Pyridoxine Research Papers - Academia.edu (original) (raw)

A method for determining all of the six natural vitamin B 6 compounds and pyridoxine-␤-glucoside in urine from humans consuming their usual diet was developed. These compounds were specifically converted with 5 enzymes into a high... more

A method for determining all of the six natural vitamin B 6 compounds and pyridoxine-␤-glucoside in urine from humans consuming their usual diet was developed. These compounds were specifically converted with 5 enzymes into a high fluorescent 4-pyridoxolactone which was supersensitively determined by an isocratic HPLC. All of the compounds in urine from humans consuming their usual diets were for the first time determined together. The preparation procedure for urine samples was easy without HClhydrolysis, and the enzyme reactions took only 2 or 3 h. It required only 5 L of the urine sample for analysis of one of the compounds. Urine samples from five young Japanese males consuming their usual diet contained pyridoxal, pyridoxamine, and pyridoxine-␤-glucoside but not pyridoxine or phosphoester forms. The contents of 4-pyridoxic acid and pyridoxal correlate well with a correlation coefficient of 0.98. On the other hand, the content of pyridoxamine did not correlate with that of 4-pyridoxic acid.

Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and... more

Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and neurotransmitter synthesis. It has been reported that cytokine imbalance is involved in the progression of many CNS diseases such as neuropsychiatric disorders (depression, schizophrenia, autism, and bipolar disorder) and neurodegenerative disorders (Parkinson's and Alzheimer's disease). Here, the effects of diclofenac, different antidepressants (sertraline, venlafaxine, and fluvoxamine), and vitamin B 6 (pyridoxine) on IL-10 and tumor necrosis factor-a (TNF-a) change with and without immune challenges with lipopolysaccharide (LPS) were investigated in in vitro culture of astrocytes from 2-day-old Swiss-Albino mice. Diclofenac and Sertraline significantly (p \ 0.05) improves anti-inflammatory cytokine (IL-10) while suppress (p \ 0.05) LPS-induced elevated level of pro-inflammatory mediators (TNF-a) in astrocyte culture.

To examine the development and tracking of long-term vitamin B-6 status from infancy to early adolescence, measurements of erythrocyte pyridoxal 5'-phosphate concentration (EPLP), the erythrocyte aspartate transaminase (EAST)... more

To examine the development and tracking of long-term vitamin B-6 status from infancy to early adolescence, measurements of erythrocyte pyridoxal 5'-phosphate concentration (EPLP), the erythrocyte aspartate transaminase (EAST) stimulation test including measurements of basal activity (EASTo) and activation coefficient (alpha EAST), were made in a follow-up study of healthy children aged 2 (n = 139), 4 (n = 147), 6 (n = 157), 9 (n = 159) and 12 mo (n = 188) and 5 y (n = 148). The EAST stimulation test was repeated at 11 y (n = 153). Vitamin B-6 status, high during infancy, reached the adult level by 5 y of age. The 10th to 90th percentile ranges for EPLP values were 61-201 nmol/L at 4 mo, 49-101 nmol/L at 12 mo and 27-59 nmol/L at 5 y. The respective ranges for Easto were 16-24 microkat/L at 4 mo, 13-19 microkat/L at 12 mo, 9-14 microkat/L at 5 y and 25-39 microkat/L at 11 y of age. For alpha EAST values were 1.29-1.54 at 4 mo, 1.48-1.77 at 12 mo, 1.70-2.07 at 5 y and 2.00-2.57 at...

Vitamin B6 represents a highly important group of compounds ubiquitous in all living organisms. It has been demonstrated to alleviate oxidative stress and in its phosphorylated form participates as a cofactor in >100 biochemical... more

Vitamin B6 represents a highly important group of compounds ubiquitous in all living organisms. It has been demonstrated to alleviate oxidative stress and in its phosphorylated form participates as a cofactor in >100 biochemical reactions. By means of a genetic approach, we have identified a novel mutant, rsr4-1 (for reduced sugar response), with aberrant root and leaf growth that requires supplementation of vitamin B6 for normal development. Cloning of the mutated gene revealed that rsr4-1 carries a point mutation in a member of the PDX1/SOR1/SNZ (for Pyridoxine biosynthesis protein 1/Singlet oxygen resistant 1/Snooze) family that leads to reduced vitamin B6 content. Consequently, metabolism is broadly altered, mainly affecting amino acid, raffinose, and shikimate contents and trichloroacetic acid cycle constituents. Yeast two-hybrid and pull-down analyses showed that Arabidopsis thaliana PDX1 proteins can form oligomers. Interestingly, the mutant form of PDX1 has severely reduced capability to oligomerize, potentially suggesting that oligomerization is important for function. In summary, our results demonstrate the critical function of the PDX1 protein family for metabolism, whole-plant development, and vitamin B6 biosynthesis in higher plants.

