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A vitamina C e a vitamina E são antioxidantes naturais encontrados em diversas frutas e verduras frescas, em óleos vegetais e germem de trigo. Produtos cosméticos, contendo essas vitaminas em forma de ésteres, têm sido desenvolvidos e disponibilizados comercialmente, ressaltando-se que o aspecto natural dessas induz seu uso em cremes e loções. Por isso, torna-se necessário a validação de metodologias analíticas para identificar essas vitaminas em preparações cosméticas, tanto para o controle da qualidade do produto como para a segurança do consumidor. O presente trabalho tem como objetivo a validação das metodologias analíticas para determinação e quantificação do derivado do ácido ascórbico, tetraisopalmitato de ascorbila e o princípio ativo acetato de tocoferila que estão associados nas formulações cosméticas. A técnica de espectrofotometria no ultravioleta (UV) e a análise térmica foram empregadas na caracterização desses princípios ativos. Para a quantificação dos ativos foram desenvolvidas metodologias analíticas empregando as seguintes técnicas: espectrofotometria derivada no UV; eletroforese capilar e cromatografia líquida de alta eficiência (CLAE). A metodologia desenvolvida por espectrofotometria derivada no UV não demonstrou ser aplicável devido à interferência dos excipientes presentes na formulação. Para determinação dos ativos tetraisopalmitato de ascorbila e acetato de tocoferila, foi validado um método por CLAE em fase reversa, empregando-se a coluna Synergi Hidro® C18, fase móvel metanol:2-propanol (25:75), vazão 1,0 mL/min e detecçao UV à 222 nm. As amostras foram extraídas sem grande complexidade e os ativos puderam ser determinados em 3 min e 6 min, para o acetato de tocoferila e o tetraisopalmitato de ascorbila respectivamente. O desenvolvimento da metodologia por eletroforese capilar utilizando-se a técnica de MEEKC (Cromatografia Eletrocinética em Microemulsão) usando a microemulsão óleo-aquosa não demonstrou ser adequada para determinação dos princípios ativos em estudo, sendo que o trabalho terá como perspectivas a tentativa da MEEKC usando a microemulsão aquosa-oleosa. / Vitamin C and vitamin E are natural antioxidants found in many fruits and fresh vegetables, vegetable oils and seed wheat. Cosmetics containing these vitamins in the form of esters have been developed and made available commercially, highlighting the fact that the \"natural\" induces its use in these creams and lotions. Than, it is necessary the validation of analytical methodologies to identify these vitamins in cosmetic preparations, both for the control of product quality and for the safety of consumers. The present work aims the validation of analytical methodologies for determining and quantifying the derivative of ascorbic acid, ascorbyl tetraisopalmitate and the active tocopheryl acetate that are associated in cosmetic formulations. The techniques of UV spectrophotometry and the thermal analysis were used in the characterization of these active ingredients. For the quantification of the actives, analytical methodologies were developed using the following techniques: the UV first-derivative spectrophotometry (UVD), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). The methodology developed by UV first-derivative spectrophotometry do not showed to be applicable due to the interference of excipients in the formulation. To determine the actives ascorbyl tetraisopalmitate and tocopheryl acetate, a method has been validated by reverse-phase HPLC, using the column Synergi Hidro ® C18, mobile phase methanol :2-propanol (25:75), flow rate 1.0 mL / min and UV detection 222 nm. The samples were extracted without great complexity and the actives could be determined in 3 min and 6 min, for the tocopheryl acetate and ascorbyl tetraisopalmitate respectively. The development of methodology for capillary electrophoresis using the technique of MEEKC (Microemulsion Electrokinetic Chromatography) using the oil-in-water (o/w) microemulsion do not showed to be suitable for determination of active ingredients in the study, and that the work will attempt the prospects of using MEEKC the water-in-oil (w/o) microemulsion.

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.

