Efecto del factor de crecimiento fibroblástico dos (FGF-2), en la reducción de la senescencia en células madre mesenquimales aisladas de gelatina de Wharton / Fibroblastic growth factor two (FGF-2), in reducing the senescent effect on mesenchymal stem cell isolated from Wharton ́s jelly

Resumen Introducción. Las células madre mesenquimales han generado interés en la ingeniería de tejidos, debido a sus propiedades proliferativas y capacidad de reparación de tejidos, sin embargo, para un trasplante exitoso, es necesario aumentar el número de células mediante un cultivo in-vitro. Durante este proceso la capacidad proliferativa disminuye, provocando cambios en la morfología y funcionalidad celular y afectando la viabilidad del cultivo, este estado se conoce como senescencia celular y como posibles causales, se ha considerado el estrés oxidativo y la falta de factores de crecimiento. Objetivos: Evaluar el efecto de FGF-2 sobre la senescencia de un cultivo de células madre mesenquimales aisladas de gelatina de Wharton y su papel en la regulación del estrés oxidativo. Metodología. Se añadieron dosis de 3,5 y 7,5 ng de FGF-2 al cultivo. Durante los pasajes 5 y 7, se estimó tanto la senescencia celular como la presencia de ROS (especies reactivas de oxígeno). Resultados.Se obtuvo en el pasaje 5, una diferencia significativa del 99,5% entre el control (+) con respecto a los tratamientos con FGF-2, sin embargo, en el pasaje 7 se observó un aumento en la producción de la enzima ß-galactosidasa y cambios morfológicos, confirmando un estado senescente en el cultivo en todos los tratamientos evaluados. Conclusión. Las dosis utilizadas en este estudio contribuyeron positivamente a disminuir el proceso senescente en el cultivo celular, además se determinó, que el FGF-2 puede prolongar el tiempo de cultivo, retardando parcialmente la concentración de especies reactivas de oxígeno

AbstractIntroduction. Mesenchymal stem cells have been generated interest in tissue engineering, due to their proliferative properties and tissue repair capacity, however, for a successful transplant process, it is necessary to increase the number of cells in a culture expansion process. During this process the proliferative capacity is limited, causing changes in cell morphology and functionality affecting the viability of the culture, this state is known as cell senescence. Oxidative stress and deregulation of growth factors are considered as reasons. Aims. To evaluate the effect of FGF-2 on the senescence of a mesenchymal stem cells culture isolated from Wharton ́s jelly and its role in the regulation of oxidative stress. Methodology: 3,5 and 7,5 ng doses of FGF-2 were added to the culture medium from passage 2, then the senescence of the culture was evaluated and the presence of reactive oxygen species was determined during passages 5 and 7. Results. We observed that in passage 5, there is a significant difference 99.5% between the control (+) concerning the FGF-2 treatments, however, in passage 7, an increase in the production of the enzyme ß-galactosidase was observed and changes in morphology such as: increase in size and elongated shape of the cell, confirming a senescent state on the culture in all the treatments evaluated. Conclusion. The doses used in this study contributed positively to decrease this process in a cell culture, also, the FGF- 2 can prolong the cultivation time, partially decreasing the concentration of reactive oxygen species

Cytotoxic Effects of Blue Scorpion Venom (Rhopalurus junceus) in a Glioblastoma Cell Line Model.

BACKGROUND: Cancer is one of the leading cause of death worldwide. Besides current therapies and treatments to counter cancer, new alternatives are required to diminish the cell proliferation of oncogenic processes. METHODS: One of the most promissory therapy includes the use of blue scorpion venom as a specific cytotoxic agent to kill tumoral cells, including Glioblastoma multiforme. OBJECTIVES: We show evidence of the cytotoxic effect of blue scorpion venom in a cellular model of Glioblastoma multiforme. RESULTS: Our results demonstrate that 50 µg/ml of scorpion venom is capable to diminish the viability of Glioblastoma populations. CONCLUSION: It is possible that the action mechanism could be associated with a loss of membrane integrity. Additionally, some metalloproteinases as MMP2 and MMP9 may also participate in the potential action mechanism.

