GSK-3 beta inhibition and prevention of mitochondrial apoptosis inducing factor release are not involved in the antioxidant properties of SB-415286

The antioxidant effects of lithium and SB-415286, two glycogen synthase kinase-3 beta (GSK-3 beta) inhibitors, were studied in cerebellar granule neurons by measuring changes in 2, 7-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescence. GSK-3 beta inhibitors inhibit apoptosis mediated by serum and potassium withdrawal (S/K withdrawal) and GSK-3 beta activation, as measured by beta-catenin degradation. Furthermore, as both drugs prevent mitochondrial apoptosis inducing factor (AIF) release, these data indicate that GSK-3 beta inhibitors prevent caspase-independent apoptosis in cerebellar granule neurons induced by S/K withdrawal. While the most specific GSK-3 beta inhibitor, SB-415286, demonstrated antioxidant effects, Li+ 10 mM did not. These results indicate that lithium 10 mM and SB-415286 20 microM exert anti-apoptotic effects in cases of S/K withdrawal mediated by GSK-3 beta inhibition. However, these antioxidant properties are independent of GSK-3 beta inhibition and prevention of mitochondrial AIF release.     

Central vs. peripheral administration of ethanol, acetaldehyde and acetate in rats: effects on lever pressing and response initiation

The metabolites of ethanol, acetaldehyde and acetate, are biologically active, and different effects may be produced depending upon the particular metabolite and the route of administration. These studies characterized the effects of intraperitoneal (IP) vs. intraventricular (ICV) administration of ethanol, acetaldehyde, and acetate administered to male Sprague-Dawley rats. Operant behavior was assessed by conducting a detailed temporal analysis of lever pressing with rats responding on a fixed ratio 5 schedule of food reinforcement. IP administration of all three drugs produced a rate-decreasing effect on the total number of responses. Acetaldehyde and acetate were much more potent than ethanol at reducing lever pressing. The interresponse time (IRT) distribution also was more potently altered by IP administration of ethanol metabolites than by ethanol itself. The total lever pressing and IRT distributions of ethanol- and acetaldehyde- treated rats were not significantly affected when these drugs were administered ICV, while acetate produced a marked suppression of fast responses and an increase in pausing. The metabolites of ethanol are more potent than ethanol itself in terms of altering patterns of lever pressing. Thus, the effects of ethanol administration could in part be due to the actions of its biologically active metabolites.     

Guía de práctica clínica. Diagnóstico y prevención del cáncer colorrectal. Actualización 2018

This document updates the recommendations made by the Spanish Society of Family and Community Medicine and the Spanish Association of Gastroenterology for the diagnosis and prevention of colorectal cancer (CRC). In order to evaluate the quality of the evidence and determine the recommendation levels of the interventions, we used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. This document establishes optimal delay intervals based on symptoms and the faecal immunochemical test (FIT) and recommends reducing the barriers for diagnostic confirmation in symptomatic subjects. With regard to CRC screening in the average-risk population, we propose strategies to achieve the universal implementation of organised CRC screening programmes based on biennial FIT and to increase the participation of the target population, including the involvement of Primary Healthcare. This Clinical Practice Guideline recommends universal screening for Lynch syndrome with mismatch repair proteins immunohistochemistry or microsatellite instability in incident CRCs and the use of gene panels in patients with adenomatous polyposis. It also updates the strategies to reduce the incidence and mortality of both CRC and other tumours associated with hereditary syndromes. Regarding non-hereditary familial CRC and surveillance after resection of adenomas, serrated lesions or CRC, we established the recommendations based on the attributable risk and the risk reduction of the proposed intervention. Finally, the document includes recommendations regarding surveillance intervals in inflammatory bowel disease and the attitude towards dysplasia.     

Guía de práctica clínica sobre el manejo del estreñimiento crónico en el paciente adulto. Parte 2: Diagnóstico y tratamiento

Constipation is a very common disorder that adversely affects well-being and quality of life. Evidence-based clinical practice guidelines are an essential element for proper patient management and safe, effective treatment.The aim of these guidelines is to provide health care professionals who care for patients with chronic constipation with a tool that allows them to make the best decisions about the prevention, diagnosis and treatment of constipation.The methodology used to draw up these guidelines is described in the Part 1. In this article we will discuss the recommendations for the diagnostic and therapeutic management of constipation.     

Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock

Purpose  

The aim of this experimental study is to investigate cardiovascular tolerance of blockade of beta-adrenergic receptors in an endotoxin model.     

Content and traffic of taurine in hippocampal reactive astrocytes

Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial to proper development. Moreover, taurine acts as a neuroprotectant in various diseases; in epilepsy, for example, it has the capacity to reduce or abolish seizures. In the present study, taurine levels has been determine in mice treated with Kainic Acid (KA) and results showed an increase of this amino acid in hippocampus but not in whole brain after 3 and 7 days of KA treatment. This increase occurs when gliosis was observed. Moreover, taurine transporter (TAUT) was found in astrocytes 3 and 7 days after KA treatment, together with an increase in cysteine sulfinic acid decarboxylase (csd) mRNA, that codifies for the rate‐limiting enzyme of taurine synthesis, in the hippocampus at the same times after KA treatment. Glial cultures enriched in astrocytes were developed to demonstrate that these cells are responsible for changes in taurine levels after an injury to the brain. The cultures were treated with proinflammatory cytokines to reproduce gliosis. In this experimental model, an increase in the immunoreactivity of GFAP was observed, together with an increase in CSD and taurine levels. Moreover, an alteration in the taurine uptake‐release kinetics was detected in glial cells treated with cytokine. All data obtained indicate that astrocytes could play a key role in taurine level changes induced by neuronal damage. More studies are, therefore, needed to clarify the role taurine has in relation to neuronal death and repair. © 2010 Wiley‐Liss, Inc.