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1

KUZUYA, FUMIO. "Vitamin B6 and Arteriosclerosis." Nagoya University School of Medicine, 1993. http://hdl.handle.net/2237/17526.

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2

Tambasco, Studart Marina. "Analysis of vitamin B6 biosynthesis in Arabidopsis thaliana /." Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17120.

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Studart, Marina Tambasco. "Analysis of vitamin B6 biosynthesis in Arabidopsis thaliana." kostenfrei, 2007. http://e-collection.ethbib.ethz.ch/view/eth:29544.

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4

Gandhi, Amit. "VITAMIN B6 METABOLISM AND REGULATION OF PYRIDOXAL KINASE." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/2008.

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Pyridoxal 5'-phosphate (PLP) is the cofactor for over 140 vitamin B6 (PLP)-dependent enzymes that are involved in various metabolic and biosynthetic pathways. Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two key enzymes that metabolize nutritional forms of vitamin B6, including pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM) to the active cofactor form, PLP. Disruption of the PLP metabolic pathway due to mutations in PNP oxidase or PL kinase result in PLP deficiency, which is implicated in several neurological pathologies. Several ingested compounds are also known to result in PLP deficiency with concomitant neurotoxic effects. How these mutations and compounds affect B6 metabolism is not clearly understood. On the other hand, an emerging health problem is the intake of too much vitamin B6 as high doses of the reactive PLP in the cell exhibits toxic effects, including sensory and motor neuropathies. The overall aim of this research is to understand the catalytic function of PL kinase and the regulatory pathway of PLP metabolism. Using site-directed mutagenesis (Asp235Asn, Asp235Ala), kinetic and structural studies, we have shown that Asp235 may play a catalytic role in PL kinase phosphorylation activity. We also show that human PL kinase binds its substrates, PL and MgATP synergistically, and that the enzyme requires Na+ (or K+) and Mg2+ for its activity. Using kinetic study, we show severe induced MgATP substrate inhibition of PL kinase in the presence of its product, PLP, and we postulate this to be due to the formation of a non-productive ternary complex (Enzyme•PLP•MgATP). Consistently, our crystal structure of human PL kinase (2.1 Å) co-crystallized with MgATP and PLP showed both MgATP and PLP trapped at the active site. Our hypothesis is that this abortive ternary complex might be a physiological process, and that PL kinase uses this mechanism to self-regulate its activity. Our inhibition studies show theophylline, a bronchodilator as a mixed competitive inhibitor of human PL kinase with Ki of 71 μM. Our structural study (2.1 Å) shows theophylline bound at the substrate, PL binding site of human PL kinase. We also identified several potential PL kinase inhibitors from the DrugBank Chemical Compound database. Some of these compounds, including enprofylline, theobromine, caffeine, and lamotrigine, which incidentally exhibit similar neurotoxic effects as theophylline, show significant inhibitory effect on human PL kinase. Further studies are also planned to investigate the effect of these drugs on vitamin B6 metabolism in vivo.
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5

Desai, Jigarkumar. "Pyridoxal Kinase: Its Role in Vitamin B6 Metabolism." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2254.

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Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two vitamin B6 salvage enzymes involved in metabolism of the primary inactive vitamin B6 (pyridoxal, pyridoxine and pyridoxamine) into the active cofactor form, pyridoxal 5’-phosphate (PLP). PLP, arguably the most important vitamin, is required by numerous vitamin B6 (PLP-dependent) enzymes as a co-factor. These enzymes serve vital roles in the metabolism of glucose, lipids, amino acids, heme, DNA/RNA and many neurotransmitters. High levels of vitamin B6 are linked to neurotoxicity, due to the non-specific interactions of PLP with non-B6 proteins. This problem is controlled, in part, by maintaining a low in vivo concentration of free PLP (~1 μM); raising the intriguing question of how the cell regulates, as well as, supplies sufficient PLP to meet the requirements of B6 enzymes. Similar to PLP excess, PLP deficiency, due to mutations in PL kinase and PNP oxidase or drug-induced inhibition of their activity, has been implicated in many pathological conditions. The objective of this study is to elucidate the mechanisms underlying PLP regulation by PL kinase, and its subsequent transfer to dozens of PLP-dependent enzymes. A second objective is to gain valuable information into whether a missense mutation (S261F) in PL kinase could affect the enzyme activity and/or structure. A third objective is to understand how vitamin B6 metabolism by PL kinase is disrupted by the neurotoxic compound, ginkgotoxin. The mutant (hPL kinase S261F) was obtained using site-directed mutagenesis. It was then expressed, purified and analyzed by circular dichroism, fluorescence spectroscopy, enzyme kinetics and native-PAGE. Our results showed no considerable differences between wild-type enzyme and the mutant, suggesting the mutation to be non-pathogenic. PLP was found to inhibit PL kinase by binding to the substrate PL site in the presence of substrate MgATP to form an abortive ternary complex (PL kinase-PLP-MgATP). The physiological significance of this ternary complex was also analyzed and it was found to be a source of PLP transfer to apo B6 enzymes. Enzyme kinetics, affinity chromatography and fluorescence polarization techniques were used to test our hypothesis that the reactive PLP is transferred from PL kinase to apo-B6 enzymes via channeling. Channeling should provide an efficient and protected way for PLP transfer from the kinase or oxidase to apo-B6 enzymes. Our results provide a strong support to the channeling mechanism. Ginkgotoxin was found to be a competitive inhibitor of PL kinase with a Ki of 18 μM. X-ray crystallographic analysis of its binding mode to PL kinase confirmed its binding to the substrate PL site of the enzyme. A unique hydrophobic interaction between its lipophilic side chain 4’-OCH3 and nearby Tyr127 and Val231, in addition to the conserved PL binding interactions, was found to be responsible for its higher affinity to the enzyme.
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6

Van, der Westhuizen Christian Abraham. "Kinetic studies of vitamin B6 metabolism in humans." Diss., University of Pretoria, 2001. http://hdl.handle.net/2263/22786.

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The primal aim of this thesis was to establish whether kinetic aspects of vitamin B6 metabolism predispose to earlier observed racial differences found in plasma pyridoxal-5'-phosphate (PLP). The active forms of vitamin B6 namely plasma PLP and pyridoxal (PL) as well as the three enzymes expressed in the erythrocyte involved in B6 metabolism, PL kinase, PLP phosphatase and pyridoxamine -5'- phosphate (pyridoxine -5'- phosphate) [PMP(PNP) ] oxidase were measured by high performance liquid chromatography. Phase one supported earlier experimental evidence and lower plasma PLP concentrations were found in blacks in a group of200 male volunteers recruited from the South African National Defence Force (SANDF). The respective enzyme activities involved in vitamin B6 metabolism, from the same test subjects, suggested similar PLP production from PMP and PL as well as PLP dephosphorylation which result in the release of PL into the circulating fluid. Since applied exclusion criteria eliminated the majority of biochemical, physiological, genetical - and disease related factors that influence vit B6 status, dietary factors and individual preferences regarding food intake, were most likely to be responsible for the significantly lower circulating plasma PLP encountered in blacks. Phase two compared pharmacokinetic parameters between 7 black - and 9 white test subjects recruited from the South African Police Services after a single 10 mg oral supplement ofpyridoxine hydrochloride. Statistical analysis of the parameters elimination half-life, elimination rate constant, clearance, volume of distribution, mean residence time, maximum peak concentration and time to maximum peak concentration failed to demonstrate any significant differences between the two groups. These results suggest consistent appearance rate, distribution and metabolism for the metabolites PLP and PL in the study population. A tendency in slower appearance rate, for both the metabolites PLP and PL, were observed in blacks and needs to be investigated further. The end product of vitamin B6 metabolism, 4-pyridoxic acid, which was expressed in terms of 24 hour urine volume, again failed to illustrate any significant differences between blacks and whites. These results suggested similar excretion properties in my population study. Furthermore, the pharmacokinetic parameters calculated for plasma PLP and PL respectively, were found to display one-compartment - and two-compartment pharmacokinetic model characteristics. This mono- and bi exponential elimination characteristics displayed by PLP and PL respectively could be of value in future research efforts in terms of sampling time. The distribution half-life can be determined by the calculation of two-compartment macro-rate constants. Fasting blood-samples should be collected when true baseline values are needed in the case of PL. Following vit B6 supplementation, one should allow at least 5 times the distribution half-life (5-6 hr in the case of PL) before blood-sampling in order to achieve true pharmacological response. Phase three of this study was conducted to illustrate the metabolic interplay ofthe enzymes PL kinase and PMP (PNP) oxidase involved in PLP production. The kinetic parameters, Michaelis- Menten constant and maximum velocity rate, at varying substrate concentrations, for the enzymes PL kinase and PMP (PNP) oxidase, were compared in 14 white - and 14 black male test subjects recruited from the SANDF. Both the average Michaelis-Menten constant and maximum velocity rate were higher in whites, but these differences were not statistically significant. The high individual variability for both parameters calculated, can possibly be ruled out if a crystalline enzyme form is used and should be investigated further.
Dissertation (MSc (Chemical Pathology))--University of Pretoria, 2006.
Chemical Pathology
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7

Speitling, Annette. "Wirkungen akut und chronisch hochdosierter Vitamin-B6-Gaben : biokinetische Untersuchungen am Menschen /." Giessen : Wiss. Fachverl, 1991. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=003444484&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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8

Consiglieri, Vladi Olga. "Doseamento da vitamina B6 por espectrofotometria derivada no ultravioleta." Universidade de São Paulo, 1992. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-10072008-170738/.

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Uma metodologia rápida e seletiva foi desenvolvida para a quantificação da piridoxina em medicamentos. O método foi padronizado para aplicação da espectrofotometria derivada no ultravioleta na análise direta da vitamina em preparações multivitamínicas sólidas (cápsulas) e líquidas (solução oral e injetável). As interferências do espectro UV convencional devidas aos excipientes (veículos) e demais fármacos presentes foram eliminados. As retas de calibração foram calculadas, obtendo-se, para a derivada de 1ª ordem, o coeficiente de correlação linear de 0.99997. Os resultados foram estatisticamente estudados e determinaram-se o desvio padrão, coeficiente de variação e intervalo de confiança. O método foi empregado na análise de amostras comerciais e simuladas e os resultados, quando comparados com aqueles provenientes da aplicação do método da Farmacopéia Americana XXII rev., evidenciaram nítidas vantagens quanto à exatidão e precisão, além da facilidade operacional.
A rapid and selecrive method for rhe dererminarion of pyridoxine in pharmaceuticals has been described. The procedure has been developed using direct UV first-derivative spectrofotometry in solid and liquid preparations (tablets, oral solution and injection). Spectral inrerferences from formulation excipienrs and other drugs in simple UV spectrophotometric methods have been eliminated by the application of the proposed method. Calibration curves have been made and the correlation coefficienr for. the first-order derivative was 0,99997. Standard deviation, coefficient of variation and confidence interval were calculated. The method was applied in the analysis of commercial and simulated samples. The results when compared with those obtained by using the USP 22nd. ed. official method shows clear advanrages related to accuracy, precision and practical application.
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9

Pittaya, Kanchanapakonchai Amnuay Thithapandha. "Effects of vitamin B6 on CC14 toxicities in rats /." abstract, 1986. http://mulinet3.li.mahidol.ac.th/thesis/2529/29E-Pittaya-K.pdf.

