk intake was being displaced by sweetened beverages amongst low income boys and food insecure girls.
Population wide measures to increase dietary vitamin D intake should be examined in Canadian youth.
Il y a peu de connaisances concernant le statut vitamin D des jeunes Canadiens. Nos objectifs étaient de: (i) décrire le statut vitamin D des jeunes Québécois en utilisant un échantillon représentatif; (ii) examiner la contribution de la diète, l'activité physique et l'adiposité a expliquer la variance du 25-hydroxyvitamin D, {25(OH)D.}, le meilleur biomarqueur du statut vitamine D; et (iii) examiner l'influence du statut socio-économique et l'insécurité alimentaire sur le consommation des produits laitiers, du calcium et de la vitamine D alimentaire.
Pour décrire le statut vitamine D on a utilisé les données transversales d'un échantillon représentatif des jeunes Québecois agés de 9, 13 et 16 ans. Pour le deuxième objectif, 159 jeunes, âgés 8-11 ans avec des parents (au moins un) qui étaient obèses ou avaient le syndrome métabolique etaient utilisés pour une analyse transversale dans l'étude Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Le tissu adipeux a été mesuré avec le dual X-ray absorptiometry (DXA) et l'activité physique était mésurer par accéléromètre. Finalement, on a utilisé des données du Canadian Community Health Survey (CCHS), un échantillon de 8960 jeunes, agés de 9-18 ans qui avaient un rappel alimentaire de 24 heures, le poids et la taille mesuré, l'information sociodémograhique et le statut de sécurité alimentaire.
Dans l'étude QUALITY et le QCAHS plus de 90% des jeunes avaient un statut de vitamine D sub-optimal {plasma 25(OH)D < 75 nmol} à la fin de l'hiver et au début du printemps. Dans l'étude QCAHS, les adolescents avaient une prévalence de déficience de vitamine D élevé {25(OH)D < 27.5 nmol} (> 10%) et les filles venant des foyers défavorisés avait des niveaux de vitamine D plus bas. Dans l'étude QUALITY, un augmentation d'un écart-type de la consommation du lait et l'activité physique était associée avec une augmentation du niveau de vitamin D de 2.9 nmol/L and 2.1 nmol/L respectivement. Dans l'étude CCHS nous avons remarqué que les garçons de milieux défavorisés et les filles avec une insécurité alimentaire consommaient moins de lait et le lait étaitremplacé par les breuvages sucrés.
Des mesures pour augmenter la consommation de vitamine D parmi les jeunes Canadiens devraient être examinées.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O presente estudo teve como objetivo determinar os níveis séricos de vitamina A e sua proteína ligadora (RBP) em crianças de 6 – 71 meses de idade, matriculadas em uma Unidade Básica de Saúde, situada na periferia do município de Botucatu, SP. Para isso, se determinou os níveis de retinol sérico em 202 crianças pelo método espectofotométrico e a RBP pelo método de nefelometria. Os resultados foram analisados em dois grupos etários, G1 constituído pelas crianças entre 6 a 23 meses de idade e G2 pelas crianças entre 24-71meses de idade. A mediana dos níveis séricos de retinol foi de 31,1μg/dl para o grupo total, de 27,2μg/dl e 32,0μg/dl para os grupos etários G1 e G2 respectivamente, sendo essa diferença estatisticamente significante (p<0,05). A mediana dos níveis séricos da RBP foi de 2,7mg/dl para o grupo total e 3,0mg/dl, 2,6mg/dl, para os grupos etários G1 e G2 respectivamente, sendo essa diferença estatisticamente significante (p<0,05). A prevalência de hipovitaminose A em nível bioquímico (retinol < 20μg/dl) foi de 15,3% para o grupo total, de 25,9% e 11,1% para os grupos etários G1 e G2 respectivamente. Não houve associação estatisticamente significante entre o estado nutricional de vitamina A e as variáveis sexo, número de pessoas na família, constituição familiar, idade materna, escolaridade materna e uso de suplementos vitamínicos nos dois grupos etários, com exceção da renda familiar per capita no grupo etário G2. O estudo demonstrou a existência de deficiência subclínica de vitamina A nestas crianças, chamando atenção para a vulnerabilidade do grupo etário de 6 – 23 meses de idade, revelando a importância de estudos mais detalhados em crianças menores de 24 meses, bem como, a separação de grupos etários quando se estuda fatores de risco...
