Pyridoxal Research Articles

Pyridoxal 5′-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy

ObjectiveTo investigate the utility of serum pyridoxal 5′-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. MethodsBlood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. ResultsSerum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. ConclusionsThe serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.

SIMULTANEOUS ESTIMATION OF ISONIAZID AND PYRIDOXINE HYDROCHLORIDE IN TABLET DOSAGE FORM BY SPECTROPHOTOMETRY ULTRAVIOLET WITH AREA UNDER CURVE METHOD

Objective: This study aimed to develop spectrophotometry ultraviolet (UV) method by area under curve (AUC) to determine the levels of isoniazid (INH) and pyridoxine hydrochloride (PDX) in commercial tablets.Methods: Spectrophotometry UV method by AUC tested is carried out by optimizing the type of solvent, methanol, mixture of methanol, and phosphate buffer pH 4, pH 5, and pH 6 at a ratio of 90:10. The AUC value of each spectrum in various concentrations is calculated to selected wavelength range analysis. Then, this method was applied to determine the levels of INH and PDX in commercial tablets.Results: The application of AUC spectrophotometry UV method for determining the levels of INH and PDX was performed on wavelength range 262.2–272.2 nm and 289.8–299.8 nm, respectively. The selection of wavelengths based on wavelengths gives the best result. The mean % recoveries were found to be at 99.69% and 101.09% for INH and PDX, respectively.Conclusion: The method is successfully applied to analyze INH and PDX in pharmaceutical formulation simultaneously with no interference from excipients as indicated by all validation parameters which were within the acceptable range.

Inhibition effect of pyridoxamine on lipid hydroperoxide-derived modifications to human serum albumin.

Pyridoxamine (PM) is a promising drug candidate for treating various chronic conditions/diseases in which oxidative stress and carbonyl compounds are important factors affecting pathogenicity. These abilities of PM are mainly attributed to its inhibition of advanced glycation and lipoxidation end product formation, by scavenging reactive carbonyl species. PM might therefore prevent protein damage from lipid hydroperoxide-derived aldehydes such as 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE) by trapping them. It was previously reported that PM reacts with ONE to produce pyrrolo-1,3-oxazine (PO8) through the formation of pyrido-1,3-oxazine (PO1/PO2). In this study, we found that ONE and HNE yield an identical product containing a pyrrole ring (PO7, PH2) upon reaction with PM. The structure of PO7/PH2 was shown by LC-MS and NMR analyses to be 1-(2-hydroxy-6-hydroxymethyl-3-methylpyridin-4-ylmethyl)-2-pentylpyrrole. PO1, PO7/PH2, and PO8 were the main stable PM-ONE/HNE adducts. In the incubation of human serum albumin (HSA) with ONE or HNE, Lys residues provided the most favorable modification sites for both aldehydes, and the number of HNE-modified sites was higher than that of ONE-modified sites. When HSA was allowed to react with a linoleic acid hydroperoxide in the presence of ascorbic acid, ONE modified more residues (10 Lys, 3 His, 2 Arg) than did HNE (8 His, 2 Lys), indicating the relative reactivity of aldehydes towards amino acid residues. Upon treatment with increasing concentrations of PM, the concentrations of ONE-modified HSA peptides, but not of HNE-modified peptides, were reduced significantly and dose-dependently. Concomitantly, the formation of PM-ONE adducts increased in a dose-dependent manner. The inhibition effect of PM was also confirmed in the cell system subjected to oxidative stress. Our results demonstrate that PM can inhibit lipid hydroperoxide-derived damage to proteins by trapping ONE preferentially, and the resulting PM-ONE adducts can be used as a dosimeter for ONE production to determine the levels of lipid peroxidation.