Refilins are short-lived Actin-bundling proteins that regulate lamellipodium protrusion dynamics.

Refilins (RefilinA and RefilinB) are members of a novel family of Filamin binding proteins that function as molecular switches to conformationally alter the Actin filament network into bundles. We show here that Refilins are extremely labile proteins. An N-terminal PEST/DSG(X)2-4S motif mediates ubiquitin-independent rapid degradation. A second degradation signal is localized within the C-terminus. Only RefilinB is protected from rapid degradation by an auto-inhibitory domain that masks the PEST/DSG(X)2-4S motif. Dual regulation of RefilinA and RefilinB stability was confirmed in rat brain NG2 precursor cells (polydendrocyte). Using loss- and gain-of-function approaches we show that in these cells, and in U373MG cells, Refilins contribute to the dynamics of lamellipodium protrusion by catalysing Actin bundle formation within the lamella Actin network. These studies extend the Actin bundling function of the Refilin-Filamin complex to dynamic regulation of cell membrane remodelling.

Evaluación del efecto del Compvit-B sobre la neuropatía periférica en pacientes con SCA2 en estadio ligero de la enfermedad / Evaluation of the effect of Compvit-B on peripheral neuropathy in patients with mild SCA2

Introducción: la Ataxia Espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa severa que representa un serio problema de salud en Cuba, debido a las altas tasas de prevalencia e incidencia y a la ausencia de tratamientos curativos. Objetivos: evaluar el efecto y la seguridad del tratamiento con altas dosis de vitaminas del complejo B (Compvit-B) sobre la neuropatía periférica en pacientes con SCA2. Métodos: se realizó una investigación prospectiva de intervención clínica en 20 enfermos en estadio ligero los que se sometieron a un protocolo terapéutico mediante la administración intramuscular del COMPVIT B por 12 semanas. Durante las primeras 4 semanas los individuos recibieron dos bulbos semanales y a partir de la 5ta semana un solo bulbo. Inmediatamente antes y después del tratamiento los pacientes fueron evaluados mediantes exámenes clínicos y electrofisiológicos. Resultados: una vez concluido el tratamiento, los pacientes mostraron un aumento significativo de las amplitudes de los potenciales de acción sensitivos de nervios mediano y sural, y en este último nervio se observó además reducción de la latencia y aumento de la velocidad de conducción. Los parámetros de la conducción nerviosa motora no se modificaron. Los potenciales evocados somatosensoriales de nervio mediano arrojaron una reducción significativa de la latencia del potencial de Erb. De manera interesante se observó una la disminución significativa de la frecuencia de aparición de las contracturas musculares dolorosas en el 53 por ciento de los casos después del tratamiento. Durante el estudio no se registraron eventos adversos...

Introduction: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which constitutes a serious health problem in Cuba due to its high prevalence and incidence rates and the lack of curative treatments. Objectives: Evaluate the effect and safety of the treatment with high doses of B-complex vitamins (Compvit-B) on peripheral neuropathy in patients with SCA2. Methods: A prospective clinical intervention study was conducted of 20 patients in the mild stage of the disease undergoing a therapeutic protocol consisting in intramuscular injection of Compvit-B for 12 weeks. Patients were administered two ampoules weekly in the first 4 weeks and one from the fifth week onwards. Immediately before and after the treatment patients underwent clinical and electrophysiological examination. Results: Upon completion of the treatment patients showed a significant increase in the amplitude of the sensitive action potentials of the median and sural nerves. In the latter case there was also a decrease in latency and an increase in conduction velocity. Motor nerve conduction parameters were not modified. Somatosensory evoked potentials of the median nerve showed a significant reduction in the latency of Erb's potential. A significant decrease was also found in the frequency of painful muscle contractures in 53 percent of the cases after treatment. Adverse events were not recorded during the study...

