Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules.

Paeonia suffruticosa is a magnificent and long-lived woody plant that has traditionally been used to treat various diseases including inflammatory, neurological, cancer, and cardiovascular diseases. In the present study, we demonstrated the biological mechanisms of paeonoside (PASI) isolated from the dried roots of P. suffruticosa in pre-osteoblasts. Herein, we found that PASI has no cytotoxic effects on pre-osteoblasts. Migration assay showed that PASI promoted wound healing and transmigration in osteoblast differentiation. PASI increased early osteoblast differentiation and mineralized nodule formation. In addition, PASI enhanced the expression of Wnt3a and bone morphogenetic protein 2 (BMP2) and activated their downstream molecules, Smad1/5/8 and ß-catenin, leading to increases in runt-related transcription factor 2 (RUNX2) expression during osteoblast differentiation. Furthermore, PASI-mediated osteoblast differentiation was attenuated by inhibiting the BMP2 and Wnt3a pathways, which was accompanied by reduction in the expression of RUNX2 in the nucleus. Taken together, our findings provide evidence that PASI enhances osteoblast differentiation and mineralized nodules by regulating RUNX2 expression through the BMP2 and Wnt3a pathways, suggesting a potential role for PASI targeting osteoblasts to treat bone diseases including osteoporosis and periodontitis.

Development of a bioreactor system for cytotoxic evaluation of pharmacological compounds in living cells using NMR spectroscopy.

INTRODUCTION: The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive way. This paper details a step-by-step protocol to implement a bioreactor system able to maintain cell viability during NMR acquisitions, at high cell densities and for several hours, enabling toxicological evaluation of pharmacological compounds in living cells. METHOD: HeLa cells were immobilized in agarose gel threads and continuously perfused with oxygenated medium inside a 5 mm NMR tube. Signals corresponding to intracellular high-energy phosphorous compounds were continuously monitored by 31P NMR to assess cell energy levels, intracellular pH and intracellular free Mg2+ concentrations ([Mg2+]f) under control and in the presence of two different cytotoxic drugs, calix-NH2 or 5-fluorouracil (5-FU). RESULTS: The bioreactor system was effective in maintaining cell energy levels as well as intracellular pH and [Mg2+]f along time, with a good 31P NMR signal to noise ratio. Calix-NH2 and 5-FU decreased cell energy levels by 35% and 39%, respectively, with a negligible increase in intracellular [Mg2+]f, and without affecting intracellular pH. DISCUSSION: The immobilization and perfusion system here detailed, along with 31P NMR, is useful in toxicological evaluation of new pharmacological compounds, enabling the continuous assessment of drugs' effect on energy levels, intracellular pH and [Mg2+]f in intact cells, for several hours without compromising cell viability.

Seguridad de la resonancia mágnetica en pacientes con neuroestimuladores medulares: nuestra experiencia / Safety of magnetic resonance in patients with implanted spinal cord neurostimulators: our experience

Introducción: En la ultima década la resonancia magnética (RM) ha sido introducida como una herramienta rutinaria de diagnóstico clínico por imagen, siendo considerada como una prueba no invasiva y segura. Sin embargo se ha contraindicado su utilización en pacientes que poseen dispositivos electrónicos implantados, entre ellos neurostimuladores medulares y corticales. A diferencia del avance de la tecnología en neuroesti-mulación y su aplicación clínica, hay pocos estudios que avalen la seguridad de la RM en pacientes con neuroestimuladores implantados. Nuestra hipótesis es que la RM es un método diagnóstico seguro en los pacientes con neuroestimuladores implantados. Nuestro trabajo tiene como finalidad aportar más pruebas objetivas acerca de esta cuestión. Material y Métodos: Serie de 8 pacientes con neuroestimuladores implantados (ITRELL III modelo 7425, Medtronic) sometidos a 9 estudios de RM (1,5 T General Electric Sigma Excite) durante el 2005, siguiendo el protocolo de Liem van Dongen en los que se vigiló la aparición de efectos adversos relacionados, durante e inmediatamente después del estudio de imagen. Resultados: Durante los estudios de RM no se produjeron incidencias, ni efectos adversos, en ninguno de los casos, tanto en los que el estudio se realizó en zonas alejadas del implante del neuroestimulador, como en los que se realizó en la misma zona anatómica. Una vez concluido el estudio de RM no se objetivó ninguna referencia de los pacientes a sensaciones relacionadas con el calentamiento o interacción electromagnética de la RM con su neuroestimulador. Tampoco se produjo ningún fallo en la reprogramación de los neuroestimuladores, excepto en un caso en el que fue imposible reprogramar el neuroestimulador una vez concluido el estudio de RM. Conclusiones: Todo parece indicar que en la mayoría de los casos la RM puede ser aplicada de forma segura en pacientes con sistemas de neruroestimulación implantados, siguiendo el protocolo de Liem-van Dongen, pero al parecer existen determinadas circunstancias en las que no queda totalmente claro la fiabilidad de esta recomendación. En el caso de la paciente en la que no fue posible reprogramar su neuroestimulador después de la RM en nuestro estudio, pudiera haber ocurrido un fallo de batería, o bien un daño en el circuito electrónico del generador. El no haber podido examinar el generador con problemas, no nos permite establecer una sospecha fundada sobre el conjunto de hechos que pueden haber concurrido en la producción del fallo. En cualquier caso se impone la realización de más estudios para esclarecer de forma más fiable las condiciones seguras de realización de la RM en pacientes con neuroestimuladores implantados (AU)