Molecular Interactions of Saccharides and Their Derivatives with Thiamine HCl and Pyridoxine HCl Vitamins in Aqueous Solutions: Calorimetric, Viscometric, and NMR Spectroscopic Studies

Limiting standard enthalpies of dilution (ΔdilH°) and Jones–Dole viscosity B-coefficients of various polyhydroxy solutes, viz., saccharides, their methyl and deoxy derivatives, and sugar alcohol in 0.05, 0.15, 0.25, and 0.35 mol·kg–1 thiamine HCl(aq) and pyridoxine HCl(aq) solutions have been determined from heat change (q) and viscosity (η) data at T = 288.15–318.15 K and pressure p = 0.1 MPa. The corresponding transfer parameters (ΔtrΔdilH°, ΔtrB), change in heat capacity (ΔdilC°p,2,m), and enthalpic (hAB and hABB) and viscometric (ηAB and ηABB) pair and triplet interaction coefficients have also been derived. The dB/dT coefficients have been calculated and discussed in terms of the kosmotropic or chaotropic nature of solutes in aqueous solutions of vitamins. The present results have also been compared with previously reported studies carried out in l-ascorbic acid.(17) Further, NMR spectroscopy has been employed to understand the nature of interactions occurring in ternary solution {polyhydroxy solute ...

Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep.

Anecdotal evidence indicates that supplementation with vitamin B6 (pyridoxine) before bed can enhance dream vividness and recall. In a single pilot study, Ebben, Lequerica, and Spielman (2002) found that vitamin B6 had a dose-dependent effect of increasing scores on a composite measure of dream vividness, bizarreness, emotionality, and color. The present research replicated this study using a larger and more diverse sample of 100 participants from across Australia. We conducted a randomized, double-blind, placebo-controlled investigation of the effects on dreaming and sleep of ingesting 240 mg vitamin B6 (pyridoxine hydrochloride) before bed for five consecutive days. We also included an exploratory condition involving a B complex preparation containing a range of B vitamins. We found that vitamin B6 significantly increased the amount of dream content participants recalled but did not significantly affect dream vividness, bizarreness, or color, nor did it significantly affect other sleep-related variables. In contrast, participants in the B complex group showed significantly lower self-rated sleep quality and significantly higher tiredness on waking. We discuss the potential for using vitamin B6 in research on lucid dreaming.

Simultaneous spectrophotometric determination of thiamine and pyridoxine in multivitamin dosage forms using H-point standard addition and Vierodt᾿s methods

Two simple, reliable and accurate spectrophotometric methods were described for the simultaneous determination of thiamine hydrochloride (THC) and pyridoxine hydrochloride (PYH) in pharmaceutical formulation without any pre-separation procedures. These methods are based on the difference in the color observed from diazotization coupling methods of THC and PYH. When the diazonium salts formed from the reaction of HNO2 with p-nitroaniline (PNA), they were coupled with THC and PYH in sodium hydroxide medium and the formed dyes had maximum absorption bands at 452 nm for THC and 482 nm for PYH. All experimental parameters were optimized to reduce experimental error. The first method was based on the Vierodt᾿s method, in which the two wavelengths 452 and 482 nm λmax of THC and PYH, respectively, were selected for the formation of simultaneous equation. In the second method the H-point standard addition method (HPSAM) was applied, when absorbances at wavelengths pair, 452 and 500 nm, were monitored with the addition of a standard solution of THC to a solution containing a fixed concentration of THC and PYH. The results from applying Vierodt᾿s and HPSA methods showed that THC and PYH can be determined simultaneously in the concentration range 1.5–11.0 μg mL−1 (LOD = 0.48 μg mL−1) and 0.4–5.0 μg mL−1 (LOD = 0.23 μg mL−1), respectively. The methods were successfully applied for simultaneous determination of THC and PYH in different synthetic and pharmaceutical products. To assess the obtained vitamins (THC and PYH) analysis by both methods (Vierodt᾿s and HPSAM) in the several pharmaceutical formulations, the results are compared with that obtained by HPLC method as a reference, and good agreements between the results indicate the reliability of the proposed methods.

