Effects of pyruvate administration on infarct volume and neurological deficits following permanent focal cerebral ischemia in rats

Recent experimental evidences indicate that pyruvate, the final metabolite of glycolysis, has a remarkable protective effect against different types of brain injury. The purpose of this study was to assess the neuroprotective effect and the neurological outcome after pyruvate administration in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in rats. Three doses of pyruvate (250, 500 and 1000 mg/kg, i.p.) or vehicle were administered intraperitoneally 30 min after pMCAO. In other set of experiments, pyruvate was given either before, immediately after ischemia or in a long-term administration paradigm. Functional outcome, mortality and infarct volume were determined 24 h after stroke. Even when the lowest doses of pyruvate reduced mortality and neurological deficits, no concomitant reduction in infarct volume was observed. The highest dose of pyruvate increased cortical infarction by 27% when administered 30 min after pMCAO. In addition, when pyruvate was given before pMCAO, a significant increase in neurological deficits was noticed. Surprisingly, on the contrary of what was found in the case of transient global ischemia, present findings do not support a great neuroprotective role for pyruvate in permanent focal cerebral ischemia, suggesting two distinct mechanisms involved in the effects of this glycolytic metabolite in the ischemic brain

Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces blood-brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats

Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the progression of ischemic brain damage. In the present study, we investigated the effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin E2 (PGE2) levels, myeloperoxidase (MPO) activity, Evans Blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischemia in the rat. Postischemic treatment with nimesulide markedly reduced the increase in PGE2 levels in the ischemic cerebral cortex 24 h after stroke and diminished infarct size by 48 % with respect to vehicle-treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischemic episode. These studies provide the first experimental evidence that COX-2 inhibition with nimesulide is able to limit BBB disruption and leukocyte infiltration following transient focal cerebral ischemia. Neuroprotection afforded by nimesulide is observed even when the treatment is delayed until 6 h after the onset of ischemia, confirming a wide therapeutic window of COX-2 inhibitors in experimental stroke. On the other hand, selective inhibition of COX-1 with VAS had no significant effect on the evaluated parameters. These data suggest that COX-2 activity, but not COX-1 activity, contributes to the progression of focal ischemic brain injury, and that the beneficial effects observed with non-selective COX inhibitors are probably associated to COX-2 rather than to COX-1 inhibition

Clinical evolution of hypertension and proteinuria in patients who developed preeclampsia.

This a report of the clinical follow-up of women affected by preeclampsia.Introduction: Preeclampsia-eclampsia has been one of the main cause of maternal morbidity-mortality in developing countries, affecting 10% of pregnancies. In Mexico, in the recent years it has been estimated at about 2 to 35 new cases per 100 pregnancies. Objective: To report the evolution and severity of blood pressure and proteinuria; and their repercussion on renal function after delivery, in patients who developed preeclampsia. Methods: It was a descriptive analysis of 24 preeclamptic women on clinical follow up until normalization of blood pressure. Results: We observed lower serum albumin, higher severity of 24 hrs proteinuria level and longer duration of hypertension in those women who presented with the highest levels in diastolic blood pressure at the beginning and end of the study

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

Results from several studies indicate that cyclooxygenase-2 (COX-2) is involved ischemic brain injury. The purpose of this study was to evaluate the neuroprotective effects of the selective COX-2 inhibitor nimesulide on cerebral infarction and neurological deficits in a standardized model of transient focal cerebral ischemia in rats. Three doses of nimesulide (3, 6 and 12 mg/kg; i.p.) or vehicle were administered immediately after stroke and additional doses were given at 6, 12, 24, 36 and 48 h after ischemia. In other set of experiments, the effect of nimesulide was studied in a situation in which its first administration was delayed for 3 to 24 h after ischemia. Total, cortical and subcortical infarct volumes and functional outcome (assessed by neurological deficit score and rotarod performance) were determined 3 days after ischemia. The effect of nimesulide on prostaglandin E2 (PGE2) levels in the injured brain was also investigated. Nimesulide dose-dependently reduced infarct volume and improved functional recovery when compared to vehicle. Of interest is the finding that neuroprotection conferred by nimesulide (reduction of infarct size and neurological deficits and improvement of rotarod performance) was also observed when treatment was delayed until 24 h after ischemia. Further, administration of nimesulide in a delayed treatment paradigm completely abolished PGE2 accumulation in the postischemic brain, suggesting that COX-2 inhibition is a promising therapeutic strategy for cerebral ischemia to target the late-occurring inflammatory events which amplify initial damage

El Método del Árbol de Causas Aplicado a la Investigación de Accidentes Laborales

In every activity that takes place either in the work place or at home, there are always present risk factors that can triggeran accidentor incident. The aimof the investigation and analysis of accidents is to identify these risk factors to control or eliminate them through programs and, thus, reducing the maximum likelihood of these accidents from recurring. The Causal Tree Method, used in the investigation of accidents or incidents, ends up determining the primary causes that are to be eliminated or controlled since these are precisely the ones that cause the problem. This method, applied to accidents or incidents, provides agraphical perspective on the concatenation of the causes that generated them.En toda actividad que se realice ya sea a nivel laboral o a nivel del hogar están siempre presentes Factores de Riesgos que pueden desencadenar un accidente o incidente. El objetivo de la investigación y análisis de los accidentes es determinar estos factores de riesgos para, con programas de control, eliminarlos y con esto disminuir al máximo la posibilidad de que estos se repitan. El Método del Árbol de Causas, utilizado en la investigación de accidentes o incidentes, culmina con la determinación de las causas primarias que son las que, en defi nitiva, es preciso eliminar o controlar porque estas son, precisamente, las que originan el problema. Este método, aplicado sobre un accidente o incidente, nos proporciona, gráfi camente, la concatenación de las causas que terminó materializado en accidente o incidente laboral