Modulatory effect of vitamin B6 on sex hormone receptors, thyroid, and kisspeptin/kiss1r system in the uterus of pseudopregnant bitches.

This study evaluated whether the treatment of pseudopregnancy in bitches with vitamin B6 modulates uterine expression of receptors for progesterone (PR), oestrogen (ERα), androgen (AR), thyroid hormone (TRα) and the kisspeptin/Kiss1r system. Eighteen pseudopregnant bitches were treated for 20 days in groups receiving placebo (n = 6); cabergoline (5 µg/kg/day; n = 6); or vitamin B6 (50 mg/kg/day; n = 6). Blood was collected on the 1st day of drug administration and 120 h later to measure serum prolactin (PRL). After treatment, they were ovariohysterectomized and uterine fragments were collected for histomorphometry and immunohistochemical evaluation of PR, ERα, AR, TRα, Kiss1 and Kiss1r. After 120 h of cabergoline or vitamin B6 treatment, PRL levels were reduced in the bitches, confirming the antiprolactinemic effect of these drugs. Furthermore, regardless of treatment, the animals exhibited uterine histomorphometry consistent with dioestrus. The PR showed strong immunostaining in all regions and an increase in scores was observed for this receptor in animals treated with vitamin B6 in deep glands. In contrast, ERα and Kiss1R receptors showed weak to no immunostaining in all uterine regions and no changes between groups. Regarding AR, most animals treated with vitamin B6 showed increased trends in the deep gland and myometrium marking scores. In contrast, in both vitamin B6 and cabergoline treatments, a reduction in TRα marking scores was observed compared to the control group. In addition, on the endometrial surface, a reduction was observed in the marked area of Kiss1 after administration of cabergoline when compared to the pseudopregnant control group. These findings shed valuable insight into the use of vitamin B6 as a drug with actions similar to cabergoline in reducing PRL and uterine modulation in bitches.

Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos / Neurotropic B vitamins and peripheral neuropathy: State of the art and agreement of experts

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Effect of pyridoxine or cobalamin supplementation on apoptosis and cell cycle progression in a human glioblastoma cell line.

Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression. AIM: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG. METHOD: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot. RESULT: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined. CONCLUSION: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.

Nitrogen and sulfur co-doped graphene quantum dot-modified electrode for monitoring of multivitamins in energy drinks.

A glassy carbon electrode was modified with nitrogen and sulfur co-doped graphene quantum dots immobilized in chitosan for the monitoring of multivitamins. The graphene quantum dots were synthesized using a simple citric acid/l-cysteine pyrolysis procedure. The co-doping with nitrogen and sulfur in the graphene matrix was confirmed by spectroscopic techniques. Electron microscopy results showed that the synthesized quantum dots had a diameter of 3.4 ± 1.4 nm. Electrochemical techniques showed excellent current responses to vitamin oxidation provided by the modified electrode compared to the bare electrode. The parameters of square wave voltammetry were optimized in order to obtain the best current responses and to study the electrochemical oxidation of vitamins. The calibration plots for vitamins B2, B6 and B12 were constructed in 0.1 mol L-1 sodium acetate buffer (pH 5.0) with limits of detection of 0.30, 30.1 and 0.32 nmol L-1, respectively. Lastly, the modified electrode was effectively implemented in the quantification of vitamins in classic and fruit-based energy drink samples.

The 6-week Effects of HIIT on Biomarkers of Tissue and Oxidative Damage in Wistar Rats Previously Supplemented with Pyridoxine.

We aimed to analyze the effects of long high-intensity interval training (HIIT) associated with pyridoxin supplementation on tissue and oxidative injury markers in animals. Male Wistar rats were divided into three groups (n = 8): sedentary (GS), HIIT (GH), and HIIT + pyridoxine (GHP). The HIIT comprised 18 sessions of 7 repetitions of 2min × 2min rest, 3 times per week. Pyridoxine was administered to the GHP group 1h before the exercise. The Thiobarbituric acid reactive substances (TBARS) and sulfhydryl group (SH) were analyzed as markers of oxidative stress and CK, LDH, ALT and AST as tissue lesions. There was an increase in the correlation between CK and LDH of 172.86% and 268.83% in the GH group compared with the GS group, respectively. There was a reduction in CK (34.37%) and LDH (34.74%) compared with the GH group, which had an increase of 229.03% in ALT. Pyridoxine supplementation reduced ALT by 80.62% in the GHP group compared with no-supplementation GH group. In addition, there was a reduction in plasma MDA (52.92%), liver (20.30%) and cardiac (22.06%) tissues in GHP compared to GH. It was possible to conclude that administration of pyridoxine attenuated oxidative stress, and tissue injuries induced by HIIT.