Aims: Over the past decade, nuclear magnetic resonance imaging (MRI) has been introduced as a safe, non-invasive routine clinical diagnostic tool. However, its use has been contraindicated in patients with implanted electronic devices, such as motor cortex and spinal cord neurostimulators. Despite the rapid growth in neurostimulation technology and its clinical application, there have been few studies addressing the safety of performing MRI procedures in patients with implanted neurostimulators. Our hypothesis is that MRI is a safe diagnostic technique in patients with implanted neurostimulators. The aim of our study is to offer some objective proof towards this point. Methods: Eight patients with implanted neurostimulators (ITRELL III Model 7425, Medtronic) undergoing 9 MRI procedures (1,5 T General Electric Sigma Excite) in 2005 are presented, following the Liem van Dongen´s protocol, with a focus in the appearance of adverse effects, during and immediately after the imaging study. Results: During the MRI studies there were no overall adverse effects detected in any case, in those in which the scanning was performed on a location away from the site of the implanted neurostimulators, nor in those in which it was performed in the same anatomic region. Once the MRI study concluded, no patient reported any sensation of discomfort attributable to heating or the electromagnetic interaction of the MRI with the neurostimulators. Neither there was any failure in the neurostimulators rescheduling, except in one case in which it was impossible its reprogrammation once the study was completed. Conclusions: In general, all these investigations indicate that in most cases MRI can be performed safely in patients with implanted stimulators, following the Liem van Dongen´s protocol, but it seems that under some circumstances this recommendation is not completely reliable. In the case of our patient in which the neurostimulator was impossible to reschedule after the MRI, this may have been caused by a battery failure, or there could have been a breakup in the generator’s electronic circuit. As the generator could not be examined, a hypothesis about the train of events leading to its failure was not established. In any case more studies are desirable to reliably explain the safety conditions required for the performance of MRI in patients with implanted neurostimulators (AU)

Efecto biológico de la resonancia magnética sobre la mosca de la fruta drosophila malanogaster

En este artículo se describre la investigación en la cual fueron sometidas moscas de la fruta D. Melanogaster de las cepas White y vestigial a un campo de Resonancia Magnética por 171 horas con el fin de determinar, posibles alteraciones en el nivel genético

Preoperative metabolic analysis of donor corneas using magnetic resonance spectroscopy.

Successful corneal transplantation was accomplished following metabolic phosphorus magnetic resonance analysis. Four cat corneas were analyzed using phosphorus-31 magnetic resonance following storage in modified McCarey-Kaufman (M-K) medium for 24 h. Corneas were re-stored in M-K medium and transplanted 24 h after MR analysis. Four control corneas (contralateral eye, no magnetic resonance analysis performed) were also transplanted following storage in M-K medium under identical conditions. Successful corneal transplantation was accomplished with minimal ATP tissue levels. Corneas stored for 48 h maintained a pH of 7.3. The phosphorus-31 spectral modulus, which is the ratio of the high-energy phosphates to the low-energy phosphates, was calculated using the spectral integral (range, 0.49-0.77). No difference in endothelial cell density or morphology was detected between corneas following magnetic resonance analysis and control corneas when evaluated by specular microscopy.