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10

Footitt, E. J. "Vitamin B6 and serotonin metabolism in neurological disorders of childhood." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1413008/.

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Pyridoxal 5’-phosphate (PLP) is the active form of vitamin B6 in man where it functions as a cofactor for more than 140 enzyme catalysed reactions. Several inherited diseases characterised by seizures have been described which result in an intracellular deficiency of PLP; laboratory measurement of B6 forms an important element in the diagnosis and monitoring of these disorders. A review of PLP measured by HPLC in CSF from patients with neurological disorders showed that variance is greater than indicated by previous studies and the age-related reference limit was revised. This thesis also describes the metabolic disorders that may lead to PLP depletion and examines the relationship of CSF PLP to sulphite accumulation, medications and seizures in patient groups. B6 exists as six different vitamers and is catabolised to 4-pyridoxic acid for urinary excretion. An LC-MS/MS method was developed which could measure all vitameric forms in plasma. Its application to children with B6 responsive seizure disorders showed that patients with inborn errors of metabolism have characteristic B6 profiles which allow them to be differentiated from each other and control populations. PLP is the cofactor for aromatic L-amino acid decarboxylase (AADC) which catalyses the final step in serotonin biosynthesis. This thesis tested the hypothesis that hyperserotonaemia observed in some patients with autism is related to an abnormality in this pathway by investigating the relationship between plasma B6 vitamers, AADC activity and whole blood serotonin in a group of patients and controls. Plasma AADC activity was significantly reduced in autistic subjects; this is considered in the context of current biochemical and molecular understanding and its possible relevance to disease mechanisms is discussed.
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11

Mayengbam, Shyamchand S. "Characterization, quantification, and in vivo effects of vitamin B6 antagonists from flaxseed on amino acid metabolism in a rodent model of moderate vitamin B6 deficiency." ACS Publications, 2014. http://hdl.handle.net/1993/30741.

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Vitamin B6, or more specifically the active form pyridoxal 5ʹ-phosphate (PLP), plays a crucial role as a cofactor for numerous enzymes linked to carbohydrate, fatty acid, and amino acid metabolism. There is a high prevalence of moderate vitamin B6 deficiency in the population that may be further exacerbated through the ingestion of vitamin B6 antagonists present in the food supply. For example, flaxseed contains the anti-pyridoxine factor 1-amino D-proline (1ADP) in the form of a dipeptide called linatine. In order to address these issues, the current study was designed to: 1) characterize and quantify the total amount of anti-pyridoxine factors present in flaxseed through the use of UPLC/ESI-MS analysis, 2) investigate the in vivo effects of synthetic and flaxseed-derived 1ADP on amino acid metabolism using a rat model of moderate B6 deficiency, and 3) identify novel biomarkers of vitamin B6 inadequacy using a LC-Qtof-MS based non-targeted metabolomics approach. The total anti-pyridoxine content, measured as 1ADP equivalents, in the flaxseed extract was found to be 177-437 μg/g of whole flaxseed, depending on the variety tested. Plasma biochemical analyses revealed that B6 vitamers, particularly PLP concentrations were reduced (P≤0.001), due to 1ADP ingestion (10 mg/kg diet) irrespective of the sources. Oral ingestion of flaxseed-derived 1ADP in moderately vitamin B6-deficient rats increased plasma cystathionine (P≤0.001), and decreased plasma α-aminobutyric acid (P≤0.001) and glutamic acid (P=0.017) concentrations compared to the controls. However, the ingestion of synthetic 1ADP elicited greater perturbations in amino acid profile compared to the flaxseed-derived 1ADP, which was predominantly in the form of the dipeptide linatine. Additionally, oral ingestion of the synthetic as well as the flaxseed-derived 1ADP significantly (P≤0.05) inhibited the activities of hepatic PLP-dependent enzymes involved in transsulphuration reactions of methionine metabolism. The use of a non-targeted metabolomics approach identified ten potential lipophilic markers of vitamin B6-insufficiency: glycocholic acid, glycoursodeoxycholic acid, murocholic acid, N-docosahexaenoyl GABA, N-arachidonoyl GABA, lumula, nandrolone, orthothymotinic acid, cystamine and 3-methyleneoxindole. These data serve to highlight potential deleterious effects of anti-pyridoxine factors linked to flaxseed in a population at risk for moderate vitamin B6 deficiency.
October 2015
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12

Almeida, Lana Carneiro. "Preditores dietéticos das concentrações séricas ou plasmáticas de homocisteína, ácido fólico, vitaminas B12 e B6 em mulheres." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/6/6133/tde-25062007-175008/.

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Objetivo Examinar a correlação entre fatores dietéticos, obtidos por questionário de freqüência alimentar (QFA) validado, e concentrações séricas ou plasmáticas de homocisteína (hcy), ácido fólico, vitaminas B12 e B6 em mulheres de São Paulo. População e métodos Foram analisados os dados dietéticos de 1.434 mulheres de 21 a 65 anos de um estudo caso-controle sobre consumo alimentar e lesões neoplásicas do colo uterino realizado em três hospitais públicos da cidade de São Paulo, excluindo-se os casos de câncer invasivo. Todas participantes tiveram sua ingestão alimentar usual avaliada por entrevista, usando um QFA, e forneceram amostras sangüíneas em jejum para separação de plasma e soro. Concentrações séricas de ácido fólico e vitamina B12 séricos foram analisadas por técnica de fluoroimunoensaio, enquanto concentrações plasmáticas de hcy e vitamina B6 foram analisadas por Cromatografia Líquida de Alta Performance em fase reversa. Correlações entre ingestão estimada de nutrientes, ajustados pelas calorias totais, e alimentos com as variáveis bioquímicas foram avaliadas em modelos de regressão linear múltiplos, após ajuste para co-variáveis, tais como idade, Índice de Massa Corporal (IMC), estilo de vida (incluindo tabagismo), morbidade ginecológica pregressa ou atual, história obstétrica e uso de anticoncepcional oral. Resultados Embora apenas 6,2% das participantes do estudo tenham apresentado concentrações séricas de ácido fólico abaixo do valor de referência (7 nmol/L), 45,7% e em 97,1% tiveram um consumo estimado de folato inferior a 180 ug/dia e 400 ug/dia, respectivamente. Modelos de regressão múltiplos mostraram correlação positiva entre ácido fólico sérico e ingestão estimada de proteína, ferro, folato, vitaminas B1, B3, B6, A, C e frutas/sucos cítricos e de vegetais verdes, e correlação inversa entre ácido fólico sérico e consumo estimado de gorduras, doces e leite e derivados. Resultados similares foram obtidos após ajuste adicional para fibra da dieta, exceto com consumo de folato e de vegetais verdes, que perderam a significância estatística como preditores independentes das concentrações séricas de ácido fólico. Concentrações séricas de vitamina B12 abaixo do ponto de corte de 148 pmol/L foram observadas em 11,0% da amostra; a maioria delas (70,4%) apresentou ingestão estimada de vitamina B12 igual ou superior à recomendação (2 ug/dia). As concentrações séricas de vitamina B12 foram positivamente correlacionadas com consumo estimado de produtos lácteos e das vitaminas B2 e B12. A ingestão de fibra, vitamina E e leguminosas foi inversamente correlacionada com as concentrações séricas de vitamina B12. Ingestão de vitamina B6 abaixo das recomendações de 1,3 mg/dia (≤50 anos) e 1,5 mg/dia (>50 anos) foi observada em 49% das participantes. Nenhuma correlação foi encontrada entre dados da dieta e concentrações plasmáticas de vitamina B6. As concentrações plasmáticas de hcy foram positivamente correlacionadas com o consumo estimado de carboidratos e doces, e inversamente correlacionadas com o consumo estimado de proteína, colesterol, ferro, zinco de origem animal, vitaminas A, B2, B12 e B6, e pescados. Entretanto, essas correlações perderam a significância após ajuste adicional por proteína da dieta, um dos mais fortes preditores das concentrações plasmáticas de hcy. Conclusão Nutrientes e alimentos selecionados da dieta mostraram-se preditores independentes das concentrações séricas de ácido fólico e de vitamina B12, indicando as principais fontes alimentares desses nutrientes nesta população e em outras similares. A forte correlação negativa entre concentração plasmática de Hcy e proteína da dieta sugere base para o planejamento de futuras intervenções nutricionais. Nenhuma correlação foi observada entre concentração plasmática de vitamina B6 e fatores dietéticos estimados.
Objective To examine whether measurements of dietary intakes, obtained with a validated quantitative food frequency questionnaire (FFQ), correlated with serum or plasma levels of folic acid, vitamins B12 and B6 and homocystein (hcy) measured in low-income women living in São Paulo, Brazil. Population and methods We analyzed dietary data from 1434 women aged 21-65 years enrolled in a case-control study of diet and cervical cancer carried out in three public hospitals of São Paulo. Data for women with invasive cervical cancer were excluded. All participants had their usual dietary intake assessed by interview, using a validated FFQ, and provided a fasting blood sample for serum and plasma separation. Serum concentrations of folic acid and vitamin B12 were measured by fluorimmunoassay, while serum levels of vitamin B6 and plasma levels of hcy were measured by reversed-phase high performance liquid chromatography. Correlations between estimates of food and energy-adjusted nutrient intakes and levels of folic acid, vitamins B12 and B6 and hcy were assessed using multiple linear regression models, adjusted for covariates such as age, body mass index, lifestyle (including smoking), past and current gynecologic morbidity and obstetric history, and use of oral contraceptives. Results Although only 6.2% of the study participants had serum folic acid levels below the reference value of 7 nmol/L, 45.7% and 97.1% had a dietary intake of folic acid estimated to be less than 180 g/day and 400 g/day, respectively. Multiple linear models showed serum folic acid levels to be positively correlated with the estimated intake of protein, iron, folate, vitamins B1, B3, B6, A and C, citrus fruits and juices and green vegetables, and negatively correlated with the estimated intake of fat, sweets and dairy products. Similar results were obtained after a further adjustment for fiber intake in the model, except for the estimated intake of folic acid and green vegetables, which lost their statistical significance as independent predictors of serum folic acid levels. Serum levels of vitamin B12 below the cut-off point of 148 pmol/L were found in 11.0% of study participants; most of them (70.4%) had their vitamin B12 intake estimated to be equal or greater than the reference value of 2 g/day. Serum levels of vitamin B12 were positively correlated with the estimated intake of dairy products and vitamins B2 and B12. The estimated intakes of fiber, vitamin E and beans were negatively correlated with serum levels of vitamin B12. Dietary vitamin B6 was estimated to be below the recommended levels of 1.3 mg/day (age  50 years) or 1.5 mg/day (age > 50 years) in 49.0% of study participants. No correlation was found between estimated intakes of foods and nutrients and plasma levels of vitamin B6. Hcy concentrations were positively correlated with the estimated intake of carbohydrates and sweets, and negatively correlated with the estimated intake of protein, cholesterol, iron, zinc of animal origin, vitamins A, B2, B12 and B6 and fishes. However, these correlations were no longer significant after additional adjustment for dietary protein, the strongest predictor of hcy plasma levels. Conclusion The estimated dietary intakes of selected foods and nutrients were shown to be independent predictors of measured serum levels of folic acid and vitamin B12, providing a basis for indentifying the main dietary sources of these nutrients in this and similar populations. The strong negative correlation between plasma levels of hcy and dietary protein provides a basis for future nutritional interventions. No correlation was found between plasma concentrations of vitamin B6 and estimated dietary intakes.
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Porter, Charmaine L. Locy Robert D. "Functional identification and characterization of an Arabidopsis thaliana gene involved in vitamin B6 biosynthesis." Auburn, Ala., 2005. http://hdl.handle.net/10415/1261.

