Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia

Despite intense investigation, mechanisms that facilitate the emergence of the pre-eclampsia phenotype in women are still unknown. Placental hypoxia, hypertension, proteinuria and oedema are the principal clinical features of this disease. It is speculated that hypoxia-driven disruption of the angiogenic balance involving vascular endothelial growth factor (VEGF)/placenta-derived growth factor (PLGF) and soluble Fms-like tyrosine kinase-1 (sFLT-1, the soluble form of VEGF receptor 1) might contribute to some of the maternal symptoms of pre-eclampsia. However, pre-eclampsia does not develop in all women with high sFLT-1 or low PLGF levels, and it also occurs in some women with low sFLT-1 and high PLGF levels. Moreover, recent experiments strongly suggest that several soluble factors affecting the vasculature are probably elevated because of placental hypoxia in the pre-eclamptic women, indicating that upstream molecular defect(s) may contribute to pre-eclampsia. Here we show that pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy. 2-ME ameliorates all pre-eclampsia-like features without toxicity in the Comt(-/-) pregnant mice and suppresses placental hypoxia, hypoxia-inducible factor-1alpha expression and sFLT-1 elevation. The levels of COMT and 2-ME are significantly lower in women with severe pre-eclampsia. Our studies identify a genetic mouse model for pre-eclampsia and suggest that 2-ME may have utility as a plasma and urine diagnostic marker for this disease, and may also serve as a therapeutic supplement to prevent or treat this disorder.

Deconstrucción de los relatos evangélicos de la pasión. Sobre el arraigo de la ficción en la Historia de las religiones

Las más elementales exigencias de rigor crítico e independencia siguen a menudo sin cumplirse hoy en día en la reconstrucción histórica de la figura del judío Yeshua ben Yosef (Jesús el galileo), en parte porque el carácter inconsistente de las fuentes evangélicas no es tomado en serio. El presente artículo analiza las incongruencias de los relatos de la pasión, muestra en ellos los indicios de un proceso de despolitización, y señala el carácter insostenible de varias afirmaciones clave de muchos historiadores contemporáneos sobre el predicador galileo.

Dante y la imaginación agente: el "narrador" de la "Commedia" y la transparencia perfecta de la profetología árabo-judía

This research pursues two avenues of thought: 1. Prophetology—that is, the theory dealing with the gnoseological status of the prophetic gift—and 2. That of a rationalistic philosophical culture, common to Christians and Jews and used for mystical and “anthropological” ends—that is, the quest for the perfection of the human being. In the former instance, the discussion deals exclusively with natural prophesy as it appears in the Arab tradition, which was spread throughout the Christian and Jewish cultures of the thirteenth and fourteenth centuries through Maimonides’ Guide for the Perplexed. This type of prophecy, for the spread of which the Latin translation of Maimonides’ work was decisive, was adopted—with variations—by a number of authors who formed part of Dante’s culture, particularly Albertus Magnus, in the Christian sphere, and Judah Romano and Abulafia in the Jewish sphere. With regard to the latter—i.e., the common philosophical culture—this relates to the High Medieval sacralized formulation that instrumentalised—through the study and application of a given exegesis—an Averroist model of demonstration of the condition of the possibility of thought: the instrument of scientific demonstration becomes a propaedeutic for salvation; that is, an instrument of a mystical nature for the achievement of personal and civil perfection. The philosophy that supports this model— Averroes’ noetics—along with its exegetic instrumentalization, formed a fundamental part of the intellectual climate of the Italy (and, above all Florence) in which Dante’s works were written...

Empleo de la diplomacia preventiva por parte de la Organización de Naciones Unidas en el conflicto de Kosovo de 1998-1999

En el interés de alcanzar la estabilidad y promover el mantenimiento de la paz internacional, la diplomacia preventiva nace como un concepto generador de estrategias encaminadas a actuar antes, durante y después del conflicto. El siguiente documento busca analizar el funcionamiento de los instrumentos de diplomacia preventiva empleados por las Naciones Unidas en la crisis de Kosovo de 1998 y 1999. Esta crisis surgida a raíz del conflicto entre el gobierno serbio y un movimiento disidente, conocido como el Ejército de Liberación Albano-Kosovar, que pretendía darle un perfil más autónomo al territorio y a la población albano-kosovar, reveló una serie de debilidades estructurales que sigue enfrentando este mecanismo en la resolución de conflictos étnicos al interior de los Estados.