A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia.

Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγc(null) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies.

Estrogens and atherosclerosis.

Numerous epidemiological as well as experimental studies have suggested that estradiol (E2) prevents atherosclerosis development. However two controlled prospective and randomized studies in women using hormone replacement therapy (HRT) did not confirm this beneficial effect. We then decided to use mouse models of atherosclerosis to define the possible mechanisms involved and the reasons for the discrepancy. We have shown that, although serum cholesterol decreases, this influence on lipid metabolism is negligible. Surprisingly, E2 induces an inflammatory-immune response towards a T helper cell (Th1) profile with increasing interferon-gamma production that could destabilize atheromatous plaques, and could account for the increase in the frequency of cardiovascular events in women undergoing HRT. At the level of the endothelium, E2 induces an increase in nitric oxide (NO) biodisponibility, but this phenomenon does not concern the development of fatty streaks. Nevertheless, the atheroprotective effect is apparently mediated at the level of the endothelium by a mechanism that has still to be characterized in molecular terms. These new acquisitions constitute a basis for new pharmacological developments allowing the prevention of deleterious effects and preserving the beneficial ones.

La investigación en enfermería como instrumento de cambio en la práctica y en la formación de recursos humanos / Nursing research as an instrument for change in practice and manpower training

La enfermería en América Latina enfrenta el desafío de integrarse al mismo tiempo a la comunidad científica internacional de enfermería y la comunidad científica nacional. Para alcanzar este doble objetivo, hay que considerar los condicionantes del sector salud y la situación económico-social. La crisis mundial determinó la crisis en el sector salud. La meta de salud para todos en el año 2000, al proponer la sustitución del modelo de atención vigente en los países, con énfasis en los servicios hospitalarios, por una estrategia de atención primaria, ofrece a la enfermería la oportunidad de redefinir y expandir su papel, pero el hecho cierto es que acaba por determinar la pérdida del control de la situación. De otro lado se inicia una fase de transición de una enfermería comunitaria a una enfermería social, centrada en el ser humano, con un cuerpo socialmente investido por el trabajo y ocupando distintas posiciones en la sociedad. Aunque en esta perspectiva la investigación tiene que ser un factor de mejoría de la práctica de enfermería, se observa una desvinculación entre una y otra. Se describe en este artículo la evolución de la investigación en enfermería en el Brasil, los marcos históricos y su estado actual. Se destaca la importancia de la divulgación del conocimiento y las dificultades para su incorporación a la práctica y a la formación de recursos humanos. Finalmente se considera la función transformadora de la investigación en enfermería como práctica social