Except for tyrosine, the amino acid requirement of parenterally fed (PN) human neonates has not been derived. Methionine and cysteine are indispensable and dispensable sulphur amino acids respectively. Cysteine is synthesized from methionine. Cysteine is unstable in solution, and is left out or added in very small amounts to amino acid solutions. Methionine is added to compensate for the lack of cysteine, assuming that the neonate will convert methionine to cysteine to meet the body’s metabolic demand. Methionine is hepatotoxic and there is evidence that the neonate has limited ability for its conversion to cysteine. To determine the requirement of the neonate for methionine, PN-fed, stable, post-surgical neonates received graded intakes of methionine. The mean methionine requirement was estimated to be 49 mg.kg-1.day-1, which is 48 to 90% of the methionine content of current commercial amino acid solutions. Because cysteine is the rate limiting substrate for glutathione (GSH) synthesis and current methods of determining amino acid requirement measure requirement for protein synthesis, SAA requirements for maintenance of GSH status was deleniated in healthy adult males and in PN-fed human neonates. GSH kinetics was measured in healthy men receiving the mean methionine requirement and graded intakes of cysteine. GSH synthesis did not change with the addition of cysteine. Additionally, PN-fed post-surgical neonates recieved a methionine-adequate cysteine-free PN followed by cysteine supplemented PN for two 3-day periods and GSH kinetics measured on days 3 and 6. There was no change in GSH synthesis in response to cysteine supplementation. It is concluded that the PN-fed human neonate is capable of synthesizing enough cysteine from methionine not only for protein synthesis but for GSH synthesis. For both healthy men and stable post-surgical neonates, the requirement for GSH synthesis is met at the sulphur amino acid requirement derived using the indicator amino acid technique

Except for tyrosine, the amino acid requirement of parenterally fed (PN) human neonates has not been derived. Methionine and cysteine are indispensable and dispensable sulphur amino acids respectively. Cysteine is synthesized from methionine. Cysteine is unstable in solution, and is left out or added in very small amounts to amino acid solutions. Methionine is added to compensate for the lack of cysteine, assuming that the neonate will convert methionine to cysteine to meet the body’s metabolic demand. Methionine is hepatotoxic and there is evidence that the neonate has limited ability for its conversion to cysteine. To determine the requirement of the neonate for methionine, PN-fed, stable, post-surgical neonates received graded intakes of methionine. The mean methionine requirement was estimated to be 49 mg.kg-1.day-1, which is 48 to 90% of the methionine content of current commercial amino acid solutions. Because cysteine is the rate limiting substrate for glutathione (GSH) synthesis and current methods of determining amino acid requirement measure requirement for protein synthesis, SAA requirements for maintenance of GSH status was deleniated in healthy adult males and in PN-fed human neonates. GSH kinetics was measured in healthy men receiving the mean methionine requirement and graded intakes of cysteine. GSH synthesis did not change with the addition of cysteine. Additionally, PN-fed post-surgical neonates recieved a methionine-adequate cysteine-free PN followed by cysteine supplemented PN for two 3-day periods and GSH kinetics measured on days 3 and 6. There was no change in GSH synthesis in response to cysteine supplementation. It is concluded that the PN-fed human neonate is capable of synthesizing enough cysteine from methionine not only for protein synthesis but for GSH synthesis. For both healthy men and stable post-surgical neonates, the requirement for GSH synthesis is met at the sulphur amino acid requirement derived using the indicator amino acid technique

[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.

