Metabolismo da homocisteína e defeitos do tubo neural : um estudo bioquímico e molecular no sul do Brasil

Os defeitos de fechamento de tubo neural constituem uma das malformações mais freqüentes na espécie humana, apresentando alta morbi-mortalidade. Sua etiologia é considerada multifatorial, estando envolvidos fatores genéticos e ambientais. Estes fatores estão relacionados principalmente com o metabolismo da homocisteína. Realizamos um estudo de caso-controle com o objetivo de estudar os fatores bioquímicos e genéticos relacionados ao DTN na nossa população. Em pares de afetados com DTN e suas mães e pares de pacientes normais e suas mães foram avaliados dosagem de folato, vitamina B12, homocisteína e polimorfismos da enzima metileno tetraidrofolato redutase (MTHFR), C677T e A1298C. A dosagem de folato nos casos foi 11,37 ng/mL(±6,72) e nos controles 5,64 ng/mL(±4,16) (p<0,001). O folato sérico das mães foi 7,27 ng/mL (±4,48) e 3,90 ng/mL (±1,77) nas mães controles (p<0,001). A média de dosagem de vitamina B12 foi de 641,88 pg/mL ((±262,21) nos casos e 743,27 pg/mL (±433,52) nos controles (p= 0,205). A média de dosagem de vitamina B12 nas mães dos casos foi 354,75 pg/mL (±142,06) e 465,25 pg/mL (±194,91) nas mães controles (p=0,004). O nível de homocisteína plasmático médio foi 6,89 μmol/L(±4,48) para os casos e 5,41 μmol/L (±2,55) para os controles (p=0,099). Nas mães dos casos a dosagem média de homocisteína foi 7,23 μmol/L (±2,64) e 7,00 μmol/L (±2,24) nas mães controles (p=0,666). Não houve diferença entre a freqüência dos genótipos C677T e A1298C da MTHFR nos casos e controles e suas mães. Para o polimorfismo C677T as freqüências dos alelo C e T foram respectivamente 0,6585 e 0,3414 nos pacientes com DTN; 0,6590 e 0,3410 nos controles; 0,6460 e 0,3540 nas mães dos casos e 0,6136 e 0,3860 nas mães controles. Para o polimorfismo A1298C as freqüências dos alelos A e C foram respectivamente 0,7436 e 0,2564 nos pacientes com DTN; 0,7610 e 0,2390 nos controles; 0,8055 e 0,1945 nas mães dos casos e 0,8065 e 0,1935 nas mães controles. Identificamos que indivíduos homozigotos 677TT apresentam um maior nível de homocisteína e este é inversamente relacionado com os níveis de vitamina B12. Estes achados sugerem que uma alteração metabólica relacionada ao metabolismo da homocisteína e principalmente devido à diminuição da vitamina B12 seja um fator de risco para DTN na nossa população.

Total gastrectomy with substitution of stomach by jejunal pouch with and without duodenal passage. Study in rats

A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagusduodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. Methods: Male Wistar rats weighing 282±17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. Results: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p<0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p>0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p<0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p<0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p<0.05). Conclusion: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage

Estudo de polimorfismos em genes relacionados ao metabolismo do ácido fólico e sua associação com o desenvolvimento de fendas orais não-sindrômicas

The congenital facial clefts are characterized by incomplete formation of the structures that separate the oral and nasal cavity. It is known that several environmental and genetic factors are involved in its development, among these, polymorphisms associated with folic acid metabolism have been investigated. In this sense, the objective was to observe the frequency of polymorphisms C677T and A1298C methylenetetrahydrofolate reductase gene (MTHFR), methionine synthase A2756G of (MTR), A66G of methionine synthase reductase (MTRR) A80G and the reduced folate carrier (RFC1) in patients with non-syndromic oral clefts, trying to match them with their development. Methods: We studied 140 patients with non-syndromic oral clefts and their mothers and 175 control subjects with their mothers, who underwent a questionnaire to obtain family information. Were collecting blood for DNA extraction from patients and their mothers to identify the genotypes of both by PCRRFLP, in addition to carrying out the determination of glucose, AST, ALT and serum creatinine, folic acid and vitamin B12 Serum and plasma homocysteine, and the hemogram. Results: Most patients have cleft lip and palate (55.8%), followed by isolated cleft palate (24.2%) and cleft lip (20%). Regarding gender, 62% of patients were male and 48% female and, after subdivision of the type of screwdriver according to sex was found a prevalence of males in the cracks of the type lip and palate (69 %) and lip (69.2%) and in the case of cleft palate was a female predominance (59%). The average concentration of serum folate in the group of mothers of cleft patients was significantly lower (13.8 ± 2.4 ng / mL) compared with the group of mothers of control subjects (18.8 ± 3.4 ng / mL) This was also observed for the group of cleft children as compared to controls, the dosage of folic acid had a significant difference with values of 15.6 ± 0.6 (ng / mL) and 17.9 ± 0.6 (ng / mL), respectively. For the biochemical measurements of glucose, AST, ALT and creatinine were not statistically different, nor was observed for haematological parameters performed. In assessing the frequency of polymorphisms C677T and A1298C MTHFR, A2756G MTR, MTRR A66G and A80G of the RFC1 there was no statistically significant difference in genotype distribution between cases and controls both for mothers and in the cleft. Conclusion: Although not observed association of polymorphisms with the development of cracks, the decrease in serum folate in the group of cleft patients and their mothers may reflect a disturbance in the metabolism of this metabolite, necessitating further studies such as studies methylation and expression to further elucidate the involvement of folate in the development of oral clefts

Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training

Objective This study investigated how consumption of orange juice associated with aerobic training affected serum lipids and physical characteristics of overweight middle-aged womenMethods The experimental group consisted of 13 women who consumed 500 mL/d of orange juice and did 1 h aerobic training 3 times a week for 3 months The control group consisted of another 13 women who did the same aerobic training program but did not consume orange juiceResults At the end of the experiment the control group lost an average of 15% of fat mass (P < 0 05) and 25% of weight (P < 0 05) whereas the experimental group lost 11% of fat mass and 1 2% of weight (P < 0 05) Consumption of orange juice by the experimental group was associated with Increased dietary intake of vitamin C and folate by 126% and 61% respectively Serum LDL-C decreased 15% (P < 0 05) and HDL-C increased 18% (P < 0 05) in the experimental group but no significant change was observed in the control group Both groups improved the anaerobic threshold by 20% (P < 0 05) but blood lactate concentration decreased 27% in the experimental group compared to the 17% control group suggesting that experimental group has less muscle fatigue and better response to trainingConclusions The consumption of 500 mL/d of orange juice associated with aerobic training in overweight women decreased cardiovascular disease risk by reducing LDL-C levels and increasing HDL-C levels This association also decreased blood lactate concentration and increased anaerobic threshold showing some improvement in the physical performance (C) 2010 Elsevier B.V. All rights reserved

Avaliação do polimorfismo no gene da metilenotetrahidrofolato redutase e concentração de folato e vitamina B12 em pacientes portadores do HIV-1 em tratamento com anti-retrovirais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Tratamento dietético da hiper-homocisteinemia na doença arterial periférica

A homocisteína está envolvida na gênese da aterosclerose e, assim, é considerada um importante e prevalente fator de risco na doença arterial periférica. O estado nutricional vitamínico deficiente, em especial do folato, é a principal causa de hiper-homocisteinemia nesses casos. Embora ainda não haja consenso sobre a dose exata e a forma de utilização do folato em suplementos e sobre adequação alimentar ou fortificação de cereais para o tratamento da hiper-homocisteinemia, diversos estudos realizados em pacientes com doença vascular periférica mostraram que o folato, isoladamente, pode reduzir as concentrações de homocisteína, bem como a concentração de alguns marcadores biológicos do processo de aterosclerose. No entanto, estudos recentes não comprovaram esse benefício sobre o processo inflamatório associado à hiper-homocisteinemia. Desta forma, embora a utilização isolada do folato seja uma terapêutica custo-efetiva no controle da hiper-homocisteinemia, seu impacto na evolução das doenças arteriais ainda persiste inconclusivo. Esta revisão abordará os efeitos obtidos com as diversas formas de utilização do folato no tratamento da hiper-homocisteinemia.

Haematological response and growth performance of Nile tilapia (Oreochromis niloticus L.) fed diets containing folic acid

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dietas vegetarianas e desempenho esportivo

As evidências atuais apontam benefícios da dieta vegetariana para a saúde humana. Contudo, a partir da adoção de práticas vegetarianas mais restritivas, confirmam-se os riscos à saúde. As dietas vegetarianas são caracterizadas pelo elevado consumo de carboidratos, fibras, magnésio, potássio, folato e antioxidantes, podendo apresentar deficiências em aminoácidos e ácidos graxos essenciais, cálcio, zinco, ferro e cobalamina. Pesquisas experimentais em humanos indicam que vegetarianos e não-vegetarianos apresentam capacidade aeróbica semelhante. em relação ao desempenho em atividades de força e potência muscular, as pesquisas são escassas, mas as existentes não apontam diferenças significativas. Situações de risco cardiovascular têm sido confirmadas, devido ao provável quadro de hiperhomocisteinemia, em decorrência da baixa ingestão de cobalamina. As dietas vegetarianas são isentas de creatina, o que resulta em estoques musculares mais baixos nessa população. Possivelmente ocorrem alterações hormonais e metabólicas em resposta às dietas vegetarianas, como baixos níveis de testosterona e androstenediona. A função imune parece não ser prejudicada. Dessa forma, a prática de dietas vegetarianas apresenta-se compatível com a prática esportiva cotidiana, desde que bem planejada para evitar deficiências nutricionais.

