A pancreatite crônica alcoólica (PCA) tem o álcool como seu principal fator etiológico, a relação entre ingestão de álcool e estado nutricional é complexa e as características nutricionais dos portadores de PCA são pouco conhecidas. Neste trabalho, foram avaliados três grupos de pacientes do sexo masculino, o primeiro (A) com 20 pacientes com PCA, o segundo (B) com 12 etlistas crônicos não pancreatopatas e não hepatopatas e o terceiro (C) com 16 indivíduos não etlistas, não pancreatopatas e não hepatopatas. Para analisar os três grupos utilizaram-se a avaliação antropométrica, a quantificação da ingestão alcoólica, quando existente, o inquérito dietético obtido por Recordatório de 24 horas, a composição corpórea, obtida por bioimpedância elétrica, exames séricos relacionados à avaliação hepática e pancreática, dosagem de vitaminas e de sais minerais, além de marcadores inflamatórios, como proteína C reativa, seroamiloide A e leptina, além de exames de imagem, como ultrassonografia abdominal e/ou tomografia computadorizada de abdômen. A PCA (Grupo A) não se associou à queda da ingestão dietética, porém houve redução da massa magra, evidenciando desnutrição protéica; os etilistas sem pancreatite (Grupo B) apresentaram menor massa magra em relação aos pacientes do grupo C e foi possível demonstrar que a composição corpórea e o perfil inflamatório são distintos e relevantes, não apenas na PCA (Grupo A), mas também nos etilistas sem lesão pancreática (Grupo B), que também devem ser melhor estudados e acompanhados ao longo do seu curso clínico. Em síntese, encontraram-se evidências de subnutrição e aberrações metabólicas tanto nos casos de alcoolismo com lesão pancreática quanto nos etilistas aparentemente sem lesão pancreática ou hepática. Achado até o momento não relatado pela literatura / Alcoholic pancreatitis has alcohol as the primary etiologic factor. The relationship between alcohol intake and nutritional status is complex and the nutritional characteristics of patients with this disease are unknown. In this study, we evaluated three groups of male patients, one (A) with 20 patients with alcoholic pancreatitis, another (B) with 12 alcoholics without pancreatic or liver disease and the last (C) with 16 non - alcoholics , free from any systemic disease or organ insufficiency. To analyze the three groups, we used anthropometric assessment, quantification of alcohol intake, dietary recall, body composition estimated by bioimpedance analysis, biochemical tests related to liver and pancreatic function, dosage of vitamins and minerals, inflammatory markers namely C-reactive protein, leptin and serum amyloid A, in addition to imaging studies such as abdominal ultrasonography and computed tomography of the abdomen whenever required. Group A was not associated with decrease in food intake, but there was a reduction in lean body mass, indicating undernutrition. Alcoholics without pancreatitis (group B) also showed lower lean mass compared to patients in group C, demonstring that changes in body composition and inflammatory status are distinct and relevant also in alcoholics without pancreatic injury (Group B). They should be better studied and monitored throughout their clinical course. In synthesis evidence of undernutrition and metabolic aberrations were demonstrated in both alcoholism with pancreatic damage and in nominally healthy alcoholics, a finding not hitherto reported in the literature

A metionina sintase redutase (MTRR) catalisa a redução da cobalamina (Cbl) oxidada a metilcobalamina. Em presença de folato, a metionina sintase (MTR) utiliza a metilcobalamina como cofator na metilação da homocisteína (tHcy) a metionina. O objetivo deste estudo foi avaliar os efeitos dos polimorfismos MTR A2756G e MTRR A66G nas concentrações dos metabólitos marcadores de deficiência de Cbl e folato em gestantes e neonatos. Os genótipos dos polimorfismos MTR A2756G e MTRR A66G foram obtidos por PCR-RFLP. O genótipo MTR 2756AA foi relacionado aos maiores valores de tHcy em gestantes e MMA em neonatos. Gestantes com genótipos MTRR 66AG e GG e com menores concentrações de Cbl apresentaram maior risco de apresentar concentrações elevadas de tHcy. Neonatos com genótipos com MTRR 66AG e GG apresentaram menores valores de SAM. Os polimorfismos MTR A2756G e MTRR A66G interferem nas reações dependentes de Cbl e folato em gestantes e neonatos. / Methionine synthase reductase (MTRR) catalyzes the reductive reaction of oxidized cobalamin to methylcobalamin. When folate is present, methionine synthase (MTR) uses methylcobalamin cofactor at homocysteine to methionine methylation process. The aim of this study was to evaluate the effects of MTR A2756G and MTRR A66G polymorphisms on total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM) concentrations and SAM/SAH ratio in Brazilian pregnant women and their newborns. Genotypes of two polymorphisms were determined by PCR-RFLP. MTR 2756AA genotype was associated with higher tHcy and MMA levels in mothers and babies, respectivelly. Lower cobalamin concentrations associated with MTRR 66AG and GG genotypes increased risk to elevated tHcy levels in pregnant women. The SAM levels were lower in neonates with MTRR 66AG e GG genotypes. The polymorphisms MTR A2756G and MTRR A66G could affect cobalamin and folate dependent reactions in pregnant women and newborns.