A spectrophotometric procedure has been developed for rapid and fairly accurate determination of vitamin BE in B complex and multivitamin preparations. Vitamin BE is determined by the measurement of difference in absorbance value (AA) in... more

A spectrophotometric procedure has been developed for rapid and fairly accurate determination of vitamin BE in B complex and multivitamin preparations. Vitamin BE is determined by the measurement of difference in absorbance value (AA) in different solvents at 328 mp.

The chemical analysis and quality control of Ginkgo leaves, extracts, phytopharmaceuticals and some herbal supplements is comprehensively reviewed. The review is an update of a similar, earlier review in this journal [T.A. van Beek, J.... more

The chemical analysis and quality control of Ginkgo leaves, extracts, phytopharmaceuticals and some herbal supplements is comprehensively reviewed. The review is an update of a similar, earlier review in this journal [T.A. van Beek, J. Chromatogr. A 967 (2002) 21-55]. Since 2001 over 3000 papers on Ginkgo biloba have appeared, and about 400 of them pertain to chemical analysis in a broad sense and are cited herein. The more important ones are discussed and, where relevant, compared with the best methods published prior to 2002. In the same period over 2500 patents were filed on Ginkgo and the very few related to analysis are mentioned as well. Important constituents include terpene trilactones, i.e. ginkgolide A, B, C, J and bilobalide, flavonol glycosides, biflavones, proanthocyanidins, alkylphenols, simple phenolic acids, 6-hydroxykynurenic acid, 4-O-methylpyridoxine and polyprenols. In the most common so-called "standardised" Ginkgo extracts and phytopharmaceuticals several of these classes are no longer present. About 130 new papers deal with the analysis of the terpene trilactones. They are mostly extracted with methanol or water or mixtures thereof. Supercritical fluid extraction and pressurised water extraction are also possible. Sample clean-up is mostly by liquid-liquid extraction with ethyl acetate although no sample clean-up at all in combination with LC/MS/MS is gaining in importance. Separation and detection can be routinely carried out by RP-HPLC with ELSD, RI or MS, or by GC/FID or GC/MS after silylation. Hydrolysis followed by LC/MS allows the simultaneous analysis of terpene trilactones and flavonol aglycones. No quantitative procedure for all major flavonol glycosides has yet been published because they are not commercially available. The quantitation of a few available glycosides has been carried out but does not serve a real purpose. After acidic hydrolysis to the aglycones quercetin, kaempferol and isorhamnetin and separation by HPLC, quantitation is straightforward and yields by recalculation an estimation of the original total flavonol glycoside content. A profile of the genuine flavonol glycosides can detect poor storage or adulteration. Although the toxicity of Ginkgo alkylphenols upon oral administration has never been undoubtedly proven, most suppliers limit their content in extracts to 5 ppm and dozens of papers on their analysis were published. One procedure in which a methanolic extract is directly injected on a C8 HPLC column appears superior in terms of sensitivity (<5 ppm), separation, simplicity and validation and will be incorporated in the European Pharmacopoeia. Alternatively GC/MS and ELISA methods can be used. A sharp contrast to the plethora of papers on terpene trilactones, flavonol glycosides, and ginkgolic acids forms the low number of papers on biflavones, proanthocyanidins, simple phenolics, simple acids, and other constituents that make up the remaining 70% of Ginkgo standardised extracts. More research in this direction is clearly needed. For the analysis of Ginkgo proanthocyanidins (7%) for instance, no reliable assays are yet existing. Finally the growing literature on pharmacokinetic and fingerprinting studies of Ginkgo is briefly summarised.

The chemical analysis and quality control of Ginkgo leaves, extracts, phytopharmaceuticals and some herbal supplements is comprehensively reviewed. The review is an update of a similar, earlier review in this journal [T.A. van Beek, J.... more