The present study aimed at determining the serum levels of vitamin A and its binding protein (RBP) in children aging 6 to 71 months, enrolled in a Health Basic Unit located in the periphery of Botucatu city, SP. For this, the serum retinol levels were determined in 202 children through the spectrophotometric method, and the RBP through the nephelometry method. The results were analyzed in two groups of age, G1 made up by children aging 6 to 23 months, and G2 by children aging 24 to 71 months. The retinol serum levels median was 31,1μg/dl for the total group, 27,2μg/dl and 32,0μg/dl for G1 and G2, respectively, being such difference statistically significant (p<0,05). The RBP serum levels median was 2,7mg/dl for the total group, and 3,0mg/dl, 2,6mg/dl for G1 and G2, respectively, being such difference statistically significant (p<0.05). The prevalence of hypovitaminosis A at biochemical level (retinol <20μg/dl) was 15,3% for the total group, 25,9% and 11,1% for G1 and G2, respectively. There was no statisticallly significant association between vitamin A nutritional status and the variables sex, number of family members, familiar constitution, mother’s age, mother’s schooling and use of vitaminic supplements in both groups of age, except of family income per capita... (Complete abstract click electronic access below)
FAPESP: 97/02002-6

Orientador: Maria José Roncada
Resumo: Este estudo avaliou a ingestão da vitamina A em gestantes que realizavam acompanhamento pré-natal em centro de Saúde de Catanduva, SP a adequação utilizou os critérios propostos pela DRI (Dietary Reference Intakes) de vitamina A, de acordo com as recomendações para EAR (estimated average requirement) de 550µg ER e da UL (tolerable upper intake level) de 3000µg ER. Foram estudadas setenta e duas gestantes, com idade entre 19 e 37 anos, em diferentes estágios da gestação. Para avaliação da ingestão dos alimentos fontes foi utilizado o inquérito dietético simplificado proposto pelo IVACG (International Vitamin A Consultative Group), já validado. O consumo de alimentos fortificados, de suplementos vitaminicos com vitamina A e os possíveis tabus e aversões alimentares atribuidos aos alimentos fontes de vitamina A também foram avaliados, utilizando-se questionários específicos...(Resumo completo, clicar acesso eletrônico abaixo)
Mestre

The objective of this dissertation was to study the disposition and absorption of riboflavin and ascorbic acid in healthy male subjects as a function of age. Deficiencies of these vitamins have been found in the elderly and malabsorption is suspected in this population. Absorption of riboflavin was examined by administration of an oral dose of 200 mg of riboflavin-5'-phosphate (FMN) and disposition was studied following a 30 min constant rate IV infusion of FMN equivalent to 25 mg of riboflavin. Ascorbic acid absorption was examined by administration of a 5 g oral dose and disposition was studied following a 1 g IV dose. Test doses of these vitamins were administered to subjects ranging in age from 33 to 85 years. High performance liquid chromatographic assays were developed for the determination of riboflavin and ascorbic acid in plasma and urine. The method for riboflavin separated FMN and flavin adenine dinucleotide under isocratic conditions. Quantification of the three flavins was achieved by fluorescence detection. The assay system for ascrobic acid used a postcolumn reaction for the fluorometric detection of a dehydroascorbic acid derivative. This method used isoascorbic acid as the internal standard. Finally, similar specificity between a "methoxyaniline" colorimetric method and the chromatographic method was observed for the quantification of ascorbic acid in plasma and urine. Albumin plasma concentration and riboflavin protein binding were decreased with age (p < 0.05). The in vitro stability of ascorbic acid in whole blood and plasma decreased with age (p < 0.05, n = 17). The results of this study indicate no age-related alterations in parameters associated with the gastrointestinal absorption of these vitamins. Increased relative renal excretion of riboflavin with age may explain the deficiency of this vitamin. On the other hand, ascorbic acid deficiency with age may be explained by decreased stability of the vitamin in blood.

Les leucémies aiguës myéloblastiques (LAM) sont un groupe hétérogène de pathologies malignes représentant environ 70% des leucémies aiguës. Il existe une prolifération, dans le cadre des LAM de cellules immatures appartenant à la lignée myéloïde appelées myéloblastes ou communément blastes. Les traitements actuels reposent essentiellement sur la chimiothérapie antimitotique. L’homéostasie du fer est une cible dans le traitement des LAM en induisant la différentiation des blastes. Le mécanisme implique la modulation des ROS. Leur action est synergique avec celle de la Vitamine D (VD) au travers de l’activation de la voie des MAPK. Cette association a été utilisée chez plusieurs patients avec succès permettant un doublement de leur espérance de vie. Nous avons ensuite montré que l’expression du récepteur expression vitamine D (VD) est altérée dans les états indifférenciés / immatures sous-types de LAM et que la diminution de l'expression du VDR et de ces gènes cibles est corrélée à un mauvais pronostic chez les patients. Le mécanisme moléculaire entraînant le blocage de l'expression VDR implique la méthylation de son promoteur. Les souris invalidées pour le VDR ont une expansion du compartiment des cellules souches hématopoïétiques demeurant à un état quiescent ainsi qu’une diminution des niveaux du stress oxydatif en leur sein. En outre, la transformation maligne des cellules déficientes en VDR a abouti à une différenciation myéloïde limitée, à l'augmentation du nombre de progéniteurs hématopoïétiques précoces et ces cellules présentaient un potentiel d'auto-renouvellement accru et étaient résistantes aux inhibiteurs de la méthyltransférase et à la chimiothérapie. Enfin, l'induction de l'expression du VDR dans les modèles de LAM par un traitement combinant des agents de déméthylation et les agonistes de VDR a permis de diminuer la séminalité, de promouvoir la différenciation cellulaire, de bloquer la croissance tumorale et de restaurer la sensibilité à la chimiothérapie. Par conséquent, nous proposons que le VDR est un gène maître contrôlant la séminalité et la prolifération / différenciation cellulaire des cellules souches hématopoïétiques normales et leucémiques. Ainsi, la combinaison d'agents déméthylants et d’agonistes de VDR pourrait à l’avenir être proposée en thérapeutique pour traiter les LAM