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.

This diploma thesis is focused on microdetermination of cobalt by UV-VIS spectrophotometry with organic agents and comparison with atomic absorption spectrometry. In the first part properties, occurance and importance of cobalt in the environment are desribed, complete with as a part of vitamine B12. Attention is also given to cobalt compounds, especially in the oxidative states +II and +III. Methods of preconcentration and preparation cobalt determination in real samples are adduced. In this thesis are described some optical analytical methods with accept on spectrophotometric agents for determination of cobalt. The experimental part of this thesis icludes optimalization of the spectrophotometric determination of cobalt with choosen organic agents 4-(2-pyridylazo)resorcin and 2-(5-Brom-2-pyridylazo)-5-diethylaminophenol and optimalization of atomic absorption spectrometry for cobalt determination. All of real samples of water (surface, underground, mineral and waste) were measured by both 4-(2-pyridylazo)resorcin and 2-(5-Brom-2-pyridylazo)-5-diethylaminophenol via UV-VIS and via atomic absorption spectrometry. Results of determinations were compared. A sample of vitamine B12 was measured too by all techniques.

Heart Failure is a leading cause of death and disability worldwide. The identification of risk factors of heart failure in healthy individuals is key to improve disease prevention and reduce mortality. Metals exposures are recently established cardiovascular disease risk factors, but their association with heart failure remains understudied and prospective studies across diverse populations are needed. Metals are widespread in the environment, some of the sources of exposure include drinking water, air, and soil contamination. Some population groups, particularly American Indian, Hispanic/Latino, and Black communities in the United States are exposed to higher levels of environmental metals as a result of sociodemographic and structural factors including structural racism. These population groups suffer a higher burden of heart failure compared to White populations. Importantly, the burden of heart failure in American Indian communities in the United States, a population group with high rates of diabetes, hypertension, and other cardiovascular disease risk factors, is underreported, and key risk factors of heart failure in these population groups remain understudied. This dissertation characterized relevant risk factors of heart failure in American Indian participants from the Strong Heart Study. Towards the goal of identifying novel preventable cardiovascular disease risk factors, it comprehensively assessed the sources of exposure and biomarkers for multiple non-essential and essential metals with a focus on characterizing drivers of disparities in drinking water metal concentrations. Then, it evaluated the role of exposure to multiple metals (individually and as a mixture) on the risk of heart failure and overall cardiovascular disease and all-cause mortality, leveraging three geographically and racially and ethnically diverse population-based cohorts: the Multi-Ethnic Study of Atherosclerosis (MESA), the Strong Heart Study (SHS), and the Hortega cohort. Last, it identified and evaluated new opportunities for the mitigation of metal toxicity through nutritional interventions. Chapter 1 provides background information about heart failure epidemiology and pathophysiology, the role of environmental metals on cardiovascular disease, and introduces the dissertation framework necessary to contextualize the work included in this dissertation. Chapter 2 estimated the incidence of heart failure in the SHS, a large epidemiological cohort of American Indian adults from Arizona, Oklahoma, North Dakota, and South Dakota, followed from 1989-1991 through 2019. A parsimonious heart failure-risk prediction equation that accounts for relevant cardiovascular risk factors affecting American Indian communities was developed. The incidence rate of heart failure was 9.5 per 1,000 person-years, with higher rates across participants with diabetes, hypertension, and albuminuria. Significant predictors for heart failure risk at 5 and 10 years included age, smoking, albuminuria, and previous myocardial infarction. Diabetes diagnosis and higher levels of HbA1c were significant predictors of risk at 10 and 28 years. Models achieved a high discrimination performance (C-index (95%CI): 0.81 (0.76, 0.84) at 5 years, 0.78 (0.75, 0.81) at 10 years, and 0.77 (0.74, 0.78) up to 28 years), and some associations varied across HF subtypes. Chapter 3 developed a comprehensive overview of the main sources and routes of exposure, biotransformation, and