Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide.

We have previously reported that tolbutamide prevents the inhibition of gap junction communication in astrocytes. Here, we show that tolbutamide increases gap junction communication and connexin 43 expression in poorly coupled C6 glioma cells. The increase in communication is concurrent with the inhibition of the rate of proliferation due to a block of the progression of C6 glioma cells through the S phase of the cell cycle. The effects of tolbutamide were quantitatively similar to that found after the elevation of intracellular cAMP. Furthermore, the effects of tolbutamide and cAMP were additive. The possible beneficial effect of tolbutamide on gene therapy for gliomas is discussed.

La comunicación intercelular en cultivo de astrocitos como medida de eficacia terapéutica en la esclerosis múltiple tratada con interferón / Intercellular communication in the astrocyte culture as a measure of therapeutic efficacy in multiple sclerosis treated by interferon

Introducción. La medida de la eficacia terapéutica en la esclerosis múltiple depende del seguimiento clínico de los pacientes y del seguimiento de las modificaciones de la resonancia magnética. No existen marcadores biológicos y la medición de interleucinas y otros mediadores de la inflamación no han resultado útiles en el seguimiento clínico de estos enfermos. La respuesta de los astrocitos a esos mediadores de inflamación da como resultado modificaciones en su capacidad de comunicación intercelular. Objetivo. Comprobar si el cultivo de astrocitos con suero de pacientes con esclerosis múltiple en distinta situación clínica y terapéutica da lugar a modificaciones en la comunicación intercelular. Pacientes y métodos. Se cultivan astrocitos con suero de tres pacientes en brote clínico de la enfermedad no tratados y se compara con el cultivo con suero de esos mismos pacientes tras haber sido tratados durante un año con interferón. Resultados. En los cultivos de astrocitos, el suero de pacientes en brote de la enfermedad y sin tratamiento con interferón da lugar a una disminución estadísticamente significativa en la comunicación intercelular con respecto al suero de esos mismos pacientes tras haber recibido éstos tratamiento con interferón durante un año (*p< 0,05; **p< 0,01). Conclusión. La medición de las modificaciones en la comunicación intercelular en cultivo de astrocitos podría utilizarse como marcador de actividad inflamatoria en el suero de pacientes con esclerosis múltiple y, por tanto, como indicador de eficacia terapéutica (AU)

[Intercellular communication in the astrocyte culture as a measure of therapeutic efficacy in multiple sclerosis treated by interferon]. / La comunicación intercelular en cultivo de astrocitos como medida de eficacia terapéutica en la esclerosis múltiple tratada con interferón.

INTRODUCTION: Measurement of therapeutic efficacy in multiple sclerosis depends on the clinical and magnetic resonance findings on follow up. There are no biological markers. Measurement of interleukins and other markers of inflammation has not proved useful in the follow up of these patients. The response of astrocytes to mediators of inflammation gives rise to modification in their capacity for intercellular communication. OBJECTIVE: To find whether culture of astrocytes in serum from patients with multiple sclerosis at different clinical stages and on different treatments gives rise to modification in intercellular communication. PATIENTS AND METHODS: Astrocytes were cultured in serum from three patients with an untreated acute clinical episode of multiple sclerosis, and the results compared with those obtained after serum culture when the patients had been treated with interferon for a year. RESULTS. In astrocyte culture using serum from patients with an acute episode of multiple sclerosis, but not on treatment with interferon, there was a statistically significant reduction in intercellular communication as compared to astrocytes cultured with serum from these same patients treated with interferon for one year (*p< 0.05; **p< 0.01). CONCLUSION: Measurement of the modifications in intercellular communication on astrocyte culture may be used as a marker for inflammatory activity in the serum of patients with multiple sclerosis, and therefore as an index of therapeutic efficacy.