The 6-week Effects of HIIT on Biomarkers of Tissue and Oxidative Damage in Wistar Rats Previously Supplemented with Pyridoxine.

We aimed to analyze the effects of long high-intensity interval training (HIIT) associated with pyridoxin supplementation on tissue and oxidative injury markers in animals. Male Wistar rats were divided into three groups (n = 8): sedentary (GS), HIIT (GH), and HIIT + pyridoxine (GHP). The HIIT comprised 18 sessions of 7 repetitions of 2min × 2min rest, 3 times per week. Pyridoxine was administered to the GHP group 1h before the exercise. The Thiobarbituric acid reactive substances (TBARS) and sulfhydryl group (SH) were analyzed as markers of oxidative stress and CK, LDH, ALT and AST as tissue lesions. There was an increase in the correlation between CK and LDH of 172.86% and 268.83% in the GH group compared with the GS group, respectively. There was a reduction in CK (34.37%) and LDH (34.74%) compared with the GH group, which had an increase of 229.03% in ALT. Pyridoxine supplementation reduced ALT by 80.62% in the GHP group compared with no-supplementation GH group. In addition, there was a reduction in plasma MDA (52.92%), liver (20.30%) and cardiac (22.06%) tissues in GHP compared to GH. It was possible to conclude that administration of pyridoxine attenuated oxidative stress, and tissue injuries induced by HIIT.

Stability of B vitamins, vitamin E, xanthophylls and flavonoids during germination and maceration of sorghum (Sorghum bicolor L.).

The impact of maceration and germination on the concentration of bioactive compounds still needs to be evaluated. The stability of B complex vitamins (thiamine, riboflavin, pyridoxine), vitamin E (α, ß, γ, δ tocopherols and tocotrienols), xanthophylls (lutein and zeaxanthin) and flavonoids (3-deoxyanthocyanidins-3-DXAs, flavones and flavanones) was evaluated in sorghum grains subjected to maceration and germination, using High Performance Liquid Chromatography. Maceration and germination reduced thiamine and pyridoxine concentrations (retentions ranging from 3.8 to 50.2%). Riboflavin and Vitamin E concentrations were not affected by maceration. Germination increased riboflavin and reduced vitamin E. 3-DXAs were sensitive to maceration and germination (retentions of 69.6% and 69.9%, respectively). Flavones contents decreased with germination. Our results indicate that, after germination and/or maceration, sorghum had important nutritional and functional value. Thus, its intake, mainly in macerated forms, should be encouraged, since concentrations of riboflavin, vitamin E and flavones were not altered during this processing.

Neonatal pyridoxine administration long lastingly accelerates cortical spreading depression in male rats, without affecting anxiety-like behavior.

Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD).Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session).Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed.Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.

Update on Safety Profiles of Vitamins B1, B6, and B12: A Narrative Review.

The neurotropic B vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are essential for proper functioning of the nervous system. Deficiencies may induce neurological disorders like peripheral neuropathy (PN) and mainly occur in vulnerable populations (eg, elderly, diabetics, alcoholics). As epidemiologic cohort studies raised safety concerns about vitamin B6/B12 intake being potentially associated with increased risks of hip fracture (HF) and lung cancer (LC), we explored these aspects and performed comprehensive literature searches. However, we suggest not to neglect actual high-risk factors (eg, smoking in LC, higher age in HF) by focusing on individual nutrients, but to examine the complex interaction of numerous factors involved in disease development. Because it warrants continued consideration, we also provide an update on neurotoxicity associated with vitamin B6. We consider that neurological side effects due to vitamin B6 intake are rare and only occur with high daily doses and/or longer treatment duration. The benefit-risk ratio of high-dose treatment with neurotropic B vitamins in indications like PN is therefore considered advantageous, particularly if dosing recommendations are followed and serum levels monitored.