The chemical analysis and quality control of Ginkgo leaves, extracts, phytopharmaceuticals and some herbal supplements is comprehensively reviewed. The review is an update of a similar, earlier review in this journal [T.A. van Beek, J. Chromatogr. A 967 (2002) 21-55]. Since 2001 over 3000 papers on Ginkgo biloba have appeared, and about 400 of them pertain to chemical analysis in a broad sense and are cited herein. The more important ones are discussed and, where relevant, compared with the best methods published prior to 2002. In the same period over 2500 patents were filed on Ginkgo and the very few related to analysis are mentioned as well. Important constituents include terpene trilactones, i.e. ginkgolide A, B, C, J and bilobalide, flavonol glycosides, biflavones, proanthocyanidins, alkylphenols, simple phenolic acids, 6-hydroxykynurenic acid, 4-O-methylpyridoxine and polyprenols. In the most common so-called "standardised" Ginkgo extracts and phytopharmaceuticals several of these classes are no longer present. About 130 new papers deal with the analysis of the terpene trilactones. They are mostly extracted with methanol or water or mixtures thereof. Supercritical fluid extraction and pressurised water extraction are also possible. Sample clean-up is mostly by liquid-liquid extraction with ethyl acetate although no sample clean-up at all in combination with LC/MS/MS is gaining in importance. Separation and detection can be routinely carried out by RP-HPLC with ELSD, RI or MS, or by GC/FID or GC/MS after silylation. Hydrolysis followed by LC/MS allows the simultaneous analysis of terpene trilactones and flavonol aglycones. No quantitative procedure for all major flavonol glycosides has yet been published because they are not commercially available. The quantitation of a few available glycosides has been carried out but does not serve a real purpose. After acidic hydrolysis to the aglycones quercetin, kaempferol and isorhamnetin and separation by HPLC, quantitation is straightforward and yields by recalculation an estimation of the original total flavonol glycoside content. A profile of the genuine flavonol glycosides can detect poor storage or adulteration. Although the toxicity of Ginkgo alkylphenols upon oral administration has never been undoubtedly proven, most suppliers limit their content in extracts to 5 ppm and dozens of papers on their analysis were published. One procedure in which a methanolic extract is directly injected on a C8 HPLC column appears superior in terms of sensitivity (<5 ppm), separation, simplicity and validation and will be incorporated in the European Pharmacopoeia. Alternatively GC/MS and ELISA methods can be used. A sharp contrast to the plethora of papers on terpene trilactones, flavonol glycosides, and ginkgolic acids forms the low number of papers on biflavones, proanthocyanidins, simple phenolics, simple acids, and other constituents that make up the remaining 70% of Ginkgo standardised extracts. More research in this direction is clearly needed. For the analysis of Ginkgo proanthocyanidins (7%) for instance, no reliable assays are yet existing. Finally the growing literature on pharmacokinetic and fingerprinting studies of Ginkgo is briefly summarised.

a b s t r a c t HPLC stability-indicating method has been developed for the simultaneous determination of some watersoluble vitamins (ascorbic acid, thiamine hydrochloride, riboflavin-5 -phosphate sodium, pyridoxine hydrochloride,... more

a b s t r a c t HPLC stability-indicating method has been developed for the simultaneous determination of some watersoluble vitamins (ascorbic acid, thiamine hydrochloride, riboflavin-5 -phosphate sodium, pyridoxine hydrochloride, nicotinamide, d(+)-panthenol) and two preservatives (methylparaben and sodium benzoate) in multivitamin syrup preparation. Water-soluble vitamins, preservatives and their degradants were separated on Zorbax SB-Aq (C 18 ) (250 mm × 4.6 mm, 5 m) column at an ambient temperature. Combined isocratic and gradient elution was performed with a mobile phase consisting of 0.0125 M hexane-1-sulfonic acid sodium salt in 0.1% (m/v) o-phosphoric acid, pH 2.4-2.5 (solvent A) and acetonitrile (solvent B) at the flow-rate 1 ml min −1 . Starting with solvent A an isocratic elution was performed for 15 min, then the composition was changed to 85% of A and 15% of B during the next 20 min and it was constant for 5 min, then the composition was changed to 70% of A and 30% of B during next 15 min and it was constant for 5 min and finally was changed to 100% of A as at the beginning of the elution. Detection was performed with diode array detector at 210, 230 and 254 nm. Multivitamin syrup preparation was subjected to stress testing (forced degradation) in order to demonstrate that degradants from the vitamins, preservatives and/or product excipients do not interfere with the quantification of vitamins and preservatives. Typical validation characteristics: selectivity, accuracy, precision, linearity, range, limit of quantification and limit of detection were evaluated for vitamins and preservatives.

Background Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B,,, or vitamin B,.... more

Background Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B,,, or vitamin B,. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcoholrelated hyperhomocysteinemia.