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 &#946;-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 &#946;-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&#177;0,25 a 119&#177;1,961 &#181;g/g para vitamina C, 19,43&#177;1,70 a 45,00&#177;3,61&#181;g/g para vitamina E 3,77&#177;0,10 a 99,27&#177;2,45 &#181;g/g para &#946;-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 &#946;-caroteno. O valor pró-vitamínico A das amostras desidratadas variou de 0,26 a 6,48 &#181;g/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 &#946;-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 &#946;-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 &#946;-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 &#946;-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 &#946;-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&#177;0.25 and 119&#177;1.96&#181;g/g for vitamin C; 19.43&#177;1.70 and 45.00&#177;3.61&#181;g/g for vitamin E and 3.77&#177;0.10 and 99.27&#177;2.45&#181;g/g for &#946;-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 &#946;-carotene were observed. The provitamin A value was between 0.26 and 6.48&#181;g/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), &#946;-carotene (Arecaceae, Cecropia and Fabaceae) and lipids (Arecaceae and Fabaceae). Other ones were negatively correlated, such as Mimosa caesalpineafolia and Poaceae types with &#946;-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 &#946;-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 prééclampsie est responsable du quart des mortalités maternelles et est la deuxième cause de décès maternels associés à la grossesse au Canada et dans le monde. L’identification d’une stratégie efficace pour la prévention de la prééclampsie est une priorité et un défi primordial dans les milieux de recherche en obstétrique. Le rôle des éléments nutritifs dans le développement de la prééclampsie a récemment reçu davantage d’attention. Plusieurs études cliniques et épidémiologiques ont été menées pour déterminer les facteurs de risque alimentaires potentiels et examiner les effets d’une supplémentation nutritive dans le développement de troubles hypertensifs de la grossesse. Pour déterminer les effets de suppléments antioxydants pris pendant la grossesse sur le risque d’hypertension gestationnelle (HG) et de prééclampsie, un essai multicentrique contrôlé à double insu a été mené au Canada et au Mexique (An International Trial of Antioxidants in the Prevention of Preeclampsia – INTAPP). Les femmes, stratifiées par risque, étaient assignées au traitement expérimental quotidien (1 gramme de vitamine C et 400 UI de vitamine E) ou au placebo. En raison des effets secondaires potentiels, le recrutement pour l’essai a été arrêté avant que l’échantillon complet ait été constitué. Au total, 2640 femmes éligibles ont accepté d’être recrutées, dont 2363 (89.5%) furent incluses dans les analyses finales. Nous n’avons retrouvé aucune évidence qu’une supplémentation prénatale de vitamines C et E réduisait le risque d’HG et de ses effets secondaires (RR 0,99; IC 95% 0,78-1,26), HG (RR 1,04; IC 95% 0,89-1,22) et prééclampsie (RR 1,04; IC 95% 0,75-1,44). Toutefois, une analyse secondaire a révélé que les vitamines C et E augmentaient le risque de « perte fœtale ou de décès périnatal » (une mesure non spécifiée au préalable) ainsi qu’une rupture prématurée des membranes avant terme. Nous avons mené une étude de cohorte prospective chez les femmes enceintes recrutées dans l’INTAPP afin d’évaluer les relations entre le régime alimentaire maternel en début et fin de grossesse et le risque de prééclampsie et d’HG. Un questionnaire de fréquence alimentaire validé était administré deux fois pendant la grossesse (12-18 semaines, 32-34 semaines). Les analyses furent faites séparément pour les 1537 Canadiennes et les 799 Mexicaines en raison de l’hétérogénéité des régimes alimentaires des deux pays. Parmi les canadiennes, après ajustement pour l’indice de masse corporelle (IMC) précédant la grossesse, le groupe de traitement, le niveau de risque (élevé versus faible) et les autres facteurs de base, nous avons constaté une association significative entre un faible apport alimentaire (quartile inférieur) de potassium (OR 1,79; IC 95% 1,03-3,11) et de zinc (OR 1,90; IC 95% 1,07-3,39) et un risque augmenté de prééclampsie. Toujours chez les Canadiennes, le quartile inférieur de consommation d’acides gras polyinsaturés était associé à un risque augmenté