biomarkers of exposure and internal dose for 12 metals/metalloids, including 8 non-essential elements (arsenic, barium, cadmium, lead, mercury, nickel, tin, uranium) and 4 essential elements (manganese, molybdenum, selenium, and zinc), providing a set of recommendations for the use and interpretation of metal biomarkers in epidemiological studies. Chapter 4 conducted the first nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the conterminous United States using geospatial models. The association between county-level racial/ethnic composition and public water arsenic and uranium concentrations (2000-2011)was assessed. Higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents were associated with 6% (95% CI: 4-8%), and 7% (3-11%) higher levels of arsenic, and 17% (13-22%), and 2% (-4-8%), higher levels of uranium, respectively, in public drinking water, after accounting for relevant social and geological indicators. Higher county-level proportions of non-Hispanic Black residents were associated with higher arsenic and uranium in the Southwest, where concentrations of these contaminants are high. These findings identified the key role of structural racism as driver of drinking water metal concentrations inequalities. Chapter 5 evaluated the prospective association between urinary metal levels, a established biomarker of internal dose, and incident heart failure across three geographically and ethnically/racially diverse cohorts: MESA and SHS in the United States, and the Hortega Study in Spain. These findings consistently identified significant associations across cohorts for cadmium (pooled hazard ratio: 1.15 (95% CI: 1.07, 1.24), tungsten (1.07 (1.02, 1.12)), copper (1.31 (1.18, 1.45)), molybdenum (1.13 (1.05, 1.22)), and zinc (1.22 (1.14, 1.32))). Higher levels of urinary metals analyzed as a mixture were significantly associated with increased incident heart failure risk in MESA and SHS, and non-significantly increased in the Hortega Study, which has a smaller number of events. Chapter 6 assessed the prospective association of urinary metals with incident cardiovascular disease and all-cause mortality in MESA, including a total of 6,599 participants at baseline (2000-2001), followed through 2019. Significant associations between higher levels of urinary cadmium, tungsten, uranium, cobalt, copper, and zinc, and higher risk of CVD and all-cause mortality were identified. A positive linear dose-response was identified for cadmium and copper with both endpoints. The adjusted HRs (95%CI) for an interquartile range (IQR) increase in the mixture of these six urinary metals and the correspondent 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56), and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91), and -2.0% (-2.6, -1.5) for all-cause mortality. Chapter 7 investigated the effects of a nutritional intervention with folic acid (FA) and B12 supplementation on arsenic methylation in children exposed to high levels of drinking water arsenic in Bangladesh. The randomized controlled trial included a total of 240 children 8-11 years old. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMA, a non-toxic arsenic metabolite, by 14.0% (95%CI: 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95%CI: 0.09, 0.35). Similarly, there was a 1.62% (95%CI: 0.43, 2.83) significantly higher urinary %DMAs and -1.10% (CI: -1.73, -0.48) significantly lower urinary %MMAs compared to placebo group after 1 week. These results confirmed that FA+B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Altogether, the findings presented in this dissertation consistently identify the role of urinary metals as robust risk factors of heart failure, overall cardiovascular disease and all-cause mortality across diverse populations. With consistent findings across multiple assessments of the dose response relationship and mixture approaches. Additionally, this dissertation work contributes to address disparities in environmental exposures and heart failure burden, respectively, by characterizing the impact of structural racism drinking water metal exposures disparities and identifying relevant risk factors of heart failure in American Indian populations who are historically underrepresented in epidemiological cohorts. Last, this dissertation identifies the role of folic acid and B12 supplementation to reduce arsenic toxicity in children. These findings have direct clinical and policy implications, as they can inform the development of novel clinical guidelines to incorporate environmental factors in clinical risk prediction, and they can inform drinking water regulation and infrastructure efforts to support at risk communities and inform population-level nutritional recommendations and policies.