The aim of the clinical study was to evaluate the effect of Testofen, a standardized Trigonella foenum-graecum (Fenugreek) extract and mineral formulation, on male libido (sexual drive, urge or desire) in a double blind randomized placebo... more

The aim of the clinical study was to evaluate the effect of Testofen, a standardized Trigonella foenum-graecum (Fenugreek) extract and mineral formulation, on male libido (sexual drive, urge or desire) in a double blind randomized placebo controlled study. The study recruited 60 healthy males aged between 25 and 52, without erectile dysfunction and randomized to an oral dose (two tablets per day) of the active treatment (600 mg Testofen per day) or placebo for 6 weeks. The primary outcome measure was the DISF-SR (male) self-administered QOL total score and the four domain scores. The secondary outcome was specific quality of life parameters. Testofen had an overall positive effect on physiological aspects of libido. In particular, there was a significant increase in the subdomains of sexual arousal and orgasm. Testofen had a positive effect on QOL in self-reported satisfaction with muscle strength, energy and well-being but did not have an effect on mood or sleep. Serum prolactin and testosterone levels remained within the reference range. It was concluded that Testofen demonstrated a significant positive effect on physiological aspects of libido and may assist to maintain normal healthy testosterone levels. Copyright © 2011 John Wiley & Sons, Ltd.

Evidence, obtained with in situ perfused rat liver, indicated that pyridoxine is taken up from the peffusate by a non-concentrative process, followed by metabolic trapping. These conclusions were reached on the basis of the fact that at... more

Evidence, obtained with in situ perfused rat liver, indicated that pyridoxine is taken up from the peffusate by a non-concentrative process, followed by metabolic trapping. These conclusions were reached on the basis of the fact that at low concentrations (0.125/~M), the 3H of [3H]pyridoxine accumulated against a concentration gradient, but high concentrations (333 /~M) of pyridoxine or 4<leoxypyridoxine prevented this apparent concentrative uptake. Under no conditions did the tissue water : perfusate concentration ratio of [3H]pyridoxine exceed unity.

Inherited disorders of neurotransmitters are a group of neurometabolic syndromes attributable to a primary disturbance of neurotransmitter metabolism or transport. This is an enlarging group of recognized disorders requiring specialized... more

Inherited disorders of neurotransmitters are a group of neurometabolic syndromes attributable to a primary disturbance of neurotransmitter metabolism or transport. This is an enlarging group of recognized disorders requiring specialized diagnostic procedures for detection. This review considers clinical disorders of biopterin, catecholamines, serotonin, glycine, pyridoxine, and GABA metabolism. Newly described syndromes such as cerebral folate deficiency and pyridoxal-5-phosphate dependency are included. The disorders of the metabolic pathways of biopterin, catecholamines, and serotonin are linked due to their common synthetic components. Glycine encephalopathy represents an enlarging phenotype related to abnormalities of the glycine degradative cleavage system. Both pyridoxine and pyridoxal-5-phosphate dependency need to be considered in refractory neonatal seizures. The most common disorder of GABA metabolism is SSADH deficiency, which has a broad phenotype of mental retardation, epilepsy, ataxia, and hyporeflexia and which invokes the combined problems of elevated brain GABA and GHB.

Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is... more

Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination (Diclectin 1 ) (n ¼ 131) to placebo (n ¼ 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5 0 phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin 1 exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady-state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6.

The new dimeric [Cu 2 (OAc) 4 (2-Clpym) 2 ] complex of 2-chloropyrimidine (2-Clpym) ligand was synthesized, where 2-Clpym coordinated via the nitrogen atom and acts as monodentate ligand. The water molecules of dimeric Cu 2 (OAc) 4 (H 2... more

The new dimeric [Cu 2 (OAc) 4 (2-Clpym) 2 ] complex of 2-chloropyrimidine (2-Clpym) ligand was synthesized, where 2-Clpym coordinated via the nitrogen atom and acts as monodentate ligand. The water molecules of dimeric Cu 2 (OAc) 4 (H 2 O) 2 salt replaced by two 2-Clpym ligands producing the new complex. The nature of synthesized complex was determinated by elemental and spectrochemical (IR, UV-Vis) analysis. Also, the geometries of ligand and complex have been fully optimized using density functional theory (B3LYP) method. The obtained structural parameters are in good agreement with the experimental data, reported for the similar compounds. Also, the calculated and experimental wavenumbers confirm validity of the optimized structures for the ligand and Cu complex.

Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs.... more

Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayedrelease tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis Ò , and has been on the Canadian market since 1979, currently under the brand name Diclectin Ò . The efficacy of Diclegis Ò /Diclectin Ò has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis Ò / Diclectin Ò for the treatment of NVP to justify its use as first-line treatment for NVP.

Homocystinuria was diagnosed in 15 (0.59%) cases on screening 2560 children for aminoacidopathies. The commonest presenting features were ectopia lentis (95%) and mental retardation (86%). Other features included, dental anomalies (40%),... more

Homocystinuria was diagnosed in 15 (0.59%) cases on screening 2560 children for aminoacidopathies. The commonest presenting features were ectopia lentis (95%) and mental retardation (86%). Other features included, dental anomalies (40%), osteoporosis (40%), behavioral problems (33%) and arachnodactyly (13%), Diagnosis was confirmed by iodoplatinate staining of one dimensional paper chromatography of urine.

