Analysis of clinical phenotype and gene variation of pyridoxine-dependent epilepsy caused by ALDH7A1 gene mutation / 中华神经科杂志

Objective:To analyze the clinical phenotype and genotype characteristics of children with pyridoxine-dependent epilepsy (PDE) and provide evidence for diagnosis.Methods:Clinical data of 3 children with PDE enrolled in the Department of Neurology of Hunan Children′s Hospital from July 2016 to December 2020 were collected, and whole-exome sequencing (WES) was used for analysis. Pathogenic variants were analyzed and screened using bioinformatics tools combined with clinical phenotype. Sanger sequencing was used to analyze the source of mutations in children′s core family members.Results:Cases 1 (female) and 2 (male) were siblings, both of whom had convulsions within 24 hours after birth. WES results showed that the siblings carried compound heterozygous mutations of c.796C>T (p.R266 *) and c.1553G>C (p.R518T) in the ALDH7A1 gene, coming from the father and mother of the siblings respectively. Both of the mutations have been reported as pathogenic. Case 3, female, developed convulsions at the age of 1. WES results revealed that she carried compound heterozygous mutations of c.1094-109T>A and c.7C>T (p.R3C) in the ALDH7A1 gene, coming from her father and mother respectively. After searching HGMDPro, PubMed, 1000 Genomes, and dbSNP databases, both of the 2 mutations of c.1094-109T>A and c.7C>T (p.R3C) were not reported. The pathogenicity predictions of the 2 mutations were carried out by different biological information analysis software. The results showed that both of the mutations were harmful. All the 3 children had no epileptic seizures after treatment with increased doses of vitamin B6. Conclusions:When infants have unexplained convulsions, especially in the neonatal stage, PDE caused by ALDH7A1 gene mutation should be considered. Pyridoxine precision treatment has a good effect. The 2 de novo mutations of c.1094-109T>A and c.7C>T (p.R3C) enrich the mutation spectrum in the ALDH7A1 gene. WES has the auxiliary significance in the diagnosis of epilepsy.

O uso do cloridrato de piridoxina para induzir estro em cadelas / The use of pyridoxine chloridrate to induce estrus in female dogs

Os agonistas dopaminérgicos são utilizados para induzir estro em cadelas, pois atuam na síntese e liberação de prolactina. Objetivou-se avaliar o efeito da piridoxina como indutor de estro em cadelas por agir na neurotransmissão dopaminérgica. Foram selecionadas 40 cadelas em anestro, divididas em quatro grupos experimentais, tratadas com 10mg/kg/dia (G1) e 50mg/kg/dia (G2) de cloridrato de piridoxina, 5µg/kg/dia (G3) de cabergolina e grupo controle/placebo (G4) por até 20 dias. Foram realizadas citologias vaginais a cada 24h para acompanhamento do ciclo estral e análises hormonais (FSH, LH e PRL) no dia zero e 120h do início do tratamento. As cadelas do G3 (100%) manifestaram proestro após 12 dias de tratamento aproximadamente, tempo inferior aos demais grupos (P<0,05). Apenas uma cadela do G1 e uma do G2 ficaram gestantes contra oito fêmeas do G3 e nenhuma do G4 (P<0,05). As concentrações plasmáticas de prolactina foram reduzidas nas fêmeas do G2 e G3 (P<0,05). As demais avaliações hormonais não sofreram influência do tratamento (P>0,05). O cloridrato de piridoxina foi ineficiente para induzir estro em cadelas, mas foi capaz de suprimir a prolactina, de forma semelhante à cabergolina, quando utilizado na dose de 50mg/kg/dia.(AU)

Dopaminergic agonists are used to induce estrus in female dogs as they act in the synthesis and release of prolactin. The objective of this study was to evaluate the effect of pyridoxine as an inducer of estrus by acting on dopaminergic neurotransmission. A total of 40 female dogs in anestrous were divided into four experimental groups treated with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride, 5µg/kg/day (G3) of cabergoline and control group/placebo (G4) for up to 20 days. Vaginal cytologies were performed every 24h for follow-up of the estrous cycle and hormonal analyzes (FSH, LH and PRL) on day zero and 120 hours after the start of treatment. The female dogs from G3 (100%) showed proestrus after 12 days of treatment, less time than the other groups (P< 0.05). Only one female from G1 and one from G2 were pregnant against eight from G3 and none from G4 (P< 0.05). Plasma concentrations of prolactin were reduced by treatment in females from G2 and G3 (P< 0.05). The other hormonal evaluations were not influenced by the treatment (P> 0.05). Pyridoxine chloridrate was inefficient to induce estrus in female dogs but was able to suppress prolactin when used at a dose of 50mg/kg/day.(AU)

Validation of endotoxin test for high concentration vitamin B6 injection / 药学实践杂志

Objective To establish a bacterial endotoxin test method for high concentration vitamin B6 injection. Method The test was taken according to the bacterial endotoxin test in Chinese pharmacopoeia 2015 edition. Result By diluting the sample concentration to 1.04 mg/ml with the buffer of pH6.5-7.5, and using λ=0.06 EU/ml of TAL reagent, the interference could be effectively avoided. Conclusion The method was useful, which could be used to test the bacterial endotoxin in high concentration vitamin B6 injection. The bacterial endotoxin limit was defined as 0.06 EU/mg.