Acute myeloid leukemia (AML) is a heterogeneous group of malignancies representing approximately 70% of acute leukemias. There is a proliferation of immature cells belonging to the myeloid lineage commonly called myeloblasts or blasts. Current treatments are mainly based on antimitotic chemotherapy. Iron homeostasis is a target for the treatment of AML blasts inducing cell differentiation. The mechanism involves the modulation of ROS. Their action is synergistic with that of Vitamin D (VD) through the activation of MAPK. This association has been used successfully in several patients for a doubling of life expectancy. Then, we show that Vitamin D receptor (VDR) expression was impaired in undifferentiated/immature AML subtypes and that decreased expression of VDR and VDR-targeted genes was correlated with a negative prognosis of patients. Molecular mechanism resulting in the blockade of VDR expression involved VDR promoter methylation. VDR-deficient mice showed an expansion of the hematopoietic stem cell compartment which presented an improved quiescent status and decreased ROS levels that have been shown to be involved in both AML differentiation and stem cells longevity. Moreover, malignant transformation of VDR-deficient cells resulted in limited myeloid differentiation, increased numbers of early hematopoietic progenitors and those cells presented an enhanced self-renewal potential and were resistant to DNA methyltransferase inhibitors and to chemotherapy. Finally, induction of VDR expression in AML models by combined treatment of demethylating agents and VDR agonists decreased stemness, promoted cell differentiation, blocked tumor propagation and restored sensitivity to chemotherapy. Therefore, we propose that VDR is a master gene controlling stemness and proliferation/cell differentiation of normal hematopoietic stem cells and leukemic cells. Thus, combination of demethylation agents and VDR agonists may be used therapeutically to treat AML

Mestrado em Engenharia Química
A vitamina D3 é um micronutriente essencial para o metabolismo do cálcio, sendo esta maioritariamente sintetizada na pele do ser humano, quando exposta a radiação UVB. Contudo, inúmeros factores têm vindo a reduzir a nossa exposição à luz solar, diminuindo assim os níveis de vitamina D3 no corpo humano a nível global e aumentando a preocupação por parte de diversas instituições médicas a nível mundial. Para superar esta deficiência em vitamina, a vitamina D3 tem sido adicionada à alimentação humana através de alimentos fortificados e de suplementos alimentares. Para satisfazer a procura da população em vitamina D3, este trabalho apresenta uma unidade de cristalização com dois estágios que opera em contínuo à escala micro. O objectivo deste trabalho é projectar e optimizar esta unidade de cristalização por forma a desenvolver uma unidade de produção de cristais de vitamina D3 mais económica, mais sustentável, e com elevado rendimento de cristais aproriados para aplicações farmacêuticas. O primiero estágio da unidade de cristalização projetada corresponde a uma coluna de vidro onde a nucleação é intensificada através de cristalização por evaporação e por adição de anti-solvente. Este cristalizador opera a 40 ºC e o caudal volumétrico é controlado manualmente. O segundo estágio é um cristalizador tubular onde a cristalização ocorre por redução da temperatura para promover o crescimento dos núcleos produzidos no estágio anterior. Esta é operada a 7 ºC e em 59 s de tempo de residência. Após o segundo estágio, um filtro está integrado no sistema para recolher os cristais de vitamina D3 sintetizados. Este trabalho está dividido em duas partes. A primeira abrange a optimização da unidade de cristalização, a qual foi conseguida estudando o efeito da razão volúmica entre o anti-solvente e o solvente no desempenho da cristalização. O melhor resultado foi obtido para a proporção volúmica de 3, a qual permitiu alcançar 52 % de rendimento absoluto e 60 % de eficiência de filtração. Adicionalmente, por forma a melhorar o rendimento e a eficiência de filtração, ensaios experimentais foram realizados onde a corrente de permeado (da filtração) foi reciclada. Porém, as melhorias esperadas não se verificaram, o que significa que ensaios experimentais adicionais são necessários para sustentar uma conclusão sólida relativamente ao efeito do reciclo no processo em estudo. A reprodutibilidade do processo desenvolvido e optimizado também necessita ser melhorada. A segunda parte corresponde à caracterização dos cristais de vitamina D3 produzidos durante os ensaios de optimização. Os cristais apresentam uma forma prismática e aglomeração significativa. A distribuição de tamanhos dos cristais é ampla, extendendo-se desde, aproximadamente, 0.25 μm a quase 500 μm. Adicionalmente, a estrutura dos cristais produzidos não corresponde à estrutura termodinamicamente mais estável. Excluindo o seu hábito, as características dos cristais produzidos não são adequadas para aplicações na indústria farmacêutica. No entanto, sugestões são apresentadas para melhorar ambas as características dos cristais e a optimização do processo.
Vitamin D3 is an essential micronutrient for calcium metabolism, which is mainly synthesized in the skin of the human organism when irradiated with UVB light. However, a variety of factors have been reducing our exposition to sunlight, and thus the levels of vitamin D3 in the body have been decreasing, rising the concern of numerous medical institutions worldwide. To overcome such vitamin deficiency, the vitamin D3 has been added to the diet through fortified food and dietary supplements. To address the population demands on vitamin D3, this project presents a two-stage crystallization unit that operates continuously at a microscale. The aim of this project is to design and optimize this crystallization unit in order to develop an economical and sustainable high yield production unit of vitamin D3 crystals suitable for subsequent pharmaceutical applications. The first stage of the designed crystallization unit corresponds to a glass column where nucleation is enhanced by evaporation and anti-solvent crystallization. This crystallizer operates at 40 ºC and the volumetric flow rate is manipulated manually. The second stage is a tubular crystallizer where a cooling crystallization takes place to further grow the nuclei generated in the previous step; it is carried out at 7 ºC and 59 s of residence time. At the end of the second stage, a filter is placed to collect the synthesized vitamin D3 crystals. This work is divided in two main parts. The first part comprehends the optimization of the crystallization unit, which was accomplished by studying the influence of the anti-solvent/solvent volumes ratio on the performance of the crystallization. The best results were obtained for the volume ratio of 3, where 52 % of absolute yield was achieved as well as 60 % of filter efficiency. Furthermore, other experiments were performed where the permeate stream (of the filtration) was recycled to improve both yield and filter efficiency. However, such expected improvements were not confirmed, which means that additional experiments are needed to support any reliable conclusion regarding the effect of recycling on the process. The reproducibility of the crystallization process developed and optimized needs to be improved as well. The second part corresponds to the characterization of the crystals produced during the optimization assays. The crystals exhibit a prismatic habit and a significant degree of agglomeration. The crystal size distribution is large, extending from ca. 0.25 μm to almost 500 μm. Furthermore, the obtained solid-state form is not the thermodynamically stable one. Besides the crystal habit, the properties of the obtained crystals are not yet suitable for a pharmaceutical application. Nonetheless, suggestions of improvement are presented for both crystals characterization and optimization of the crystallization process.