An assay for the simultaneous quantitative determination of riboflavin and pyridoxine in eight different complementary infant meal products has been developed in order to (1) estimate the daily intake of these vitamins from commercial... more

An assay for the simultaneous quantitative determination of riboflavin and pyridoxine in eight different complementary infant meal products has been developed in order to (1) estimate the daily intake of these vitamins from commercial infant food consumption, and (2) ascertain their nutritional suitability relative to dietary guidelines for the 6-9 months age group. The method involves mild hydrolysis of the foods, an extraction of the supernatant by centrifugation followed by quantitative determination using ultra-high performance liquid chromatography. Separation of the two water soluble vitamins is achieved within one minute and the resultant sample is also LC-MS compatible. Despite wide individual differences between brands (p = 6.5e-12), no significant differences were observed in the level of pyridoxine between the meat and vegetable-based varieties (p = 0.7) per 100 g of commercial infant food. Riboflavin was not detected in any of the samples where the detection limit was below 0.07 lg/mL. In terms of the Reference Nutrient Intake (RNI) of pyridoxine for 6-9 months old infants, the complementary infant meal products analysed herein provided less than 15% of the RNI values with mean (SD) values of 12.87 (±4.46)% and 13.88 (±4.97)% for the meat-and vegetable-based recipes, respectively. The estimated total daily intake of riboflavin and pyridoxine from the consumption of commercial complementary food was found to be satisfactory and in accordance with the Dietary Reference Values (DRVs). The intake of both riboflavin and pyridoxine was estimated to be mainly derived from the consumption of formula milk which could be a cause of concern if the quality of an infant's milk diet is compromised by an inadequate or lack of supplemented milk intake. The results of this study suggest that the selected commercial complementary infant foods in the UK market may not contain the minimum levels of riboflavin and pyridoxine required for the labelling declaration of the micronutrient content of such products as recommended by Commission Directive 2006/125/EC.

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia... more

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B 12 , B 6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B 12 , and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (PϽ0.05), whereas the effect of MTHFR genotype was stronger (Pϭ0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype. (Arterioscler Thromb Vasc Biol. 1999;19:1316-1324.) Key Words: homocysteine Ⅲ methionine loading test Ⅲ methylenetetrahydrofolate reductase Ⅲ vitamins Ⅲ familial hyperhomocysteinemia Ⅲ premature vascular disease E levated plasma total homocysteine (tHcy) levels, either

We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a D 1 -piperideine-6-carboxylate (P6C)-a-aminoadipic... more

We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a D 1 -piperideine-6-carboxylate (P6C)-a-aminoadipic semialdehyde (a-AASA) dehydrogenase. The accumulating P6C inactivates pyridoxal 5¢-phosphate (PLP) by forming a Knoevenagel condensation product. Measurement of urinary a-AASA provides a simple way of confirming the diagnosis of PDS and ALDH7A1 gene analysis provides a means for prenatal diagnosis.

A method was developed for the quantitative analysis of six water-soluble vitamins (thiamine, nicotinamide, riboflavine, pyridoxine, ascorbic acid and pantothenic acid) in a pharmaceutical formulation, using free solution capillary zone... more

A method was developed for the quantitative analysis of six water-soluble vitamins (thiamine, nicotinamide, riboflavine, pyridoxine, ascorbic acid and pantothenic acid) in a pharmaceutical formulation, using free solution capillary zone electrophoresis (CZE) in uncoated fused silica capillaries and UV detection. The influence of different parameters, such as the nature of the buffer anionic component and buffer concentration on the CZE separation of vitamins was investigated using four vitamins of the B group as model compounds. A good compromise between resolution, analysis time and analyte stability was obtained by use of a 50 mM borax buffer of pH 8.5. This CZE method was found to be very useful for the separation of more complex samples, a mixture of ten water-soluble vitamins being completely resolved in about 10 min. However, cyanocobalamine could not be separated t¥om nicotinamide in this CZE system, the two compounds being in uncharged form at the pH used. These two compounds could easily be resolved by micellar electrokinetic chromatography (MEKC), the anionic surfactant dodecylsulfate being added to the running buffer at 25 mM concentration. In the pharmaceutical formulation, some excipients were found to be adsorbed to the capillary surface, giving rise to a progressive decrease of the electroosmotic flow and consequently to a simultaneous increase of analyte migration times. A capillary wash with sodium hydroxide had to be made between successive runs in order to minimize these effects. Good results with respect to linearity, precision and accuracy were obtained in the concentration range studied for the six vitamins, using nicotinic acid as internal standard. © 1997 Elsevier Science B.V.