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14

Dunn, Karen A. "The relationship between vitamin B6 and the degree of PMS symptomatology /." Staten Island, N.Y. : [s.n.], 1990. http://library.wagner.edu/theses/nursing/1990/thesis_nur_1990_dunn_relat.pdf.

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Presoto, Ana Elisa Ferreira. "Vitaminas do complexo B e ferro em farinhas de cereais." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/9/9131/tde-21112017-145753/.

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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.
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Andrade, Jirrah Pedro de. "Desenvolvimento e eficácia clínica de dermocosméticos para a pele acneica contendo vitamina B3 e derivados de vitamina B6 e zinco." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-30012014-081127/.

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A acne é uma doença de pele com alta prevalência e seu tratamento é importante para evitar lesões cutâneas permanentes ou o agravamento de transtornos psicológicos provenientes do abalo à autoestima. Dessa forma, o desenvolvimento de formulações dermocosméticas eficazes que possam melhorar as condições desse tipo de pele é de grande valia. Dentre os ativos com potenciais benefícios para o controle de alguns dos principais fatores causadores da acne, estão a vitamina B3, um derivado de vitamina B6 e o PCA zinco. Assim o objetivo deste estudo foi o desenvolvimento de formulações dermocosméticas para a pele acnéica contendo vitamina B3, derivado lipossolúvel de vitamina B6 e PCA zinco bem como a avaliação da estabilidade e eficácia clínica dessas formulações. Para tal, foram desenvolvidas diferentes formulações, as quais, em um primeiro momento, foram avaliadas quanto à estabilidade frente à adição do ingrediente ativo Zinc PCA. Após esta etapa, os demais ingredientes ativos foram adicionados e as formulações foram submetidas a testes preliminares de estabilidade e ao estudo da estabilidade física por determinação do comportamento reológico. A formulação mais estável foi avaliada quanto à compatibilidade cutânea e também em relação à comedogenicidade do veículo. A formulação composta pelos ingredientes ativos foi avaliada, ainda, quanto as suas características sensoriais e eficácia clínica. Os estudos de eficácia foram realizados por meio de métodos objetivos e subjetivos, após seis semanas do uso da formulação. Os métodos objetivos consistiram no uso de metodologias in vivo, não invasivas (métodos biofísicos e de imagem), sendo avaliados parâmetros relacionados à hidratação, função barreira, conteúdo lipídico, pH cutâneo, contagem de porfirinas, de microcomedões e de lesões inflamatórias. Em relação aos métodos subjetivos, foi realizada a percepção da eficácia por meio de um questionário para a comparação da pele antes e após o tratamento. Os resultados mostraram que, de todas as formulações desenvolvidas, apenas uma mostrou-se estável frente aos testes de estabilidade realizados. A formulação (veículo e adicionada de ingredientes ativos) apresentou compatibilidade cutânea considerada como \"muito boa\", de acordo com o teste realizado, e o veículo sem potencial comedogênico. Na avaliação sensorial as frequências obtidas para os parâmetros considerados como ruins foram baixas, indicando que o sensorial da formulação mostrou-se adequado para as finalidades propostas. No estudo de eficácia clínica, a formulação não alterou a hidratação e a função barreira da pele e mostrou-se eficaz na redução da contagem de porfirinas e das lesões inflamatórias (p<0,05). A avaliação clínica por métodos subjetivos mostrou a eficácia da formulação quanto à melhora da acne inflamatória, oleosidade da pele, hidratação e maciez. Por fim, os resultados obtidos mostraram que a formulação desenvolvida é eficaz e compatível com a pele, bem como a importância da pesquisa e desenvolvimento para a obtenção de formulações estáveis, seguras, eficazes e com sensorial adequado.
Acne is a skin disease with high prevalence and its treatment is important to prevent permanent skin lesions or the aggravation of psychological disorders due to self-esteem shaken. This way, the development of effective dermocosmetic formulations, that can improve the conditions of this skin type, is very important. Vitamin B3, a vitamin B6 derivative and zinc PCA are among the active ingredients which present potential benefits in the controlling of some pathogenic factors of acne. Thus, the aim of this research was to develop cosmetic formulations for acneic skin containing vitamin B3, vitamin B6 lipophilic derivative and zinc PCA, as well as the evaluation of stability and clinical efficacy. For this purpose, were developed different formulations which, at first, were evaluated in terms of stability face to zinc PCA addition. After this, the others active ingredients were added and the formulations were submitted to preliminary tests of stability and physical stability studies by rheological behavior determination. The most stable formulation was subject to skin compatibility evaluation and vehicle comedogenicity. The formulation with the active ingredients was also evaluated regarding their sensorial characteristics and clinical efficacy. Efficacy studies were performed by means of objective and subjective methods, after a sixweek- period of use of the formulation. The objective methods consisted in non-invasive in vivo methodologies (biophysical techniques and image analysis) where were evaluated hydration, barrier function, lipid content, skin pH and the counting of porphyrins, microcomedones and inflammatories lesions. In relation to subjective methods, was performed the efficacy perception using a questionnaire in order to compare the skin before and after the treatment. The results showed that among the formulations developed, only one kept stable after the stability tests. The formulations were considered as \"very good\" on skin compatibility test and showed no comedogenic potential. In sensorial evaluation, frequencies obtained for the parameters considered bad were low, which indicate the sensorial of the formulation was adequate for the purposes. In clinical efficacy study, the formulation under study did not alter the parameters related to hydration and skin barrier function and was effective in reducing the counting of porphyrins and inflammatories lesions (p<0,05). Clinical evaluation by subjective methods showed the formulation effectiveness regarding the improvement of inflammatory acne, skin oiliness, hydration and softness. Finally, the results obtained showed the formulation developed is effective and compatible with the skin and, besides the importance of research and development for obtaining stable, safe and effective formulations with suitable sensorial.
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17

Ho, Chia-ling. "Vitamin B6 status of young and older adult women in Metro Vancouver." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62700.

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18

Sousa, Bruno Soares de. "Investigação do potencial ansiolítico de Magnésio e Vitamina B6 em uma única administração em humanos." Universidade Federal da Paraí­ba, 2013. http://tede.biblioteca.ufpb.br:8080/handle/tede/4295.

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The objective this study was to investigate the potential anxiolytic Magnesium and Vitamin B6 in college students using a model of experimental induction of anxiety, through the assessment of physiological and psychological parameters. The study was an experimental, randomized and controlled. It was composed of sixty students, female, distributed in one of four experimental groups: Control; Magnesium, Magnesium + B6, Vitamin B6. The human anxiety was induced by Simulated Public Speaking (TSFP) and was assessed by physiological parameters (Systemic Blood Pressure, Heart Rate, Temperature of Extremity , Electrical Skin Conductance) and psychological parameters (State - Trait Anxiety Inventory). The behavior of physiological and psychological measures was accompanied on the four times of testing, Baseline (B), Pre - stress (PT), Performance (S) and Final (F) and were evaluated in two ways: behavior between the supplemented groups and between the phases in each respective time groups. During speech, the diastolic blood pressure was lower in B6 versus control (P <.05), there was also a decrease in the conductance B6 group (P <0.01) in the Magnesium + B6 group (P <0.05) and group B6 (P <0.05) compared to the control group. In the final moment, the conductance was lower in B6 compared with controls (P <0.05). The STAI-T showed that the university had moderate levels of anxiety (STAI-T 40-60 points). In the comparison between groups was observed that all individuals of the respective groups already started the test with a moderate degree of anxiety (STAI-E 40 - 60 points). At the last moment there was a decrease in E-STAI score in both groups, where they began to be classified with low levels of anxiety (STAI-E <40 points) (P> 0.05). The use of magnesium and vitamin B6, at a concentration of 200 mg enough results showed that proves its efficacy in controlling some symptoms of anxiety induced experimentally here, exhibited lower values for CEP and anticipatory anxiety having vitamin B6 submitted lower values of DBP at the performance of the speech, which means to say that in the control group participants showed less variability.
O objetivo deste estudo foi investigar o potencial ansiolítico do Magnésio e da Vitamina B6 em estudantes universitárias utilizando um modelo de indução experimental de ansiedade, por meio da avaliação dos parâmetros fisiológicos e psicológicos. O estudo teve caráter experimental, randomizado e controlado. Foi composto por sessenta estudantes, do sexo feminino, distribuídas em um dos quatro grupos experimentais: Controle; Magnésio; Magnésio + B6; Vitamina B6. A ansiedade humana experimental foi induzida pelo Teste de Simulação de Falar em Público (TSFP) e foi avaliada por meio de parâmetros fisiológicos (Pressão Arterial Sistêmica, Frequência Cardíaca, Temperatura de Extremidades, Condutância Elétrica da Pele) e de parâmetros psicológicos (Inventário de ansiedade Traço e Estado). O comportamento das medidas fisiológicas e psicológicas foi acompanhado nos quatro momentos do teste, Basal (B), Pré - estresse (PT), Performance (S) e Final (F) e foram avaliados de duas formas: comportamento entre os grupos suplementados e entre as fases em cada um dos respectivos grupos.No momento do discurso a pressão arterial diastólica foi menor no grupo B6 comparado ao controle (P<0,05), houve ainda diminuição da condutância no grupo B6 (P<0,01), no grupo Magnésio + B6 (P<0,05) e no grupo B6 (P<0,05) comparados ao grupo controle. No momento final a condutância foi menor no grupo B6 comparado ao controle (P<0,05). O IDATE-T demonstrou que as universitárias apresentavam níveis de ansiedade moderado (IDATE-T 40-60 pontos). Na comparação entre os grupos observou-se que todos os indivíduos dos respectivos grupos já iniciavam o teste com um grau de ansiedade moderada (IDATE-E 40 - 60 pontos). No momento final houve diminuição no escore do IDATE-E em ambos os grupos, onde os mesmos passaram a ser classificados com grau de ansiedade baixa (IDATE-E < 40 pontos) (P>0,05). A utilização de Magnésio e de vitamina B6, na concentração de 200 mg apresentou resultados suficientes que comprovam sua eficácia no controle de alguns sintomas da ansiedade, aqui induzida de forma experimental, apresentando menores valores de CEP durante a ansiedade antecipatória e tendo a vitamina B6 apresentado valores menores da PAD no momento da performance do discurso, o que significa afirmar que em relação ao grupo controle as participantes apresentaram menor variabilidade.
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19

Coutinho, Leonam Gomes. "Estudo do papel da prote?na multifuncional APE1/Ref-1 sobre a resposta inflamat?ria na meningite bacteriana." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12649.