Introdução As deficiências de vitaminas, verificadas em indivíduos com HIV/Aids em terapia antirretroviral de alta potência (HAART) têm sido associadas à piora do curso clínico da doença e maior risco de mortalidade. Objetivo Mostrar a distribuição das concentrações séricas de vitaminas A e E, e beta-caroteno em adultos com infecção pelo HIV/Aids e estudar a associação de suas concentrações, segundo diferentes esquemas de HAART. Métodos Foram selecionados 182 adultos de 20 a 59 anos de idade, de ambos os sexos, com HIV/Aids em HAART estável por no mínimo 6 meses, e com níveis de linfócitos T-CD4+ 200 células/mm3. Os indivíduos foram divididos em três grupos por esquema de HAART utilizado: inibidores de transcriptase reversa análogos de nucleosídeo (ITRN) associados a inibidores de transcriptase reversa não análogos de nucleosídeo (ITRNN); ITRN associada a inibidores de protease (IP); ITRN associadas a outras classes (inibidores de fusão, inibidores de integrase, inibidores de entrada e IP associada a essas medicações). A determinação dos micronutrientes foi realizada por cromatografia líquida de alta eficiência. Foram verificadas variáveis sócio-demográficas e econômicas, estilo de vida, história da doença, uso de medicações e variáveis antropométricas e laboratoriais. Para medir os efeitos das variáveis explanatórias (esquemas de tratamento, tempo de uso e adesão ao último esquema) sobre cada variável resposta (retinol, alfa-tocoferol e beta-caroteno), foram realizadas análises de regressão linear múltipla. Sexo, idade, escolaridade, tabagismo, prática de atividade física, tempo de infecção por HIV, presença de comorbidades, relação cintura-quadril e níveis de linfócitos T-CD4+ e colesterol foram usadas como variáveis de controle. Resultados Foram encontradas concentrações deficientes e baixas de vitaminas A (<0,70Nmol/L) e E (16,2Nmol/L), e beta-caroteno (<0,13Nmol/L) em 3,83 por cento, 18,68 por cento e 23,62 por cento dos indivíduos, respectivamente. Menores concentrações médias de vitamina E foram observadas em indivíduos em uso de ITRN associado a classes mais recentes de antirretrovirais (p= 0,037). Indivíduos com maiores índices de relação cintura-quadril apresentaram maiores concentrações de retinol (p=0,012) e menores concentrações de beta-caroteno (p=0,036). Foram também observadas associações positivas, pequenas e estatisticamente significantes entre as concentrações médias de retinol, alfatocoferol e beta-caroteno com os níveis de colesterol. Conclusão Os resultados sugerem que as alterações nas concentrações de vitamina A e E, e beta-caroteno podem estar relacionadas a múltiplos fatores, incluindo os esquemas de terapia antirretroviral
Introduction Deficiency of vitamins found in individuals with HIV/AIDS on highly active antiretroviral therapy (HAART) has been associated with an increased risk of disease progression and mortality. Objective To show the distribution of serum concentrations of vitamins A and E and beta-carotene in adults with HIV/AIDS, and to study the association of their concentrations, according to different regimens of HAART. Methods We selected 182 men and women aged 20-59 years with HIV/AIDS on stable HAART for at least six months and with levels of CD4+ T-lymphocytes 200 cells/mm3. Individuals were divided into three groups according to the HAART regimen used: nucleoside reverse transcriptase inhibitors (NRTI) combined with nonnucleoside reverse transcriptase inhibitors (NNRTI); NRTI combined with protease inhibitors (PI); NRTI combined with other classes (fusion inhibitors, integrase inhibitors, entry inhibitors, and PI associated with these medications). Determinations of vitamins A and E and beta-carotene were performed by high-performance liquid chromatography. Socio-demographic and economic variables, lifestyle, disease history, medication use, and anthropometric and laboratory variables were assessed. Multiple regression analyses were used to measure the effects of the explanatory variables (treatment regimens, duration and adherence to the last treatment regimen) on each response variable (retinol, alpha-tocopherol and beta-carotene). Sex, age, education, smoking, physical activity, duration of HIV infection, comorbidity, waist-to-hip ratio and levels of CD4+ T-lymphocytes and cholesterol were used as control variables. Results Deficient and low concentrations of vitamin A (<0,70Nmol/L) and E (16,2Nmol/L), and betacarotene (<0,13Nmol/L) were 3,83 per cent, 18,68 per cent and 23,62 per cent, respectively. Lower concentrations of vitamin E (p= 0,037) were observed in individuals using NRTI combined with the most recent classes of antiretrovirals. Individuals who had higher measurements of waist-to-hip ratio presented higher concentrations of retinol (p= 0,012) and lower concentrations of betacarotene (p=0,036). We also observed positive small statistically significant associations between mean concentrations of retinol, alpha-tocopherol and beta-carotene with cholesterol levels. Conclusion The results suggest that changes in the concentrations of vitamins A and E and beta-carotene may be related to multiple different factors, including antiretroviral therapy regimens