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF... more

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF with (Hyperoxalurics, n=55) or without hyperoxaluria (Normooxalurics, n=57) as well as in 100 healthy male control subjects. Pyridoxal 5Õ-phosphate serum concentration (S-pyridoxal 5ÕP) and 24-h urinary excretion of 4-pyridoxic acid (U-4pyridoxic acid) were measured using HPLC; 24-h urinary excretion of oxalate (U-oxalate) was measured concurrently. A subgroup of subjects (40 Hyperoxalurics, 15 Normooxalurics and 50 controls) underwent the same measurements before and after 7day pyridoxine loading per os (pyridoxine hydrochloride, 300 mg/d). Under usual conditions, U-4pyridoxic acid was similar in the three groups, whereas mean S-pyridoxal 5ÕP was significantly lower (p<0.0001) in the Hyperoxalurics (59.6±21.2 nmol/L) and in the Normooxalurics (64.9± 19.7 nmol/L) than in the controls (86.0±31.0 nmol/L). No correlation could be found between U-oxalate and U-4pyridoxic acid or S-pyridoxal 5ÕP. After B6 loading, S-pyridoxal 5ÕP was still significantly lower in the Hyperoxalurics (415±180 nmol/L, p<0.001) and in the Normoox-alurics (429±115 nmol/L, p=0.036) than in the controls (546±180 nmol/L), although there was no difference between groups for U-4pyridoxic acid. No correlation in any group could be found between changes in U-oxalate and changes in U-4pyridoxic acid or S-pyridoxal 5ÕP. Although there is no vitamin B6 deficiency in ICSF with or without hyperoxaluria, these patients, on average, have lower levels of S-pyridoxal 5ÕP than healthy subjects. However, this slight decrease does not seem to account for idiopathic hyperoxaluria.

A new strategy for the analysis of natural products uses a combination of quantitative (1)H NMR (qHNMR) and adsorbent-free countercurrent separation (CS) methodology to establish a quantification method for ginkgotoxin... more

A new strategy for the analysis of natural products uses a combination of quantitative (1)H NMR (qHNMR) and adsorbent-free countercurrent separation (CS) methodology to establish a quantification method for ginkgotoxin (4'-O-methylpyridoxine) in Ginkgo biloba preparations. The target analyte was concentrated in a one-step CS process using the ChMWat +2 solvent system (CHCl3-MeOH-H2O, 10:5:5) and subsequently assayed by qHNMR. While commercial G. biloba seeds contained 59 μg of ginkgotoxin per seed, the compound was below the limit of detection (9 ppm) in a typical leaf extract. Due to the enrichment potential and loss-free operation of CS, the combination of CS and qHNMR is a generally suitable approach for threshold assays aimed at quantifying target compounds such as botanical negative markers at the low ppm level. As the proof of principle is demonstrated for relatively small CS capacities (20 mL, 1:40 loading) and modest NMR sensitivity (n = 16, 400 MHz, 5 mm RT probe), the ...

The influence of the co-factor pyridoxine, vitamin B6, on the activity of aromatic amino acid decarboxylase enzyme was studied by positron emission tomography, PET in the brain of the Rhesus monkey using the precursor for serotonin... more

The influence of the co-factor pyridoxine, vitamin B6, on the activity of aromatic amino acid decarboxylase enzyme was studied by positron emission tomography, PET in the brain of the Rhesus monkey using the precursor for serotonin synthesis 5-hydroxy-L-tryptophan (5-HTP) radiolabelled with ~1C in the [3-position. The rate constant for the formation of serotonin in the corpus striatum was calculated using a two tissue compartment model with reference area in the brain.

Topical etidocaine during laparoscopic tubal occlusion for postoperative pain relief. Obstet Gynecol 1986; 67: 447-49. 8 Cook PT, Lambert TF. An investigation of the effectiveness of bupivacaine applied to the endometrial wall and... more

Topical etidocaine during laparoscopic tubal occlusion for postoperative pain relief. Obstet Gynecol 1986; 67: 447-49. 8 Cook PT, Lambert TF. An investigation of the effectiveness of bupivacaine applied to the endometrial wall and fallopian tubes in reducing pain after laparoscopic sterilization. Anesth Intens Care 1986; 14: 148-51. 9 Smith BE, MacPherson GH, De Jonge M, Griffiths JM. Rectus sheath and mesosalpinx block for laparoscopic sterilization. Anaesthesia 1991; 46: 875-77. 10 Helvacioglu A, Weis R. Operative laparoscopy and post-operative pain relief. Fertil Steril 1992; 57: 549-52. 11 Alexander CD, Wethcheler BV, Thompson RE. Bupivacaine infiltration of the mesosalpinx in ambulatory surgical laparoscopic tubal sterilization.

