Vitaminas B1, B6, B12 y neuropatías periféricas: Consenso de expertos / Vitamins B1, B6, and B12 and peripheral neuropathies: International expert consensus

RESUMEN A partir de una revisión bibliográfica de la literatura se ha planeado y desarrollado un consenso de expertos internacionales sobre la utilización de las vitaminas B1, B6, B12 en sus déficits y en la neuropatía periférica que puede estar asociada a la misma, como tema que precia de esa aproximación aclaratoria para optimizar su manejo. Se plantearon varias cuestiones de discusión que se consideraron importantes y dignas de ser abordadas y aclaradas, conservando nueve de ellas para su discusión ulterior buscando el consenso en tres rondas consecutivas. Se han propuesto 41 recomendaciones sobre el manejo de estas condiciones, con unanimidad por parte de los participantes en el consenso. Con ellas se ha intentado aclarar puntos oscuros o controvertidos, facilitando la actitud del clínico ante ellos en la práctica médica actual.

ABSTRACT Based on a bibliographic review of the literature, a consensus of international experts has been carried out on the use of vitamins B1, B6, B12, in their deficiencies, and in the peripheral neuropathy that may be associated with them, to optimize the management of these conditions. Several questions considered important and worthy of being addressed and clarified were raised, retaining nine of them for further discussion to achieve consensus. Forty one recommendations on the management of these conditions have been proposed, with unanimity of the participants in the consensus. This has been an attempt to clarify controversial points, assisting the clinician's attitude in current medical practice.

S100A4-neutralizing monoclonal antibody 6B12 counteracts the established experimental skin fibrosis induced by bleomycin.

OBJECTIVES: Our previous studies have demonstrated that the Damage Associated Molecular Pattern (DAMP) protein, S100A4, is overexpressed in the involved skin and peripheral blood of patients with SSc. It is associated with skin and lung involvement, and disease activity. By contrast, lack of S100A4 prevented the development of experimental dermal fibrosis. Herein we aimed to evaluate the effect of murine anti-S100A4 mAb 6B12 in the treatment of preestablished experimental dermal fibrosis. METHODS: The effects of 6B12 were assessed at therapeutic dosages in a modified bleomycin-induced dermal fibrosis mouse model by evaluating fibrotic (dermal thickness, proliferation of myofibroblasts, hydroxyproline content, phosphorylated Smad3-positive cell count) and inflammatory (leukocytes infiltrating the lesional skin, systemic levels of selected cytokines and chemokines) outcomes, and transcriptional profiling (RNA sequencing). RESULTS: Treatment with 7.5 mg/kg 6B12 attenuated and might even reduce pre-existing dermal fibrosis induced by bleomycin as evidenced by reduction in dermal thickness, myofibroblast count and collagen content. These antifibrotic effects were mediated by the downregulation of TGF-ß/Smad signalling and partially by reducing the number of leukocytes infiltrating the lesional skin and decrease in the systemic levels of IL-1α, eotaxin, CCL2 and CCL5. Moreover, transcriptional profiling demonstrated that 7.5 mg/kg 6B12 also modulated several profibrotic and proinflammatory processes relevant to the pathogenesis of SSc. CONCLUSION: Targeting S100A4 by the 6B12 mAb demonstrated potent antifibrotic and anti-inflammatory effects on bleomycin-induced dermal fibrosis and provided further evidence for the vital role of S100A4 in the pathophysiology of SSc.

The vicious circle between homocysteine, methyl group-donating vitamins and chronic levodopa intake in Parkinson's disease.

A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generating mechanisms in levodopa-treated patients with Parkinson's disease. We conclude to recommend levodopa-treated patients to substitute themselves with methyl group-donating vitamins. This is harmless in terms of application of folic acid, methylcobalamin or hydroxocobalamin. Moreover, we suggest a crucial discussion on the value of the various popular hypotheses on Parkinson's disease-generating mechanisms. Findings from studies with acute levodopa exposure describe oxidative stress generation and impaired methylation capacity, which causes gene dysfunction. Their repeated occurrences contribute to onset of mitochondrial dysfunction, iron enrichment and pathologic protein accumulation in the long term. Current research underestimates these epigenetic, metabolic consequences of chronic levodopa application. Supplementary treatment strategies are recommended to avoid levodopa-related side effects.

Desarrollo de la formulación Compvit-B® inyectable / Development of Compvit-B® injectable formulation

El incremento de la incidencia de las polineuropatías en Cuba a principio de la década de los 90 del pasado siglo, hizo necesario la aplicación de medicamentos con propiedades antineuríticas, compuestos por vitaminas del grupo B, que hasta el momento no existían en el país por los altos precios a los que se comercializan internacionalmente. Objetivo: obtener una formulación que en su composición contenga una asociación de altas dosis de las vitaminas B1, B6 y B12, cuyos efectos positivos en el tratamiento de las neuropatías ya son conocidos. Métodos: se evaluaron integralmente ocho variantes diferentes de una formulación inyectable, con la presencia o no de etilendiaminotetraacético (EDTA) y alcohol bencílico, y el proceso de liofilización incluido o no en su flujo productivo de acuerdo con la propuesta de la tecnología del fabricante. Resultados: se seleccionó la variante 8, la que cumple con los parámetros establecidos por la tecnología del fabricante y el Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED). Se obtuvo un producto farmacéutico inyectable, liofilizado de factura nacional llamado Compvit-B®, compuesto por 100 mg de B1, 100 mg de B6 y 5 000 µg de B12, que cumple con las especificaciones propuestas y que exigen los órganos regulatorios en la producción de medicamentos para uso humano. Conclusiones: La variante seleccionada permitió desarrollar el producto farmacéutico Compvit-B® que es un medicamento farmacológicamente estable y de calidad, y cuya licencia sanitaria para su generalización y producción fue otorgada por el CECMED...

"At the beginning of the 1990´s, the increased incidence of polyneuropathies in Cuba made it necessary to apply vitamin B group-derived drugs with neuroprotective properties. this kind of drugs was infrequent in the country at that time because of their high prices at the international market. Objectives: to obtain a formulation containing a combination of high dose of vitamins B1, B6 and B12 which have known positive effects on the treatment of neuropathies. Methods: comprehensive assessment of eight different variants of injectable formulation, with or without ethylenediaminetetraacetic acid (EDTA) and benzyl alcohol, and of the lyophilization process included in the flow of production or not, in line with the technology suggested by the manufacturer. Results: the variant number 8 was selected since it meets the set parameters according to the manufacturer's technology and to the Center for the State Quality Control of Drugs. A Cuban-made injectable and lyophilized pharmaceutical called Compvit-B®, made up of 100 mg B1, 100 mg B6 and 5 000 µg B12, was obtained. It meets the established specifications and the requirements by the regulatory bodies for the manufacture of drugs for human use. Conclusions: the selected variant allowed developing the Compvit-B ® pharmaceutical, which is a pharmacologically stable drug of quality, and the health licensing for the general use and the production of this drug was granted by the Center for the State Quality Control of Drugs (CEDMED)...