Introdução - O receptor de vitamina D (VDR) é expresso em vários tecidos e quando este se encontra na sua forma ativada, modula a expressão de diversos genes. Esses incluem variações dos níveis circulantes de 1,25(OH) 2 D , variações na densidade mineral óssea, secreção e sensibilidade à insulina em resposta à glicose, suscetibilidade à diabetes tipo 1 e 2, obesidade, dislipidemias e hipertensão arterial. Atualmente, evidências têm sugerido o envolvimento da vitamina D com a síndrome metabólica. Objetivo - Investigar a concentração sérica da vitamina D e sua relação com a síndrome metabólica e avaliar a potencial associação entre estes fatores com a presença de polimorfismos no gene do receptor de vitamina D (VDR) em indivíduos adultos. Métodos - Trata-se de um estudo transversal, onde foram avaliados 372 indivíduos adultos. Foram coletadas amostras sanguíneas para dosagens laboratoriais da 25(OH)D 3 , PTH e exames bioquímicos relacionados à SM, além disso foram realizadas avaliações antropométricas (peso, altura, IMC). A síndrome metabólica (SM) foi classificada usando o critério proposto pelo National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). A resistência a insulina foi estimada pelo cálculo de HOMA IR e a função da célula pelo cálculo de HOMA . A 25(OH)D foi dosada por HPLC e a insuficiência foi determinada pelo ponto de corte da curva Roc (52,6nmol/l). Foram avaliados também PTH intacto e cálcio sérico. Os polimorfismos BsmI e FokI foram detectados através da digestão das enzimas de restrições específicas para cada polimorfismo e confirmados através da técnica PCR alelo específico (ASPCR) ou amplificação de mutação refratária (ARMs) nos indivíduos com e sem SM (52 por cento vs. 48 por cento , respectivamente). A análise estatística inclui construção da curva ROC, teste T de Student, testes de correlação, teste de equilíbrio de Hardy-Weinberg, ANOVA, regressão logística binária (Odds Ratio). Estas análises foram conduzidas no software SPSS para Windows, versão 18 e p < 0,05 foi considerado significante. Resultados - A idade média dos participantes foi 51(15) anos, o IMC médio 29(6) kg/m 3 2 e 48 por cento apresentaram SM. Como esperado, os 3 indivíduos com SM apresentaram maiores valores de idade 57(12) anos, IMC 32(6) Kg/m , circunferência de cintura 103(13) cm, pressão sistólica 138(17) mmHg e diastólica 83(10) mmHg, glicemia de jejum 98(12) mg/dl, triglicérides 165(76) mg/dl, índices HOMA-IR 2.2(1.7) e 116(95), e menores valores de colesterol HDL colesterol 41(11) mg/dl. Com relação às concentrações séricas de 25(OH)D propostas pela análise da curva ROC, 43 por cento dos indivíduos com SM e 57 por cento dos indivíduos sem SM apresentam insuficiência desta vitamina. Correlações entre 25(OH)D 3 3 com PTH (r = -0.153; p = 0.005) e com circunferência da cintura (r = -0.106; p = 0.05) foram observada em todos os participantes. Considerando os polimorfismos do gene VDR, nos pacientes com SM, não houve associação entre o polimorfismo BsmI e os componentes da SM, HOMA e IR, 25(OH)D e PTH. No entanto, indivíduos sem SM, mas com homozigose para polimorfismo BsmI (genótipo recessivo bb ), apresentaram concentrações mais baixas de 25(OH)D 3 3 do que aqueles com o genótipo BB normal. Além disso, os indivíduos com SM e heterozigose para o polimorfismo FokI (genótipo Ff) têm maiores concentrações de PTH e HOMA do que aqueles com genótipo normal FF. Nesse mesmo grupo, os indivíduos com o genótipo recessivo ff têm maior resistência à insulina do que aqueles com genótipo Ff. Por outro lado, os pacientes sem SM, mas carregando o genótipo Ff, apresentaram maiores concentrações de triglicerídeos e baixos níveis de HDL do que aqueles com genótipo FF. A presença de um alelo f no genótipo (Ff ou ff) é, aparentemente, o suficiente para aumentar os níveis de triglicérides e resistência à insulina, quando comparados ao genótipo normal FF. Conclusão - Os resultados demonstram que o polimorfismo FokI no gene VDR associa-se a resistência à insulina e maiores concentrações de PTH em pacientes que apresentam SM. Além disso, o polimorfismo BsmI associa-se a menores concentrações de 25(OH)D em indivíduos sem SM. Portanto, esses novos dados indicam que polimorfismos no gene do VDR estão associados a diferentes fenótipos dos componentes da SM
Introduction - The vitamin D receptor (VDR) is expressed in many tissues and when it is in its activated form modulates the expression of several genes. These include changes in circulating levels of 1,25(OH)2D3, variations in bone mineral density, sensitivity and secretion of insulin in response to glucose, susceptibility to type 1 and 2 diabetes mellitus, obesity, dyslipidemia and hypertension. Currently, evidences have suggested the involvement of vitamin D with the metabolic syndrome. Objective - To investigate the serum concentrations of vitamin D and its relationship with metabolic syndrome (MS) and to evaluate the potential association between these factors with the presence of polymorphisms in vitamin D receptor gene in individuals adults. Methods - This is a cross-sectional study, which evaluated 243 adults and elderly. We collected blood samples for measurements of 25(OH)D3, iPTH, biochemical tests related to MS, and anthropometric evaluation (weight, height, BMI) were also assessed. MS was classified using the criteria proposed by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Insulin resistance and cell secretion were estimated by calculating HOMA IR and HOMA , respectively. The 25(OH)D3 was measured by HPLC and insufficiency was determined by the Roc curve cut-off (52.6 nmol/L). Intact PTH and serum calcium were also evaluated. The BsmI and FokI polymorphisms were detected by enzymatic digestion with specific enzymes and confirmed by allele specific PCR (ASPCR) or amplification of refractory mutation (ARM) in individuals with or without MS (52 per cent vs. 48 per cent , respectively). Statistical analyses include construction of Roc curves, Student T test, correlation tests, Hardy-Weinberg test, ANOVA, binary logistic regression (odds ratio), and TwoStep Cluster. These analyses were conducted with SPSS for Windows, version 18 and p < 0.05 was considered significant. Results - The mean age of participants was 51(15) years, mean BMI was 29(6) kg/m2, and 48 per cent of individuals presented MS. As expected, subjects with MS showed higher values of age (57(12) years), BMI was 32(6) kg/m2, waist circumference was 103(13) cm, systolic blood pressure was 138(17) mmHg, diastolic was 83(10) mmHg, fasting glucose was 98(12) mg/dl, triglycerides was 165(76) mg/dl, HOMA-IR was 2.2(1.7), HOMA was 116(95), and lower levels of HDL cholesterol was observed (41 mg/dl(11)). With respect to serum 25(OH)D3 proposed by ROC curve analysis, 43 per cent of individuals with MS and 57 per cent of individuals without MS presented insufficiency of this vitamin. Correlations between 25(OH)D3, iPTH (r = -0,153, p = 0.005), and waist circumference (r = -0,106, p = 0.05) were observed in all participants. Considering the VDR gene polymorphisms, in patients with MetSyn, there is no association among BsmI polymorphism and components of MetSyn, HOMA IR and , 25(OH)D3, and PTH. However, subjects without MetSyn, but with homozygosis for BsmI polymorphism (recessive bb genotype), presented lower levels of 25(OH)D3 than those with normal BB genotype. In addition, individuals with MetSyn and heterozygosis for FokI polymorphism (Ff genotype) have higher concentrations of PTH and HOMA than those with normal FF genotype. In this same group, subjects with the recessive ff genotype have higher insulin resistance than those with Ff genotype. On the other hand, patients without MetSyn, but carrying the Ff genotype, have higher concentration of triglycerides and lower levels of HDL than those with FF genotype. Interestingly, the presence of one allele f in the (Ff or ff) genotype is apparently enough to increase triglycerides levels and insulin resistance, when compared to the normal FF genotype. Conclusion - The results show that FokI polymorphism in the VDR gene is associated to insulin resistance and higher concentrations of PTH in patients with MetSyn. Moreover, BsmI polymorphism is related to a lower concentration of 25(OH)D3 in individuals without MetSyn. Therefore, the results indicated that VDR gene polymorphisms are associated to different phenotypes of MetSyn components

Introdução: A deficiência de vitamina A (DVA) constitui grave problema de saúde pública em muitas regiões do mundo, atingindo principalmente o grupo matemo-infantil e aumentando a morbimortalidade na infância. A suplementação materna pode ser uma estratégia eficaz no combate ao problema. Objetivos: Verificar o impacto da suplementação materna com vitamina A sobre a concentração de retinol do leite matemo e do soro no binômio mãe-filho, além de estimar a prevalência da DVA neste grupo, verificar a associação entre mãe e filho e a influência de alguns fatores envolvidos na gênese da DVA. Casuística e métodos: 33 puérperas receberam cápsulas com 200.000 UI de vitamina A entre o 20º e o 30º dias pós-parto (grupo suplementado) e 33 receberam cápsulas idênticas com óleo de soja (grupo placebo). Amostras de sangue e leite matemos foram colhidas antes (T0) e após (T1) a intervenção (três meses pós-parto). Sangue dos lactentes foi colhido aos três meses. O retinol foi analisado pelo método de HPLC. Concentrações inferiores a 0,70 \'mü\'mol/l no soro e 1,05 \'mü\'mol/l no leite foram indicativas de DVA. Peso e altura foram aferidos e dados sociodemográficos e clínicos foram obtidos através de entrevista. Resultados: Concluíram a pesquisa 61 pares mãe-filho. Nas mães suplementadas, a concentração sérica de retinol aumentou de 1,05 \'+ OU -\' 0,31 \'mü\'mol/l no T0 para 1,17\'+ OU -\' 0,34 \'mü\'mol/l no T1 (p=0,026), mostrando diferença estatisticamente significante em relação ao grupo placebo, cuja média foi 1,02 \'+ OU -\' 0,28 \'mü\'mol/l (p=0,032). No leite materno, houve redução significativa da concentração de retinol somente no grupo que não recebeu a vitamina (1,98 \'+ OU -\' 0,78 \'mü\'mol/l no T0 e 1,34 \'+ OU -\' 0,89 \'mü\'mol/l no T1, p=0,003). Nos lactentes, não houve diferença estatística nas médias de retinol entre os grupos (0,64\'+ OU -\' 0,30 \'mü\'mol/l e 0,69 \'+ OU -\' 0,26 \'mü\'mol/l). Quanto à DVA materna sérica, encontrou-se 6,7% (TO) e 16,7% (T1) no grupo placebo e 6,5% (TO) e 3,2% (T1) no suplementado. DVA no leite materno foi observada em 7,4% (T0) e 55,6% (T1) das amostras do grupo placebo e 22,6% (T0) e 16,1% (T1) do suplementado. A DVA esteve presente em 66% dos lactentes (69% no grupo placebo e 63,3% no suplementado). Apenas uma puérpera apresentou subnutrição e um lactente apresentou risco nutricional. DVA materna associou-se à DVA no leite (p=0,015) e houve correlação positiva significante entre retinol sérico materno e do leite (r = 0,28; p=0,032). Não houve influência das variáveis paridade, escolaridade, renda, uso de polivitamínico, febre e diarréia no retinol de puérperas e lactentes. O retinol sérico materno não se alterou com o IMC, mas a idade das puérperas se correlacionou positivamente com o retinol (r = 0,29; p=0,024). Conclusões: A suplementação materna com 200.000 UI de vitamina A mostrou impacto positivo na concentração de retinol da mãe e do leite materno, porém não atingindo o lactente. Apesar de a população estudada ter sido considerada eutrófica em praticamente sua totalidade, elevada prevalência de DVA foi encontrada, principalmente nos lactentes de três meses de idade, questionando-se o ponto de corte empregado para esta faixa etária