d’HG (OR 1,49; IC 95% 1,09-2,02). Aucun des nutriments analysés n’affectait les risques d’HG ou de prééclampsie chez les Mexicaines. Nous avons entrepris une étude cas-témoins à l’intérieur de la cohorte de l’INTAPP pour établir le lien entre la concentration sérique de vitamines antioxydantes et le risque de prééclampsie. Un total de 115 cas de prééclampsie et 229 témoins ont été inclus. Les concentrations de vitamine E ont été mesurées de façon longitudinale à 12-18 semaines (avant la prise de suppléments), à 24-26 semaines et à 32-34 semaines de grossesse en utilisant la chromatographie liquide de haute performance. Lorsqu’examinée en tant que variable continue et après ajustement multivarié, une concentration de base élevée de gamma-tocophérol était associée à un risque augmenté de prééclampsie (quartile supérieur vs quartile inférieur à 24-26 semaines : OR 2,99, IC 95% 1,13-7,89; à 32-34 semaines : OR 4,37, IC 95% 1,35-14,15). Nous n’avons pas trouvé de lien entre les concentrations de alpha-tocophérol et le risque de prééclampsie. En résumé, nous n’avons pas trouvé d’effets de la supplémentation en vitamines C et E sur le risque de prééclampsie dans l’INTAPP. Nous avons toutefois trouvé, dans la cohorte canadienne, qu’une faible prise de potassium et de zinc, tel qu’estimée par les questionnaires de fréquence alimentaire, était associée à un risque augmenté de prééclampsie. Aussi, une plus grande concentration sérique de gamma-tocophérol pendant la grossesse était associée à un risque augmenté de prééclampsie. / Preeclampsia (PE) accounts for about one-quarter of cases of maternal mortality, and ranks second among the causes of pregnancy-associated maternal deaths in Canada and worldwide. The identification of an effective strategy to prevent PE is a priority and fundamental challenge in obstetrics research. The role of nutritional factors in the etiology of PE has recently received increased attention. Many clinical and epidemiological studies have been conducted to investigate potential dietary risk factors for PE and to examine the effects of nutritional supplementation on the development of hypertensive disorders of pregnancy. To investigate the effects of prenatal antioxidant supplementation on the risk of gestational hypertension (GH) and PE, a double blind, multicenter trial (The International Trial of Antioxidants for the Prevention of Preeclampsia – the INTAPP trial) was conducted in Canada and in Mexico. Women were stratified by their risk status and assigned to daily experimental treatment (1 gram vitamin C and 400 IU vitamin E) or to placebo. Due to concerns about potential adverse effects, recruitment for the trial was stopped before the full sample had been achieved. A total of 2640 consenting eligible women had been recruited at that point with 2363 women (89.5%) included in the final analysis. We found no evidence that prenatal supplementation of vitamins C and E reduced the risk of GH and its adverse conditions (RR: 0.99, 95% CI 0.78-1.26), GH (RR 1.04, 95% CI 0.89-1.22), and PE (RR 1.04, 95% CI 0.75-1.44). However, in a secondary analysis, we found that vitamins C and E increased the risk of ‘fetal loss or perinatal death’ (a non-pre-specified outcome) as well as preterm premature rupture of membranes (PPROM). We conducted a prospective cohort study on pregnant women enrolled in the INTAPP trial to investigate the associations between maternal diet in early and late pregnancy and the risk of PE and GH. A validated food frequency questionnaire (FFQ) was administered twice during pregnancy (12-18 weeks, 32-34 weeks). Analyses were conducted separately for 1537 Canadian and 799 Mexican women as there were significant heterogeneities in various nutrient intakes between the two countries. Among Canadian women, after adjusting for pre-pregnancy body mass index (BMI), treatment group, risk stratum (high versus low) and other baseline risk factors, we found that the lowest quartiles of potassium (OR 1.79, 95% CI 1.03-3.11) and zinc (OR 1.90, 95% CI 1.07-3.39) intake were significantly associated with an increased risk of PE. Also in Canadian women, the lowest quartile of polyunsaturated fatty acids was associated with an increased risk of GH (OR 1.49, 95% CI 1.09-2.02). None of the nutrients analyzed were found to be associated with PE and GH risk among Mexican women. We further conducted a case control study ancillary to the INTAPP trial to assess the relationship between plasma concentration of