Evaluación del efecto del Compvit-B sobre la neuropatía periférica en pacientes con SCA2 en estadio ligero de la enfermedad / Evaluation of the effect of Compvit-B on peripheral neuropathy in patients with mild SCA2

INTRODUCCIÓN: la Ataxia Espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa severa que representa un serio problema de salud en Cuba, debido a las altas tasas de prevalencia e incidencia y a la ausencia de tratamientos curativos. OBJETIVOS: evaluar el efecto y la seguridad del tratamiento con altas dosis de vitaminas del complejo B (Compvit-B) sobre la neuropatía periférica en pacientes con SCA2. MÉTODOS: se realizó una investigación prospectiva de intervención clínica en 20 enfermos en estadio ligero los que se sometieron a un protocolo terapéutico mediante la administración intramuscular del COMPVIT B por 12 semanas. Durante las primeras 4 semanas los individuos recibieron dos bulbos semanales y a partir de la 5tasemana un solo bulbo. Inmediatamente antes y después del tratamiento los pacientes fueron evaluados mediantes exámenes clínicos y electrofisiológicos. RESULTADOS: una vez concluido el tratamiento, los pacientes mostraron un aumento significativo de las amplitudes de los potenciales de acción sensitivos de nervios mediano y sural, y en este último nervio se observó además reducción de la latencia y aumento de la velocidad de conducción. Los parámetros de la conducción nerviosa motora no se modificaron. Los potenciales evocados somatosensoriales de nervio mediano arrojaron una reducción significativa de la latencia del potencial de Erb. De manera interesante se observó una la disminución significativa de la frecuencia de aparición de las contracturas musculares dolorosas en el 53% de los casos después del tratamiento. Durante el estudio no se registraron eventos adversos. CONCLUSIONES: el presente estudio identifica una nueva opción terapéutica sintomática en la SCA2, brinda nuevas evidencias sobre las bases fisiopatológicas y el manejo clínico de las contracturas musculares dolorosas y justifican la realización de estudios más amplios en pacientes y portadores de la mutación, los que presentan tales manifestaciones muchos antes de debutar con la ataxia.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which constitutes a serious health problem in Cuba due to its high prevalence and incidence rates and the lack of curative treatments. OBJECTIVES: Evaluate the effect and safety of the treatment with high doses of B-complex vitamins (Compvit-B) on peripheral neuropathy in patients with SCA2. METHODS: A prospective clinical intervention study was conducted of 20 patients in the mild stage of the disease undergoing a therapeutic protocol consisting in intramuscular injection of Compvit-B for 12 weeks. Patients were administered two ampoules weekly in the first 4 weeks and one from the fifth week onwards. Immediately before and after the treatment patients underwent clinical and electrophysiological examination. RESULTS: Upon completion of the treatment patients showed a significant increase in the amplitude of the sensitive action potentials of the median and sural nerves. In the latter case there was also a decrease in latency and an increase in conduction velocity. Motor nerve conduction parameters were not modified. Somatosensory evoked potentials of the median nerve showed a significant reduction in the latency of Erb's potential. A significant decrease was also found in the frequency of painful muscle contractures in 53% of the cases after treatment. Adverse events were not recorded during the study. CONCLUSIONS: The study identifies a new therapeutic option for symptomatic SCA2, and provides new evidence of the pathophysiological bases and clinical management of painful muscle contractures. Broader studies should be conducted with patients and carriers of the mutation, who typically present such manifestations long before developing ataxia.

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)...