Background: Vitamin A deficiency (VAD) is a severe public health problem in many regions of the world, affecting mainly the mother-infant group and increasing the morbimortality in childhood. The maternal supplementation can be an effective strategy to combat this problem. Objectives: To evaluate the impact of maternal vitamin A supplementation on serum and breast milk retinol concentrations; to estimate the VAD prevalence; to assess the association between mother and infant and the influence of some factors involved in the genesis of VAD. Subjects and Methods: 33 lactating women received capsules with 200.000 lU of vitamin A between the 20th day and the 30th day after delivery (supplemented group) and 33 lactating women received identical capsules with soybean oil (placebo group). Maternal blood and milk samples were collected before (T0) and after (T1) the intervention (three months after delivery). Infants\' blood was collected at three months old. Retinol was determined by HPLC method. Levels lower than 0.70 \'mü\'mol/l in serum and 1.05 \'mü\'mol/l in milk indicated V AD. Weight and height measurements were collected and socio-demographic and clinical data were obtained through interview. Results: 61 mother-infant pairs concluded the study. In supplemented mothers, the serum retinol concentration increased from 1.05 \'+ OU -\' 0.31 \'mü\'mol/l at T0 to 1.17 \'+ OU -\' 0.34 \'mü\'mol/1 at T1 (p=0.026), showing statistically significant difference in relation to placebo group, whose mean was 1.02 \'+ OU -\' 0.28 \'\"mü\'mol/l (p=0.032). In breast milk, there was significant reduction of retinol concentration only in the group that did not received the vitamin (1.98 \'+ OU -\' 0.78 \'mü\'mol/l at T0 and 1.34 \'+ OU -\' 0.89 \'mü\'mol/l at T1, p=0.003). In infants, there was not statistically difference in retinol means between groups (0.64 \'+ OU -\' 0.30 \'mü\'mol/l and 0.69 \'+ OU -\' 0.26 \'mü\'mol/l). Regarding serum maternal VAD, it was found 6.7% (T0) and 16.7% (T1) in placebo group and 6.5% (T0) and 3.2% (T1) in supplemented group. Breast milk VAD was found in 7.4% (T0) and 55.6% (T1) of the placebo and 22.6% (T0) and 16.1% (T1) of the supplemented group samples. The VAD was present in 66% of infants (69% in the placebo and 63.3% in the supplemented group). Only one lactating mother had malnutrition and one infant presented nutritional risk. Maternal VAD was associated to breast milk VAD (p=0.015) and maternal serum retinol was positively correlated to breast milk retinol (r = 0.28; P = 0.032). There was no influence of variables parity, education, income, use of multivitamin, fever and diarrhea on both infants and mothers retinol. The maternal serum retinol did not change with BMI, but the age of the lactating women was positively correlated to retinol (r = 0.29; P = 0.024). Conclusions: The maternal supplementation with 200.000 lU of vitamin A showed positive impact on maternal serum and milk retinol concentration, but it did not reach the infant. Although the study population was considered healthy in almost its entirety, high prevalence of VAD was found, mainly in infants from three months old, leading us to question the cut-off point used for this age group

Background: Legumes are beneficial for the environment, nutritious and coupled with various health benefits. However, they lack the essential vitamin B12 and a vitamin B12 deficiency can lead to hazardous health problems. Tempeh is a fermented legume product that has the potential of carrying vitamin B12. Aim: The aim of this thesis is to investigate consumers' awareness of vitamin B12 and explore the indications for the possibility to introduce tempeh - a fermented legume product. Method: A quantitative survey was carried out within four different areas of Stockholm using a clustering sample technique with 195 participants who were recruited outside supermarkets through convenience sampling. Results: The majority of the subjects had moderate consumption of legumes and was open to trying tempeh even though they had never heard about it. While their knowledge of vitamin B12 was limited, the biggest risk groups, vegans and the elderly, were aware that they were a risk group but only a minority of them knew the correct vitamin B12 food sources. Conclusion: The participants in this study had little knowledge about vitamin B12 food sources, deficiencies or risk groups. Since their legume consumption was regular and they were positive towards trying tempeh even though they had never heard about tempeh before, there is potential for it in the market. However, more studies are needed to research the bioavailability of vitamin B12 in tempeh even though new research gives hope that it can be a possibility.