antioxidant vitamins and the risk of PE. A total of 115 PE cases and 229 matched controls were included. Vitamin E concentrations were measured longitudinally at 12-18 weeks (prior to supplementation), 24-26 weeks, and 32-34 weeks of gestation using high-performance liquid chromatography (HPLC). When examined as a continuous variable, and after multivariate adjustment, elevated baseline gamma-tocopherol concentrations were associated with an increased risk of PE (OR 1.35, 95% CI 1.02-1.78). Analyses of repeated measurements indicated that elevated gamma-tocopherol levels were associated with an increased risk of PE (highest vs. lowest quartile at 24-26 weeks: OR 2.99, 95% CI 1.13-7.89; at 32-34 weeks: OR 4.37, 95% CI 1.35-14.15). We found no associations between alpha-tocopherol concentrations and the risk of PE. In summary, we found no effects of vitamins C and E supplementation on the risk of PE in the INTAPP trial. However, in the Canadian cohort we found that lower intakes of potassium and zinc as estimated by the FFQ were associated with an increased risk of PE. Moreover, higher plasma concentration of gamma-tocopherol during pregnancy was associated with an increased risk of PE.

La prise d’un supplément d’acide folique en période préconceptionnelle réduit le risque d’une anomalie du tube neural (ATN), une malformation du système nerveux. Dans le but d’en réduire la prévalence, la Société des Obstétriciens et Gynécologues du Canada a émis de nouvelles directives cliniques en 2007 qui tenaient compte de différents facteurs de risque pour les ATN et pour qui la dose recommandée variait selon le profil de risque de la femme, allant de 0,4 à 5,0 mg d’acide folique. Jusqu’à présent, peu de données sont disponibles sur les effets de la prise d’une haute dose d’acide folique. Les objectifs de cette étude étaient: 1) d’évaluer la concordance entre la supplémentation en acide folique chez les femmes enceintes et les nouvelles recommandations canadiennes; 2) d’identifier les déterminants d’une utilisation concordante et 3) d’évaluer si la prise de hautes doses d’acide folique en période périconceptionnelle réduisait le risque de malformations congénitales autre que les ATN. Pour répondre à ces objectifs, une étude transversale et une étude écologique ont été effectuées. La première incluait 361 femmes enceintes recrutées aux cliniques d’obstétriques du CHU Sainte-Justine et la deuxième utilisait le Registre Québécois des Grossesses, issu du jumelage de trois banques de données administratives au Québec (RAMQ, Med-Écho et ISQ), où 152 392 couples mère-enfant ont été identifiés. Seul 27% des femmes enceintes ayant participé à l’étude transversale avaient une supplémentation en acide folique, avec ou sans ordonnance, concordante aux lignes directrices canadiennes. La concordance variait selon leur profil de facteurs de risque pour les ATN. Notre étude écologique montre que la prévalence annuelle de l’utilisation de haute dose d’acide folique (avec ordonnance) en période périconceptionnelle a augmenté de 0,17% à 0,80% (p < 0,0001) entre 1998 et 2008 et que la prévalence des malformations congénitales majeures a augmenté de 15% au cours de la même période (3,35% à 3,87%, p<0,0001). Les résultats de nos deux études montrent que l’acide folique n’est pas largement utilisé par les femmes en âge de procréer et ce, peu importe la dose. De nouvelles campagnes de santé publique devront être mises sur pied, afin d’inciter les femmes à consommer de l’acide folique avant et pendant leur grossesse. Également, la prise de haute dose d’acide folique ne semble pas avoir diminué le risque de malformations congénitales, à l’échelle populationnelle. / The use of folic acid during the preconceptionnal period reduces the risk of neural tube defects (NTD), a malformation of the nervous system. In order to reduce it’s prevalence, the Society of Obstetricians and Gynaecologists of Canada proposed new practice clinical guidelines, in 2007, on the use of pre-conceptional vitamin/folic acid supplementation for the prevention of NTDs, with specific recommendations to prevent recurrences and occurrences among women with intermediate to high health risk factors and for whom the dose was different. The objectives of this study were to evaluate the concordance between the new guidelines and folic acid use in real life; 2) to identify predictors associated with a recommended folic acid supplementation, and 3) to evaluate if the use of folic acid could reduce the risk of congenital malformations other than NTDs. A cross-sectional study and an ecological study have been conducted. 