EVALUATION OF A MODIFIED BIOMATERIAL OF TYMPANOTONUS FUSCATA SHELL POWDER II: FORMULATION OF PYRIMETHAMINE AND PYRIDOXINE HYDROCHLORIDE TABLETS

A novel modified biomaterial of periwinkle shell powder, MBPSP was developed from Tympanotonus fuscata . It was assessed as a bulking agent in the formulation of pyrimethamine and pyridoxine hydrochloride tablets adopting dicalcium phosphate dihydrate (DCP) as a standard. A 100 g of the ground periwinkle shell was broken down in 166.0 ml of 2 M hydrochloric acid, clarified and treated with 5 M sodium hydroxide. The thick white precipitate obtained was washed severally and to it, ortho-phosphoric acid was dropped in bits until a thick, dehydrated bulk was attained which was dried at 60 o C and classified with 250 μm sieve. The product was coded MBPSP. Two batches of granules containing pyrimethamine (25 mg) and pyridoxine hydrochloride (50 mg) were generated by the wet granulation employing MBPSP alongside DCP. The granules were lubricated with magnesium stearate and talc and compacted into tablets at 7.55kN using a 10.50 mm diameter die and flat-faced punch fixed in a hydraulic hand press. The tablet produced were evaluated using the British Pharmacopoeia specifications. The weight variation for the pyrimethamine or pyridoxine hydrochloride tablets containing MBPSP or DCP were 0.06, 0.1, 0.097 and 0.143 % respectively. The total drug content for the individual lots of tablets for either pyrimethamine or pyridoxine hydrochloride was within 85.00-115.00 % of their label claim. Higher mechanical strength were noted for the batch of tablets manufactured with DCP and containing pyrimethamine and pyridoxine hydrochloride than MBPSP. Though the entire batches of tablets for the two drugs manufactured with either MBPSP or DCP disintegrated in less than 5.00 min with no significant difference in their individual disintegrating time (p>0.05), pyridoxine hydrochloride tablets prepared with DCP disintegrated in lesser time when compared to MBPSP (p<0.05). Only the pyrimethamine tablets prepared with MBPSP attained 75.00 % drug release in 45.00 min in line with the United States Pharmacopoeia (USP) criteria. Therefore, MBPSP could be another very useful bulking agent in the formulation of pyrimethamine immediate-release tablets by the wet granulation technique. Keywords : Modified biomaterial, Tympanotonus fuscata, periwinkle, shell, pyrimethamine, pyridoxine hydrochloride, tablet.

Efficiency of inosine glycyl-cysteinyl-glutamate disodium and pyridoxine in acute poisoning by unsymmetrical dimethylhydrazine

Effectiveness of pyridoxine hydrochloride and inosine glycyl-cysteinyl-glutamate dinatrium (molixan) in monotherapy and in combination in acute poisoning by unsymmetrical dimethylhydrazine on survival, blood biochemical indicators and the state of plasma coagulation hemostasis was assessed. Unsymmetrical dimethylhydrazine was administered intraperitoneally at a dose of 115 mg/kg (LD50) once. Drugs under examination were also admistered intraperitoneally: pyridoxine hydrochloride in a dose of 50 mg/kg once, 30 minutes after the administration of unsymmetrical dimethylhydrazine, the inosine glycyl-cysteinyl-glutamatedinatrium (molixan) in a dose of 60 mg/kg seven times: 30 minutes after the administration of unsymmetrical dimethylhydrazine, and then daily for 6 days. Biochemical parameters of blood, plasma coagulation hemostasis, were evaluated 7 days after the administration of unsymmetrical dimethylhydrazine. The use of pyridoxine as a monotherapy and in combination with molixan prevents death of experimental animals and the development of convulsive syndrome. In addition, the combination of molixan with pyridoxine eliminates the development of toxic lesions of liver that is having hepatoprotective effect. The efficiency of molixan as hepatoprotector, apparently, related to the fact that in its structure it is a combined preparation containing the peptide and purine components. The peptide component (glycyl-cysteinyl-glutamate dinatrium) is a pharmacological analogue of oxidized glutathione, purine is represented by inosine. Oxidized glutathione has cytoprotective activity, inhibits the cytolysis of hepatocytes, and reduces the severity of inflammatory process during toxic damage of liver cells by the products of metabolism of xenobiotics. Inosine also has hepatoprotective properties. As a precursor to the synthesis of adenosine triphosphoric acid and nucleotides, it stimulates a number of metabolic processes in body, supports energy balance in various tissues, particularly in liver and myocardium.