Detection of Altered Risk Factors in Hospitalized Patients with Coronary Artery Disease

OBJECTIVE: To assess biochemical, anthropometric, and dietary variables considered risk factors for coronary artery disease. METHODS: Using anthropometrics, dietary allowance, and blood biochemistry, we assessed 84 patients [54 males (mean age of 55± 8 years) and 30 females (mean age of 57±7 years)], who had severe ( > or =70% coronary artery obstruction) and nonsevere forms of coronary artery disease determined by cardiac catheterization. The severe form of the disease prevailed in 70% of the males and 64% of the females, and a high frequency of familial antecedents (92% ' 88%) and history of acute myocardial infarction (80% ' 70%) were observed. Smoking predominated among males (65%) and diabetes mellitus among females (43%). RESULTS: Males and females had body mass index and body fat above the normal values. Females with nonsevere lesions had HDL > 35 mg/dL, and this constituted a discriminating intergroup indicator. Regardless of the severity of the disease, hyperglycemia and hypertriglyceridemia were found among females, and cholesterolemia > 200 mg/dL in both sexes, but only males had LDL fraction > 160 mg/dL and homocysteine > 11.7 mmol/L. The male dietary allowance was inadequate in nutrients for homocysteine metabolism and in nutrients with an antioxidant action, such as the vitamins B6, C, and folate. Individuals of both sexes had a higher lipid and cholesterol intake and an inadequate consumption of fiber. The diet was classified as high-protein, high-fat, and low-carbohydrate. CONCLUSION: The alterations found had no association with the severity of lesions, indicating the need for more effective nutritional intervention.

Carcinogênese de cabeça e pescoço: impacto do polimorfismo MTHFD1 G1958A

OBJETIVO: Investigar o polimorfismo MTHFD1 G1958A envolvido no metabolismo do folato no risco para o câncer de cabeça e pescoço e verificar a associação entre esse polimorfismo com fatores de risco e características clínico-histopatológicas. MÉTODOS: Estudo retrospectivo que avaliou o polimorfismo MTHFD1 G1958A em 694 indivíduos (240 pacientes e 454 controles), por meio da técnica de análise de polimorfismo de comprimento de fragmento de restrição. Para análise estatística foram utilizados os testes de regressão logística múltipla e qui-quadrado. RESULTADOS: Tabagismo e idade superior a 42 anos foram preditores da doença (p < 0,05). Os genótipos MTHFD1 1958GA ou AA foram associados ao tabagismo (p = 0,04) e etilismo (p = 0,03) e estão presentes em maior proporção em tumores com estádios mais avançados (p = 0,04) e em pacientes com menor sobrevida (p = 0,03). CONCLUSÃO: A presença do polimorfismo MTHFD1 G1958A associada aos hábitos tabagista e etilista aumenta o risco para desenvolvimento de câncer de cabeça e pescoço.

Synthesis, characterization and thermal behaviour of light trivalent lanthanides folates on solid state

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sister-chromatid exchanges in β-thalassaemic patients under conditions of in vivo and in vitro depletion of folic acid

In order to investigate the effect of folate depletion, lymphocyte sister-chromatid exchange (SCE) rates were compared among homozygous β-thalassaemic patients with low folic acid levels, heterozygous β-thalassaemic patients with normal folate levels and healthy persons with normal haemoglobin, in cultures with both normal and depleted folate conditions. Significantly higher SCE rates were found in homozygous patients in all assays, but the in vitro folate depletion did not induce an increase in SCE frequency in any group.

Head and neck carcinogenesis: Impact of MTHFD1 G1958A polymorphism

Objective: To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics. Methods: Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. Results: Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more ofen found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). Conclusion: Te presence of MTHFD1 G1948A polymorphism associated with smoking and alcoholism raises the head and neck cancer risk.

Synthesis, characterization and thermal behaviour of solid-state compounds of folates with some bivalent transition metals ions

Solid-state M-L compounds, where M stands for bivalent Mn, Co, Ni, Cu and Zn and L is folate (C19H17N7O6), have been synthesized. Simultaneous thermogravimetry and differential scanning calorimetry (TG-DSC), X-ray powder diffractometry, infrared spectroscopy (FTIR), TG-DSC coupled to FTIR, elemental analysis and high-resolution continuum source flame atomic absorption spectrometry technique (HR-CS FAAS) were used to characterize and to study the thermal behaviour of these compounds. The results provided information concerning the composition, dehydration, thermal stability and thermal decomposition. © 2013 Akadémiai Kiadó, Budapest, Hungary.

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects

Abstract. Background: This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. Methods. The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Results: Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Conclusion: Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. © 2013 Aptekmann and Cesar; licensee BioMed Central Ltd.