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Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-?. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition
A meningite bacteriana (MB) ? uma doen?a infecciosa que permanece com altas taxas de mortalidade e morbidade em todo o mundo, principalmente em pa?ses subdesenvolvidos, apesar dos avan?os na antibioticoterapia. Um dos principais mecanismos associados ?s sequelas durante a MB ? a elevada resposta inflamat?ria, que promove uma exacerbada quantidade de esp?cies reativas de oxig?nio (ERO) levando ?s c?lulas a apoptose ou necrose. A ativa??o de enzimas de reparo de DNA durante o estresse oxidativo tem sido demonstrada nas mais diversas desordens. Uma importante enzima envolvida neste processo ? a endonuclease apur?nica/apirimidinica1/fator redox-1 (APE1/Ref-1). Ela ? uma prote?na multifuncional envolvida no reparo de DNA e na redu??o de fatores envolvidos com a resposta inflamat?ria, tais como o fator nuclear kappa B (NFkB) e prote?na ativadora 1 (AP-1). Este estudo teve como objetivo identificar o envolvimento de APE1/Ref-1 na resposta inflamat?ria visando a possibilidade de sua utiliza??o como alvo terap?utico na redu??o de sequelas durante a MB. Para isto, inicialmente foi realizado uma an?lise no perfil de express?o de citocinas em l?quor de pacientes com meningite causada por Streptococcus pneumoniae e Neisseriae meningitidis visando selecionar moduladores inflamat?rios de interesse para ensaios em cultura de c?lula subsequentes. Em seguida, utilizando um modelo celular de indu??o com LPS foi avaliado o efeito da inibi??o da atividade de reparo e redox de APE1 sobre a express?o de citocinas inflamat?rias. Por fim, foi observada a express?o de APE1 no c?rtex (CX) e hipocampo (HC) de ratos com MB frente a uma terapia adjuvante com vitamina B6. Nossos resultados mostraram um perfil de moduladores inflamat?rios muito semelhante no l?quor dos pacientes com MB causada pelos pat?genos estudados, embora interferon gama (IFNy) tenha sido VI significativamente mais expresso em pacientes com S. pneumoniae do que N. meningitidis. Quanto ao uso dos inibidores das fun??es, redox e de reparo, de APE1/Ref-1 no modelo in vitro, houve redu??o significativa na express?o de algumas citocinas, principalmente o fator de necrose tumoral-alfa (TNF-?). Al?m disso, os inibidores demonstraram uma redu??o nos n?veis de ERO nas c?lulas estimuladas com LPS. No modelo animal, a express?o prot?ica de APE1/Ref-1, no CX e HC dos ratos, foi modulada ap?s introdu??o da vitamina B6. Portanto, esses dados fornecem um novo olhar para a fisiopatologia da MB, em que citocinas como IFNy podem ser usadas em um diagn?stico diferencial entre meningites causadas por S. pneumoniae e N. meningitidis. A prote?na de reparo de DNA, APE1/Ref-1, parece ser um alvo potencial na modula??o da resposta inflamat?ria e do estresse oxidativo, bem como a terapia adjuvante com vitamina B6 mostra ter um papel sobre a express?o de APE1/Ref-1. Consequentemente, o conhecimento obtido neste estudo pode ser importante na melhoria do progn?stico da MB, al?m de contribuir para entender a associa??o entre o reparo de DNA e inflama??o
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20

Turner, James P. "A case control study of the carpal tunnel syndrome, with special reference to vitamin B6 status." Thesis, University of Surrey, 1989. http://epubs.surrey.ac.uk/848093/.

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Carpal tunnel syndrome (CTS) is a condition characterised by a collection of signs and symptoms indicative of focal median nerve dysfunction within the anatomical confines of the carpal tunnel at the wrist. The syndrome appears to be multifactorial in its aetiology. It has been asociated with certain systemic disorders, (e. g. Diabetes Mellitus, Acromegaly), factors related specifically to the movements and actions of the wrists and hands, (e.g., repetitive manual work, prolonged pinching and grasping and the use of vibratory hand held tools) and other conditions or characteristics which are systemic in nature but do not necessarily represent diseases (e. g. pregnancy, side effects to certain drugs). Recent reports suggest that vitamin B6 deficiency might play a role in the development of CTS. A review of the literature has shown there to be a paucity of analytical epidemiological data concerning these hypothesized risk factors. A study was therefore undertaken to investigate the association between a set of risk factors identified in the literature, (including low vitamin B6 status) and CTS. The study design selected was that of a pair matched case-control study. In this way, associations between aspects of CTS, aspects of vitamin B6 status and other hypothesized risk factors were examined. Thirty four cases were identified (electrophysiologically) and these were matched (for sex and age +/-3 years) with controls attending physiotherapy departments for accidental injuries involving the lower half of the body. Data were collected at interview, examination, and using a self administered questionnaire. Venous blood samples were also obtained from 32 cases and 20 controls. Vitamin B6 status was assessed using an enzyme stimulation assay, (Erythrocyte Glutamate Oxaloacetic Transaminase or EGOT). No statistically significant differences between the cases and controls regarding any aspects of vitamin B6 status were evident. These findings were confirmed by comparison with a group of fifty healthy volunteer subjects, (university staff). The need for further elucidation regarding the possible role of vitamin B6 in the treatment is highlighted. Cases statistically outnumbered controls with respect to the performance of repetitive manual work (p=0.019; exposure odds ratio = 5.0) and participation in leisure pursuits (p=0.03; exposure odds ratio = 2.75) involving the use of the hands. This supports the findings of other studies reported in the literature. The cases reported significantly more oedema (p=0.04; exposure odds ratio 3.0) and stiffness, (p=0.001) than the controls. A significant impairment in the range of movement of the index finger was noted. Certain of these symptoms have been reported to occur in groups of CTS sufferers and improve upon vitamin B6 therapy. The implications of these and other findings are discussed in the light of the current knowledge of the many hypothesized risk factors.
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21

Bhunthurat, Anurak. "The Vitamin B-6 Status of Patients with Chronic Obstructive Pulmonary Disease." Thesis, North Texas State University, 1986. https://digital.library.unt.edu/ark:/67531/metadc500541/.

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The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.
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22

Zolfaghari, Sara S. "The relationship between folic acid, vitamin B12, and vitamin B6 intakes and depression in women who use hormonal oral contraceptives." Thesis, California State University, Long Beach, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1604887.

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Depression is a leading cause of disability and mortality worldwide, especially for women. No nutrition recommendations exist for depression. Oral contraceptives (OCs) have become the leading form of pregnancy prevention in the United States. Studies have associated OC use with impaired nutrient status, specifically folate, vitamin B12, and vitamin B6, which also affect brain functions. Dietary folate, vitamin B12, and vitamin B6 self-reported intakes were used to determine the relationship between depression in women who used OCs (n = 34) in a selected cohort ( n = 409) from the National Health and Nutrition Examination Survey, 2003–2008. OC users were more depressed than non-OC users; depression was associated with various quartile levels of vitamin intake (p <.001). No benefit was observed with intakes which exceeded RDAs for non-OC users; OC users were less depressed when intakes exceeded RDAs for folate, vitamin B12, and vitamin B6 by 13%, 75%, and 7%, respectively.

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23

Kruse, Vera [Verfasser], and Rima [Akademischer Betreuer] Obeid. "Auswirkung einer Folat-, Vitamin B12- und Vitamin B6-Supplementation auf den Knochenstoffwechsel zusätzlich zur Basistherapie mit Vitamin D und Kalzium / Vera Kruse. Betreuer: Rima Obeid." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/1057869171/34.

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24

Sandmark, Jenny. "Enzymatic mechanisms in biotin synthesis: vitamin B₆ catalysis and phosphoryl transfer /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-609-x/.

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25

Potter, Kathleen. "The effects of long-term homocysteine-lowering treatment with folic acid, vitamin B6 and Vitamin B12 on vascular structure and function in stroke." University of Western Australia. School of Medicine and Pharmacology, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0020.

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[Truncated abstract] An elevated total plasma homocysteine concentration (tHcy) is associated with an increased risk of myocardial infarction and ischemic stroke. Folic acid, vitamin B6 and B12 supplements significantly reduce tHcy even in people who are not overtly vitamin deficient. If homocysteine is a causal risk factor for atherothrombotic events, treatment with B-vitamins might prove a simple and cost-effective means to reduce cardiovascular risk. However, it remains unclear whether elevated tHcy causes atherosclerosis or is simply a risk marker. To prove that homocysteine is a modifiable risk factor for cardiovascular disease it is necessary to show that lowering tHcy reduces vascular risk. The aim of this study was to determine whether long-term homocysteine-lowering with B-vitamins would improve vascular structure and function in people with a history of stroke. This study was a cross-sectional sub-study of the Vitamins TO Prevent Stroke trial (VITATOPS), a multi-centre, randomised, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of B-vitamins (folic acid 2mg, vitamin B6 25mg and vitamin B12 0.5mg) in the prevention of vascular events in patients with a recent history of stroke or transient ischemic attack. 173 VITATOPS participants were recruited for the current study. Age, sex, stroke type, medications, cardiovascular risk factors and smoking history were recorded and blood pressure, height, weight, waist and hip girth were measured in all subjects at least two years after randomisation. ... After a mean treatment period of 3.9 ± 0.9 years, the subjects randomised to vitamin treatment had significantly lower tHcy than the subjects randomised to placebo (7.9mol/L, 95%CI 7.5, 8.4 versus 11.8mol/L, 95%CI 10.9, 12.8; p<0.001). There were no significant differences between groups in CIMT (0.84 ± 0.17mm vitamins versus 0.83 ± 0.18mm placebo; p=0.74) or FMD (median of 4.0%, IQR 0.9, 7.2, vitamins versus 3.0%, IQR 0.6, 6.6 placebo; p=0.48). Pooled estimates from the meta-analyses showed that B-vitamin treatment reduces CIMT by 0.10mm (95%CI –0.20, -0.01mm) and increases FMD by 1.4%, (95%CI 0.7, 2.2), although these estimates may have been influenced by positive publication bias. The improvement in FMD was significant in studies of less than eight weeks duration but not in studies with longer treatment periods. The association between tHcy and CIMT and FMD was eliminated by adjustment for renal function and long-term B-vitamin treatment did not alter the strong linear relationship between tHcy and cystatin C. Lowering tHcy did not alter arterial wall inflammation assessed by 18FDG-PET, although small subject numbers meant we were unable to exclude a minor treatment effect. Long-term homocysteine-lowering with B-vitamin treatment did not improve CIMT or FMD or reduce arterial wall inflammation in people with a history of stroke. The relationship between tHcy and these markers of vascular risk was eliminated by adjustment for renal function. Our data are consistent with the hypothesis that elevated tHcy is a risk marker for cardiovascular disease rather than a modifiable causal risk factor.
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Wodarra, Juliane [Verfasser]. "Einfluss von Blutspenden auf Vitamin B6, Vitamin B12, Folsäure, Biotin und Homocystein in Abhängigkeit von Vitamineinnahme, Lebens- und Ernährungsgewohnheiten / Juliane Wodarra." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023783266/34.