Curative effect of compound carraghenates cream combined with vitamin B6 in the treatment of hand-foot syndrome caused by capecitabine / 中国基层医药

Objective@#To observe the curative effect of compound carraghenates cream(Titanoreine) combined with vitamin B6 in the treatment of hand-foot syndrome caused by capecitabine(Xeloda).@*Methods@#From December 2015 to December 2017, 97 cases of middle and advanced colorectal cancer in the First People's Hospital of Yongkang were selected.All patients were treated by chemotherapy regimens of capecitabine as priority after operation, but later hand-foot syndrome appeared and they were randomly divided into treatment group (48 cases) and control group (49 cases) according to the digital table.In control group, only vitamin B6 30 mg was taken orally, three times daily; while in treatment group, vitamin B6(30 mg) combined with compound carraghenate cream (1g) were taken orally, three times daily after hand-foot syndrome occurred.The improvement, total efficiency, pain score during the treatment process (the first, fifth, ninth day after treatment), adverse reactions were observed before and after treatment in two groups.@*Results@#After treatment, the hand-foot syndrome in the treatment group and the control group was improved, the difference was statistically significant (treatment group: Z=6.477, P=0.000; control group: Z=4.700, P=0.000). The total effective rate of the treatment group was 87.5%(42/48), which was significantly higher than 65.3%(32/49) of the control group (χ2=6.603, P=0.010). The pain score on the ist day after treatment had no statistically significant differences between the two group[treatment group: (2.88±1.82)points, control group: (3.14±1.74)points, t=0.741, P=0.461] The pain scores on 5th and 9th day after treatment in the treatment group were (2.29±1.52)points, (1.23±1.80)points, respectively, which were lower than those in the control group [(2.94±1.38)points, (2.14±1.90)points](t=2.200, 2.430, P=0.030, 0.017). There were no statistically significant differences between the two groups in general conditions and the incidence of adverse reactions after drugs uses(all P<0.05).@*Conclusion@#Compound carraghenate cream combined with vitamin B6 has significant effect in the treatment of hand-foot syndrome caused by capecitabine, which can improve hand-foot syndrome better and help tumor patients to finish the chemotherapy successfully.

Homocisteína y trastornos neurocognitivos. ¿Una luz al final del túnel? / Homocysteine and neurocognitive disorders. A light at the end of the tunnel?

El deterioro cognitivo es uno de los procesos que acompañan al envejecimiento y puede depender de factores nutricionales, genéticos o ambientales. La identificación de factores de riesgo modificables proporciona un enfoque esencial para la prevención de dicho deterioro y de los trastornos neurocognitivos. Uno de los factores de riesgo involucrados es la elevada concentración de homocisteína plasmática, la cual se ha relacionado con hallazgos histopatológicos en demencia senil y enfermedad de Alzheimer. Los diferentes estudios sobre esta asociación revelan inconsistencia o contradicción en los resultados. El propósito de esta revisión es relacionar la posible interacción de tres factores en la instalación y progresión del deterioro neurocognitivo: a) factores de tipo nutricional (homocisteína, ácido fólico y vitamina B12), b) la utilización de pruebas para el diagnóstico de disfunción o deterioro cognitivo como el Mini Examen del Estado Mental, y c) la presencia de variantes genéticas polimórficas de la enzima metilentetrahidrofolato reductasa. Una consecuencia directa de esta triple relación es que el tratamiento con ácido fólico y vitamina B12 logra disminuir las elevadas concentraciones de homocisteína plasmática, asumiendo que una mejoría en los síntomas clínicos de deterioro cognitivo puede retrasar los cambios relacionados con progresión a estados demenciales. La intervención temprana mediante políticas de promoción y prevención de la salud mental puede ser efectiva si se comienza con la administración de ácido fólico y vitamina B12 en los estadios iniciales de la alteración cognitiva, logrando así reducir sus funestas consecuencias. Las políticas de salud pública centradas en la salud mental de ancianos pueden identificar a las personas con disfunción cognitiva inicial a través de la promoción de la salud y medidas preventivas; en esta etapa puede ser posible la administración de vitaminas B para reducir o minimizar la progresión del deterioro cognitivo, que podría conducir a trastornos neurocognitivos como la demencia y la enfermedad de Alzheimer

Cognitive impairment is one of the processes that accompany aging and may depend on nutritional, genetic or environmental factors. The identification of modifiable risk factors provides a crucial approach for the prevention of cognitive decline and neurocognitive disorders. One of the risk factors is the high concentration of plasma homocysteine and it has been associated to histopathological changes in senile dementia and Alzheimer´s disease. Clinical trials about this association has shown inconsistent and contradictory results. The purpose of this review is to describe the possible interaction of three factors related with cognitive impairment: a) nutritional factors (homocysteine, folic acid and vitamin B12), b) the use of mental tests such as the Mini Mental State Examination for the diagnosis of cognitive dysfunction, and c) the presence of polymorphic genetic variants of the methylenetetrahydrofolate reductase enzyme. A direct consequence of this triple relationship is the treatment with folic acid and vitamin B12, which decrease high concentrations of plasma homocysteine, with a potential for improvement of the clinical symptoms of cognitive decline, and possibly a delay in the progression towards neurocognitive disorder. Public health policies focused on mental health of older adults can identify people with initial cognitive dysfunction through health promotion and preventive measures, where it can be possible to administer B vitamins in order to reduce or minimize the progression of cognitive decline, that could lead to mental disturbances such as neurocognitive disorders