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. / Neural tube defects (NTD) are among the most common birth defect leading to great disabilities. The etiology is multifactorial, involving the combined action of both genetic and environmental factors. Those factors have been related to homocysteine metabolism. We performed a case control study in order to evaluate the biochemical and genetic factors related to NTD in the South of Brazil. A mother- NTD children pair and mother normal children were evaluated for folate, vitamin B12, homocysteine and two polymorphism of the methylene tetrahydrofolate reductase (MTHFR), C677T and A1298C. The folate level was 11,37 ng/mL (±6,72) in the NTD patients and 5,64 ng/mL(±4,16) in the controls (p<0,001). The folate was 7,27 ng/mL (±4,48) in the NTD mothers and 3,90 ng/mL (±1,77) in the control mothers (p<0,001). The level of vitamin B12 was 641,88 pg/mL ((±262,21) in the NTD case and 743,27 pg/mL (±433,52) in the controls (p= 0,205). The levels of vitamin B12 in the NTD mothers was 354,75 pg/mL (±142,06) and 465,25 pg/mL (±194,91) in the control mothers (p=0,004). The pasmatic homocysteine level was 6,89 μmol/L(±4,48) for the NTD cases and 5,41 μmol/L (±2,55) for the controls (p=0,099). The NTD mothers showed homocysteine level of 7,23 μmol/L (±2,64) and the controls mothers demonstrated 7,00 μmol/L (±2,24) (p=0,666). We could not observed a difference between the frequency of the genotypes C677T and A1298C in case and controls. The frequency of the alele C and T for the polymorphism C677T were respectively 0,6585 and 0,3414 for the NTD patients; 0,6590 and 0,3410 for the controls; 0,6460 and 0,3540 for NTD mothers; 0,6136 and 0,3860 for the control mothers. The frequencies of the allele A and C for the polymorphism A1298C were respectively 0,7436 and 0,2564 for NTD patients, 0,7610 and 0,2390 for controls; 0,8055 and 0,1945 for NTD mothers; 0,8065 and 0,1935 for controls mothers. We could demonstrated that the homozygous 677TT had a higher level of homocysteine and this was related to low level of vitamin B12. Those findings suggest that biochemical and genetic factors related to homocysteine metabolism and vitamin B12 deficiency are a risk factor to NTD in our population.

The thesis entitled “Syntheses and Characterization of Novel Materials for Efficacious Anticancer Drug Delivery and Selective Sensing of Bioanalytes” encompasses the syntheses and characterization of various novel materials those are primarily used for efficacious pH-targeted chemotherapy, selective sensing and quantification of ATP inside a single living cell and also for specific sensing of female sex pheromone of certain agriculturally important pests. In recent era of cancer research, pH guided anticancer drug delivery is an emerging field by which not only the drug-sensitive, but also the drug-resistant cancer cell lines can be targeted efficiently. Scientists have paid lot of attentions to this area of research to design biocompatible, pH-responsive drug delivery vehicles, where most of the literatures are end up with complex, elaborated synthetic procedures and use of expensive chemicals. There are only a few reports in the literature on small molecule based drug delivery vehicles, which is not well explored. Herein some of the biocompatible, pH-sensitive lipid and short peptide sequences are synthesized in easy and short synthetic procedures and successfully tested for their efficacious anticancer drug delivery properties by various biophysical and biological techniques. A pH and reduction dual bio-responsive short peptide sequences are also generated in simple steps for the same cause. The formation of different nanostructures from the self-assembly of these short peptides is probed from high level of theoretical calculations and ultimately a well known chemotherapeutic drug, doxorubicin, has been delivered efficiently both to the drug-sensitive and drug-resistant cancer cell lines. In a particular case, in vivo study has also been performed to establish the drug delivery efficacy of those serum-stable vehicles that led to proficient reduction of tumour volume as compared to the free drug. On the other hand, a few of the molecules are synthesized and characterized by various analytical means for the selective sensing and quantification of adenosine 5’-triphosphate (ATP) inside a single living cell. Unique surface functionalized templates are also fabricated over MEMS devices for specific sensing of female sex pheromone of Helicoverpa armigera and Bactocera oleae pest in an agricultural field to detect the early pest infestation. Toward this end, an extensive study on the design, syntheses and characterization of different novel materials is presented below.

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. / Neural tube defects (NTD) are among the most common birth defect leading to great disabilities. The etiology is multifactorial, involving the combined action of both genetic and environmental factors. Those factors have been related to homocysteine metabolism. We performed a case control study in order to evaluate the biochemical and genetic factors related to NTD in the South of Brazil. A mother- NTD children pair and mother normal children were evaluated for folate, vitamin B12, homocysteine and two polymorphism of the methylene tetrahydrofolate reductase (MTHFR), C677T and A1298C. The folate level was 11,37 ng/mL (±6,72) in the NTD patients and 5,64 ng/mL(±4,16) in the controls (p<0,001). The folate was 7,27 ng/mL (±4,48) in the NTD mothers and 3,90 ng/mL (±1,77) in the control mothers (p<0,001). The level of vitamin B12 was 641,88 pg/mL ((±262,21) in the NTD case and 743,27 pg/mL (±433,52) in the controls (p= 0,205). The levels of vitamin B12 in the NTD mothers was 354,75 pg/mL (±142,06) and 465,25 pg/mL (±194,91) in the control mothers (p=0,004). The pasmatic homocysteine level was 6,89 μmol/L(±4,48) for the NTD cases and 5,41 μmol/L (±2,55) for the controls (p=0,099). The NTD mothers showed homocysteine level of 7,23 μmol/L (±2,64) and the controls mothers demonstrated 7,00 μmol/L (±2,24) (p=0,666). We could not observed a difference between the frequency of the genotypes C677T and A1298C in case and controls. The frequency of the alele C and T for the polymorphism C677T were respectively 0,6585 and 0,3414 for the NTD patients; 0,6590 and 0,3410 for the controls; 0,6460 and 0,3540 for NTD mothers; 0,6136 and 0,3860 for the control mothers. The frequencies of the allele A and C for the polymorphism A1298C were respectively 0,7436 and 0,2564 for NTD patients, 0,7610 and 0,2390 for controls; 0,8055 and 0,1945 for NTD mothers; 0,8065 and 0,1935 for controls mothers. We could demonstrated that the homozygous 677TT had a higher level of homocysteine and this was related to low level of vitamin B12. Those findings suggest that biochemical and genetic factors related to homocysteine metabolism and vitamin B12 deficiency are a risk factor to NTD in our population.