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27

Kronenberger, Thales. "Implicações estruturais de mutantes da piridoxal quinase de Plasmodium falciparum." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-12082014-140851/.

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O metabolismo de vitamina B9 é um alvo terapêutico conhecido para malária. A vitamina B6 foi validada como essencial para o parasita. Esse trabalho analisa bioquimica- e estruturalmente mutantes da enzima piridoxal quinase, pela combinação de análises in silico associadas a ensaios bioquímicos. A estrutura da PdxK de P. falciparum permitiu a localização do sítio ativo e da interface de dimerização. Logo foram sugeridas mutações que alterassem esses resíduos para investigar sua importância. Dinâmica molecular sugere que a dimerização é responsável pela estabilidade do sítio ativo, algo coerente com a diminuição da atividade enzimática na maioria das mutantes. Filtração em gel aponta um equilíbrio entre a conformação monômero-dímero mostrando que as mutações na interface não estão relacionadas a dimerização, mas envolvidas com a estabilização do folding na região do sítio ativo. A mesma é recoberta por uma tampa que impede a auto-hidrólise do ATP, há também um resíduo serina que estabiliza a conformação do piridoxal durante a catálise, as mutações em ambas as regiões levaram a inativação da enzimática. A hipótese de que a interação da PfPdxK com ligantes de RNA não se mostrou conclusiva.
Vitamin B9 metabolism is a known drug-target for malaria. Vitamin B6 was validated as essential for the parasite. We analysed biochemically and structurally the plasmodial dimeric pyridoxal kinase. PfPdxKs allowed us to determine the localisation of the active site as well the interface between the two monomers and to identify the involved residues. Molecular dynamics shows that the PdxKs dimerization is important for the active sites stability, which was confirmed by the decrease of activity in mutants related to this region. Gel filtration revealed equilibrium of monomer-dimer conformation and therefore the interface mutations decrease in activity might not be directly related to the dimerization processes, but rather to the active site organisation. The active site region shows a serine involved in keeping the pyridoxals conformation during catalyses and the identified lid region covering the ATP binding site is responsible for preventing auto-hydrolysis. Substitution of the respective amino acid to alanine resulted in enzyme inactivation. In silico analysis of the PfPdxK spacer region identified nucleic acid binding sides, however RNA binding experiments failed so far and the possibility of protein-RNA binding remains for elucidation.
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Hobbs, Lisa M. "Dietary vitamin B6 supplementation promotes the growth of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in Sprague Dawley rats." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/44023.

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In vitro data from our laboratory demonstrate that vitamin B6 (B6) supplementation of estrogen receptor - positive and - negative breast cancer cells is growth inhibitory. Others have reported that dietary B6 supplementation resulted in increased fibrosarcoma pyridoxal phosphate (PLP) concentrations and a significant inverse relationship between tumor PLP concentration and tumor volume in mice. This suggests that, in contrast to data reported for normal cells, tumor cells are capable of accumulating supplemental B6. In the current study, we investigated the effects of dietary B6 supplementation on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats. Specifically, we aimed to identify the effect of pyridoxine (PN) supplementation on tumor growth and vitamin uptake by tumor cells. To accomplish this, 50 d old female Sprague Dawley rats were gavaged with 15 mg DMBA and fed a diet containing either 7, 350, or 1050 mg PN-HCl/kg diet, which is the equivalent of 1, 50, or 150x the National Research Council's B6 requirement for rats, respectively. These levels of PN have previously been shown to produce no overt signs of toxicity in rats. Throughout the experiment, the percent of rats with tumors and the average number of tumors per rat remained similar between groups. Mammary tumor growth rates were significantly increased in response to dietary B6 supplementation (P < 0.05). Liver PLP and pyridoxal (PL) concentrations did not differ between dietary treatment groups. Plasma PL and PLP concentrations were significantly higher in the group fed the 150x diet compared with the 1x diet (P < 0.001, P < 0.05). Mammary tissue PL concentrations of the 150x group were significantly higher (P < 0.05) than the 1x group, but no differences were observed in mammary PLP concentrations. Similarly to mammary tissue, no differences between groups were observed in tumor PLP concentration. However, tumor PL concentrations in both the 50x and 150x dietary treatment groups were significantly higher than those from the rats fed the 1x diet (P < 0.002). These data demonstrate that previously reported inhibitory effects of supplemental B6 on breast cancer growth in vitro do not occur in response to dietary supplementation at 50 or 150 times the B6 requirement in vivo. In fact, dietary B6 at 150x the requirement may actually promote mammary tumor growth. In light of these results, investigation of the effects of supplemental B6 on cancer growth in humans is warranted. Supported by American Cancer Society Grant # IRG-99-225-01.
Master of Science
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29

Powell, Lisa. "Effects of various diets on vitamin B-6 and cholesterol levels in ten men aged 21-37." Virtual Press, 1990. http://liblink.bsu.edu/uhtbin/catkey/722433.

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Vitamin B-6 is a vitamin often promoted by the popular press as a cure all. It's role is also being studied in regard to pre-menstrual syndrome, myocardial infarction and alterations in lipid and fatty acid metabolism. This study was designed to investigate whether there was a difference between vitamin B-6 blood levels, during a baseline study, a period of vitamin B-6 depletion and vitamin B-6 supplemention in ten men ages 21-37. The effect of each diet on total cholesterol was also investigated.The experimentally accessible population for this study Laboratory as part of a larger study conducted by Dr. Stephen Coburn of the Fort Wayne State Developmental Center.Analysis of the data indicated:1) A significant difference between red blood cell pyridoxal phosphate and blood plasma levels of vitamin B-6 during the baseline, depletion and supplementation phases in ten men 21-37.2) Total serum cholesterol levels fell significantly through all phases of the study. High density lipoproteins fell significantly during the depletion phase but did not rise significantly during the supplementation phase. Low density lipoproteins showed no significant difference during the three phases of the study. When dietary records were evaluated mean dietary intake during the baseline and supplementation phases of the diet met the Recommended Dietary Allowance (RDA) for vitamin B-6. Mean protein intake also met the RDA with 102.1 grams during the baseline phase and 106.1 grams during the supplementation phase. These intakes are consistent with those found in previous studies conducted by the USDA. Mean intake of fat was lower than the 30 percent of calories recommended by the American Heart Association but wide variation existed among subjects.No physical symptoms of vitamin B-6 deficiency manifested themselves during the study. Subjects reported no other problems associated with low vitamin B-6 intakes.The data indicated that vitamin B-6 intake effects the amount of red blood cell plasma pyridoxal phosphate and plasma vitamin B-6. No clear effect can be found between vitamin B-6 intake and serum cholesterol levels. "Normal" diets also appeared to provide adequate vitamin B-6 to meet both RDA's and somatic needs. Wide variation seems to exist, however, among individuals.
Department of Home Economics
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30

Cowing, Brandy Ellen. "Vitamin B6 Decreases Proliferation and DNA Synthesis in Human Mammary Carcinoma Cell Lines In Vitro." Thesis, Virginia Tech, 2000. http://hdl.handle.net/10919/31644.

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The growth of many breast cancers is stimulated by the action of the hormone estrogen. Hormonal therapy used to treat these estrogen-dependent breast cancers acts by interfering with the action of estrogen. Current treatments, such as tamoxifen, are not consistently useful due to development of resistance to these drugs. Tamoxifen treatment can also lead to the development of other gynecological cancers, therefore the discovery of novel treatment options for breast cancer is critical. Vitamin B6 is well documented for its role as a modulator of steroid hormones. Pyridoxal phosphate (PLP), the active form of Vitamin B6, may interfere with the action of the estrogen receptor (ER) by blocking the hormone-binding and/or DNA-binding site of the ER. The objective of this study was to examine the effects of Vitamin B6 supplementation on cell proliferation and estrogen-dependent gene expression in breast cancer cells. To accomplish this, estrogen-dependent (MCF-7 and T-47D) and estrogen-independent (BT-20) breast cancer cells were grown in medium supplemented with 0,100, or 300 µM pyridoxal (PL) in the absence or presence of 0.01µM estradiol. Cell counts and [3H]-thymidine incorporation into DNA were assessed in all cell lines. The expression of pS2, an estrogen-sensitive gene, was performed using RNA extracted from MCF-7 cells. PL supplementation was found to significantly decrease total cell numbers and DNA synthesis in both the estrogen-dependent (ER+) and -independent (ER-) breast cancer cells, but did not alter the expression of pS2. These results indicate that PL significantly impairs growth of breast cancer cells and may be exerting its effects via a steroid-independent mechanism.
Master of Science
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31

Baumgart, Anna [Verfasser]. "Die Bedeutung von Vitamin B6-Defizienzen für ätiologisch ungeklärte Epilepsien des frühen Kindesalters / Anna Baumgart." Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/113823401X/34.

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32

Chan-Huot, Monique [Verfasser]. "Modeling the properties and function of the enzymic cofactor vitamin B6 by NMR / Monique Chan-Huot." Berlin : Freie Universität Berlin, 2011. http://d-nb.info/1025509943/34.

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33

Richts, Björn [Verfasser]. "Vitamin B6 metabolism and underground metabolic routes in the Gram-positive bacterium Bacillus subtilis / Björn Richts." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1237633621/34.

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34

Grün, Ingolf. "Determination of vitamin B-6, available lysine and pyridoxyllysine in a new instant baby food product." Thesis, Virginia Tech, 1989. http://hdl.handle.net/10919/45974.

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The purpose of this study was to compare the nutrient content of a new instant baby food product to jar baby food of similar product formulation. Instant and jar "Vegetable and Beef" and "Bananas" products processed in 1985 and 1987 were analyzed for available lysine, vitamin B-6 and pyridoxyllysine content.

The available lysine content of 100 grams of baby food was found to be higher in the instant products, but when adjusted for protein content, available lysine was higher in the jar products. This indicates that drum-drying used for the instant products is more detrimental in regard to lysine availability than retorting. The vitamin B-6 content of the instant products was found to be higher than that of the jar products. However, due to the addition of ingredients with little or no vitamin B-6 content to the jar products, no conclusion about processing effects on vitamin B-6 content can be made. Products processed in 1985 tended to be lower in nutrient content than the products processed in 1987. Pyridoxyllysine, a compound thought to affect vitamin B-6 bioavailability, could not be detected in any of the baby foods, either by amino acid or HPLC analysis.