Effect of Compound Folic Acid on Learning and Memory of Cognitive Impairment Model / 中国药学杂志

OBJECTIVE: To investigate the protective effects of folic acid (A) with vitamin B12 (B) and vitamin B6 (C) on the learning and memory impairment of multiple cerebral infarction dementia (MID) in rats and the potential mechanisms. METHODSE: The compound folic acid preparation components were used alone, in combination with each other and in combination. SD rats were randomly divided into sham operation, model group, positive control group (co-dergocrine mesylate tablets), group A, group B, group C, group AB, group AC, group BC and group ABC. The effect of folic acid, vitamin B12 and vitamin B6 on learning and memory function of MID model induced by autologous thrombus injection in rats was studied. RESULTS: Compared with the model group, the escape latency of the ABC group was significantly shortened on the 5th day (P<0.05), the number of crossing platforms was significantly increased (P<0.05), and the number of crossing target quadrants was significantly increased (P<0.05). CONCLUSION: Folic acid combined with vitamin B12 and vitamin B6 has synergistic effect. The mechanism of action may be through the protection of hippocampal nerve cell damage, to improve cognitive function, especially to prevent spatial memory disorders.

Application of modified microbubble test in peripherally inserted central venous catheters tip positioning / 中华危重病急救医学

Objective@#To analyze the specificity and sensitivity of the modified microbubble test in identifying the peripherally inserted central venous catheters (PICC) tip based on the chest X-ray location as the "gold standard", and to find out an accurate and noninvasive PICC tip positioning method that can save time and cost.@*Methods@#Convenient sampling method was conducted. The patients under PICC guided by ultrasound in intensive care unit (ICU) or PICC clinic of the First Affiliated Hospital of Nanchang University from August 2017 to February 2018 were enrolled. All patients were followed up by ultrasound guided PICC catheter placement, modified microbubble test and chest X-ray localization. The relationship between the density of microbubbles in modified microbubble test and the location of PICC tip in chest X-ray localization was analyzed. Using chest X-ray localization as the "gold standard", the diagnostic evaluation indexes such as specificity and sensitivity of PICC tip identification by modified microbubble test were calculated.@*Results@#A total of 120 patients were enrolled during the study period, excluding those who refused to participate in the study, unclear right atrial ultrasound, conscious intolerance, unclear chest X-ray, and finally 108 patients completed the modified microbubble test and chest X-ray tip localization. According to the chest X-ray localization results of 108 patients, 69 patients (63.9%) were in ideal locations, 33 (30.6%) were in dissatisfactory position, and 6 (5.5%) were in malposition. There was no significant difference in gender, age, tube placement, depth of catheterization, placement of catheterization room, and catheterization among the three groups. In the modified microbubble test, there were 74 patients (68.5%) with gradeⅠmicrobubble, 25 (23.2%) with gradeⅡ microbubble, and 9 (8.3%) with grade Ⅲ microbubble. There was a correlation between microbubble density and the tip position of the catheter, showing a moderate intensity correlation, and the contingency coefficient was 0.662. The sensitivity of the modified microbubble test for PICC tip positioning was 95.7% (66/69), the specificity was 89.7% (35/39), the rate of missed diagnosis was 4.4% (3/69), the misdiagnosis rate was 10.3% (4/39), the positive predictive value was 94.3% (66/70), the negative predictive value was 92.1% (35/38), and the Youden index was 0.85. The consistency between the two methods was good, and the Kappa value was 0.86.@*Conclusions@#Compared with the chest X-ray localization method, the modified microbubble test method has high sensitivity and specificity in identifying PICC in the position, and the operation is simple, noninvasive, with less time and low cost. The modified microbubble test can be used as a screening test for PICC tip position, especially in ICU. When there are technical limitations or suspicious patient, further chest X-ray is necessary.

Application of modified microbubble test in peripherally inserted central venous catheters tip positioning / 中华危重病急救医学

Objective To analyze the specificity and sensitivity of the modified microbubble test in identifying the peripherally inserted central venous catheters (PICC) tip based on the chest X-ray location as the"gold standard", and to find out an accurate and noninvasive PICC tip positioning method that can save time and cost. Methods Convenient sampling method was conducted. The patients under PICC guided by ultrasound in intensive care unit (ICU) or PICC clinic of the First Affiliated Hospital of Nanchang University from August 2017 to February 2018 were enrolled. All patients were followed up by ultrasound guided PICC catheter placement, modified microbubble test and chest X-ray localization. The relationship between the density of microbubbles in modified microbubble test and the location of PICC tip in chest X-ray localization was analyzed. Using chest X-ray localization as the "gold standard", the diagnostic evaluation indexes such as specificity and sensitivity of PICC tip identification by modified microbubble test were calculated. Results A total of 120 patients were enrolled during the study period, excluding those who refused to participate in the study, unclear right atrial ultrasound, conscious intolerance, unclear chest X-ray, and finally 108 patients completed the modified microbubble test and chest X-ray tip localization. According to the chest X-ray localization results of 108 patients, 69 patients (63.9%) were in ideal locations, 33 (30.6%) were in dissatisfactory position, and 6 (5.5%) were in malposition. There was no significant difference in gender, age, tube placement, depth of catheterization, placement of catheterization room, and catheterization among the three groups. In the modified microbubble test, there were 74 patients (68.5%) with gradeⅠmicrobubble, 25 (23.2%) with gradeⅡmicrobubble, and 9 (8.3%) with grade Ⅲ microbubble. There was a correlation between microbubble density and the tip position of the catheter, showing a moderate intensity correlation, and the contingency coefficient was 0.662. The sensitivity of the modified microbubble test for PICC tip positioning was 95.7% (66/69), the specificity was 89.7% (35/39), the rate of missed diagnosis was 4.4% (3/69), the misdiagnosis rate was 10.3% (4/39), the positive predictive value was 94.3% (66/70), the negative predictive value was 92.1% (35/38), and the Youden index was 0.85. The consistency between the two methods was good, and the Kappa value was 0.86. Conclusions Compared with the chest X-ray localization method, the modified microbubble test method has high sensitivity and specificity in identifying PICC in the position, and the operation is simple, noninvasive, with less time and low cost. The modified microbubble test can be used as a screening test for PICC tip position, especially in ICU. When there are technical limitations or suspicious patient, further chest X-ray is necessary.