Several methods are developed for the determination of two binary mixtures containing cyclizine hydrochloride with pyridoxine HCl (mixture (mix.) 1); and cinnarizine with piracetam (mix. 2). The resolution of the two binary mixtures has... more

Several methods are developed for the determination of two binary mixtures containing cyclizine hydrochloride with pyridoxine HCl (mixture (mix.) 1); and cinnarizine with piracetam (mix. 2). The resolution of the two binary mixtures has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression applied to UV spectra of the mixture and graphical spectrophotometric method as second derivative of the ratio spectra ( 2 DD). In addition, HPLC methods were developed depending on using RP18 column with mobile phase consisting of acetonitrile/0.05 M KH 2 PO 4 (50:50, v/v, pH 4.0) with UV detection at 239 nm for mix. 1, and mobile phase consisting of acetonitrile/0.05 M KH 2 PO 4 /triethylamine (50:50:0.2, v/v/v, pH 3.0) with UV detection at 227 nm for mix. 2. The proposed methods were successfully applied for the determination of the two binary combinations in synthetic mixtures and commercial tablets.

The objective of this study was to investigate whether zinc, along with pyridoxine, is effective in improving performance and egg quality of laying hens. One hundred and twenty, 28-week-old Hy-Line laying hens were assigned to four... more

The objective of this study was to investigate whether zinc, along with pyridoxine, is effective in improving performance and egg quality of laying hens. One hundred and twenty, 28-week-old Hy-Line laying hens were assigned to four treatment groups, 30 hens each. The birds were fed a basal diet or the basal diet supplemented with either 30 mg of zinc/kg of diet, 8 mg of pyridoxine/kg of diet, or 30 mg of zinc plus 8 mg of pyridoxine/kg of diet. Feed conversion (P < 0.01) and egg production (P < 0.01) improved most when both zinc and pyridoxine were supplemented to the diet. Eggshell weights were also greatest (P < 0.01) when the diet was supplemented with both pyridoxine and zinc. Egg-shape index was, however, greatest with zinc-supplemented diet (P < 0.004). Haugh unit was greatest in eggs of hens fed a diet supplemented with both zinc and pyridoxine (P < 0.01). Dietary zinc and pyridoxine supplementations together increased plasma calcium and phosphorous concentrations (P < 0.002). The results of the present study suggested that zinc (30 ppm) and pyridoxine (8 ppm) supplements, when used together, are recommended in terms of a better performance and egg quality in laying hens.

The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3,... more

The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo, we examined the ability of a nerve growth factor-expressing recombinant replication-defective herpes simplex virus-based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor-expressing vector prevented the development of pyridoxine-induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease.

Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent. We studied the associations of dietary... more

Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent. We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events. The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

The early onset of atherosclerotic lesions in homocystinuric individuals has implicated homocyst(e)ine in the development of atherosclerosis. Two trials were conducted in which diets totally or partially deficient in vitamin B-6 were fed... more

The early onset of atherosclerotic lesions in homocystinuric individuals has implicated homocyst(e)ine in the development of atherosclerosis. Two trials were conducted in which diets totally or partially deficient in vitamin B-6 were fed to pigs to investigate the accumulation of homocyst(e)ine in the plasma and the development of vascular lesions. In one trial plasma free homocyst(e)ine levels were 179 and 43 mumol/liter in deficient and adequate pigs, respectively, on day 24, while cysteine levels were 39 and 155 mumol/liter. The concentration of plasma protein-bound homocysteine and cysteine reflected the plasma-free values. Because pigs deficient in pyridoxine could be used only over short time intervals, pigs in trial 2 received 0, 0.03, 0.3 or 3 mg (i.e., 0, 2, 20 or 200% of allowance) of supplemental pyridoxine . HCl per kilogram diet. After 12 weeks pigs deficient and adequate in vitamin B-6 were injected intravenously with Evan's blue dye and the vascular trunk perfused...

Objective-To determine the current best practice for treatment of infantile spasms in children.