Validated Analytical Methods for the Determination of Drugs Used in the Treatment of Hyperemesis Gravidarum in Multiple Formulations.

Quantitative multicomponent analysis is considered an analytical goal to save time and cost in analysis. Hence, this work aimed to provide sensitive and selective UV-spectrophotometric, chemometric manipulation, and ultra-performance LC (UPLC) methods for the determination of well-known coformulated antiemetics used in pregnancy, namely pyridoxine HCl (PYR), meclozine HCl, and cyclizine. The developed UV-spectrophotometric methods are dual wavelength in ratio spectra and first derivative of the ratio spectra with which PYR was determined selectively at 290.8 nm, whereas the other drugs in a ternary mixture were determined from their ratio spectra using a spectrum of PYR as a divisor in 0.1 M HCl. An ecofriendly partial least-squares regression chemometric method was applied to raw UV absorbance data for the determination of the ternary mixture in a 218-355 nm range using a three-factor, three-level design with water as the green solvent. A gradient UPLC method was developed and successfully resolved the ternary mixture within 5 min. Different ratios of water (adjusted to pH 3 with phosphoric acid) and methanol were delivered at 0.5 mL/min as the mobile phase into a Hypersil Gold C18 column (50 × 2.1 mm, 1.9 µm). The developed methods were successfully applied to different pharmaceutical formulations containing the aforementioned drugs and validated according to the International Conference on Harmonization guidelines. The results obtained were reproducible and reliable and can be applied for routine analysis and QC in laboratories.

Надання допомоги вагітним з істміко-цервікальною недостатністю за наявності нутритивної магнієвої недостатності

The objective: of the study was the feasibility of further improvement of giving medical aid to pregnant women with cervical insufficiency, especially with nutritional magnesium deficiency. Materials and methods. The observation group was made of 50 women, in which in 13–16 week of pregnancy was diagnosed cervical insufficiency with presence of nutritional magnesium deficiency (amount of magnesium in blood &lt;0.8 mmol/1). Level of magnesium ions in blood plasma of pregnant women was determined by colorimetric method using the analyzer Cobas 600c (501 module) and test systems Roche Diagnostics (Switzerland). The degree of CIn was determined with Shtembera scale. To correct magnesium deficiency was recommended Magnicum (PJSC «Kyiv Vitamin Factory») 2 tablets 2 times a day with meals. One tablet contains magnesium lactate dihydrate 470 mg, equivalent to 48 mg of magnesium and pyridoxine hydrochloride (vitamin B6) 5 mg. Results. One of the pathogenetic factors of CIn is nutritional magnesium deficiency in pregnant women. The results of correlation analysis showed the presence of a strong feedback (r =-0.83) between the concentration of magnesium ions in the blood serum of pregnant women and the inner diameter orifice of uterine cervix, and direct communication of medium strength (r=0.38) with a length of cervix. In studying of the correlations between blood parameters and morphometric parameters of cervix, was established a close relationship (r=0.78) between the length of cervix and parameters of vascular resistance in small arteries of cervix. At the same time, a weak correlation (r=-0.41) between the diameter of the inner orifice of cervix and hemodynamic parameters in small cervical arteries suggests that the change in diameter of the orifice is secondary in relation to disturbances in blood flow in small cervical arteries. Conclusion. Usage of Magnicumu provides effective correction of hypomagnesemia in pregnant, prevents the progression of CIn, reduces the frequency of miscarriage, reduces number of surgical cerclage of cervix, prevents complications during labor. Key words: Cervical insufficiency, nurtitional magnesium deficiency, Magnicum.