Ácido fólico em excesso: efeitos sobre o metabolismo das vitaminas B2 e B6, o catabolismo do triptofano e a resposta imune / Folic acid excess: effects on vitamin B2 and B6 metabolism, tryptophan catabolism and immune response

Introdução: A suplementação com ácido fólico (AF) é recomendada em algumas condições para evitar a deficiência de folato, como para mulheres no período periconcepcional e durante a gestação. Atualmente, existe uma preocupação quanto ao consumo excessivo de AF pela população pelo uso de suplementos com altas doses dessa vitamina. As vitaminas B6 e B2 agem como cofatores no metabolismo de um carbono, e o uso de altas doses de AF pode influenciar o metabolismo de ambas vitaminas e, consequentemente, interferir em metabolismos importantes das quais elas participam, como a via das quinureninas, e no sistema imune. Objetivo: Avaliar os efeitos da intervenção diária com uma alta dose de AF (5 mg) por 90 dias sobre marcadores do estado das vitaminas do complexo B, e as consequências sobre os metabólitos da via das quinureninas e o sistema imune em adultos saudáveis. Material e Métodos: 64 indivíduos saudáveis foram submetidos à intervenção diária com 5 mg de AF por 90 dias. Coletas de sangue foram realizadas antes (baseline) e após 45 e 90 dias de intervenção. As concentrações séricas de folato e vitamina B12 foram avaliadas por métodos microbiológicos. As concentrações séricas das vitaminas B6 (piridoxal 5'-fosfato (PLP), piridoxal (PL) e ácido 4-piridóxico (PA)), B2 (riboflavina e flavina mononucleotídeo (FMN)), B1 (tiamina e tiamina monofosfato (TMP)) e B3 (ácido nicotínico, nicotinamida e N1-metilnicotinamida), bem como de triptofano, quinurenina e metabólitos, foram avaliadas por LC-MS/MS. A proteína C-reativa ultrassensível (PCRus) foi determinada por imunoturbidimetria, e as concentrações séricas de interleucina (IL)-6, IL-8, IL-10, interferon gama (IFN-γ) e fator de necrose tumoral alfa (TNF-α) foram avaliadas por ensaio multiplex. A expressão de RNAm de DHFR (dihidrofolato redutase), MTHFR (metilenotetrahidrofolato redutase), IL8, TNFA e IFNG em leucócitos mononucleares (PBMC) foram avaliadas por PCR em tempo real. O número de células T regulatórias (Treg) (CD3+, CD4+, CD25high, FoxP3+, CD127-) foi avaliado após incubação dos PBMC com PMA e ionomicina ou veículo por 18h, por imunofenotipagem. Resultados: Houve um grande aumento das concentrações de folato sérico após 45 e 90 dias de intervenção com AF. Não houve diferença nas concentrações de vitamina B12 antes e após a intervenção. As concentrações séricas de PLP foram semelhantes antes e após a intervenção, entretanto, um aumento de PL sérico foi observado após 45 e 90 dias, e de PA após 45 dias, quando comparado ao baseline. Riboflavina e FMN foram maiores após 45 e 90 dias em relação ao baseline. A tiamina sérica foi menor após 45 dias, e as concentrações de TMP foram maiores após 90 dias quando comparados aos períodos anteriores. Não houve diferença nas concentrações de vitamina B3 antes e após a intervenção. Dentre os metabólitos da via das quinureninas, apenas o ácido antranílico apresentou aumento após 45 e 90 dias, enquanto o ácido picolínico diminuiu após 90 dias. PCRus, IL-6, IL-8, IL-10, IFN-γ e TNF-α séricos foram semelhantes no baseline e após a intervenção. Um aumento da expressão de RNAm de DHFR e TNFA foi observado após, respectivamente, 90 dias e 45 e 90 dias de intervenção. Após 90 dias de intervenção com AF, foi observada diminuição do número de células Treg após estímulo com PMA e ionomicina. Conclusão: O uso diário de 5 mg de AF foi associado a alterações nas concentrações séricas de marcadores do estado de vitaminas do complexo B e da via das quinureninas, bem como a diminuição do número de células Treg