X-linked sideroblastic anemia (XLSA) is caused by mutations of the erythroid-specific 6-aminolevulinate synthase gene (ALAS2) resulting in deficient heme synthesis. The characteristic hypochromic, microcytic anemia typically becomes... more

X-linked sideroblastic anemia (XLSA) is caused by mutations of the erythroid-specific 6-aminolevulinate synthase gene (ALAS2) resulting in deficient heme synthesis. The characteristic hypochromic, microcytic anemia typically becomes manifest in the first three decades of life. Hematologic response to pyridoxine is variable and rarely complete. We report two unrelated cases of highly pyridoxine-responsive XLSA in geriatric patients previously diagnosed with refractory anemia and ringed sideroblasts. A previously unaffected 77-yr-old male and an 81-yr-old female were each found to have developed severe hypochromic, microcytic anemia with ringed sideroblasts in the bone marrow, which responded dramatically to pyridoxine with normalization of hemoglobin values. Sequence analysis identified an A to C transversion in exon 7 (K299Q) of the ALAS2 gene in the male proband and his daughter. In the female proband a

In 1989, the Community Bureau of Reference started a research program to improve the quality of vitamin analysis in food. To achieve this task, vitamin methodology was evaluated and tested by interlaboratory studies and the preparation of... more

In 1989, the Community Bureau of Reference started a research program to improve the quality of vitamin analysis in food. To achieve this task, vitamin methodology was evaluated and tested by interlaboratory studies and the preparation of certified reference materials, which will be used for quality control of vitamin measurements. The main improvements in methodology were achieved by testing and standardizing the extraction condition and enzymatic hydrolysis procedures. Results for each individual material are derived from five replicate determinations using at least two independent methods: liquid chromatography (HPLC) and microbiological assay for vitamins B 1 , B 2 , and B 6 ; and radioprotein binding and microbiological assays for vitamin B 12 . The certificate of analysis for four reference materials gives mass fraction values for water-soluble vitamins. These certified values were based on the acceptable statistical agreement of results from collaborating laboratories. Certified values with uncertainties (mg/kg dry matter) for each CRM are as follows: 4.63 (0.20) and 4.10 (0.51) for vitamins B 1 and B 6 , respectively, in CRM 121 (wholemeal flour); 6.51 (0.

In search for better mimics of the glutathione peroxidase enzymes, pyridoxine-like diselenides 6 and 11, carrying a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6 via aromatic... more

In search for better mimics of the glutathione peroxidase enzymes, pyridoxine-like diselenides 6 and 11, carrying a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6 via aromatic nucleophilic substitution of the 2-bromo substituent. LiAlH4 caused reduction of all four ester groups and returned 11 after acidic work-up. The X-ray structure of 6 showed that the dipyridyl diselenide moiety was kept in an almost planar, transoid conformation. According to NBO-analysis, this was due to weak intramolecular Se...O (1.1 kcal/mol) and Se...N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on selenium was confirmed by NPA-analysis and seen in calculated and observed 77Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromo compound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmed that...

Results as mean±SD. pmol mefloquine/lx378=pg mefloquine/1 and mol pyrimethamine/1 x 249 =pg pyrimethamine/l. " 3 *None of the 7 patients had detectable levels of SP or mefloquine in their sera before treatment. tPatients whose... more

Results as mean±SD. pmol mefloquine/lx378=pg mefloquine/1 and mol pyrimethamine/1 x 249 =pg pyrimethamine/l. " 3 *None of the 7 patients had detectable levels of SP or mefloquine in their sera before treatment. tPatients whose smears were negative on days 6 and 7.

4-Deoxypyridoxine (4-DPD) is a potent antagonist of Vitamin B6 coenzyme which inhibits IL-1, lymphocyte proliferation and has demonstrated that tollerance to skin grafts can be induced by administering splenic cells to... more

4-Deoxypyridoxine (4-DPD) is a potent antagonist of Vitamin B6 coenzyme which inhibits IL-1, lymphocyte proliferation and has demonstrated that tollerance to skin grafts can be induced by administering splenic cells to pyridoxine-deficient mice. Chronic inflammation induced by dorsal injections of 200 ~tt of a 1:40 saturated crystal solution of potassium permanganate (KMnO4) in mice treated or untreated with 4-DPD (400 ~tg/dose), has been investigated. After 7 days all mice developed a subcutaneous granulomatous tissue indicative of a chronic inflammatory response, at the site of injection. KMnO4-treated mice injected intraperitoneally with 4-DPD (400 ~tg/dose) on 5 consecutive days (the first at the same time of induction of the granuloma) show a significant decrease in size and weight ofgranuloma when compared to mice not treated with 4-DPD (Controis). In addition, in all mice treated with 4-DPD there was a strong inhibition of TNFct in serum (P<0.01) and in supernatant fluids (P<0.05) from minced granuloma, while IL-6 was inhibited in the supernatant fluids (P<0.05) of minced granulomas but was not detected in the serum of treated and untreated mice. In this study we show for the first time the antiinflammatory effect of 4-DPD on chronic inflammation and the inhibitory effect of TNF and IL~6 generation in supernatant fluids from minced

The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 μmol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation... more

The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 μmol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 μmol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.