Thesis (Ph. D.)--Ohio State University, 2004.
Title from first page of PDF file. Document formatted into pages; contains xiv,148 pages; also includes graphics Includes bibliographical references (p. 121-136). Available online via OhioLINK's ETD Center

Background: Older people presenting with hip fractures requiring surgery have a high prevalence of hypovitaminosis D, which is an important modifiable risk factor for falls and fractures. Inadequate sun exposure is the main reason for vitamin D deficiency in older people. Vitamin D supplements, with or without calcium have been shown to reduce falls and fracture risk in this population. Undertreated pain is a risk factor for delirium and a barrier to rehabilitation interventions following a hip fracture. A small number of randomised controlled trials (RCTs) have shown increased 25-OHD levels with a loading dose of vitamin D may improve falls and fractures. Low vitamin D levels have also been implicated in pain generally, as well as static and dynamic pain responses to mobility. It is not known whether oral vitamin D replenishment using a loading dose is effective, and if it is, what is the interplay this is with patient characteristics, in particular self-reported pain rating levels, lower limb mobility and 25-OHD levels. Aims: The aims of this research were (1) to characterise the predictive factors of 25-OHD levels; (2) to characterise the predictive factors of self-reported pain after hip fracture; (3) to determine the benefit of early loading-dose oral vitamin D replenishment and determine the 25-OHD response; (4) to evaluate safety profile of an initial high-dose (250,000IU) vitamin D followed by daily maintenance for 6 months; (5) to monitor its effects on functional mobility, falls, fractures, grip strength, health related quality of life and mortality. Methods: Participants of the REVITAHIP RCT cohort (mean age of 220 participants was 83.9 (SD 7.2) years and 77.1% were women): Active (111) and Placebo (107) participants were randomised to loading dose (250000IU vitamin D3) vs placebo followed by 6 months maintenance oral therapy (vitamin D3/calcium: 800IU/600mg) daily. Primary outcome measures are 2.4m gait-velocity, with secondary outcome measures of falls, fractures (Week-4), 25-OHD levels, quality-of-life measure (EQ-5D), mortality at weeks-2, 4 and 26 with additional measures of pain (via the numerical rating scale [NRS]) were correlated with patient characteristics in this cohort. Results: Hypovitaminosis D (25-OHD <50nmol/L) was present in 46.8% of participants and 15.4% had 25-OHD levels lower than 30nmol/L. Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel Index scores and lower post-operative NRS pain levels. Further, the mean (SD) NRS pain score was 3.5 (2.3). More than half (61.9%, n=113) had NRS>3 and 18.1% (n=52) had NRS>5. Using the EQ-5D pain sub-score, 78.1% had moderate pain or discomfort and 7.9% had extreme pain or discomfort. Using a multivariate regression model, postoperative NRS was significantly higher in persons with a higher comorbidity count, those previously living independently alone, and surgical fixation with hemiarthroplasty. After loading dosing administration, 25-OHD levels were significantly higher for the Active group when compared to the Placebo group at 2 weeks (73 vs 66 nmol/L; p=.019) and at 4 weeks (83 vs 75nmol/L; p=.030). At week 4, the Active group had a significantly lower percentage of people with suboptimal 25-OHD levels (3.2% vs 15.4%, p=.019). At week 4, participants in the Active group had a gait velocity over 2.4m of 0.42m/s compared with 0.39m/s in the placebo group (p=.490). To week 4, seven (6.3%) participants in the Active group reported 1 or more falls compared to twenty-three (21.1%) in the Placebo group (χ2 = 4.327; p=.024) but there were no differences in fractures (2.7% vs 2.8%, p=.964) or grip strength. The number of deaths was non-significantly lower in the Active group compared with the Placebo group at 4 weeks (1 vs 3, p = .295). There was a trend for Active participants to have a higher total EQ-5D scores at Week 26 (88.1+/-13.2 vs 84.3+/-15.8, F=2.87, p=.092). Active participants were significantly more likely to present with ‘no pain or discomfort’ at Week 26 (96.4% vs 88.8%, p=.037). One case of hypercalcemia at 2 weeks was noted in the Active group which normalised after 4 and 26 weeks. Discussion and Conclusions: This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture. Hypovitaminosis D was not as prevalent as previously documented. Patients taking vitamin D supplements and with higher premorbid Barthel Index, reflecting greater independence and activity, tended to have higher 25-OHD levels at baseline. Further, lower NRS pain ratings following surgery were associated with higher vitamin D levels. Overall, the levels of pain reported by this cohort are acceptable although approximately 10% to 15% had higher than reasonable levels of pain. Despite a higher than expected baseline 25-OHD level and moderate increases in 25-OHD levels, participants in the Active REVITAHIP group resulted in a greater percentage with target 25-OHD levels (>50nmol/L) compared with the placebo group with no significant differences in gait velocity at 4 weeks. Lower numbers of falls and improved pain control were noted in the Active group over the study period. In this cohort, there was a higher than expected baseline 25OH level which could have underestimated the effect of the intervention in a group with lower baseline 25-OHD levels.