Advanced spectrophotometric chemometric methods for resolving the binary mixture of doxylamine succinate and pyridoxine hydrochloride.

The prediction power of partial least squares (PLS) and multivariate curve resolution-alternating least squares (MCR-ALS) methods have been studied for simultaneous quantitative analysis of the binary drug combination - doxylamine succinate and pyridoxine hydrochloride. Analysis of first-order UV overlapped spectra was performed using different PLS models - classical PLS1 and PLS2 as well as partial robust M-regression (PRM). These linear models were compared to MCR-ALS with equality and correlation constraints (MCR-ALS-CC). All techniques operated within the full spectral region and extracted maximum information for the drugs analysed. The developed chemometric methods were validated on external sample sets and were applied to the analyses of pharmaceutical formulations. The obtained statistical parameters were satisfactory for calibration and validation sets. All developed methods can be successfully applied for simultaneous spectrophotometric determination of doxylamine and pyridoxine both in laboratory-prepared mixtures and commercial dosage forms.

The effects of vitamin B6 compounds on cell proliferation and melanogenesis in B16F10 melanoma cells

B16F10 murine melanoma cells are frequently used for the study of cancer and melanogenesis. The cells are usually cultured in Dulbecco's Modified Eagle Medium, with the addition of 20 µM pyridoxal (PL) or pyridoxine (PN) for vitamin B6. The difference between these vitamin B6 compounds is thought not to affect cell proliferation, whereas their influence on other physiological effects is poorly understood. In the present study, the effects of PL and PN on cell proliferation and melanogenesis in B16F10 cells were compared. At 500 µM PL significantly suppressed cell growth but the growth inhibitory effect of PN was weak. Although neither of the vitamin B6 compounds affected cell growth at 20 µM, melanogenesis was suppressed by 20 µM PL compared with the effect of PN. In addition, the expression levels of tyrosinase, which is the rate-limiting enzyme, correlated with the melanin content. The results of the present study indicate that PL may be more useful for melanoma therapy and suppression of skin pigmentation than PN. The results also signify the importance of medium selection for cell culture.

Deficiency of dietary pyridoxine disturbed the intestinal physical barrier function of young grass carp (Ctenopharyngodon idella)

The aim of this study was to assess the effects of dietary pyridoxine (PN) deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular tight junction in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (231.85 ± 0.63 g) were fed six diets containing graded levels of PN (0.12–7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed that compared with the optimal PN level, PN deficiency (1) increased the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), decreased the activities and mRNA levels of antioxidant enzymes such as copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) (P < .05); (2) up-regulated the mRNA levels of cysteinyl aspartic acid-protease-3 (caspase-3), caspase-7, caspase-8, caspase-9, Bcl-2 associated X protein (Bax), apoptotic protease activating factor-1 (Apaf-1) and Fas ligand (FasL), and down-regulated the mRNA levels of inhibitor of apoptosis proteins (IAP), B-cell lymphoma protein-2 (Bcl-2) and myeloid cell leukaemia-1 (Mcl-1) (P < .05); (3) down-regulated the mRNA levels of ZO-1, occludin [only in middle intestine (MI)], claudin-b, claudin-c, claudin-f, claudin-3c, claudin-7a, claudin-7b and claudin-11, and up-regulated the mRNA levels of claudin-12 and claudin-15a (P < .05), which might be partly linked to Kelch-like-ECH-associated protein 1a (Keap1a)/NF-E2-related factor 2 (Nrf2), p38 mitogen-activated protein kinase (p38MAPK) and myosin light chain kinase (MLCK) signalling in the intestines of fish. However, the activities and mRNA levels of MnSOD, the mRNA levels of Keap1b, c-Jun N-terminal protein kinase (JNK) and claudin-15b in three intestinal segments, and the mRNA levels of occludin in the proximal intestine (PI) and distal intestine (DI) were not affected by graded levels of PN. These data indicate that PN deficiency could disturb the intestinal physical barrier function of fish. Additionally, based on the quadratic regression analysis for MDA content and GST activity, the dietary PN requirements for young grass carp were estimated as 4.85 and 5.02 mg/kg diet, respectively.