B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin.

BACKGROUND: Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency. AIM: This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways. DISCUSSION: We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter-related and complement each other. CONCLUSION: Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.

Encuesta sobre el uso de la metadoxina en hepatopatías de pequeños animales en Colombia / Survey on the use of metadoxine in liver diseases of small animals in Colombia / Enquete sobre o uso da metadoxina em hepatopatias de pequenos animais na Colômbia

Resumen La metadoxina es un fármaco con potencial efecto antioxidante y antifibrótico suministrado en medicina humana esencialmente en el tratamiento para esteatohepatitis aguda o crónica por etanol. Numerosos ensayos clínicos e investigaciones experimentales soportan su indicación; no obstante, en medicina veterinaria no hay estudios de campo con tal propósito, pese a que reportes aislados de su indicación en hepatopatías secundarias existen en bases de datos latinoamericanas. El objetivo del presente estudio fue reportar la prescripción de metadoxina en hepatopatías de caninos y felinos en la práctica rutinaria en Colombia. Aplicando herramientas de la web en línea, se realizó una encuesta orientada a establecer algunas pautas de tratamiento con metadoxina en dicho campo. Los resultados demostraron que el 55 % de los veterinarios participantes instauraron al menos una vez la metadoxina en caninos y felinos. El 74,6 % de estos reportó una evolución favorable. Como terapia conjunta, modificaciones en la dieta, silimarina y ácido ursodeoxicólico fueron prescritos en el 80, 45,5 y 38,2 % de los casos, respectivamente. Se detectó una amplia variación respecto a la dosis, la vía, la frecuencia y la duración del protocolo terapéutico. En cuanto a la prescripción oral, la dosis fue 17,3 ± 11,4 mg/dl cada 12 h. Los resultados obtenidos confirman el uso de la metadoxina como tratamiento de hepatopatías en caninos y felinos en Colombia. De aquí se resalta la necesidad de efectuar ensayos clínicos que pongan a prueba el efecto de la metadoxina sobre la evolución clínica y paraclínica y el pronóstico de determinadas hepatopatías en caninos y felinos.

Abstract Metadoxine is a drug with a potential antioxidant and antifibrotic effect that is essentially used in human medicine in the treatment of acute or chronic alcoholic steatohepatitis. Numerous clinical trials and experimental investigations support its use; however, in veterinary medicine there are no field studies on this topic, although there exist isolated reports of its indication in secondary liver diseases in Latin American databases. The present study aimed to report on the prescription of metadoxine in canine and feline hepatopathies in routine practice in Colombia. Applying online web tools, a survey was conducted to establish some treatment guidelines for the use of metadoxine in the said field. Results showed that 55% of participating veterinarians prescribed metadoxine at least once in canines and felines. 74.6% of them reported a favorable evolution. As a joint therapy, dietary modifications, silymarin, and ursodeoxycholic acid were also prescribed in 80, 45.5, and 38.2% of the cases, respectively. A wide variation was detected regarding the dose, application route, frequency, and the duration of the therapeutic protocol. Regarding oral prescription, the dose was 17.3 ± 11.4 mg/dl every 12 hours. The results confirm the use of metadoxine as a treatment for hepatopathies in dogs and cats in Colombia. This highlights the need to carry out clinical trials that test the effect of metadoxine on the clinical and paraclinical evolution and prognosis of certain hepatopathies in dogs and cats.

Resumo A metadoxina é um fármaco com potencial efeito antioxidante e anti-fibrótico administrado em medicina humana essencialmente no tratamento para esteato-hepatite aguda ou crônica por etanol. Numerosos ensaios clínicos e investigações experimentais sustentam sua indicação; não obstante, em medicina veterinária não há estudos de campo com tal propósito, em que pese relatos isolados de sua indicação em hepatopatias secundárias existam em bases de dados latino-americanas. O objetivo do presente estudo foi relatar a prescrição de metadoxina em hepatopatias de caninos e felinos na prática rotineira na Colômbia. Aplicando ferramentas da web em linha, se realizou uma enquete orientada a estabelecer algumas pautas de tratamento com metadoxina neste campo. Os resultados demostraram que 55 % dos veterinários participantes utilizaram ao menos uma vez a metadoxina em caninos e felinos. O 74,6 % destes relatou uma evolução favorável. Como terapia conjunta, modificações na dieta, silimarina e ácido ursodeoxicólico foram prescritos no 80, 45,5 e 38,2 % dos casos, respectivamente. Se detectou uma ampla variação com respeito a dose, a via, a frequência e a duração do protocolo terapêutico. Quanto à prescrição oral, a dose foi 17,3 ± 11,4 mg/dl a cada 12 horas. Os resultados obtidos confirmam o uso da metadoxina como tratamento de hepatopatias em caninos e felinos na Colômbia. Daqui se ressalta a necessidade de efetuar ensaios clínicos que ponham à prova o efeito da metadoxina sobre a evolução clínica e para clínica e o prognóstico de determinadas hepatopatias em caninos e felinos.