361 women were recruited in obstetrics outpatient clinic at the CHU Ste-Justine for the first study and 152,392 pregnancies and babies were identified in the Quebec Pregnancy Registry, which results from the linkage of three administrative health care databases from Quebec (RAMQ, Med-Echo and ISQ) for the second study. Only 27% of the wowen recruited for the first study had periconceptional folic acid supplementation intake that was concordant with guideline. Concordance varied according to their health risk factors profile for NTD. Our ecological study showed that the annual prevalence of periconceptional folic acid use increased from 0.17% to 0.80% (p < 0,0001) from 1998 to 2008 and birth prevalence of major congenital malformations increased by 15% (3.35% to 3.87%, p < 0,0001) during the same period. Our findings highlight the fact that folic acid is not widely used by women of childbearing age, regardless of the dose. There is a need for new public health programs to encourange women to consume folic acid every day before and during pregnancy. Moreover, the use of high dose folic acid does not seem to be correlated with a decline in the prevalence of major congenital malformations, on a populational level.

[Truncated abstract] An elevated total plasma homocysteine concentration (tHcy) is associated with an increased risk of myocardial infarction and ischemic stroke. Folic acid, vitamin B6 and B12 supplements significantly reduce tHcy even in people who are not overtly vitamin deficient. If homocysteine is a causal risk factor for atherothrombotic events, treatment with B-vitamins might prove a simple and cost-effective means to reduce cardiovascular risk. However, it remains unclear whether elevated tHcy causes atherosclerosis or is simply a risk marker. To prove that homocysteine is a modifiable risk factor for cardiovascular disease it is necessary to show that lowering tHcy reduces vascular risk. The aim of this study was to determine whether long-term homocysteine-lowering with B-vitamins would improve vascular structure and function in people with a history of stroke. This study was a cross-sectional sub-study of the Vitamins TO Prevent Stroke trial (VITATOPS), a multi-centre, randomised, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of B-vitamins (folic acid 2mg, vitamin B6 25mg and vitamin B12 0.5mg) in the prevention of vascular events in patients with a recent history of stroke or transient ischemic attack. 173 VITATOPS participants were recruited for the current study. Age, sex, stroke type, medications, cardiovascular risk factors and smoking history were recorded and blood pressure, height, weight, waist and hip girth were measured in all subjects at least two years after randomisation. ... After a mean treatment period of 3.9 ± 0.9 years, the subjects randomised to vitamin treatment had significantly lower tHcy than the subjects randomised to placebo (7.9mol/L, 95%CI 7.5, 8.4 versus 11.8mol/L, 95%CI 10.9, 12.8; p<0.001). There were no significant differences between groups in CIMT (0.84 ± 0.17mm vitamins versus 0.83 ± 0.18mm placebo; p=0.74) or FMD (median of 4.0%, IQR 0.9, 7.2, vitamins versus 3.0%, IQR 0.6, 6.6 placebo; p=0.48). Pooled estimates from the meta-analyses showed that B-vitamin treatment reduces CIMT by 0.10mm (95%CI –0.20, -0.01mm) and increases FMD by 1.4%, (95%CI 0.7, 2.2), although these estimates may have been influenced by positive publication bias. The improvement in FMD was significant in studies of less than eight weeks duration but not in studies with longer treatment periods. The association between tHcy and CIMT and FMD was eliminated by adjustment for renal function and long-term B-vitamin treatment did not alter the strong linear relationship between tHcy and cystatin C. Lowering tHcy did not alter arterial wall inflammation assessed by 18FDG-PET, although small subject numbers meant we were unable to exclude a minor treatment effect. Long-term homocysteine-lowering with B-vitamin treatment did not improve CIMT or FMD or reduce arterial wall inflammation in people with a history of stroke. The relationship between tHcy and these markers of vascular risk was eliminated by adjustment for renal function. Our data are consistent with the hypothesis that elevated tHcy is a risk marker for cardiovascular disease rather than a modifiable causal risk factor.

