Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.

Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective: To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with ALI or ARDS receiving mechanical ventilation. P–V curves were fitted to a sigmoidal equation with a mean R2 of 0.994 ± 0.003. Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with high intraclass correlation coefficients. Bias and limits of agreement for LIP, UIP and PMC obtained with the two methods in the same patient were clinically acceptable.

Proteomic analysis of peach fruit mesocarp softening and chilling injury using difference gel electrophoresis (DIGE)

Background: Peach fruit undergoes a rapid softening process that involves a number of metabolic changes. Storing fruit at low temperatures has been widely used to extend its postharvest life. However, this leads to undesired changes, such as mealiness and browning, which affect the quality of the fruit. In this study, a 2-D DIGE approach was designed to screen for differentially accumulated proteins in peach fruit during normal softening as well as under conditions that led to fruit chilling injury. Results:The analysis allowed us to identify 43 spots -representing about 18% of the total number analyzed- that show statistically significant changes. Thirty-nine of the proteins could be identified by mass spectrometry. Some of the proteins that changed during postharvest had been related to peach fruit ripening and cold stress in the past. However, we identified other proteins that had not been linked to these processes. A graphical display of the relationship between the differentially accumulated proteins was obtained using pairwise average-linkage cluster analysis and principal component analysis. Proteins such as endopolygalacturonase, catalase, NADP-dependent isocitrate dehydrogenase, pectin methylesterase and dehydrins were found to be very important for distinguishing between healthy and chill injured fruit. A categorization of the differentially accumulated proteins was performed using Gene Ontology annotation. The results showed that the 'response to stress', 'cellular homeostasis', 'metabolism of carbohydrates' and 'amino acid metabolism' biological processes were affected the most during the postharvest. Conclusions: Using a comparative proteomic approach with 2-D DIGE allowed us to identify proteins that showed stage-specific changes in their accumulation pattern. Several proteins that are related to response to stress, cellular homeostasis, cellular component organization and carbohydrate metabolism were detected as being differentially accumulated. Finally, a significant proportion of the proteins identified had not been associated with softening, cold storage or chilling injury-altered fruit before; thus, comparative proteomics has proven to be a valuable tool for understanding fruit softening and postharvest.

Individual prediction of automobile bodily injury claims liabilities

[spa] La mayoría de siniestros con daños corporales se liquidan mediante negociación, llegando a juicio menos del 5% de los casos. Una estrategia de negociación bien definida es, por tanto, fundamental para las compañías aseguradoras. En este artículo asumimos que la compensación monetaria concedida en juicio es la máxima cuantía que debería ser ofrecida por el asegurador en el proceso de negociación. Usando una base de datos real, implementamos un modelo log-lineal para estimar la máxima oferta de negociación. Perturbaciones no-esféricas son detectadas. Correlación ocurre cuando más de una siniestro se liquida en la misma sentencia judicial. Heterocedasticidad por grupos se debe a la influencia de la valoración del forense en la indemnización final.

Individual prediction of automobile bodily injury claims liabilities

[spa] La mayoría de siniestros con daños corporales se liquidan mediante negociación, llegando a juicio menos del 5% de los casos. Una estrategia de negociación bien definida es, por tanto, fundamental para las compañías aseguradoras. En este artículo asumimos que la compensación monetaria concedida en juicio es la máxima cuantía que debería ser ofrecida por el asegurador en el proceso de negociación. Usando una base de datos real, implementamos un modelo log-lineal para estimar la máxima oferta de negociación. Perturbaciones no-esféricas son detectadas. Correlación ocurre cuando más de una siniestro se liquida en la misma sentencia judicial. Heterocedasticidad por grupos se debe a la influencia de la valoración del forense en la indemnización final.

Recommendations on percutaneous coronary intervention for the reperfusion of acute ST elevation myocardial infarction

Little information is currently available from the various societies of cardiology on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Since primary PCI is the main method of reperfusion in AMI in many centres, and since of all cardiac emergencies AMI represents the most urgent situation for PCI, recommendations based on scientific evidence and expert experience would be useful for centres practising primary PCI, or those looking to establish a primary PCI programme. To this aim, a task force for primary PCI in AMI was formed to develop a set of recommendations to complement and assist clinical judgment. This paper represents the product of their recommendations.