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats.

BACKGROUND: Neurological disorders suggest that the excitotoxicity involves a drastic increase in intracellular Ca2+ concentrations and the formation of reactive oxygen species. The presence of these free radicals may also affect the dopaminergic system. The aim of this work was to determine if riboflavin (B2) and pyridoxine (B6) provide protection to the brain against free radicals generated by 3-nitropropionic acid (3-NPA) by measuring the levels of dopamine (DA) and selected oxidative stress markers. METHODS: Male Fisher rats were grouped (n = 6) and treated as follows: group 1, control (NaCl 0.9%); group 2, 3-NPA (20 mg/kg); group 3, B2 (10 mg/kg); group 4, B2 (10 mg/kg) + 3-NPA (20 mg/kg); group 5, B6 (10 mg/kg) and group 6, B6 + 3-NPA. All treatments were administered every 24 h for 5 days by intraperitoneal route. After sacrifice, the brain was obtained to measure DA, GSH, and lipid peroxidation, Ca2+, Mg2+, ATPase and H2O2. MAIN FINDINGS: Levels of dopamine increased in cortex, striatum and cerebellum/medulla oblongata of animals that received 3-NPA alone. The lipid peroxidation increased in cortex, striatum, and cerebellum/medulla oblongata, of animals treated with B2 vitamin alone. ATPase dependent on Ca+2, Mg+2 and H2O2 increased in all regions of animals that received 3-NPA alone. CONCLUSION: The results confirm the capacity of 3-NPA to generate oxidative stress. Besides, the study suggests that B2 or B6 vitamins restored the levels of DA and reduced oxidative stress in brain of rats. We believe that these results would help in the study of neurodegenerative diseases.

Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

Abstract This study described a broad clinical characterization of classical homocystinuria (HCU) in Brazil. This was a cross-sectional, observational study including clinical and biochemical data from 72 patients (60 families) from Brazil (South, n = 13; Southeast, n = 37; Northeast, n = 8; North, n = 1; and Midwest, n = 1). Parental consanguinity was reported in 42% of families. Ocular manifestations were the earliest detected symptom (53% of cases), the main reason for diagnostic suspicion (63% of cases), and the most prevalent manifestation at diagnosis (67% of cases). Pyridoxine responsiveness was observed in 14% of patients. Only 22% of nonresponsive patients on treatment had total homocysteine levels <100 mmol/L. Most commonly used treatment strategies were pyridoxine (93% of patients), folic acid (90%), betaine (74%), vitamin B12 (27%), and low-methionine diet + metabolic formula (17%). Most patients diagnosed with HCU in Brazil are late diagnosed, express a severe phenotype, and poor metabolic control. Milder forms of HCU are likely underrepresented due to underdiagnosis.

Comparison of the action of diclofenac alone versus diclofenac plus B vitamins on mobility in patients with low back pain.