Introduction: Folic acid (FA) supplementation is recommended in some conditions to avoid folate deficiency, as women during periconceptional period and pregnancy. Currently, there is a concern about the excessive consumption of FA by population by using supplements with high doses of this vitamin. Vitamins B6 and B2 are cofactors of enzymes of one carbon metabolism and, consequently, may disturb key metabolism in which they participate, as kynurenine pathway, and the immune system. Aim: To assess the effects of a daily intervention with high dose of FA (5 mg) for 90 days on biomarkers of complex B vitamins status and its outcomes in kynurenine pathway metabolites and immune system in healthy adults. Material and Methods: 64 healthy individuals were submitted to a daily intervention with 5 mg of FA for 90 days. Blood samples were collected before (baseline) and after 45 and 90 days of intervention. Serum folate and vitamin B12 were assessed by microbiological assays. Serum vitamin B6 (pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (PA)), vitamin B2 (riboflavin and flavin mononucleotide (FMN)), vitamin B1 (thiamin and thiamin monophosphate)) and vitamin B3 (nicotinic acid, nicotinamide and N1-methylnicotinamide), as well as tryptophan, kynurenine and metabolites, were assessed by LC-MS/MS. C-reactive protein (hs-CPR) was assessed by immunoturbidimetry, and serum interleukin (IL)-6, IL-8, IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were assessed by multiplex assay. Mononuclear leukocytes mRNA expression of DHFR (dihydrofolate reductase), MTHFR (methylenetetrahydrofolate reductase), IL8, TNFA and IFNG were assessed by real time PCR. Regulatory T Cell (Treg) number (CD3+, CD4+, CD25high, FoxP3+, CD127-) was determined after mononuclear leukocytes incubation with PMA and ionomycin or vehicle for 18h, by immunophenotyping. Results: A great increase on serum folate was observed after 45 and 90 days of FA intervention. No differences in serum vitamin B12 were observed before and after intervention. Serum PLP was similar before and after intervention, however, an increase in serum PL was observed after 45 and 90 days, and in PA after 45 days, when compared to baseline. Riboflavin and FMN were increased after 45 and 90 days than in baseline. Serum thiamine was decreased after 45 days than in baseline. Serum TMP was increased after 90 days when compared with previous timepoints. No differences in vitamin B3 were observed after and before FA intervention. Among kynurenine pathway metabolites, anthranilic acid was increased after 45 and 90 days, while picolinic acid was decreased after 90 days. hs-CPR, serum IL-6, IL-8, IL-10, IFN-γ and TNF-α were similar at baseline and after intervention. An increase on mRNA expression of DHFR and TNFA was observed after, respectively, 90 days and 45 and 90 days of intervention. After 90 days of FA intervention, it was observed a decrease on Treg cell number after PMA and ionomycin stimulation. Conclusion: Daily use of 5 mg of FA was associated with changes in serum markers of B-complex vitamins status and kynurenine pathway, as well as decreased number of Treg cells

Evaluation of anti-depressant activity of zinc and vitamin B6 as adjuvants to fluoxetine in an animal model of depression

Background: Depression is a significant public health problem. It is estimated by the World Health Organization that more than 300 million people suffer from depression globally. Micronutrient deficiencies have been constantly linked to depression. The currently used drugs in treatment of depression modulate the excitatory and/or the inhibitory neurotransmission pathways through different mechanisms. The aim of the present study was to compare the antidepressant effect of the micronutrients, zinc and vitamin B6, as adjuvants to Fluoxetine in Albino Wistar rats.Methods: Eighteen albino wistar rats of 180-280grams of either sex were used in the study to evaluate the anti-depressant activity after approval from the Institutional Animal Ethics Committee. They were divided into three groups of six rats each (3 groups). Group 1 was control group which received only distilled water, group 2 was standard group which received fluoxetine and group 3 was test group which received zinc, vitamin B6 and fluoxetine. The anti-depressant activity was measured using the forced swimming test (FST) which works on the principles of behavioral despair. Data analysis was done using IBM SPSS software, version 25.0 and p value <0.05 was considered statistically significant.Results: The rats of the standard and test groups had latency periods’ means of 268.83±30.16, 126.17±22.33 and 125.33±11.86 on 254.83±13.00, 118.67±8.16 and 127.17±6.68 seconds on days 1, 7 and 14 respectively (p <0.001) and the rats of the standard and test groups had despair periods’ means of 177.00±7.46, 95.17±10.65, 93.17±7.47and 167.17±14.82, 97.33±7.63 and 87.50±4.1 seconds on days 1, 7 and 14 respectively (p <0.001).Conclusions: Supplementation of zinc and vitamin B6 to the standard treatment fluoxetine yielded better anti-depressant activity than fluoxetine alone in rats subjected to stress.