The instant products were found to be at least equal to the jar products with regard to available lysine and vitamin B-6 content. All products also appear to provide sufficient amounts of these nutrients to infants less than one year of age.


Master of Science
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35

Beg, Mohammed Asim. "Host-parasite relationships in vitamin B6 deficient cotton rats (Sigmodon hispidus) infected with Litomosoides carinii (Nematoda, filarioidea)." Thesis, University of Salford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386552.

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36

Yamamura, Ei-tora. "Biochemical and molecular biological studies on enzymatic synthesis of vitamin B6 derivatives and optically active carboxylic acids." Kyoto University, 2020. http://hdl.handle.net/2433/245820.

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Kyoto University (京都大学)
0048
新制・論文博士
博士(農学)
乙第13305号
論農博第2880号
新制||農||1074(附属図書館)
学位論文||R2||N5242(農学部図書室)
富山大学大学院理工学研究科生命環境科学専攻
(主査)教授 小川 順, 教授 阪井 康能, 教授 栗原 達夫
学位規則第4条第2項該当
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37

Rosenberg, Jonathan. "Vitamin B6 Production in Bacillus subtilis." Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E32C-B.

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38

Rueschhoff, Elizabeth Ellen. "Vitamin B6 metabolism in Arabidopsis thaliana." 2009. http://www.lib.ncsu.edu/theses/available/etd-09032009-121530/unrestricted/etd.pdf.

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39

Chen, Wen-shan Chou 1964. "Effect of glycosylated vitamin B-6 intake on the excretion of vitamin B-6 in women." Thesis, 1992. http://hdl.handle.net/1957/27185.

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The effect of dietary glycosylated vitamin B-6 on the bioavailability of vitamin B-6 was determined in 4 women. A 44-d metabolic-balance diet study was divided into a preliminary 8-d adjustment period followed by two 18-d experimental periods. The subjects were divided into two groups in a crossover design to compare the effect of low- and high-glycosylated vitamin B-6 diets on the bioavailability of vitamin B-6. The total vitamin B-6 content in the low- and high-glycosylated vitamin B-6 diets was 1.506 mg (8.91 nmol) and 1.897 mg (11.22 μmol), respectively, in which 11 and 22% was the glycosylated form, respectively. Daily 24-h urine specimens were collected by each subject throughout the study; 7- or 8-d fecal collections were made at the end of each experimental period. The four subjects' mean urinary total vitamin B-6 excretion during the low- and high-glycosylated vitamin B-6 periods was 0.76 ± 0.20 and 0.67 ± 0.06 μmol/24 h, respectively; fecal total vitamin B-6 excretion was 2.98 ± 0.43 and 4.56 ± 0.87 μmol/24 h, respectively. Expressed as % of total vitamin B-6 intake, the mean urinary total vitamin B-6 excretion was lower during the high-glycosylated vitamin B-6 period (6.0 ± 0.8%) than during the low-glycosylated vitamin B-6 period (8.5 ± 2.4%); in contrast, their mean fecal vitamin B-6 excretion during the high-glycosylated vitamin B-6 period (40.7 ± 8.2%) was greater than the low-glycosylated vitamin B-6 period (33.6 ± 5.4%). In addition, approximately 11% of ingested glycosylated vitamin B-6 was excreted in urine. These results suggest that dietary glycosylated vitamin B-6 is not completely bioavailable to humans, and the extent of its utilization is not affected by dietary glycosylated vitamin B-6 intake.
Graduation date: 1993
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40

Ju, Hsiao Li, and 蕭莉茹. "Vitamin B6 intakes and status to evaluatethe vitamin B6 requirement of 13-18 years-aged adolescents in Tainan." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/10768447157720788288.

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碩士
國立成功大學
生物學系
90
Abstract The characteristic growth rate in adolescence raises requirement for nutrients, thus affecting the nutritional status, especially of vitamin B6 due to its role in the protein metabolism. Studies regarding vitamin B6 status are limited in Taiwan. None was conducted for the adolescents. Therefore, the purpose of this study was to evaluate the vitamin B6 requirement of adolescents aged 13-18 years in Tainan. The subjects participating in the study were 146 boys and 145 girls (a total of 291) who were recruited by stratified random sampling from 27 middle schools and 19 high schools. Daily intakes of vitamin B6 and protein were analyzed according to the 3-day dietary record including 2 weekdays and 1 weekend day. Plasma concentrations of pyridoxal-5-phosphate (PLP) and 24-hrs of urinary 4-pyridoxic acid (4-PA) excretion were analyzed by HPLC. Erythrocyte transaminases activity coefficients (EALT-AC and EAST-AC) were also analyzed. Anthropometric measurements of adolescents (height, body weight, midarm circumference and body fat percentage) were collected by a trained technical people. Recommendations for vitamin B6 intakes were suggested on the basis of the effects of vitamin B6 intake on plasma PLP, EALT-AC, EAST-AC and urinary excretion of adolescents. The Estimated Average Requirements (EAR) for vitamin B6 were determined and the Recommended Dietary Allowance (RDA) for vitamin B6 were calculated according to the methodology of Dietary Reference Intakes (RDIs). Anthropometric measurements of 291 adolescents in this study were similar to or slightly higher than those of NAHSIT (Nutrition and Health Survey in Taiwan) 1993-1996, indicating the normal growth and development. Among these, 230 (110 boys and 120 girls) completed the dietary and biochemical study. All subjects had plasma PLP > 20 n mol/L. Urinary 4-PA ≦3 mmol/ day were observed in 5.00 ﹪boys and 12.00 ﹪girls. EALT-AC≧1.25 were observed in 20.00 ﹪boys and 28.00 ﹪girls. EAST-AC≧1.80 were observed in 24.00 ﹪boys and 40.00 ﹪girls. These values are considered indicatives of vitamin B6 inadequacy. Mean daily intakes of energy, protein and vitamin B6 were significantly higher in boys than girls. Plasma PLP concentration and urinary 4-PA excretion of the boys were significantly higher than the girls. The percentages of inadequacy for EALT-AC and EAST-AC were significantly higher in girls than in boys. Mean daily intakes of energy and protein did not differ significantly between 13-15 and 16-18 years aged groups. Mean daily intake of vitaminB6 for 16-18 years was significantly higher than 13-15 years-aged. Plasma PLP concentration did not differ significantly between 13-15 and 16-18 years aged groups. Urinary 4-PA excretion of the adolescents aged 16-18 years was significantly higher than that of 13-15 years-aged. The percentages of inadequacy for EALT-AC and EAST-AC of 13-15 years were significantly higher than those of 16-18 years-aged. In conclusion, vitamin B6 status of adolescents aged 13-18 years showed the inadequacy in the short-term intakes of vitamin B6 reflected by the inadequate urinary 4-PA excretion observed in 5-12 % of adolescents in this study. All subjects had plasma PLP >20 n mol/L indicating that vitamin B6 intakes were adequate to meet physiological metabolism within 7-10 days. However, vitamin B6 status was suggested to be inadequate for long-term (6-8 wks) due to the high percentages (20-40%) of inadequacy for EALT-AC and EAST-AC. The Estimated Average Requirements for vitamin B6 which of satisfy biochemical indicators in plasma, erythrocyte and urine were determined and used to calculate Recommended Dietary Allowances (RDAs) by multiplying 120%. This study suggested that RDAs for vitamin B6 were 1.20 mg and 1.28 mg for boys aged 13-15 and 16-18 years, respectively. The RDAs for vitamin B6 were 1.04 mg and 1.16 mg for girls aged 13-15 and 16-18 years, respectively.
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41

Hou, Hui-Ching, and 侯慧卿. "Inflammation alters vitamin B6 metabolism in vivo." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/p9z4pf.

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碩士
國立中興大學
食品暨應用生物科技學系所
102
Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease with unclear etiology and pathogenesis. Pyridoxal 5’-phosphate (PLP) is the major B6 vitamins form, and a variety of disease conditions have repeatedly been found to be associated with low levels of plasma PLP. Inverse associations have been shown between plasma PLP and biomarkers of human inflammation. Collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AA) rats are commonly used as models for studying human with rheumatoid arthritis (RA). The objective of the present study is to investigate vitamin B6 metabolism during inflammation in vivo. Twenty-two 6-week-old female Lewis rats were housed in individual IVC cages under pathogen-free condition on a 12-hour day/night cycle and fed with the AIN93M diet during the experimental period. Arthritis was induced at the age of 10-week and were sacrificed at the age of 15-weeks during chronic inflammation. The volume of paw significantly increased in both AA and CIA groups during inflammation while body weight significantly decreased. Arthritis induction did not alter 24-hour urinary excretion of vitamin B6 in both models. However, inflammation resulted in drastic alterations in vitamin B6 in both liver and certain extra-hepatic tissues except for the spleen. The lower circulating plasma PLP levels observed in the CIA group reflected a decrease in hepatic PLP contents, as a positive correlation was observed between the two (r=0.731 p=0.039, n=8). The mechanism by which arthritis causes vitamin B6 mobilization during inflammation is under investigation.
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42

Chang, Hsin-Yueh, and 張馨月. "Vitamin B6 status and metabolism in rheumatoid arthritis." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/38806691068629835441.

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博士
國立中興大學
生物科技學研究所
99
Rheumatoid arthritis (RA) has been related with low vitamin B6 status and impaired vitamin B6 function. Three enzymes are involved in the metabolism of vitamin B6 in different tissues. These enzymes are pyridoxal (pyridoxamine, pyridoxine) phosphate phosphatase (PDXP), pyridoxal (pyridoxamine, pyridoxine) kinase (PDXK) and pyridoxine (pyridoxamine) phosphate oxidase (PNPO). There is the possibility that inadequate vitamin B6 levels in RA patients might be result from abnormal vitamin B6 metabolism. The purpose of this study is to examine these enzymes expression in vitamin B6 metabolism and disclose the relationships between these enzymes and vitamin B6 levels in circulating and tissues. In human study, we investigated the plasma and erythrocyte B6 levels in RA patients and controls. Hepatic PDXP gene expressions and hepatic PDXK enzyme activity in animals were affected by prednisolone treatment. In addition, plasma B6 levels were affected in mice by long-term prednisolone treatment. Furthermore, prolonged nonsteroidal antiinflammatory drugs (NSAIDs) treatment attenuated hepatic, kidney and erythrocyte B6 levels in animals. Moreover, it should be concerned about long-term NSAIDs use because their adverse effect on attenuating vitamin B6 status.
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43

D'ALESSIO, FEDERICO. "Regulation of vitamin B6 metabolism in Escherichia coli." Doctoral thesis, 2020. http://hdl.handle.net/11573/1470147.

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The catalytically active form of vitamin B6, pyridoxal 5'-phosphate (PLP), acts as a coenzyme in a variety of different enzymatic reactions. PLP is essential for the normal growth and development of all the organisms, but only plants and microorganisms can synthetise it de novo, while the other organisms must recycle it from nutrients. The PLP is a very reactive molecule thanks to its aldehyde group and its intracellular concentration must be kept low to avoid undesired toxic reaction in the organism. The regulation of the free PLP concentration in cells occurs through a variety of mechanism, such as its dephosphorylation to PL or, as recently discovered, through the binding to PLP Binding Protein. In Escherichia coli an important candidate for this role has recently been discovered: YggS is a non-catalytic protein able to bind PLP. It belongs to the COG0325 family, a class of protein sharing structure homology with PLP-dependent enzymes, such as alanine racemase and some decarboxylases that have the same Fold-type III. The metabolism of PLP in E. coli has been studied for years. In this work, our group have deepened the regulation of the PLP metabolism, studying and elaborating the state of the art, and crossing the available literature data with those produced in our lab about the regulation of the expression of the genes involved in PLP homeostasis and focusing the analysis on the most important genes. Our studies have also analysed in vivo the phenotypes linked to the genes involved in PLP homeostasis when E. coli is grown in different media and in presence of vitamers, in order to better understand the role of the analysed genes. The study has also considered the expression of the genes involved in PLP homeostasis in presence of vitamin B6 vitamers and during different growth phases. Finally, given the importance of the gene yggS in E. coli, the attention was focused on the characterization of the protein YggS, whose role has not yet been discovered. This protein is hypothesised to be both a PLP binding protein and a carrier of this important cofactor to the apo PLP-dependent enzymes. Our studies were focused on YggS capacity to bind PLP and, using mutant forms of this protein, we have verified and studied the transfer mechanism of PLP to the apo PLP-dependent enzymes.
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44

MASCOLO, Elisa. "Relationship between Vitamin B6, DNA damage and diabetes." Doctoral thesis, 2021. http://hdl.handle.net/11573/1531464.

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The active form of vitamin B6, the pyridoxal-5’ phosphate (PLP) is a cofactor for more than 150 reactions involved in protein, carbohydrate and lipid metabolism. In addition, it is able to counteract Reactive Oxygen Species (ROS) and Advanced Glycation End products (AGEs). In eucaryotes PLP is produced, in the salvage pathway, by the concerted action of pyridoxal kinase (PDXK) and pyridoxamine/pyridoxine oxidase (PNPO) which recycle PLP precursor from food. PLP has been associated to different pathologies including diabetes and cancer although underlying mechanisms remain in large part still unknown. It has been previously demonstrated that mutations in Drosophila Pdxkgene (dPdxk1) cause diabetes and chromosome aberrations (CABs) and also that these phenotypes are linked by a causeeffect relationship. The first aim of this thesis has been to verify whether also the inactivation of the other gene of the salvage pathway, PNPO, encoded by sgll gene, produced the same phenotypes observed in dPdxk1 mutants. To this purpose we silenced sgll gene by RNA interference and characterized the resulting phenotypes. This analysis revealed a significant frequency of CABs and diabetic phenotypes such as hyperglycemia, small body size, impaired lipid storage and accumulation of AGEs associated to Sgll depletion. These results allowed us to confirm the hypothesis that PLP deficiency produces CABs through the genotoxic effect of AGEs in turn triggered by high glucose. Our second aim has been to investigate whether human PDXK variants present in the population can impact on DNA integrity and can be considered predictive of cancer risk. For this purpose, we expressed four human PDXK variants (carrying missense mutations) into dPdxk1 mutant flies and tested them for CABs as well as for diabetic phenotypes, finding that none of them was able to completely rescue the CAB phenotype, hyperglycemia nor AGE accumulation. Biochemical analysis of these variants revealed a compromised catalytic activity and/or a reduced affinity for their substrates, which explained their “loss of function” behaviour. These results suggested that mutations in PDXK human gene can impact on genome integrity via AGEs and predispose to cancer. Our third purpose was to test whether low PLP levels can impact on cancer in Drosophila. Thus we tested the effects of the PLP inhibitor 4-deoxypyridoxine (4-DP) on Ras and Ras/Scr cancer models generated by mosaic analysis with repressible marker (MARCM) strategy. This analysis showed that 4-DP caused enlargement of primary tumors as well as appearance of secondary tumors in both cancer models. Taken together all the results collected in this work have contributed to confirm and elucidate the relationship between vitamin B6 diabetes and cancer.
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45

Sindihebura-Ruhumba, Pascaline. "Effect of controlled vitamin B-6 intake and pyridoxine supplementation on B-6 status of smokers." Thesis, 1999. http://hdl.handle.net/1957/27213.

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Previous studies have found that smoking may have a negative effect on vitamin B-6 indices and have demonstrated a possible association between smoking and depressed plasma pyridoxal-5'-phosphate (PLP) concentration. Individuals with plasma PLP values below the adequate level of 30 nmoles/L might benefit from consumption of vitamin B-6 supplements, but no data are available on vitamin B-6 status in smokers consuming a controlled vitamin B-6 intake and receiving a vitamin B-6 supplement. The objectives of this research were to assess vitamin B-6 status in smokers as compared to non-smokers receiving a controlled diet and to evaluate the effect of an oral vitamin B-6 supplementation in these subjects. The vitamin B-6 (B-6) status of 5 (four males / one female) smokers (S) and 4 (three males / one female) non-smokers (NS) was assessed. A constant diet was fed for 20 days and provided 1.95 mg of B-6 or 1.65 mg of B-6 for males and females, respectively. For the last 10 days, an additional 2-mg of pyridoxine (PN) was given daily. Blood samples were collected on days 1.7, 11.14 and 21; and 24 hour urine samples were collected daily. Urinary 4-pyridoxic acid (4-PA) and total B-6 (UB6) excretion, plasma B-6 vitamers (PLP, PN, pyridoxal and 4-PA) and red blood cell PLP (RBC PLP) concentrations, as well as plasma alkaline phosphatase activity (APA) were determined. Mean plasma PLP, 4-PA, and RBC PLP concentrations were significantly lower (P [less than or equal to] 0.05) at all time points in S compared to NS. With a daily supplement of 2-mg vitamin B-6, the mean plasma PLP concentration of S increased 85.8% but was 48.5% lower than that of NS consuming 1.65-1.95 mg/d of B-6. Mean plasma pyridoxal concentrations were not different between S and NS before and after supplementation. Excretion of 4-PA was not significantly different between S and NS, but the mean values of 4-PA excretion were consistently greater in NS compared to that of S throughout the 20-day study. The percent of ingested B-6 excreted as 4-PA for the S and NS was 38 and 49 in the non-supplemented period, and 47 and 53 in the supplemented period, respectively, indicating that non-smokers excreted more 4-PA than smokers. However, the difference in 4-PA excretion between S and NS was not significantly different both before and after supplementation (P>0.05). In addition, there was no significant difference between S and NS for plasma PN concentration, AP, and UB6 excretion for both periods. Results suggested an adverse effect of smoking on B-6 metabolism, thus an increased requirement of vitamin B-6 in smokers. A 2-mg PN supplement was sufficient to bring the concentration of plasma PLP in smokers to the level suggested as adequate, but it didn't bring it to the level of non-smokers.
Graduation date: 1999
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46

Witzinger, Linda. "Rolle der Pyridoxal 5´-Phosphat Phosphatase PDXP im Vitamin B6-Metabolismus muriner Erythrozyten und Hippocampi." Doctoral thesis, 2020. https://doi.org/10.25972/OPUS-21654.

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Die Phosphatase PDXP (auch bekannt als Chronophin) gehört zur Familie der HAD Phosphatasen, einer ubiquitär exprimierten Enzymklasse mit wichtigen physiologischen Funktionen. PDXP zeigt Phosphatase-Aktivität gegenüber seinem Substrat Pyridoxal 5´-Phosphat (PLP), der aktivierten Form von Vitamin B6. PDXP-defiziente Mäuse (Knockout-Mäuse) weisen im Vergleich zu Wildtypen verdoppelte PLP-Konzentrationen in Erythrozyten sowie im Gesamthirn auf. Vermutlich kommt PDXP daher eine wichtige Funktion in Erythrozyten und im Hirn zu. Ziel dieser Arbeit war es, erste Einblicke in diese Funktion(en) von PDXP zu erlangen. Hierzu wurden HPLC-basierte Analysen der erythrozytären PLP-Konzentrationen in Wildtyp- sowie PDXP-defizienten Mäusen durchgeführt. Dabei ließen sich die rund doppelt so hohen erythrozytären PLP-Level in den KO-Mäusen bestätigen. Zudem ist es gelungen, eine Methode zur Messung der endogenen Phosphatase-Aktivität von PDXP in Erythrozytenlysaten zu etablieren. So konnte im Wildtyp anhand der Verringerung der PLP-Konzentrationen pro Zeiteinheit eine erythrozytäre PDXP-Aktivität nachgewiesen werden. Dazu waren die Inkubation mit Pyridoxin, sowie die Anwendung eines Inhibitors der PDXK notwendig. Eine bis dato vermutete Funktion der PDXP, zur Mobilisation von erythrozytärem PLP während Fastenzeiten, konnte ausgeschlossen werden. So zeigte der Vergleich der erythrozytären PLP-Konzentrationen aus gefasteten mit normal gefütterten Tieren in beiden Genotypen exakt dieselbe prozentuale PLP-Verringerung. Während Nahrungszufuhr ließ sich jedoch eine Funktion der Phosphatase PDXP als „Converter“ von Pyridoxin zu Pyridoxal erkennen. Ausgehend von PN konnte im Wildtyp (über die Zwischenprodukte PNP und PLP) eine PDXP-abhängige Dephosphorylierung von PLP zu PL erfolgen. So wies der Wildtyp eine rund vierfach höhere PL-Produktion auf, verglichen mit der PDXP-defizienten Maus. Die Phosphatase PDXP erwies sich als essenziell für die erythrozytäre Konversion von Pyridoxin zu Pyridoxal. Dadurch erreicht der Organismus eine metabolische Flexibilität, die ihn bis zu einem gewissen Grad unabhängig von der Nahrungsauswahl macht. Zudem können Zellen oder Organe, denen durch das Fehlen der PNPO, die Konversion zu PLP nicht möglich ist, mit PL versorgt werden. Aus der hohen Reaktivität von PLP mit umliegenden Nucleophilen ergibt sich eine gewisse Problematik für die Zelle im Umgang mit freiem PLP. So liegt der Großteil des erythrozytären PLPs gebunden an Proteine (vor allem Hämoglobin) vor. Anhand von Filtern (MWCO, 3000) ließ sich zwischen der hier definiert als „freien“ und der „gebundenen“ Form von PLP differenzieren. So konnten erste Erkenntnisse zur Rolle von PDXP als Determinator freier PLP-Konzentrationen in Erythrozyten und insbesondere im Hippocampus erlangt werden. Im Hippocampus ergaben sich insgesamt deutlich höhere Konzentrationen an freiem PLP als in den Erythrozyten und es bestand zudem ein Unterschied zwischen den Genotypen. So wiesen die KO-Mäuse ~1/3 höhere freie PLP-Konzentrationen im Vergleich zu den Wildtypen auf. Schließlich konnte ein Effekt des Tieralters auf den PLP-Metabolismus festgestellt werden. Sowohl in den Erythrozyten als auch im Hippocampus ergaben sich alterskorrelierte Änderungen ihrer PLP-Konzentrationen. Zudem zeigten Western Blot Analysen altersbedingte Unterschiede ihrer Vitamin B6-Enzymexpressionen. So wiesen ältere Wildtypen im Hippocampus eine fünffach erhöhte PDXP-Expression verglichen mit jüngeren Tieren auf. In den Erythrozytenlysaten hingegen zeigten ältere Tiere beider Genotypen eine rund vierfach geringere PNPO-Expression gegenüber jüngeren Tieren. Die mit dem Alter eintretende physiologische Verringerung der erythrozytären PNPO-Expression würde somit für den Organismus einen Verlust seiner metabolischen Flexibilität bedeuten, die mit der Konversion von PN zu PL einhergeht
The phosphatase PDXP, also called Chronophin, is a member of the ubiquitously expressed HAD-phosphatases, which have some important physiological functions in the organism. Its substrate pyridoxal 5´-phosphate (PLP) is the active form of vita-min B6, an important cofactor of several reactions. PDXP-deficient mice (KO-mice) have PLP-concentrations in erythrocytes and in the whole brain twice as high as wildtype mice. It is assumed that PDXP therefore has an important function in erythrocytes and in the brain. The aim of the study was to gain initial insights into these functions of PDXP. For this purpose, HPLC-based analyses of the PLP-concentrations in erythrocytes from WT- and KO-mice were carried out. The doubled PLP-levels in the RBCs of KO-mice could be confirmed. In addition, a method for measuring the endogenous phosphatase activity of PDXP in red cell lysates was established. The activity of PDXP could be measured by the reduction of its substrate PLP over time. This required the incubation with pyridoxine and the inhibition of PDXK by ginkgotoxine. An assumed function of PDXP in mobilization of PL(P) from the erythrocytes in fasting conditions could be ruled out. Therefore, a comparison between the PLP-concentrations in RBCs of fasted mice with normal fed ones was done. Surprisingly the fasted KO-mice showed the same percentaged decrease of cellular PLP-level as the fasted WT-mice. During vitamin B6 intake however, a function of PDXP as being a “converter” of pyridoxine to pyridoxal was found. Starting with PN, a PDXP-mediated dephosphorylation from PLP to PL could take place in the wildtype mice (via the intermediate steps PNP and PLP). Consequently, the WT´s production of PL quadrupled compared to the KO´s. PDXP turned out to be essential for the conversion of pyridoxine to pyridoxal in erythrocytes. This conversion confers some metabolic flexibility to the organism and to a certain extent makes it independent of the choice of food. Moreover, cells and organs, that due to the absence of PNPO cannot produce PL(P) themselves, can be provided via erythrocytes. The high reactivity of PLP with surrounding nucleophiles poses a certain problem for the cell in dealing with free PLP. The majority of the PLP in RBCs is bound to proteins (primarily hemoglobin). It was distinguished between the here termed “free” PLP and the bound PLP by using filter devices with a MWCO at 3 kDa. First insights could be gained about PDXP as a determinant of free PLP-levels in erythrocytes and hippocampus. The amount of free PLP in the hippocampus was significantly higher than in the RBCs. Additionally, the hippocampus showed some differences in the con¬centration of free PLP between WT- and KO-mice. The level of free PLP in PDXP deficient mice was one third higher than in wildtype mice. Finally, some correlation between the age of the mice and their PLP-metabolism was found. The results revealed changes of the PLP-concentrations with age in the RBCs and the hippocampus. Moreover, western blot analyses showed some age-related differences in the expression of vitamin B6 enzymes. In the hippocampus older wildtype mice showed a quintupled expression of PDXP compared to younger ones. However, western blot analyses of red blood cell lysates from older animals revealed a lower expression of PNPO by a factor of four. For the organism this physiological reduction of its PNPO expression with age would mean a loss of metabolic flexibility, that is accompanied by the conversion from PN to PL
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47

Lin, Sang-Chu, and 林桑竹. "Effects of Glutamine on Vitamin B6 Biosynthesis in Arabidopsis thaliana." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/92987756308143317370.

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碩士
國立臺灣大學
植物科學研究所
104
Glutamine is one of the most abundant free amino acids in plants. As the first organic nitrogen from primary nitrogen assimilation, glutamine is a major amino donor for the synthesis of amino acids, nucleotides, and other nitrogen-containing compounds. We showed that glutamine could efficiently support Arabidopsis growth when used as a sole nitrogen source in the growth medium, but the addition of excess glutamine significantly inhibited Arabidopsis growth. We thus used appropriate glutamine concentration as sole nitrogen source to screen for “glutamine hypersensitive” mutants. One of the mutants, line 23844/pdx3-3, had dramatically reduced root growth, irregular cell arrangement, less cell proliferation and abnormal cell death in glutamine-containing medium. Line 23844 is defective in At5g49970 that encodes pyridoxine/ pyridoxamine phosphate oxidase (PDX3) of the vitamin B6 salvage pathway. The mutant has a point mutation that changes Gln226 to a stop codon. In addition to the mutant, we have obtained the genetic complementation line and PDX3 gene silencing lines that show similar phenotypes. These results suggested that the growth defects in 23844 are caused by loss-of-function in the PDX3 gene. sos4 (salt overly sensitive 4), another mutant involved in vitamin B6 salvage pathway, had similar phenotypes with pdx3-3, and pdx3-3/sos4 double mutant had more severe phenotypes. Furthermore, by analysis vitamin B6 contents in pdx3-3 and sos4, we found abnormal vitamin B6 levels in mutants. These data indicated that defects in vitamin B6 salvage pathway might result in glutamine hypersensitive phenotypes. Nevertheless, the functions of PDX3 and the vitamin B6 salvage pathway are not well understood in plants. We will further study the relationship between glutamine and vitamin B6 salvage pathway, and the regulation of vitamin B6 homeostasis.
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48

Bills, Nathan D. "In vivo and in vitro determination of the bioavailability of vitamin B-6 from plant foods containing pyridoxine glucoside." Thesis, 1990. http://hdl.handle.net/1957/25980.

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49

Kwak, Ho-Kyung. "Effect of varying levels of vitamin B-6 intake on lymphocyte mitogenic response and vitamin B-6 concentration in human peripheral blood mononuclear cells." Thesis, 2001. http://hdl.handle.net/1957/26568.

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Two studies were conducted to determine the effect of varying vitamin B-6 (B- 6) status on lymphocyte mitogenic response and pyridoxal 5'-phosphate (PLP) concentration in peripheral blood mononuclear cells (PBMC) in young women. In the first study, women were fed 1 mg/d for the first week and 1.5, 2.1 and 2.7 mg/d during 2 weeks of each of the subsequent 3 experimental periods. Plasma PLP and urinary 4: pyridoxic acid (4-PA) were increased with increasing B-6 intake. B-6 intake > 2.1 mg significantly enhanced lymphocyte proliferation, and non-significantly increased plasma interleukin-2 concentration. Lymphocyte proliferation was significantly correlated with B-6 intake, erythrocyte aminotransferase activity coefficients and plasma PLP. PBMC PLP tended to increase after 2 weeks of 2.7 mg B-6 intake, and was significantly correlated with plasma PLP. In the second study, women consumed their normal diets whose estimated mean dietary B-6 intake was 0.9 mg for 27 d. For the last 20 d, all subjects were given a multivitamin supplement containing 1.8 mg B- 6, and half of the subjects were given an additional 50 mg of B-6 supplement. Plasma PLP and urinary 4-PA were significantly higher in the group with 50 mg B-6, but lymphocyte proliferation did not significantly differ between the groups. After 10 d of supplementation, lymphocyte proliferation was significantly higher than the other time points. A significant increase in PBMC PLP was observed after 3 days and 20 days following 50 mg and multivitamin supplementation only, respectively. After 20 days of supplementation, there was no significant difference of mean PBMC PLP between the groups. PBMC PLP was significantly correlated with plasma PLP, PL and 4-PA. In both studies, no strong relationship was found between PBMC PLP and lymphocyte proliferation. The findings from these studies demonstrate no further benefit of a higher B-6 intake than 2.1 mg on lymphocyte mitogenic response, once the response was significantly enhanced with B-6 intake 0.8 mg higher than the current recommendation. Finally, results from two studies suggest that the current recommendation of vitamin B-6 for young women may not be adequate to maximize lymphocyte mitogenic response and PLP concentration in PBMC.
Graduation date: 2002
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50

Hansen, Christine M. 1953. "Effect of vitamin B-6 intake, protein intake and bioavailability on vitamin B-6 status for women." Thesis, 1995. http://hdl.handle.net/1957/27152.

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Four studies were conducted to evaluate the effect of varying levels of vitamin B-6 (B6), protein and pyridoxine glucoside (PNG) on B6 status and requirements of women. In the first two studies, women were fed a constant protein diet and vitamin B-6 intakes of 0.84 to 2.39 mg/d during 10- to 15-day experimental periods. Significant differences among intake levels were found in urinary 4-pyridoxic acid (4PA) and total vitamin B-6 (UB6), plasma pyridoxal 5'-phosphate (PLP) and total vitamin B-6 (TB6), and urinary xanthurenic acid (XA) following a tryptophan load. Significant correlations were found between B6 intake and 4PA, UB6, plasma PLP, TB6, erythrocyte alanine aminotransferase (EALT) percent stimulation, and postload urinary XA and volatile amines (VA, kynurenine plus acetylkynurenine). More than 1.33 mg B6/d (> 0.016 mg B6/g dietary protein) was required for adequate B6 status. In a third study, nine women were fed diets providing 1.25 mg B6/d and three levels of protein (0.5, 1.0 and 2.0 g/kg body weight), for 14 days each. Significant differences in urinary 4PA, plasma PLP, and postload urinary VA were found among protein levels. Nitrogen intake was significantly negatively correlated with urinary 4PA and plasma PLP, and positively correlated with EALT percent stimulation and postload urinary kynuremc acid (KA), XA and VA. Compared to men in a previous study, women excreted a greater percentage of B6 intake as 4PA, had lower plasma PLP and greater amounts of postload urinary tryptophan metabolites. At least 0.020 mg B6/g protein was required for adequate status. In a fourth study, nine women were fed diets with a high (27%) or low (9%) percentage of the B6 intake as pyridoxine glucoside, a form known to have reduced bioavailability, for 18 days each. Urinary 4PA and UB6, plasma TB6 and red blood cell PLP were significantly lower, and fecal B6 was significantly higher during the high PNG diet. The decrease in B6 status indicators on the high PNG diet suggested a loss of 15 to 18% of the total B6 intake. Taking into account bioavailability and gender differences in the effect of dietary protein, and including a safety margin, the RDA for B6 for women should be at least 0.020 mg/g dietary protein.
Graduation date: 1996
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