LA TESIS DE LA ELECCIÓN DIVINA DE LO ÓPTIMO: UNA EXCEPCIÓN EN LA TEORÍA MODAL DE LEIBNIZ

La proposición "Dios elige lo mejor" constituye una verdad incuestionable para Leibniz, y una premisa fundamental en su explicación de la existencia del mundo, tanto como en su teodicea. Leibniz sintió la necesidad de clarificar su carácter modal, dada la importancia de tal cuestión en relación con la libertad divina. Sin embargo, en el abordaje de este problema, se vio conducido a infringir los criterios de su propia teoría modal, con el fin de justificar la contingencia de tal proposición. Este trabajo intenta mostrar que la posición principal sostenida por Leibniz, en torno a la modalidad de esta proposición, constituye una suerte de excepción en el marco de su doctrina modal, y que esta ambigüedad refleja las razones profundas de las oscilaciones constatables en sus escritos sobre esta temática.

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

Acute renal failure (ARF) is a frequent complication of Gram-negative sepsis, with a high risk of mortality. Lipopolysaccharide (LPS)-induced ARF is associated with hemodynamic changes that are strongly influenced by the overproduction of nitric oxide (NO) through the cytokine-mediated up-regulation of inducible NO synthase. LPS-induced reductions in systemic vascular resistance paradoxically culminate in renal vasoconstriction. Collagen XVIII is an important component of the extracellular matrix expressed in basement membranes. Its degradation by matrix metalloproteases, cathepsins and elastases results in the formation of endostatin, claimed to have antiangiogenic activity and to be a prominent vasorelaxing agent. We evaluated the expression of endostatin/collagen XVIII in an endotoxemic ARF model. ARF was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg) followed by sacrifice 4 and 12 h later. Kidney tissue was the source of RNA and protein and the subject of histological analysis. As early as 4 h after LPS administration, blood urea, creatinine and NO levels were significantly increased compared to control. Endostatin/collagen XVIII mRNA levels were 0.71 times lower than sham-inoculated mice 4 h after LPS inoculation, returning to normal levels 12 h after LPS inoculation. Immunohistological examination revealed that acute injury caused by LPS leads to an increase of endostatin basement membrane staining in association with the decrease of CD31 endothelial basement membrane staining. These results indicate that in the early phase of endotoxemic ARF the endostatin levels were not regulated by gene expression, but by the metabolism of collagen XVIII.