Assessment of Vitamin B6 Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of vitamin B6 (pyridoxine) in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for vitamin B6 in food supplements is 4.2 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limitto 2, 6, 8, 10, 20 or 25 mg/day. Vitamin B6 is water soluble and comprises six compounds with vitamin B6 activity; pyridoxine (PN, an alcohol), pyridoxal (PL, an aldehyde) and pyridoxamine (PM, the amine) and their corresponding phosphates; pyridoxine 5’-phosphate (PNP), pyridoxal 5’ -phosphate (PLP) and pyridoaxamin 5’ –phosphate (PMP). These six forms of vitamin B6 are all present in food in addition to the glycosylated form, pyridoxine-5’-β-δ-glucoside (PNG), in some plants. In food supplements the most common vitamin B6 form is pyridoxine hydrochloride. Eighty to ninety percent of vitamin B6 in the body is found in muscles and estimated body stores in adults amount to about 170 mg with a half-life of 25-33 days. Vitamin B6 deficiency is mostly seen in combination with deficiency of other B vitamins. Symptoms of vitamin B6 deficiency are anaemia and neurological abnormalities (EFSA, 2016). Intakes of vitamin B6 from the diet alone have not been reported to cause adverse effects. Sensory neuropathy has been reported to be the most sensitive adverse health effect of vitamin B6 supplementation. VKM proposes to adopt the tolerable upper intake level (UL) set by the Scientific Committee for Food (SCF) in 2000 at 25 mg/day for vitamin B6, which was based on a lowest observed adverse effect level (LOAEL) of 100 mg/day found in one randomised controlled trial. VKM recognises that there are no well-designed dose-response studies of long-term use available. However, for adults, no adverse effects have been reported at doses with vitamin B6 up to 25 mg/day. Dietary calculations have been performed for mean intakes and in various percentiles (P5, P25, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and in adults. To illustrate the consequences of amending the maximum limit for vitamin B6 in food supplements to 2, 6, 8, 10, 20 or 25 mg/day in the different age groups, VKM has used the scenarios with P95 from food and added the alternative amounts of supplements. VKM has compared these scenarios with the tolerable upper intake levels set by the Scientific Committee for Food in 2000 for adults, adolescents and children. In these scenarios, the 2- and 4-year-old children will exceed the tolerable upper intake level with use of 6 mg/day or higher vitamin B6 in supplements. The 9-year-old children will exceed the tolerable upper intake level with supplemental use of 10 mg/day. The 13-year-old adolescents will exceed the tolerable upper intake level with 20 mg/day of vitamin B6 in supplements. Adults will exceed the tolerable upper intake level with use of 25 mg/day of vitamin B6/pyridoxine in supplements.

Clinical observation of the effects of Xihuang pills combined with sodium cantharidinate and vitamin B6 injection in the treatment of tumor-induced fever / 国际中医中药杂志

Objective To study the effects of Xihuang pills combined with sodium cantharidinate and vitamin B6 injection in the treatment of tumor-induced fever. Methods A total of 100 patients with tumor-induced fever in our hospital from March 2015 to January 2017 were enrolled in this study. The subjects were divided into the control group (n=50) and the treatment group (n=50) randomly. The control group were treated with aspirin-D L-Lysine injection, and the treatment group were treated with Xihuang pills combined with sodium cantharidinate and vitamin B6 injection. The two groups were treated for 2 periods. The clinical effects of the two groups after treatment were compared. The life quality of the two groups after treatment were compared. The serum TNF-α and IL-1β of the two groups before and after treatment were compared. The adverse reaction rates of the two groups during treatment were compared. Results The total efficacy rate of defervescence of the treatment group was 88.0％(44/50) significantly higher than 56.0％(28/50) of the control group (χ2=12.698, P=0.000). After treatment, the daily life score (1.10 ± 0.18 vs. 2.47 ± 0.21, t=35.025), social communication score (1.21 ± 0.13 vs. 2.53 ± 0.25, t=33.124), mental state score (1.08 ± 0.15 vs. 2.75 ± 0.21,t=45.758), appetite score (1.13 ± 0.16 vs. 2.56 ± 0.19, t=40.708), sleep score (1.22 ± 0.17 vs. 2.71 ± 0.20, t=40.139) of the treatment group were significantly lower than those of the control group (P<0.05). After treatment, the serum TNF-α (1.98 ± 0.07 μg/L vs. 2.86 ± 0.13 μg/L, t=42.144), IL-1β (9.20 ± 1.89 μg/L vs. 13.51 ± 2.36 μg/L, t=10.080) of the treatment group were significantly lower than those of the control group (P<0.05). There was no significantly differences of the adverse reaction rates of the two groups during treatment (χ2=0.211, P=0.646). Conclusions The Xihuang pills combined with sodium cantharidinate and vitamin B6 injection for patients with tumor-induced fever has a good efficacy and low incidence of adverse reactions, can improve the quality of life and reduce the serum levels of TNF-α and IL-1β.

B vitamins supplementation in the prevention of ischemic stroke / 国际脑血管病杂志

Reducing plasma homocysteine levels by B vitamins supplementation may be an effective intervention to prevent ischemic stroke, but early relevant clinical trials have show n that patients do not benefit from it.Recent trials have show n that folic acid supplementation can significantly reduce the risk of ischemic stroke.Therefore,the potential benefits of B vitamins in the prevention of ischemic stroke still need further study.