Introdução - Os hábitos alimentares e os nutrientes da via metabólica do folato e homocisteína possuem grande importância na manutenção da saúde. Objetivo - Investigar a relação entre padrões alimentares (PAs) e os nutrientes envolvidos nessa via metabólica, com medidas antropométricas do recém-nascido, duração da infecção por HPV em homens e concentrações de homocisteína (Hcy) em adultos. Métodos - Foram utilizados dados dos estudos de coorte ProcriAr (Influência dos fatores nutricionais e poluentes atmosféricos urbanos na saúde pulmonar de crianças: um estudo de coorte com gestantes da zona oeste do município de São Paulo, n=299); e HIM (História natural da infecção por HPV em homens, n=1.194); e do estudo transversal ISA-Capital 2008 (Inquérito de saúde do estado de São Paulo, n=281). Os padrões alimentares foram derivados por análise fatorial por componentes principais nos estudos ProcriAr e ISA-Capital 2008 e utilizando reduced rank regression (RRR) no estudo HIM. Modelos multivariados de regressão de Poisson e lineares foram utilizados nos estudos ProcriAr e HIM para identificar a relação entre PAs e medidas antropométricas do recém-nascido e duração da infecção por HPV em homens, respectivamente. Utilizando modelo de equação estrutural, investigou-se a relação entre PAs, concentrações bioquímicas de folato, vitamina B12 e ácido docosahexaenoico (DHA) e concentrações de homocisteína em adultos do estudo ISA-Capital, considerando polimorfismo da enzima metilenotetrahidrofolato redutase (MTHFR 677C>T). Os três estudos utilizaram questionário de frequência alimentar para avaliação do consumo alimentar. Resultados - No estudo ProcriAr, a maior adesão materna ao PA \"Snacks, sanduíches, doces e refrigerantes\", rico em energia, gordura, e folato sintético, esteve diretamente associada a ter um filho pequeno ao nascer (peso e/ou comprimento ao nascer, ajustado pela idade gestacional, abaixo do percentil 10 - INTERGOWTH-21st) (RR: 2,01; IC 95%: 1.13-3.57). No estudo HIM, homens com maior adesão ao \"PA3\" tiveram, em média, um aumento de 1,15 (IC95% 0,09-2,21) à 1,18 (IC95% 0,11-2,24) meses na duração da infecção por HPV. O \"PA3\" esteve positivamente correlacionado com vitamina B6 (r = 0,59), vitamina B12 (0,27) e DFE (0,07) e negativamente correlacionado com DHA (-0,37). No estudo ISA-Capital o PA \"Prudente\" esteve inversamente associado à concentração de Hcy (β = -0,12). O DHA esteve diretamente associado ao PA \"Prudente\"; composto por verduras e legumes, peixe, frutas, frango, suco natural e batata/mandioca/polenta (cozida ou assada). Conclusões - Os PAs estão associados às medidas antropométricas do recém-nascido, à duração da infecção por HPV em homens e às concentrações de homocisteína em adultos. Estes resultados reforçam a importância de estudos sobre alimentação e nutrição que considerem não somente nutrientes, mas principalmente o consumo de alimentos e suas combinações, servindo como base para a elaboração de estratégias e políticas públicas de promoção à saúde. / Introduction - The dietary habits and nutrients involved in one-carbon metabolism are of great importance in health. Objective - To investigate the relationship between dietary patterns (DP) and the nutrients involved in this metabolism, with newborn\'s anthropometric measurements, duration of HPV infection in men, and homocysteine (Hcy) levels in adults. Methods - Data from the cohort studies ProcriAr (Influence of nutritional factors and urban air pollutants on the pulmonary health of children: a cohort study with pregnant women from the western region of the city of São Paulo, n=299); and HIM (Natural history of HPV infection in men, n=1,194); and the cross-sectional study ISA-Capital 2008 (São Paulo State Health Survey, n=281) were used. The DP were estimated using factor analysis with principal component\'s estimation in ProcriAr and ISA-Capital 2008 studies and using reduced rank regression (RRR) in HIM study. Multivariate Poisson and linear regression models were used in the ProcriAr and HIM studies to identify the relationship between DP and newborn\'s anthropometric measurements and duration of HPV infection in men, respectively. Using a structural equation model, the relationship between DP, biochemical levels of folate, vitamin B12 and docosahexaenoic acid (DHA) and homocysteine levels was investigated in adults from the ISA-Capital 2008 study, considering the polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR 677C>T). The three studies used a food frequency questionnaire to evaluate dietary intake. Results - In the ProcriAr study, the higher maternal adherence to the \"Snacks, sandwiches, sweets and soft drinks\" DP, which is a DP rich in energy, fat, and synthetic folate, was directly associated with having a child small at birth (weight and/or birth length by gestational age and sex below the 10th percentile - INTERGOWTH-21st) (RR: 2.01, 95% CI: 1.13-3.57). In the HIM study, men with higher adherence to \"DP3\" had, on average, an increase from 1.15 (95% CI 0.09-2.21) to 1.18 (95% CI 0.11-2.24) months in the duration of HPV infection. \"DP3\" was positively correlated with vitamin B6 (r = 0.59), vitamin B12 (0.27) and DFE (0.07) and negatively correlated with DHA (-0.37). In the ISA-Capital study, the \"Prudent\" DP was inversely associated with Hcy levels (β = -0.12). DHA was directly associated with \"Prudent\" DP; composed of vegetables, fish, fruits, chicken, natural juice and potato/cassava/polenta (cooked or roasted). Conclusions - Dietary patterns are associated with newborn\'s anthropometric measurements, duration of HPV infection in men, and Hcy levels in adults. These results reinforce the importance of studies on food and nutrition that consider not only nutrients, but mainly the consumption of foods and their combinations, serving as a basis for the elaboration of public health promotion strategies and policies.