Estabilidad del producto farmacéutico Compvit-BÒ inyectable / Stability of injectable pharmaceutical Compvit-BÒ

Compvit-BÒ es un polifármaco inyectable liofilizado, compuesto por 100 mg de B1, 100 mg de B6 y 5 000 µg de B12. Está indicado en tratamientos de todo tipo de neuropatías y enfermedades neurodegenerativas. El objetivo de este trabajo consistió en el desarrollo tecnológico de una formulación estable. Para evaluar la calidad de este medicamento, se escalaron 3 lotes pilotos a los que se les realizaron ensayos físicos, químicos y microbiológicos con resultados satisfactorios. Los estudios de estabilidad realizados a temperatura ambiente del producto Compvit-BÒ en forma liofilizada, demostraron ser estable por 3 años y la formulación reconstituida por 72 h. Este medicamento está registrado en el órgano regulador cubano, Centro Estatal para el Control de Medicamentos, e incluido en el Cuadro Básico de Medicamentos de Cuba; se comercializa por la Industria Farmacéutica nacional y se encuentra generalizado en los servicios hospitalarios de Cuba

Compvit-BÒ is a lyophilized injectable polypharmaceutical made up of 100 mg of B1, 100 mg of B6 and 5 000 µg of B12. It is prescribed to treat all types of neuropathies and neurodegenerative diseases. The objective of this paper was the technological development of a stable formulation. For the evaluation of the quality of this drug, three pilot batches were scaled up and were subjected to physical, chemical and microbiological tests; the results were all satisfactory. The stability studies of lyophilized Compvit-BÒ were performed at room temperature. They showed that the pharmaceutical was stable for 3 years and the formulation was regenerated for 72 hours. This drug is registered at the Cuban regulating body called State Center for Drug Control and has been included in the Basic Group of Drugs in Cuba. It has been put on the market by the national drug industry. It is also widely used in the hospital services in Cuba

Estabilidad del producto farmacéutico Compvit-BÒ inyectable / Stability of injectable pharmaceutical Compvit-BÒ

Compvit-BÒ es un polifármaco inyectable liofilizado, compuesto por 100 mg de B1, 100 mg de B6 y 5 000 µg de B12. Está indicado en tratamientos de todo tipo de neuropatías y enfermedades neurodegenerativas. El objetivo de este trabajo consistió en el desarrollo tecnológico de una formulación estable. Para evaluar la calidad de este medicamento, se escalaron 3 lotes pilotos a los que se les realizaron ensayos físicos, químicos y microbiológicos con resultados satisfactorios. Los estudios de estabilidad realizados a temperatura ambiente del producto Compvit-BÒ en forma liofilizada, demostraron ser estable por 3 años y la formulación reconstituida por 72 h. Este medicamento está registrado en el órgano regulador cubano, Centro Estatal para el Control de Medicamentos, e incluido en el Cuadro Básico de Medicamentos de Cuba; se comercializa por la Industria Farmacéutica nacional y se encuentra generalizado en los servicios hospitalarios de Cuba(AU)

Compvit-BÒ is a lyophilized injectable polypharmaceutical made up of 100 mg of B1, 100 mg of B6 and 5 000 µg of B12. It is prescribed to treat all types of neuropathies and neurodegenerative diseases. The objective of this paper was the technological development of a stable formulation. For the evaluation of the quality of this drug, three pilot batches were scaled up and were subjected to physical, chemical and microbiological tests; the results were all satisfactory. The stability studies of lyophilized Compvit-BÒ were performed at room temperature. They showed that the pharmaceutical was stable for 3 years and the formulation was regenerated for 72 hours. This drug is registered at the Cuban regulating body called State Center for Drug Control and has been included in the Basic Group of Drugs in Cuba. It has been put on the market by the national drug industry. It is also widely used in the hospital services in Cuba(AU)

RefilinB (FAM101B) targets filamin A to organize perinuclear actin networks and regulates nuclear shape.