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Made available in DSpace on 2014-10-09T12:41:41Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:15Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:41:41Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:15Z (GMT). No. of bitstreams: 0 / A instalação de implantes odontológicos requer a presença de substrato ósseo adequado para garantir estabilidade e equilíbrio biomecânico. A deficiência óssea requer procedimentos de enxertia para adequar o volume para a instalação de implantes, porém a utilização de enxertos autógenos causa aumento de morbidade ao paciente e o uso de material homógeno e xenógeno apresenta dúvidas quanto à reação autoimune, transmissão de doenças e ao grau de reabsorção do enxerto. Com o grande desenvolvimento científico e tecnológico dos biomateriais, os materiais cerâmicos, tornaram-se alternativas promissoras para a recomposição da estrutura óssea perdida. As cerâmicas à base de fosfato de cálcio como a hidroxiapatita (HA) e o beta- fosfato tricálcido (beta-TCP), são materiais que apresentam qualidades desejáveis no processo de neoformação óssea como, por exemplo, a biocompatibilidade, bioatividade e osteocondutividade. A proposta deste trabalho é desenvolver e estudar corpos de prova na forma de cúpula oca de hidroxiapatita preenchidos por coágulo, beta- TCP e composto vitamínico, para estudar a osteogênese supracortical, a partir do potencial osteocondutor da cúpula de HA. As cúpulas foram obtidas por prensagem isostática a 200 MPa e sinterização ao ar a 1100°C por 60 minutos. As caracterizações físico-químicas das matérias-primas e da cúpula de HA foram realizadas por difração de raios X, microscopia eletrônica de varredura e determinação da densidade. Na caracterização biológica, foram realizados o teste de citotoxicidade in vitro e ensaio in vivo. Foram designados 9 coelhos (raça Nova Zelândia), sendo instaladas 18 cúpulas, divididas em três grupos, de acordo com o preenchimento: controle, composto vitamínico e &beta;-TCP em forma de pó. O período de reparação tecidual foi de 8 semanas, no qual foram aplicados marcadores de fluorescência. Após o período de cicatrização e eutanásia, as amostras foram incluídas em resina para a obtenção das lâminas e observadas em microscópio de fluorescência, para avaliar a quantidade de tecido ósseo neoformado, em microscópio de campo claro, para verificar as células presentes no tecido formado e por Espectroscopia de Energia Dispersiva, para análise química, da formação no interior das cúpulas. Como resultados, a cúpula de hidroxiapatita apresenta bom desempenho como arcabouço para neoformação óssea acima da cortical da tíbia de coelhos, pois manteve-se íntegra, com boa estabilidade e boa integração ao tecido ósseo, e principalmente pela neoformação óssea, demonstrando seu potencial osteocondutor. Em relação aos materiais de preenchimento, o beta-TCP apresenta maior valor de área de osso neoformado, em comparação com o coágulo. Nas cúpulas com preenchimento de composto vitamínico, não há formação de tecido ósseo pela não reabsorção do material. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP