RESUMO
Down syndrome (DS) is the most common chromosomal disorder, resulting from the failure of normal chromosome 21 segregation. Studies have suggested that impairments within the one-carbon metabolic pathway can be of relevance for the global genome instability observed in mothers of individuals with DS. Based on the association between global DNA hypomethylation, genome instability, and impairments within the one-carbon metabolic pathway, the present study aimed to identify possible predictors, within the one-carbon metabolism, of global DNA methylation, measured by methylation patterns of LINE-1 and Alu repetitive sequences, in mothers of individuals with DS and mothers of individuals without the syndrome. In addition, we investigated one-carbon genetic polymorphisms and metabolites as maternal predisposing factors for the occurrence of trisomy 21 in children. Eighty-three samples of mothers of children with DS with karyotypically confirmed free trisomy 21 (case group) and 84 of mothers who had at least one child without DS or any other aneuploidy were included in the study. Pyrosequencing assays were performed to access global methylation. The results showed that group affiliation (case or control), betaine-homocysteine methyltransferase (BHMT) G742A and transcobalamin 2 (TCN2) C776G polymorphisms, and folate concentration were identified as predictors of global Alu DNA methylation values. In addition, thymidylate synthase (TYMS) 28-bp repeats 2R/3R or 3R/3R genotypes are independent maternal predisposing factors for having a child with DS. This study adds evidence that supports the association of impairments in the one-carbon metabolism, global DNA methylation, and the possibility of having a child with DS.
Assuntos
Carbono/metabolismo , Metilação de DNA/genética , Síndrome de Down/genética , Síndrome de Down/metabolismo , Estudo de Associação Genômica Ampla , Instabilidade Genômica/genética , Relações Mãe-Filho , Mães , Adolescente , Adulto , Idoso , Elementos Alu/genética , Betaína-Homocisteína S-Metiltransferase/genética , Betaína-Homocisteína S-Metiltransferase/metabolismo , Feminino , Ácido Fólico/metabolismo , Predisposição Genética para Doença/genética , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Timidilato Sintase/genética , Transcobalaminas/genética , Transcobalaminas/metabolismo , Adulto JovemRESUMO
SCOPE: Nutrition is a major contributing factor for immunocompetence. The aim was to assess the immune status of older people after consuming milk produced by lactating cows fed with one of the following diets: control diet (C), C + vitamin E + selenium (C + A), C + sunflower oil (C + O), and C + sunflower oil + vitamin E + selenium (A + O). METHODS AND RESULTS: Sixty elderly people received one of these biofortified milks for 12 weeks. Immune response was assessed by measurement of the expression of COX-1, COX-2, MCP-1, PPAR (δ, α, and ß/δ) genes, neutrophil production of oxygen reactive species induced by immune complexes, neutrophil phagocytosis and lytic activity of the alternative pathway of the complement system, and cytokine levels. Variables were assessed before and after treatment. Our findings showed stability of some inflammatory mediators (complement activity and neutrophils burst) in treatment groups, except complement activity in C + A, and an increase of these markers in C, especially reactive oxygen species production and phagocytic activity. TNF-α was significantly increased in all groups. In C + A, IL-4 and IL-2 increased after treatment, and in the group that received the milk produced by cows fed with "O" diet, CCL20 and IL-27 increased. CONCLUSION: Overall, as compared to C, milk biofortification was associated with stabilization of the activity of alternative complement pathway and the neutrophils burst, and modulated different cytokines levels.
Assuntos
Via Alternativa do Complemento , Ácidos Graxos/administração & dosagem , Alimentos Fortificados , Leite , Neutrófilos/imunologia , Selênio/administração & dosagem , Vitamina E/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Animais , Bovinos , Citocinas/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Nonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism. OBJECTIVE: Considering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology. METHODS: Fifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor. RESULTS: Nonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals. CONCLUSION: This paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.
Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Fatores de Risco , Adulto JovemRESUMO
BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.
ContextoEsteatohepatite não alcoólica é considerada uma manifestação hepática da síndrome metabólica e está particularmente associada com a resistência insulínica, hipertensão, obesidade, anormalidades no metabolismo lipídico e da glicose.ObjetivoConsiderando a importância da obesidade e do estresse oxidativo na fisiopatogenia da esteatohepatite não alcoólica, o objetivo deste estudo foi avaliar a associação e presença da obesidade e do estresse oxidativo nesta patologia.MétodosQuinze pacientes com esteatohepatite não alcoólica (grupo esteatohepatite não alcoólica), diagnosticados de acordo com os achados histopatológicos da biópsia hepática, e 15 indivíduos sem esteatohepatite não alcoólica com sobrepeso/obesidade (grupo sem esteatohepatite não alcoólica) foram incluídos. Todos os voluntários eram acompanhados em Hospital Universitário Brasileiro. Avaliação nutricional (peso, altura, índice de massa corporal e circunferência abdominal) e bioquímica (glicemia de jejum, enzimas hepáticas, lipidograma, leptina, superóxido dismutase, glutationa peroxidase, vitaminas C e E, catalase e 8-isoprostano) foram realizadas em todos os indivíduos. O teste t de Student foi usado para análise estatística considerando o P≤0,05 como significativo.ResultadosIndivíduos do Grupo esteatohepatite não alcoólica apresentaram valores significativamente maiores de glicemia, AST, ALT, Gama GT, fosfatase alcalina, triglicérides e superóxido dismutase e menor valor de glutationa peroxidase, quando comparados ao Grupo sem esteatohepatite não alcoólica.ConclusãoEste artigo demonstra que somente a presença da obesidade não é suficiente para provocar alterações nos biomarcadores estudados. Apesar da maioria dos marcadores de estresse oxidativo apresentarem-se similar nas duas condições, os pacientes com esteatohepatite não alcoólica podem apresentar-se levemente mais afetados que os indivíduos sem esteatohepatite não alcoólica.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Estresse Oxidativo/fisiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Fatores de RiscoRESUMO
Idosos institucionalizados apresentam um risco aumentado de alteração do estado nutricional. Sendo assim, são necessários indicadores sensíveis para identificação da alteração do estado nutricional. O objetivo deste estudo é avaliar indicadores para análise do estado nutricional de idosos institucionalizados, em um período de três meses, por meio de exames bioquímicos e antropométricos. Foram selecionados 81 voluntários, com 78 ± 10 anos, sendo 53% do sexo feminino. Os dados antropométricos evidenciaram que as variáveisíndice de massa corporal, peso, massa gorda e ângulo de fase dos idosos institucionalizados diminuíram em três meses com diferença significativa no período. Dentre todos os exames bioquímicos e antropométricos, as variáveis índice de massa corporal, peso, massa gorda, ângulo de fase e lipidograma foram os indicadores da avaliação nutricional que identificaram alterações precoces e riscos nutricionais dos idosos institucionalizados no período de três meses. Vale ressaltar que indicadores nutricionais avaliados precocemente podem evitar os riscos nutricionais de idosos institucionalizados.
Institutionalized elderly have an increased risk of changes in nutritional status, therefore sensitive parameters are necessary for the identification of changes in nutritional status. The aim of this study was to evaluate parameters for analysis of the nutritional status of institutionalized elderly in a period of three months by means of biochemical and anthropometric measurements. Eighty one volunteers were selected, with 78 ± 10 years old and 53% female. Anthropometric data showed that the variables body mass index, weight, fat mass, and phase angle of the institutionalized elderly in three months decreased with significant difference between the assessments. Among all the biochemical and anthropometric measurements, body mass index, weight, fat mass, phase angle and blood fat were the indicators of nutritional assessment that identified early changes and nutritional risks of institutionalized elderly in three months. It is noteworthy that the early evaluation of nutritional indicators can prevent nutritional risk among elderly in living in rest homes.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenômenos Fisiológicos da Nutrição do Idoso , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Institucionalização/estatística & dados numéricos , Avaliação Nutricional , Casas de Saúde/estatística & dados numéricos , Estado Nutricional/fisiologia , Adiposidade/fisiologia , Índice de Massa Corporal , Brasil , Peso Corporal/fisiologia , Proteína C-Reativa/análise , Assistência de Longa Duração , Força Muscular/fisiologia , Estatísticas não ParamétricasRESUMO
This study investigates the treatment of non-alcoholic fatty liver disease (NAFLD) in rats with choline and fructooligosaccharide (FOS). The healthy control group received standard diet. The other three groups consisted of animals with NAFLD. Group Estr received standard diet; group Echo received standard diet plus choline (3 g/100 g diet); and group Efos received standard diet plus FOS (10 g/100 g diet). Food intake, weight, urinary nitrogen, urinary ammonia, total cholesterol, serum triacylglyceride, liver and heart weights, tissue nitrogen, tissue fat, vitamin E, TBARS, and reduced glutathione (GSH) were measured in hepatic and heart tissue. Choline and FOS treatments resulted in total mean fat reduction in liver and heart tissue of 0.2 and 1.7 g, respectively. Both treatments were equally effective in reducing hepatic and cardiac steatosis. There were no differences in the TBARS level among experimental and control groups, indicating that the proposed treatments had no added protection against free radicals. While all experimental groups had increased vitamin E and GSH levels, choline treatment led to a significant increase compared to control.
RESUMO
This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic ß-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet.
Assuntos
Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Resistência à Insulina , Fígado/metabolismo , Síndrome Metabólica/dietoterapia , Triglicerídeos/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Carboidratos da Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/efeitos adversos , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/efeitos adversos , Óleos de Peixe/administração & dosagem , Óleos de Peixe/efeitos adversos , Óleos de Peixe/uso terapêutico , Frutose/efeitos adversos , Regulação Enzimológica da Expressão Gênica , Peroxidação de Lipídeos , Fígado/patologia , Fígado/fisiopatologia , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Tamanho do Órgão , Estresse Oxidativo , Distribuição Aleatória , Ratos Wistar , Triglicerídeos/sangueRESUMO
Fasting and then refeeding on a high-carbohydrate diet increases serum and hepatic triacylglycerol (TAG) concentrations compared to standard diets. Fructose is a lipogenic monosaccharide which stimulates de novo fatty acid synthesis. Omega-3 (n-3) fatty acids stimulate hepatic ß-oxidation, partitioning fatty acids away from TAG synthesis. This study investigated whether dietary n-3 fatty acids from fish oil (FO) improve the hepatic lipid metabolic response seen in rats fasted and then refed on a high-fructose diet. During the post-prandial (fed) period, rats fed a FO rich diet showed an increase in hepatic peroxisome proliferator-activated receptor α (PPAR-α) gene expression and decreased expression of carbohydrate responsive element binding protein (ChREBP), fatty acid synthase (FAS) and microsomal triglyceride transfer protein (MTTP). Feeding a FO rich diet for 7 days prior to 48 h of fasting resulted in lower hepatic TAG, lower PPAR-α expression and maintenance of hepatic n-3 fatty acid content. Refeeding on a high fructose diet promoted an increase in hepatic and serum TAG and in hepatic PPAR-α, ChREBP and MTTP expression. FO did not prevent the increase in serum and hepatic TAG after fructose refeeding, but did decrease hepatic expression of lipogenic genes and increased the n-3 fatty acid content of the liver. n-3 Fatty acids can modify some components of the hepatic lipid metabolic response to later feeding with a high fructose diet.
Assuntos
Dieta , Carboidratos da Dieta/efeitos adversos , Jejum/fisiologia , Óleos de Peixe/farmacologia , Frutose/efeitos adversos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Peso Corporal , Proteínas de Transporte/metabolismo , Carboidratos da Dieta/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/uso terapêutico , Expressão Gênica , Lipogênese/genética , Fígado/metabolismo , Masculino , PPAR alfa/metabolismo , Período Pós-Prandial , Ratos Wistar , Triglicerídeos/metabolismoRESUMO
Institutionalized elderly have an increased risk of changes in nutritional status, therefore sensitive parameters are necessary for the identification of changes in nutritional status. The aim of this study was to evaluate parameters for analysis of the nutritional status of institutionalized elderly in a period of three months by means of biochemical and anthropometric measurements. Eighty one volunteers were selected, with 78 ± 10 years old and 53% female. Anthropometric data showed that the variables body mass index, weight, fat mass, and phase angle of the institutionalized elderly in three months decreased with significant difference between the assessments. Among all the biochemical and anthropometric measurements, body mass index, weight, fat mass, phase angle and blood fat were the indicators of nutritional assessment that identified early changes and nutritional risks of institutionalized elderly in three months. It is noteworthy that the early evaluation of nutritional indicators can prevent nutritional risk among elderly in living in rest homes.
Assuntos
Fenômenos Fisiológicos da Nutrição do Idoso , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Institucionalização/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Avaliação Nutricional , Estado Nutricional/fisiologia , Adiposidade/fisiologia , Idoso , Índice de Massa Corporal , Peso Corporal/fisiologia , Brasil , Proteína C-Reativa/análise , Feminino , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Estatísticas não ParamétricasRESUMO
This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0×), 75 IU (recommended daily intake, RDI), 225 IU (3× RDI), or 1500 IU (20× RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0×dDMH and 3×dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3×aDMH as compared with the other groups. All the groups, except the Control and the 0×aDMH groups, had reduced GSH levels. The 0×dDMH, 0×aDMH, and 20×aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0×aDMH group presented higher ACF rate, followed by 20×aDMH. Moreover, the 3×aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis.