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.

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.

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

Made available in DSpace on 2014-12-17T14:05:22Z (GMT). No. of bitstreams: 1 LeonamGC_TESE.pdf: 2406262 bytes, checksum: 604659dd8ff62335f952679dda971b6e (MD5) Previous issue date: 2013-03-19 / 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 / 2020-01-01 / 2020-01-01

Made available in DSpace on 2015-04-17T15:03:00Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 925146 bytes, checksum: 6a5a1d5bf083b5c0885403bb087cc93a (MD5) Previous issue date: 2013-03-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / 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.

No description available.

The effect of vitamin B-6 (B-6) status on plasma fatty acids (FA) levels and lipid metabolism was investigated in this metabolic study. Eight female subjects were fed for 28 days. For the first 7 days, they were fed a constant diet containing 2.10 mg of B-6. For the rest of the period (21 days), they were differentiated in terms of B-6 intake; 4 of them were fed a low (0.93 mg/day) and 4 a high (2.60 mg/day) B-6 diet. B-6 status indices, plasma FA concentration and lipid profile were determined. Plasma pyridoxal 5'-phosphate and total B-6 concentration (P<0.01), urinary 4- pyridoxic acid and total B-6 concentration (P<0.001) showed a significant difference between the two groups at the end of the study. Erythrocyte PLP failed to show any significant difference between the two groups throughout the diet study. There was no significant difference in the plasma FA or lipid profile between the two groups. Plasma total cholesterol (TC) of the low B-6 group decreased slightly (7 %), but was not statistically significant. When comparing day 7 and day 28 values, plasma triglycerides increased (9 %) for the high and decreased for the low B-6 group. LDL-C decreased (5 %) for the high B-6 group but did not change in the low B-6 group. HDL-C decreased slightly in both groups (~8 %). There was no clear evidence that a low intake of vitamin B-6 affects the fatty acid and lipid metabolism. Further studies are required to identify the relationship between vitamin B-6 and fatty acid and lipid metabolism in humans. / Graduation date: 1997

Research suggests that, in individuals with carpal tunnel syndrome (CTS), low plasma pyridoxal 5'-phosphate (PLP) concentrations are related to an increased incidence and severity of symptoms associated with CTS. This study was designed to determine the relationship between plasma and red blood cell PLP concentrations and the severity and incidence of CTS symptoms. Thirty people with CTS were selected for a 9 month exercise study. Subjects were divided into either vitamin users or non-vitamin users based on supplement use data gathered at the beginning of the study. Blood was drawn at 1, 6 and 9 months. CTS symptoms questionnaires and health questionnaires were also administered at these intervals. The symptoms questionnaires were used to gather data on the frequency and nature of hand and wrist symptoms. Health questionnaires focused on vitamin supplement usage including frequency, amount and length of use. Mean plasma PLP, total plasma vitamin B6 and erythrocyte PLP concentrations were significantly higher in the sixteen vitamin users when compared to the fourteen non-vitamin users (p<0.001). While there was variation in plasma PLP and total plasma vitamin B6 over time, within each group, there were no significant changes in any of the status measures over the nine month period. Mean erythrocyte PLP concentration, in particular, was stable over time. In vitamin users, the intensity of pain, numbness and tingling was significantly higher when compared to non-vitamin users. In both groups, plasma PLP was negatively correlated with pain. This correlation reached statistical significance in vitamin users at month one and nine (p<0.01), but not at month six; a statistically significant correlation between these two variables was not found in non-vitamin users at any time point. Pain was also negatively and significantly correlated with plasma total vitamin B6 and erythrocyte PLP in vitamin users. No other symptoms were significantly correlated with the status measures. These results indicate that a higher vitamin B6 status may be related to a decrease in the severity of pain experienced by some individuals with CTS. / Graduation date: 1998

The purpose of this study was to examine the effect of extreme exercise on vitamin B-6 metabolism and urea nitrogen. Nine men and five women completed two 5-day trials; Trial 1 (T1) included a 50-km ultramarathon on day 4 and during Trial 2 (T2) subjects were "inactive" on day 4. During both trials, subjects consumed a diet providing men 2.0 and women 1.5 mg of vitamin B-6. With the exception of the ultramarathon, T1 activity was replicated during T2. Twenty four-hour urine collections were completed and blood was drawn pre-race (pre), mid-race (mid), post-race (post) and 60 minutes post race (P-60). On the inactive, day blood was drawn at the same intervals. Plasma was analyzed for pyridoxal 5'-phosphate (PLP), pyridoxal, 4-pyridoxic acid (4-PA), urea nitrogen (PUN), creatinine, albumin, glucose, and lactate concentration and alkaline phosphatase activity. Urine was analyzed for 4PA, creatinine, and total urinary nitrogen (TUN). During T1, compared to pre, plasma PLP concentration increased 17% at mid, decreased 5% by post, and 19% by P-60. During T2, plasma PLP concentration decreased 13% pre to P-60. During T1, plasma 4-PA concentration increased 135% and the percent dietary vitamin B-6 that was excreted as urinary 4-PA the day of the ultramarathon was higher than that excreted the day before and the day after. During T1, from pre to post mean PUN concentration increased 36.9%, and the average rate ofincrease from pre to mid, mid to post, and post to P60 was 0.5, 1.75, and 2 mg/dL/hour, respectively. During T1 on days 3, 4, and 5,88%, 100%, and 95% of nitrogen intake was excreted in the urine compared to 86%, 83%, and 84% for the same days during T2. The day of the ultramarathon, 24-hour TUN excretion was 2 g higher than the previous day. Extreme exercise of greater than six hours initially increases the plasma concentration of PLP but ultimately results in a significant decrease in plasma PLP, an increase in plasma 4-PA, and an increase in percent of dietary vitamin B-6 (as 4-PA) excreted in the urine. Additionally, the rate of change in PUN inoeases as duration increases. / Graduation date: 2001

Serine transhydroxymethylase (STHM), a pyridoxal 5'- phosphate requiring enzyme is indirectly involved in pyrimidine deoxynucleotide metabolism. A decrease in the activity of this enzyme could lead to altered deoxycytidine (dC) metabolism. This study was undertaken to determine if a vitamin B-6 deficiency affects dC metabolism. The effect of a vitamin B-6 deficiency on the activity of STHM in liver, thymus, spleen and bone marrow was examined. In addition, the effect of a vitamin B-6 deficiency on urinary excretion of dC was examined. The effect of a vitamin B-6 deficiency on the urinary excretion and tissue retention of ³H label from ip injected ³H-dC was monitored. Rats were assigned in groups of six to one of four treatment groups: ad libitum control (ALC), pair fed control (PFC), ad libitum deficient (ALD) or meal fed deficient (MFD). At the end of weeks 2 and 6, rats from each treatment group received an ip injection of ³H-dC. Urines were collected for 24 hours following the ip inhibited due to lack of cofactor, then dTMP levels would fall. In an attempt to increase the concentration of dTMP, enzymes active in the conversion of dC and dCMP to dUMP would be expected to increase. Thus, dC salvage pathways would increase and dC synthesis would decrease as metabolism shifts toward production of deoxythymidine triphosphate (dTTP). The result would be lower urinary dC excretion. The present study was undertaken to explore the relationship between vitamin B-6 and pyrimidine deoxynucleotide metabolism. There were four hypothesis tested: Vitamin B-6 deficient rats will excrete less urinary dC than either ad libitum or pair fed controls; vitamin B-6 deficient rats will excrete a lower percentage of labeled dC in urine than control rats; vitamin B-6 deficient rats will incorporate less labeled dC into DNA than control rats but may retain more label in tissues as dC metabolites; activity of STHM from tissues of vitamin B-6 deficient rats will be lower than that from the control rats. / Graduation date: 1990