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. / Neural tube defects (NTD) are among the most common birth defect leading to great disabilities. The etiology is multifactorial, involving the combined action of both genetic and environmental factors. Those factors have been related to homocysteine metabolism. We performed a case control study in order to evaluate the biochemical and genetic factors related to NTD in the South of Brazil. A mother- NTD children pair and mother normal children were evaluated for folate, vitamin B12, homocysteine and two polymorphism of the methylene tetrahydrofolate reductase (MTHFR), C677T and A1298C. The folate level was 11,37 ng/mL (±6,72) in the NTD patients and 5,64 ng/mL(±4,16) in the controls (p<0,001). The folate was 7,27 ng/mL (±4,48) in the NTD mothers and 3,90 ng/mL (±1,77) in the control mothers (p<0,001). The level of vitamin B12 was 641,88 pg/mL ((±262,21) in the NTD case and 743,27 pg/mL (±433,52) in the controls (p= 0,205). The levels of vitamin B12 in the NTD mothers was 354,75 pg/mL (±142,06) and 465,25 pg/mL (±194,91) in the control mothers (p=0,004). The pasmatic homocysteine level was 6,89 μmol/L(±4,48) for the NTD cases and 5,41 μmol/L (±2,55) for the controls (p=0,099). The NTD mothers showed homocysteine level of 7,23 μmol/L (±2,64) and the controls mothers demonstrated 7,00 μmol/L (±2,24) (p=0,666). We could not observed a difference between the frequency of the genotypes C677T and A1298C in case and controls. The frequency of the alele C and T for the polymorphism C677T were respectively 0,6585 and 0,3414 for the NTD patients; 0,6590 and 0,3410 for the controls; 0,6460 and 0,3540 for NTD mothers; 0,6136 and 0,3860 for the control mothers. The frequencies of the allele A and C for the polymorphism A1298C were respectively 0,7436 and 0,2564 for NTD patients, 0,7610 and 0,2390 for controls; 0,8055 and 0,1945 for NTD mothers; 0,8065 and 0,1935 for controls mothers. We could demonstrated that the homozygous 677TT had a higher level of homocysteine and this was related to low level of vitamin B12. Those findings suggest that biochemical and genetic factors related to homocysteine metabolism and vitamin B12 deficiency are a risk factor to NTD in our population.