The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone.

ObjectivesAdvanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality.MethodsAn in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence.ResultsTreatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05).ConclusionsThe data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics).Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1.

Development and Validation of a RP-HPLC Method for the Simultaneous Estimation of Prochlorperazine Maleate and Pyridoxine Hydrochloride in Combined Dosage Forms

A simple, precise and economical RP-HPLC method was developed and validated for simultaneous determination of prochlorperazine maleate and pyridoxine hydrochloride in pharmaceutical dosage form. The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on C18 (250 mm× 4.6mm) 5μm column with isocratic flow. The mobile phase at flow rate of 1.2 ml/min, consisted of acetonitrile-water (60: 40 V/V), pH adjusted to 3.0 with triethylamine. The UV detection was carried out at 267.5 nm. A linear response was observed over the concentration range of 1–5μg/ml of prochlorperazine maleate and the concentration range of 5–25μg/ml of pyridoxine hydrochloride. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, ruggedness and system suitability. The results of recovery study were found to be within the prescribed limit of 98–102%. During the linearity study, it was observed that absorbance values of prochlorperazine maleate and pyridoxine hydrochloride in marketed formulation were linear and r2 close to 1 for this method of analysis. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operators has proven that the method is robust and rugged.

A case of perinatal hypophosphatasia with a novel mutation in the &lt;i&gt;ALPL&lt;/i&gt; gene: clinical course and review of the literature

.Hypophosphatasia (HPP) is a metabolic bone disease characterized by failure of bone calcification and vitamin B6 dependent seizures. It is caused by loss-of-function mutations in the ALPL gene. A newborn girl required respiratory support by nasal-directional positive airway pressure at birth, and pyridoxine hydrochloride administration for vitamin B6-dependent seizures observed from day two. Umbilical cord blood showed low alkaline phosphatase (ALP) activity and high pyridoxal phosphate levels. Radiographs showed severe rickets-like appearance of the bones. Genetic analysis of the ALPL gene revealed compound heterozygous mutations, c.1559delT/p.Ser188Pro. We diagnosed her with perinatal severe HPP, and started the patient on asfotase alfa from day six. Following enzyme replacement therapy (ERT), skeletal mineralization and respiratory insufficiency improved with no remarkable side-effects. Crying vital capacity (CVC) was used to evaluate respiratory status, which continuously improved from 13.3 mL/kg (day 22) to 20.6 mL/kg (day 113). Since no seizures occurred, pyridoxine hydrochloride was tapered off at one year of age. Strategies to manage perinatal severe HPP cases following ERT have not been established till date. A review of the literature shows that CVC may be a good indicator for weaning from ventilatory support. In addition, ERT will most likely enable withdrawal of pyridoxine treatment.

ВЛИЯНИЕ ПИРИДОКСИНА И ПРЕПАРАТОВ ГИДРОЗИДА ИЗОНИКОТИНОВОЙ КИСЛОТЫ НА НЕРВНУЮ СИСТЕМУ ПРИ ЛЕЧЕНИИ ТУБЕРКУЛЕЗА

When treating tuberculosis patients with multi-component chemotherapy it is necessary to use medications in order to manage or minimize side effects. The review presents research findings on the effect of pyridoxine and its derivatives on the nervous system and their interaction with the agents of isonicotinic acid hydrazide. The review tells about combination drugs containing pyridoxine and pyridoxine hydrochloride used for treatment of tuberculosis.