Therapeutic effect of chemotherapy combined with sodium cantharidinate vitamin b6 injection in patients with nonsmall cell lung cancer and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of chemotherapy combined with sodium cantharidinate vitamin B6 injection in the patients with non-small cell lung cancer (NSCLC) and its effect on the patients' quality of life, and to clarify its mechanism. Methods: A total of 110 NSCLC patients were divided into chemotherapy group and combined group according to the different treatment methods adopted by the patients. A total of 55 patients were treated with chemotherapy alone (chemotherapy group) and 55 patients treated with chemotherapy combined with sodium cantharidate vitamin B6 injection (combined group). The total effective rate of the patients in two groups were compared; EORTC QLO-C43 scale was used to evaluate the quality of life of the patients in two groups before and after treatment; the serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-a), and interleukin-12 (IL-12) of the patients in two groups before and after treatment were detected by double-antibody sandwich enzyme-linked immunoassay method. Results: After treatment, the total effective rate of the patients in combined group was higher than that in chemotherapy group, but the difference was not statistically significant (χ2 = 0.806, P= 0.369). Before treatment, there were no significant differences in the scores of functional scale, overall health status, symptom subscale and lung cancer specific subscale of the patients between combined group and chemotherapy group (P>0. 05). After treatment, the scores of functional scale and overall health status of the patients in combined group were significantly higher than those in chemotherapy group (P0. 05). After treatment, the serum level of VEGF of the patients in combined group was significantly lower than that in chemotherapy group (χ2= 3. 608, P<0. 05), and the serum levels of TNF-a and IL-12 were significantly higher than those in chemotherapy group (t= 3.426, P<0.05; t= 2.849, P < 0. 05). Conclusion: The effect of chemotherapy combined with sodium cantharidate vitamin B6 injection in the treatment of the NSCLC patients is good, and it can significantly improve the quality of life of the patients; its mechanism may be related to decreasing the serum VEGF level and increasing the serum TNF-α and IL-12 levels.

Simultaneous Determination of Dihydralazine Sulfate and Three Vitamins in Compound Apocynum venetum Tablets I by HPLC / 中国药房

OBJECTIVE: To establish a method for simultaneous determination of vitamin B1, dihydralazine sulfate, vitamin B6 and vitamin B5 in Compound Apocynum venetum tablets I.METHODS: HPLC method was used for content determination of 8 batches of samples from 2 enterprises. The determination was performed on Waters XBridge C18 column with mobile phase consisted of acetonitrile-0. 2％ phosphoric acid (gradient elution) at the flow rate of 0. 5 mL/min. The detection wavelengths were set at 285 nm (vitamin Bi, dihydralazine sulfate, vitamin B6) and 210 nm (vitamin B5). The column temperature was 30 ℃, and sample size was 10 μL. RESULTS: The linear ranges of vitamin Bi, dihydralazine sulfate, vitamin B6 and vitamin B5 were 41. 66-208. 3 μg/mL (r=0. 999 9), 127. 0-635. 0 μg/mL (r=0. 999 9), 40. 74-203. 7 μg/mL (r=0. 999 9) and 22. 72-113. 6 μg/mL (r= 0. 999 9), respectively. The limits of quantitation were 0. 267, 0. 274, 0. 062, 0. 124 μg/mL, respectively. The limits of detection were 0. 095, 0. 088, 0. 021, 0. 039 μg/mL, respectively. RSDs of precision, stability and reproducibility tests were all lower than 2. 0％ (n=6). The average recoveries were 98. 70％ (RSD=0. 69％, n=9),99. 74％ (RSD=1. 2％, n=9), 99. 89％ (RSD= 1. 0％, n=9), 99. 25％ (RSD=1. 2％, n=9), respectively. Among 8 batches of samples, the contents of vitamin B1, dihydralazine sulfate, vitamin B6 and vitamin B5 were 91. 44％-98. 74％, 36. 68％-95. 23％, 92. 42％-97. 90％, 91. 36％-99. 48％ of labelled amount, respectively. The contents of dihydralazine sulfate were significantly different and differed by 2. 6 times between the lowest and the highest threshold value. CONCLUSIONS: The method is accurate, reliable, simple and can be used for simultaneous determination of the above 4 components in Compound A. venetum tablets I.

Clinical value of vitamin B supplementation in senile epilepsy with hyperhomocysteinemia / 中华神经科杂志

Objective To investigate the influence of vitamin B supplementation on the plasma total homocysteine (Hcy), serum folate, serum vitamin B12, serum vitamin B6, and clinical state of senile epilepsy.Methods A total of 132 senile epilepsy patients with hyperhomocysteinemia, who visited the Second Affiliated Hospital of Soochow University from January 2013 to July 2015, were enrolled into this study.Eighty-three patients who accepted the therapy of vitamin B supplementation (folate 2.5 mg/d, vitamin B6 10.0 mg/d, vitamin B12 1.5 mg/d) were selected as treatment group, and 49 patients with no vitamin B supplementation were selected as control group.All patients were followed-up for one year.The differences of serum Hcy, folate, vitamin B12, vitamin B6 and seizure frequency, MMSE scores, Hamilton Depression Rating Scale (HDMA) scores between the treatment and the control groups were compared.According to the concentration of serum Hcy, 132 patients were divided into two groups: 75 patients (46 patients in the treatment group and 29 patients in the control group) with mild hyperhomocysteinemia (Hcy: 15.0-29.9 μmol/L), 57 patients (37 patients in the treatment group and 20 patients in the control group) with moderate-severe hyperhomocysteinemia (Hcy≥30.0 μmol/L).The differences of serum Hcy, folate, vitamin B12, vitamin B6 and seizure frequency, MMSE scores, HDMA scores between the treatment and the control group in the mild hyperhomocysteinemia group and in the moderate-severe hyperhomocysteinemia group were compared.And the influence factors of Hcy were analyzed.Results Correlation analysis revealed that Hcy was positively correlated with age (r=0.269, P=0.002), and negatively correlated with folate (r=-0.222, P=0.010).Hcy was associated with smoking (χ2=7.363,P=0.007), hypertension (χ2=6.187,P=0.013), and two or more antiepileptic drugs polytherapy (χ2=4.708,P=0.030).After vitamin B supplementation in the group of moderate-severe hyperhomocysteinemia, serum Hcy concentration ((15.68±4.85) μmol/L in the treatment group vs (31.14±11.18) μmol/L in the control group, t=5.890, P0.05).Conclusions It is necessary to monitor serum Hcy for senile epilepsy.Vitamin B supplementation is a safe and inexpensive way to reduce the concentration of Hcy, assist to control seizures and improve the clinical symptom of depression and cognitive impairment for senile epilepsy with moderate-severe hyperhomocysteinemia.