A homocisteína plasmática é considerada marcador de risco para doenças cardiovasculares e sua associação com a hipertensão arterial essencial parece ser importante no agravamento desta doença. O exercício físico tem mostrado eficácia na redução da pressão arterial e o ácido fólico suplementar a dieta como a melhor conduta para a redução da homocisteinemia. O objetivo deste trabalho foi verificar o efeito da suplementação de ácido fólico e/ou do exercício físico sobre as concentrações plasmáticas de homocisteína em hipertensos essenciais medicados. Para tanto foram estudados 69 hipertensos (57&#177;10 anos), sendo 22 do sexo masculino e 47 do sexo feminino, divididos em dois grupos: grupo 1 medicado com diurético e grupo 2 medicado sem diurético, sendo o tiazídico o diurético mais utilizado (80%). Foram realizadas avaliações médica, antropométrica, dietética, pressórica, bioquímica e o teste de aptidão cardiorrespiratória. Os indivíduos receberam suplementação com 500 &#181;g/dia de ácido fólico, em estudo do tipo cruzado, e foram submetidos a treinamento com exercícios físicos supervisionados, sendo reavaliados a cada dois meses até o final do estudo. Os grupos foram homogêneos em relação a todas as variáveis estudadas exceto a homocisteína plasmática que foi maior significativamente no grupo 1. Não houve diferença significativa entre os sexos para todas as variáveis estudadas. Os hipertensos eram em sua maioria (62%) não controlados e portadores de síndrome metabólica (77%). O exercício físico apresentou efeito benéfico na reclassificação dos hipertensos leves e moderados para a classe de limítrofes sem normalizar a pressão arterial. Não houve efeito do exercício na composição corporal e na homocisteinemia. A suplementação de ácido fólico reduziu a hiperhomocisteinemia em 11% no grupo 1 e 19% no grupo 2 frente a aumentos similares na folacemia. Em relação à pressão arterial houve normalização da homocisteinemia apenas nos hipertensos com pressão arterial normalizada. Os hipertensos limítrofes e leves apresentaram reclassificação da hiperhomocisteinemia limítrofe para moderada. A presença de diurético potencializou a normalização da pressão pelo exercício físico e indiretamente influenciou, nesses casos, a normalização da homocisteína. Entretanto, a maior redução das concentrações médias de homocisteína ocorreu coma oferta de ácido fólico na ausência de diurético. Desta forma, recomenda-se a adequação dietética do folato como adjuvante terapêutico da hipertensão arterial associadamente ao exercício físico e/ou medicamentos / The plasma homocysteine is considered to be a risk indicator for cardiovascular diseases and its association with essential hypertension seems to be important to the worsening of this disease. Physical exercises are efficient to reduce blood pressure and the dietary supplements of folic acid are considered the best way to decrease homocysteine. The aim of this study was investigate the effect of acid folic supplementation and physical exercises on plasmatic levels of homocysteine in essential hypertensive medicated individuals. In order to that, 69 hypertensive subjects were studied (22 men and 47 women) divided in two groups: group 1 medicated with diuretic and group 2 medicated without diuretic. Medical, anthropometrical, dietetic, blood pressure, biochemistry and cardio-respiratory capacity evaluations were performed. These individuals received 500 &#181;g/dia of folic acid supplementation in a cross-over design and were submitted to daily supervisioned physical exercise. They were evaluated every two months until the end of the study. The groups were similar for all variables except for the homocysteine which was significantly greater in the group 1. There were no difference for the gender to all variables. The high blood pressure was not controlled (62%) and 77% of the patients showed metabolic syndrome. The physical exercise showed benefit on the reclassification of slight and moderated hypertensives to border-line hypertension, however, it did not normalize the blood pressure. There were no effects on the body composition and on homocysteine values . Folic acid supplementation decreased 11% of hyperhomocysteinemia in the group 1 and 19% in group 2 face to similar increases in folate. Regarding to high blood pressure subjects the homocysteine normalization occurred only in hypertensive subjects with normalized blood pressure. The border and slightly hypertensive individuals had border-line hyperhomocysteine wich were reclassificated to moderated c1ass. The use of diuretic enhanced blood pressure normalization with the physical exercise and indirectly influenced the plasma homocysteine normalization. However the greater decreasing mean homocysteine concentration occurred with folic acid but in the diuretic absence. So we strong recommend an adequate folate intake as a terapheutical adjuvant to arterial hypertension treatments either with physical exercise and/or antihipertensive drugs.

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.

The formation and patterns of a monolayer are determined by the interplay of two fundamental interactions, adsorbate-substrate and intermolecular interactions. The binding strength between adsorbate and substrate affects the mobility of the adsorbate at the surface and the stability of the complex. The intermolecular interaction plays a significant role in the monolayer patterns on the epitaxial layer of the substrate. A monolayer can be formed either by a spontaneous self-assembly, or by fabrication via atomic-layer deposition (ALD). The physical and chemical properties of the resulting monolayer have a broad array of applications in fabricating functional materials for hydrophobic or hydrophilic surfaces, biological sensors, alternating the properties of the substrate, catalysis and forming ordered layered structures. In this dissertation, the investigation focuses primarily on the influence of the surface topology on the binding behaviour of adsorbate-surface complexes. The state of the art DFT-TS method is used to simulate the sulfur-containing amino acids at complex gold surfaces and examine the relationship between the binding strengths and the binding sites with various nearest neighbouring environments. The same method is also used to determine if a chemical reaction will take place for various catalytic silicon precursors at a silicon oxide surface. Simulating surface chemistry using the DFT-TS method requires intensive com- puting resources, including CPU use and computing time. Another focus of this dissertation is to increase the data generating speed by reducing the size of the sim- ulated systems without altering the outcome. A relatively small gold cluster is used to study the binding behaviours of small organic molecules on the cluster. The same strategy is also used to simulate the chemical reactions between various self-catalying silicon precursors and a water molecule. / Graduate / 2021-10-21