Objective: To assess results of the finger-to-floor distance (FFD) and the Schober test performed during the DOLOR study, and to verify correlation between Visual Analog Pain Scale scores (VAS) with these measures. Research design and methods: Previously tabulated data from the Clinical Research Forms of the DOLOR study were analyzed (statistical significance defined with a two-tailed p value < 0.05 and confidence interval of 95%). For continuous variables, the Student's T- test or analysis of variance (ANOVA) was used, and differences between pre-treatment and Visits 2, 3, and 4 in the absolute number and percentage of patients with no change, improvement, or worsening of the Schober test and the FFD test scores were calculated, and the results were analyzed with the Chi-squared test. Spearman non-parametric correlation was used for correlating VAS scores with FFD and Schober test scores at each study visit. Main outcome measures: FFD, measured in centimeters; Schober test scores. Results: Throughout the treatment period, there was a statistically significant correlation between the VAS scores and the FFD in the total patient population and within treatment groups. This was not observed for the correlation between the Schober's test scores and the VAS scores. FFD scores within treatment groups improved progressively at each study visit, as did the Schober Test scores. Conclusions: The results of this post-hoc analysis show that combination therapy with diclofenac plus vitamins B1, B6, and B12 had additional positive effects on mobility restoration among the patients of the DOLOR study and serve to highlight the correlation between mobility and pain intensity among patients presenting with low back pain. The two fundamental goals of low back pain therapy are to provide improvements in pain and function. In this sense, the combination of diclofenac with the B vitamins was particularly effective in achieving both of these goals.

Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring.

SCOPE: Vitamin B6 plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring. METHODS AND RESULTS: Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B6 supplementation or deficiency did not change hippocampal global DNA methylation. CONCLUSION: A maternal vitamin B6 -deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression.

Simultaneous determination of three species with a single-injection step using batch injection analysis with multiple pulse amperometric detection.

In this work, the possibility of simultaneous determination of three compounds with a single-injection step using batch injection analysis with multiple pulse amperometric detection (BIA-MPA) is demonstrated for the first time. A sequence of three potential pulses (+1.25 V, +1.60 V, and +1.80 V) was applied with the acquisition of three separate amperograms. 8-Chlorotheophylline was detected selectively at +1.25 V, both 8-chlorotheophylline and pyridoxine at +1.60V and 8-chlorotheophylline, pyridoxine, and diphenhydramine at +1.80 V. Subtraction between the currents detected at the three amperograms (with the help of correction factors) was used for the selective determination of pyridoxine and diphenhydramine. The proposed method is simple, inexpensive, fast (60 injections h(-1)), and present selectivity for the determination of the three compounds in pharmaceutical samples, with results similar to those obtained by HPLC (95% confidence level).

Influence of concentration on the radiolytic decomposition of thiamine, riboflavin, and pyridoxine in aqueous solution / Influencia de la concentración en la descomposición radiolítica de tiamina, riboflavina y piridoxina en solución acuosa / Influência da concentração na decomposição radiolítica de tiamina, riboflavina e piridoxina em solução aquosa

Vitamin loss during irradiation has been claimed as a critical area in food irradiation technology, especially that of thiamine (B1), which has been considered as the most sensitive to radiation. Although it has been suggested that no vitamin deficiency could result from consuming irradiated food, a long debate on the loss of vitamins and other nutrients during food irradiation has been maintained by the lack of experimental studies monitoring decomposition rates at different concentrations and doses. Since thiamine, riboflavin, and pyridoxine are labile vitamins, this study has focused on their radiolytic decomposition in dilute aqueous solutions in the presence of air. The decomposition process was followed by HPLC and UV-spectroscopy. The results obtained in aqueous solutions showed a dependence of the decomposition as a nonlinear function of the dose. Of these three compounds, the decomposition was higher for thiamine than for riboflavin and even less in pyridoxine.

La pérdida de vitaminas durante procesos de irradiación ha sido considerada como un área crítica en la tecnología de irradiación de alimentos, especialmente la tiamina (B1), que ha sido considerada como la más sensible a la radiación ionizante. La deficiencia de vitaminas en humanos no es producida por el consumo de alimentos irradiados, sin embargo, existen debates sobre la pérdida de vitaminas y otros nutrientes provocada por la irradiación de alimentos, esta discusión sigue latente debido a que hay pocos estudios experimentales de la descomposición de vitaminas a diferentes dosis y concentraciones. Esta investigación se centró en el estudio de la descomposición radiolítica de tiamina, riboflavina y piridoxina en soluciones acuosas y en presencia de aire. El proceso de descomposición fue seguido por cromatografía líquida con detección UV. Los resultados obtenidos en soluciones acuosas mostraron una dependencia no lineal entre la descomposición en función de la dosis. De estos tres compuestos, la descomposición fue mayor en tiamina que en riboflavina y menor en la piridoxina.

A perda de vitaminas durante processos de irradiação tem sido considerada uma área crítica na tecnologia de irradiação de alimentos, especialmente no caso da tiamina (B1), que tem sido considerada como a mais sensível à radiação ionizante. Embora a deficiência de vitaminas em seres humanos não seja produzida pelo consumo de alimentos irradiados, longos debates sobre as perdas de vitaminas e outros nutrientes causadas pela irradiação de alimentos tem sido mantidos devido aos estudos experimentais limitados monitorando a proporção da decomposição em diferentes concentrações de vitaminas e doses de radiação aplicadas. Considerando que a tiamina, riboflavina e piridoxina são vitaminas instáveis, o presente estudo focalizou a decomposição radiolítica dessas vitaminas em soluções aquosas diluídas e na presença de ar. O processo de decomposição foi analizado por cromatografia líquida com detecção UV. Os resultados obtidos em soluções aquosas mostraram uma dependência da decomposição como função não linear da dose. Destes três compostos, a descomposição foi mais alta para tiamina que na riboflavina e menor para piridoxina.

Medicamentos antieméticos no tratamento da náusea e vômitos associados à gestação / Antiemetic medications in the treatment of nausea and vomiting associated with pregnancy

Náusea e vômitos (NV) são os sintomas mais comuns durante a gravidez, geralmente iniciando-se entre a 6ª e a 8ª semana, atingindo a intensidade máxima em torno da 9ª semana e resolvendo-se até a 12ª semana. Embora sua etiologia seja, provavelmente, multifatorial, seu curso clínico se correlaciona com as concentrações plasmáticas da gonadotrofina coriônica humana. Por comprometerem a qualidade de vida, NV devem ser abordados com modificações dietéticas que incluem dieta fracionada e redução do consumo de alimentos gordurosos, entre outras. O uso de piridoxina pode melhorar a náusea de intensidade leve, embora não diminua significantemente os episódios de vômitos. Os anti-histamínicos são os medicamentos mais utilizados como terapia medicamentosa de primeira linha e têm sua segurança comprovada; dentre eles, o dimenidrinato determina início de ação mais rápido e menor sedação que a meclizina. Entre os antagonistas dopaminérgicos, a prometazina e a metoclopramida podem ser utilizadas, mas apresentam como desvantagem o potencial de eventos adversos maternos. O antagonista dos receptores 5-HT3, ondansetrona, pode ser considerado quando outros medicamentos não foram efetivos no tratamento de NV de intensidade grave. Do mesmo modo, os corticosteroides devem ter seu uso reservado para casos não responsivos a outros medicamentos e preferencialmente após a 10ª semana de gestação...

Revisión sistemática de la seguridad y eficacia de la combinación de doxilamina + piridoxina para el tratamiento de la náusea y el vómito durante el embarazo / Systematic review of the safety and efficacy of the combination of doxylamine + pyridoxine for the treatment of nausea and vomiting during pregnancy