The intracellular localization and shape of the nucleus plays a central role in cellular and developmental processes. In fibroblasts, nuclear movement and shape are controlled by a specific perinuclear actin network made of contractile actin filament bundles called transmembrane actin-associated nuclear (TAN) lines that form a structure called the actin cap. The identification of regulatory proteins associated with this specific actin cytoskeletal dynamic is a priority for understanding actin-based changes in nuclear shape and position in normal and pathological situations. Here, we first identify a unique family of actin regulators, the refilin proteins (RefilinA and RefilinB), that stabilize specifically perinuclear actin filament bundles. We next identify the actin-binding filamin A (FLNA) protein as the downstream effector of refilins. Refilins act as molecular switches to convert FLNA from an actin branching protein into one that bundles. In NIH 3T3 fibroblasts, the RefilinB/FLNA complex organizes the perinuclear actin filament bundles forming the actin cap. Finally, we demonstrate that in epithelial normal murine mammary gland (NmuMG) cells, the RefilinB/FLNA complex controls formation of a new perinuclear actin network that accompanies nuclear shape changes during the epithelial-mesenchymal transition (EMT). Our studies open perspectives for further functional analyses of this unique actin-based network and shed light on FLNA function during development and in human syndromes associated with FLNA mutations.

Efectos del tratamiento con Compvit B, ácido orótico o la combinación de ambos sobre la recuperación de la memoria espacial en ratas con lesión de fimbria-fornix / Effects of treatment with Compvit B, orotic acid or their combination on the recovery of spatial memory in rats with fimbria-fornix lesion

Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamínicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo(AU)

Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments(AU)

Un método experimental para lesionar un nervio periférico y evaluar conductualmente la recuperación y el efecto de tratamientos restaurativos / An experimental method to injure a peripheral nerve and to evaluate recovery and the effect of restorative treatments using behavioral techniques

Se presenta un método simple de lesión del nervio periférico por pinzamiento del nervio ciático, y de evaluación conductual de la lesión y su recuperación empleando la marcha sobre una rejilla metálica. La lesión del ciático dificulta el desplazamiento de los animales sobre este sustrato como lo demuestran el aumento significativo de la latencia de escape hacia la caja de habitación y el incremento de fallos en el apoyo de la pata lesionada. Empleando este método se evaluó el efecto de la administración poslesional del complejo vitamínico Compvit B® y del ácido orótico (un precursor de nucleótidos de pirimidina) sobre la recuperación del nervio dañado. Ambos tratamientos y su combinación, mejoraron significativamente la recuperación del nervio lesionado al ser comparados con controles tratados con solución salina(AU)

The paper describes a simple method to injure the peripheral sciatic nerve by clamping, along with a behavioral test to asses the lesion and its recovery using the gait on a metallic grid. Sciatic nerve lesion impairs the displacement of the animals on this surface as demonstrated by the significant increase in the escape latency towards the room cage and the increased number of stance failures with the injured leg. Using this method we assessed the effect of post-injury administration of Compvit B® (vitamin compound) and orotic acid (a pyrimidine-nucleotide precursor) on the recovery of injured nerve. Both treatments and its combination, improved significantly the recovery of injured nerve compared to controls treated with saline solution(AU)

Efectos del tratamiento con Compvit B, ácido orótico o la combinación de ambos sobre la recuperación de la memoria espacial en ratas con lesión de fimbria-fornix / Effects of treatment with Compvit B, orotic acid or their combination on the recovery of spatial memory in rats with fimbria-fornix lesion

Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamónicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo

Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments

Un método experimental para lesionar un nervio periférico y evaluar conductualmente la recuperación y el efecto de tratamientos restaurativos / An experimental method to injure a peripheral nerve and to evaluate recovery and the effect of restorative treatments using behavioral techniques

Se presenta un método simple de lesión del nervio periférico por pinzamiento del nervio ciático, y de evaluación conductual de la lesión y su recuperación empleando la marcha sobre una rejilla metálica. La lesión del ciático dificulta el desplazamiento de los animales sobre este sustrato como lo demuestran el aumento significativo de la latencia de escape hacia la caja de habitación y el incremento de fallos en el apoyo de la pata lesionada. Empleando este método se evaluó el efecto de la administración poslesional del complejo vitamónico Compvit B® y del ácido orótico (un precursor de nucleótidos de pirimidina) sobre la recuperación del nervio dañado. Ambos tratamientos y su combinación, mejoraron significativamente la recuperación del nervio lesionado al ser comparados con controles tratados con solución salina

The paper describes a simple method to injure the peripheral sciatic nerve by clamping, along with a behavioral test to asses the lesion and its recovery using the gait on a metallic grid. Sciatic nerve lesion impairs the displacement of the animals on this surface as demonstrated by the significant increase in the escape latency towards the room cage and the increased number of stance failures with the injured leg. Using this method we assessed the effect of post-injury administration of Compvit B® (vitamin compound) and orotic acid (a pyrimidine-nucleotide precursor) on the recovery of injured nerve. Both treatments and its combination, improved significantly the recovery of injured nerve compared to controls treated with saline solution

Refilin holds the cap.

The Refilins (RefilinA and RefilinB) are a novel family of short-lived actin regulatory proteins that are expressed during changes in cellular phenotype such as epithelial to mesenchymal transition (EMT). The Refilins promote to the formation of actin- and myosin-rich perinuclear bundles that are characteristic of cellular phenotypic switches. In epithelial cells, RefilinB is up-regulated in response to TGF-ß stimulation and function in organization of apical perinuclear actin fibers during early stage of the EMT process1. In fibroblasts, RefilinB stabilizes perinuclear parallel actin bundles which resemble actin cap 2. Refilins bind and modulate the function of Filamin A (FLNA). Upon binding to Refilins, FLNA is capable of assembling actin filaments into parallel bundles, possibly by undergoing conformational changes at the C-terminal. Perinuclear actin structures determine nuclear shape, cell morphology, cell adhesion and possibly cell proliferation and gene regulation. Identifying the role of Refilins in organizing perinuclear actin networks provides additional insight in the process of intracellular mechanotransduction that regulate changes in cellular phenotype such as those observed during EMT.

Refilins: A link between perinuclear actin bundle dynamics and mechanosensing signaling.

Actin cytoskeleton dynamics lie at the heart of cell mechanosensing signaling. In fibroblast cells, two perinuclear acto-myosin structures, the actin cap and the transmembrane actin-associated nuclear (TAN) line, are components of a physical pathway transducing extracellular physical signals to changes in nuclear shape and movements. We recently demonstrated the existence of a previously uncharacterized third apical perinuclear actin organization in epithelial cells that forms during epithelial-mesenchymal transition (EMT) mediated by TGFß (TGFß). A common regulatory mechanism for these different perinuclear actin architectures has emerged with the identification of a novel family of actin bundling proteins, the Refilins. Here we provide updates on some characteristics of Refilin proteins, and we discuss potential function of the Refilins in cell mechanosensing signaling.

The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes.

Dynamic interactions between components of the outer (OM) and inner (IM) membranes control a number of critical mitochondrial functions such as channeling of metabolites and coordinated fission and fusion. We identify here the mitochondrial AAA(+) ATPase protein ATAD3A specific to multicellular eukaryotes as a participant in these interactions. The N-terminal domain interacts with the OM. A central transmembrane segment (TMS) anchors the protein in the IM and positions the C-terminal AAA(+) ATPase domain in the matrix. Invalidation studies in Drosophila and in a human steroidogenic cell line showed that ATAD3A is required for normal cell growth and cholesterol channeling at contact sites. Using dominant-negative mutants, including a defective ATP-binding mutant and a truncated 50-amino-acid N-terminus mutant, we showed that ATAD3A regulates dynamic interactions between the mitochondrial OM and IM sensed by the cell fission machinery. The capacity of ATAD3A to impact essential mitochondrial functions and organization suggests that it possesses unique properties in regulating mitochondrial dynamics and cellular functions in multicellular organisms.