Retinoic acid (RA), an active metabolite of vitamin A, is a natural morphogen involved in development and differentiation of the nervous system. To elucidate signaling mechanisms involved in RA-induced neuritogenesis, we used human neuroblastoma SH-SY5Y cells, an established in vitro model for studying RA action, to examine the role of extracellular signal-regulated kinase (ERK) 1 and 2 in RA-induced neuritogenesis and cell survival. From immunoblotting experiments, we observed that RA induced delayed but persistent ERK1 and ERK2 phosphorylation (until 96 hr) that was reduced significantly by the specific mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126. For the subsequent studies we chose 24 hr as the reference time. Inhibition of ERK activation did not affect RA-induced neuritogenesis (percentage of neurite-bearing cells and neurite length) but significantly reduced cell survival. In addition, we analyzed the signaling pathway that mediates ERK activation. Our results suggest that RA-induced ERK phosphorylation does not follow the classic Raf kinase-dependent pathway. Protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI 3-K) are possible alternative kinases involved in the ERK signaling pathway. In fact, in the presence of the specific PKC inhibitor GF 109203X, or the specific PI 3-K inhibitor wortmannin, we observed a significant dose-dependent reduction in ERK phosphorylation. RA-induced neuritogenesis and cell survival were reduced by GF 109203X in a concentration-dependent manner. These results suggest that rather than ERK1 and ERK2, it is PKC that plays an important role during early phases of RA-induced neuritogenesis.

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Combined anticancer therapy using platinum compounds and antitubulins has increased the risk of neurotoxicity. However, the combination of low-dose cisplatin (CDDP) with toxic doses of paclitaxel significantly reduces cellular death in a human neuroblastoma SH-SY5Y cell line. To analyze the mechanisms of this protection, we evaluated various signaling molecules possibly involved in apoptosis and some relevant cell cycle regulatory proteins. CDDP does not interfere with the tubulin-stabilizing action of paclitaxel. The evaluation of molecular pathways involved in apoptosis indicates that the Bcl-2 but not the caspases may be involved in the CDDP protection of paclitaxelinduced apoptosis. The increase in p53 protein and its nuclear accumulation suggests a possible involvement of p53 in CDDP protection. The use of the chemical inhibitor of p53, pifithrin A, excluded this possibility. The study of cyclins and the flow cytometric analysis (fluorescenceactivated cell sorting) suggest that CDDP exerts a protective action by blocking cells early in the cell cycle.

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La sistematización es un proceso investigativo, reflexivo, crítico y propositivo, mediante el cual se pretende estudiar, comprender, criticar, cuestionar y aprender de las prácticas. Este estudio pretendió sistematizar la experiencia de la práctica académica profesionalizante de pregrado Administración en Salud Animal (ASA) de la Universidad de Antioquia (UdeA), la cual se desarrolla en municipios antioqueños. La ruta metodológica comprendió tres etapas: la construcción histórica de la práctica desde la memoria colectiva, el análisis crítico de la práctica y aprender desde la práctica para mejorarla. Se utilizaron los dispositivos de flujo del proceso, la entrevista semiestructurada, la conversación, el relato, la entrevista de salida a los expracticantes, el taller, la revisión e interpretación de documentos y el diario de campo. En total se visitaron 17 municipios y se entrevistaron 74 personas. Dentro de los resultados están la construcción del marco contextual de ASA, el listado y ubicación de municipios con presencia histórica de ASA, la construcción de la línea de tiempo con red de actores y sucesos, la construcción y análisis del discurso ordenador, la identificación de las fortalezas, las limitaciones y carencias de la práctica en los ámbitos universitario y municipal y las contribuciones para trascender las carencias y fortalecer la práctica. La práctica de ASA representa la materialización del potencial de la Universidad para propiciar el diálogo entre la Universidad y la sociedad por medio del apoyo a la función de los municipios en salud animal y salud pública, aunque requiere profundas intervenciones para explotar al máximo su potencial transformador y formativo.