Justificación: Más del 80% de las mujeres embarazadas experimentan en algún momento del embarazo náusea y vómito de magnitud variable que puede producir complicaciones importantes, tales como la deshidratación, el incremento de la frecuencia de hospitalizaciones y la alteración de la calidad de vida. Existe controversia sobre la seguridad de la combinación doxilamina + piridoxina para el tratamiento de la náusea y vómito durante el embarazo. Objetivos: A través de una revisión sistemática de la evidencia con metaanálisis, evaluar la seguridad y eficacia de la combinación de doxilamina + piridoxina para el tratamiento de la náusea y el vómito durante el embarazo. Material y métodos: Se incluyeron estudios de casos y controles, estudios de cohorte, ensayos clínicos o ensayos clínicos controlados, de adecuada calidad metodológica, realizados en mujeres embarazadas con náusea y vómito en quienes, dada la frecuencia y gravedad de la sintomatología, se hubiera decidido el tratamiento con doxilamina + piridoxina, al menos en una de las ramas de inclusión al estudio. Se consideraron como variables de desenlace el número de malformaciones congénitas totales observadas, así como el número de malformaciones congénitas ajustadas por tipo. Se efectuó revisión de las bases de datos PubMed (1966 a mayo de 2009), Embase (1988 a mayo 2009), LILACS (1990 a mayo 2009), ARTEMISA (Revisión de la 11ª edición hasta diciembre de 2004), Cochrane controlled trials register, Bandolier y DARE. Estadísticamente, se efectuó el cálculo de riesgo relativo a través de un modelo de efectos fijos de Mantel-Hanezel, en el caso de desenlaces binarios, y diferencia estandarizada de los promedios (SMD), en el caso de desenlaces continuos. Para todos los estimados se efectuó cálculo del intervalo de confianza al 95% (IC95%); se realizó en todos los casos prueba de heterogeneidad, utilizando prueba de Chi cuadrada de Pearson, con un valor de p < 0.05 como sinónimo de significancia. Resultados: No identificamos incremento del riesgo con el uso combinado de doxilamina + piridoxina en mujeres embarazadas con NVP para malformaciones globales con un RR ponderado de 0.97 (IC95% de 0.92 a 1.02), p 0.168, ni para malformaciones cardiovasculares [RR 0.92 (IC95% 0.80 a 1.05), p no significativa (NS)], del sistema nervioso central [RR 1.0 (IC95% 0.87 a 1.15), p NS)], defectos del tubo neural [RR 0.99 (IC95% 0.78 a 1.26), p NS)], alteraciones de extremidades [RR 1.10 (IC95% 0.88 a 1.37), p NS)], labio y paladar hendido [RR 0.85 (IC95% 0.70 a 1.03), p NS)] o malformaciones de la vía urogenital [RR 0.99 (IC95% 0.82 a 1.20), p NS)]. Desde el punto de vista de eficacia, la administración de doxilamina + piridoxina redujo significativamente el riesgo de persistir con náusea y vómito durante el embarazo [RR 0.55 (IC95% 0.41 a 0.74), p 0.0001)]. Conclusiones: Los resultados obtenidos en la actual revisión sistemática señalan un efecto significativamente benéfico de la doxilamina + piridoxina para la reducción de la náusea y el vómito del embarazo (NAVP). Al correlacionar el beneficio del medicamento con su elevado perfil de seguridad (como lo demuestran los cinco metaanálisis en donde el desarrollo de defectos cardiovasculares, del sistema nervioso central, del tubo neural, de las extremidades y genitourinario es similar al del grupo control), permite establecerlo como una alternativa farmacológica eficaz para el tratamiento de la náusea y el vómito presentes durante el embarazo y con riesgo no significativo de teratogenicidad.

More than 80% of the pregnant women, in one moment of the gestation have nausea and vomiting, than can produce important complications like deshydratation, hospital internment, and affectation of the quality of life. There are controversies about the safety of the combination of doxylamine + pyridoxine for the treatment of the nausea and vomiting of pregnancy (NVP). Objective: To evaluate the efficacy and safety of the combination of doxylamine + pyridoxine for the treatment of NVP using the methodological tool of a systematic review. Materials and methods: For the systematic review we include case-control studies, cohort's studies, and controlled trials, performed in pregnant women with NVP and that were treatment with doxylamine + pyridoxine. We considered the number of congenital defects as the principal outcome variable. We made the systematic review using the following data bases: PubMed (1966 to may 2009), Embase (1988 to may 2009), LILACS (1990 to may 2009), ARTEMISA (review of the 11ª edition to December 2004), Cochrane controlled trials register, Bandolier y DARE. The statistical analysis was made with the calculation of relative risk (RR) and 95% confidence interval (CI 95%) with the Mantel-Hanezel model. Results: There was no risk increase of congenital defects in children born of women with NVP treated with the combination of doxylamine + pyridoxine. The RR identified for all congenital defects was 0.97(IC95% de 0.92 a 1.02), p = 0.168; for cardiovascular defects the RR was 0.92 (CI95% 0.80-1.05), for neural tube defects the RR was 0.99 (CI95% 0.78-1.26), and for urinary defects the RR was 0.99 (CI95% 0.8-1.20). The administration of doxylamine + pyridoxine reduced the risk of NVP persistence with a RR of 0.55 (CI95% 0.41-0.74), p < 0.01). Conclusions: The systematic review showed that the administration of doxylamine + pyridoxine has a beneficial effect on the reduction of NVP manifestations, with a high safety to be used during pregnancy.