Visible light absorption of TiO2 nanoparticles surface-modified with vitamin B6: A comparative experimental and DFT study

Surface modification of titanium dioxide nanoparticles (TiO2 NPs) with the biologically active molecule pyridoxine hydrochloride (vitamin B6) was found to alter the optical properties. Microstructural characterization involving transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis revealed that the anatase TiO2 NPs had a narrow size distribution with an average diameter of 45 ?. The absorption onset of the surface-modified TiO2 samples was red-shifted by about 0.4 eV compared to the unmodified particles. The mode of binding between vitamin B6 and the surface Ti atoms was investigated by Fourier transform infrared spectroscopy (FTIR). From the Benesi? Hildebrand plot, the stability constant of the surface complex was found to be of the order 102 M-1. The experimental findings were supported by detailed quantum chemical calculations based on the density functional theory (DFT). Agreement was found between the experimentally measured absorption spectra of the TiO2 NPs surface-modified with vitamin B6 and the theoretically calculated electronic excitation spectra of the corresponding model system.

Impacts of Graded Doses of Pyridoxine on the Biomarkers, Aspartate Aminotransferase, lactate Dehydrogenase and Total Antioxidant Capacity in Doxorubicin-Induced Cardiotoxicity in Female Rats

Abstract:&#x0D; The aim of the current study was to investigate the possible protective effect of graded doses (5, 10, and 15mg/kg) of pyridoxine hydrochloride intraperitoneally injected against (15mg/kg) doxorubicin-induced cardiotoxicity in female rats. Fifty-six (56) Wistar albino female rats were utilized weighing 180-200 gm allocated into eight groups, seven rats each; Group I: negative control distilled water; Group II: Pyridoxine (5mg/kg); Group III: Pyridoxine (10mg/kg); Group IV: Pyridoxine (15mg/kg); Group V: doxorubicin (15 mg/kg); Group VI: Pyridoxine (5 mg/kg) prior to doxorubicin (15 mg/kg); Group VII: Pyridoxine (10 mg/kg) prior to doxorubicin (15 mg/kg); Group VIII: Pyridoxine (15 mg/kg) prior to doxorubicin (15 mg/kg). DOX caused significant elevations in serum biomarker enzymes of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and significant reduction in heart tissue homogenate content of total antioxidants capacity (TAOC). Treatment with 15mg/kg pyridoxine for four consecutive days prior to a single dose 15mg/kg doxorubicin resulted in significant reduction in serum enzymes level of AST and LDH. Treatment with 10 or 15mg/kg pyridoxine for four consecutive days prior to a single dose of doxorubicin produced significant increments in TAOC heart tissue homogenate level compared to positive control. In conclusion, pyridoxine supplementation might be a promising adjunctive agent for improving oxidative stress and biological markers for preventing DOX-induced cardiac complications.

Pyridoxamine improves survival and limits cardiac dysfunction after MI

Advanced glycation end products (AGEs) play a key role in the progression of heart failure. Whether treatments limiting AGEs formation would prevent adverse left ventricular remodeling after myocardial infarction (MI) remain unknown. We investigated whether pyridoxamine (PM) could limit adverse cardiac outcome in MI. Rats were divided into MI, MI + PM and Sham. Echocardiography and hemodynamic parameters were used to assess cardiac function 8 weeks post-surgery. Total interstitial collagen, collagen I and collagen III were quantified using Sirius Red and polarized light microscopy. PM improved survival following LAD occlusion. Pre-treatment with PM significantly decreased the plasma AGEs levels. MI rats treated with PM displayed reduced left ventricular end-diastolic pressure and tau compared to untreated MI rats. Deformation parameters were also improved with PM. The preserved diastolic function was related to the reduced collagen content, in particular in the highly cross-linked collagen type I, mainly in the peri-infarct region, although not via TGF-β1 pathway. Our data indicate that PM treatment prevents the increase in AGEs levels and reduces collagen levels in a rat model of MI, resulting in an improved cardiac phenotype. As such, therapies targeting formation of AGEs might be beneficial in the prevention and/or treatment of maladaptive remodeling following MI.