Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells.

1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro M, 1 h) produces cytochrome c release to the cytoplasm that seems to be mediated by superoxide anions and that is blocked by cyclosporin A (10 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro M), but not by the Ca2+ uniporter blocker ruthenium red (5 micro M). 5. These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. 6. Exposure of isolated bovine chromaffin mitochondria to Ca2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 micro M) and cyclosporin A (10 micro M), while it was not modified by vitamin E (50 micro M). 7. Veratridine (30 micro M, 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. 8. In conclusion, superoxide anions seem to mediate veratridine-induced cytochrome c release, decrease in total glutathione, caspase activation and cell death in bovine chromaffin cells.

CHOP plays a pivotal role in the astrocyte death induced by oxygen and glucose deprivation.

Ischemia has different consequences on the survival of astrocytes and neurons. Thus, astrocytes show a remarkable resistance to short periods of ischemia that are well known to cause neuronal death. We have used a cell culture model of stroke, oxygen, and glucose deprivation (OGD), to clarify the mechanisms responsible for the exclusive resistance of astrocytes to ischemia. The expression of genes implicated in both ischemia-induced astrocyte death and post-ischemic survival was analysed by the RNA differential display technique. Our study revealed that the expression of the CEBP homologous protein (CHOP)-coding gene is promptly an intensely upregulated following astrocyte oxygen and glucose deprivation. CHOP mRNA induction was accompanied by the activation of other genes (grp78, grp95) that, alike CHOP, are involved in the endoplasmic reticulum (ER) stress response. In addition, drugs that cause ER calcium depletion or protein N-glycosylation inhibition mimicked the effects of OGD on astrocyte survival, further supporting the involvement of ER in the astrocyte responses to OGD. Our experiments also demonstrated that upregulation of CHOP during the ER stress response is required for ischemia to cause astrocyte death. Not only the levels of CHOP mRNA and protein correlate perfectly with the degree of OGD-triggered cell injury, but also astrocyte death induced by OGD is significantly overcome by CHOP antisense oligonucleotide treatment. Nevertheless, we observed that astrocytes undergo apoptosis only when CHOP is permanently upregulated, and not when CHOP increases are transient. Finally, we found that the extent of CHOP induction is determined by the length of the ischemic stimulus. Taken together, our results indicate that permanent upregulation of CHOP is decisive for the induction of astrocyte death by OGD.

Peritonitis en diálisis peritoneal continua ambulatoria, factores medioambientales y de autocuidado / Peritonitis in continuous ambulatory peritoneal dialysis, environmental factors and self

La investigación tuvo como objetivo general describir los factores medioambientales y de autocuidado presentes en enfermos con peritonitis en tratamiento con diálisis peritoneal continua ambulatoria, en el periodo comprendido entre el 23 de abril de 2004 y el 1 de octubre de 2004, en la unidad renal de Fresenius Medical Care del hospital de San José de Bogotá. Los objetivos específicos fueron describir las características medioambientales, identificar los factores de autocuidado presentes y determinar los microorganismos causales. Hubo 17 pacientes con peritonitis, de los cuales uno falleció, tres no aceptaron participar en el estudio, dos fueron trasladados a hemodiálisis y uno cambió a Laboratorios Baxter. La muestra final fue de diez (10) enfermos. En cuanto al germen causal, tres presentaron Staphylococcus epidermidis, Streptococcus viridians y Staphylococcus aureus. Dos resultaron con cultivos negativos. La muestra corresponde a 70% sexo masculino y 30% femenino, con promedio de 51 años (desviación estándar 9,57 años), 30% trabajadores independientes, 20% pensionados, 20% en ocupaciones de hogar, 10% en zapatería y 20% sin trabajo, 10% profesional, analfabeta 10%, cursaron primaria 50% y bachillerato 30%. El 50% pertenecen al estrato 2,30% al 3, 10% al estrato 1 y estrato 4, respectivamente. El tiempo promedio en el programa fue de 34 meses (con desviación estándar 34,47 meses), con un mínimo de 12 y un máximo de 120 meses. En su totalidad realizan ellos mismos el recambio peritoneal. Los que presentaron peritonitis se relacionaron con baja escolaridad, factor que limitaría el aprendizaje del autocuidado. La educación verbal dada a los familiares y al paciente en el programa DPCA, no asegura el cuidado adecuado. La situación socioeconómica es una de las limitaciones del autocuidado, pues imposibilita la adquisición de elementos imprescindibles como las toallas desechables. Varios continúan desarrollando acciones inapropiadas que los ponen en riesgo de llegar a presentar infección, que se debe por lo regular a que siente mejoría y desea continuar con el estilo de vida que llevaba antes de enfermar.