Effect of Multi-trace Elements Injection (Ⅱ) on the Stability of Compound Trivitamin B for Injection (Ⅱ) / 中国药师

Objective:To study the stability of thiamine nitrate ( VB1 ) and pyridoxine hydrochloride ( VB6 ) in total parenteral nu-trition ( TPN) solution containing multi-trace elements injection (Ⅱ) . Methods:HPLC was used to determine the contents of VB1 and VB6 in different prescriptions in 0, 2, 4, 6, 8 and 24 h. Meanwhile, the pH value was determined and the appearance of the solution was observed. Results:The contents of VB1 and VB6 in 5% glucose solution containing multi-trace elements injection (Ⅱ) were changed mithin the range of 10%. In the TPN solution, containing multi-trace elements injection (Ⅱ) , the content of VB1 decreased by 12% in 8 h, and the content of VB6 was changed within the range of 10%. The solutions containing multi-trace elements injection (Ⅱ) were all light yellow, while the solutions without multi-trace elements injection (Ⅱ) were colorless and transparent. The pH val-ue showed no significant change in each group. Conclusion: The TPN solution containing multi-trace elements injection (Ⅱ) and compound trivitamin B for injection (Ⅱ) is recommended to be used in 8 hours.

Effect observation of sodium cantharidate and vitamin B6 combined with concurrent chemoradiotherapy in treatment of locally advanced nasopharyngeal carcinoma / 肿瘤研究与临床

Objective To study the clinical efficacy of sodium cantharidinate and vitamin B6 injection combined with concurrent chemoradiotherapy in treatment of locally advanced nasopharyngeal carcinoma (LA-NPC).Methods 115 patients with LA-NPC in Shanxi Cancer Hospital were randomly assigned to observation group (61 cases) and control group (54 cases) from February 2014 to April 2016.The patients in the observation group were treated with sodium cantharidate and vitamin B6 injection combined with concurrent chemoradiotherapy.The patients in the control group were treated with concurrent chemoradiotherapy.The differences between the two groups were compared in respect of recent curative effect,the quality of life (QOL) and the adverse reactions.Results The recent effective rate was 93.44 ％ (57/61) in the observation group and 79.63 ％ (43/54) in the control group,and there was significant difference between the two groups (x2 =4.818,P =0.049).The improvement rate of QOL was 73.77 ％ (45/61) in the observation group and 53.70 ％ (29/54) in the control group,and there was significant difference between the two groups (x2 =5.028,P =0.032).The incidence rates of oral cavity mucous membrane inflammation,hematology toxicity,pharynx and esophagus adverse reactions,the gastrointestinal tract adverse reactions and skin fibrosis in the observation group were lower than those in the control group,and there were significant differences between the two groups (all P ＜ 0.05).Conclusion The recent effect of sodium cantharidinate and vitamin B6 injection combined with concurrent chemoradiotherapy on the patients with LA-NPC is obvious.The comprehensive treatment can also reduce adverse reactions and improve the QOL.

Simultaneous Determination of 4 Components in Compound Metronidazole Clindamycin Cream by HPLC / 中国药房

OBJECTIVE:To establish the method for simultaneous determination of the content of metronidazole,clindamycin hydrochloride,spironolactone and vitamin B6 in Compound metronidazole clindamycin cream.METHODS:HPLC method was adopted.The determination was performed on Diamonsil C18 column with mobile phase consisted of acetonitrile-[0.68％ dipotassium hydrogen phosphate solution (containing 1％ triethylamine)] (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 210 nm,and column temperature was 25 ℃.The sample size was 20 μL.RESULTS:The linear ranges of metronidazole,clindamycin hydrochloride,spironolactone and vitamin B8 were respectively 20.0-120.0 i.tg/mL(r=0.999 9),10.0-60.0μg/mL(r=0.999 1),4.0-24.0 μg/mL(r=0.999 4),10.0-60.0 μg/mL (r=0.999 4).The quantitative limits were respectively 13.06,7.36,2.43,6.42 μg/mL.The detection limits were 4.18,1.82,0.76,1.79 μg/mL.RSDs of the precision,stability,repeatability tests were all less than 2％.The recovery rates were respectively 98.97％-100.91％ (RSD=0.79％,n=9),99.02％-101.80％ (RSD=1.03％,n=9),98.18％-101.05％ (RSD=1.01％,n=9) and 98.75％-101.36％ (RSD=0.87％,n=9).CONCLUSIONS:The method is simple,rapid,accurate and can be used for the determination of metronidazole,clindamycin hydrochloride,spironolactone and vitamin B6 in Compound clindamycin metronidazole cream.

Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)