Role of Adenosine A1 Receptors in Remote Ischemic Preconditioning Protection

Background: Adenosine is involved in classical preconditioning acting especially through adenosine A1 and A3 receptors. Objective: The objective of our study was to evaluate whether remote ischemic preconditioning (rIPC) activates adenosine A1 receptors before ischemia or at the onset of reperfusion to reduce myocardial infarct size. Methods: Isolated rat hearts were subjected to 30-min ischemia and 60-min reperfusion (I/R). In a second group, a rIPC protocol (3 cycles of hindlimb ischemia/reperfusion) was performed. Infarct size was measured with triphenyltetrazolium staining. Results: Remote IPC significantly decreased infarct size. This effect was abolished when DPCPX (A1 receptor blocker) or L-NAME (nitric oxide synthesis inhibitor) were administered during reperfusion. Conclusions: We demonstrated in the isolated rat heart that rIPC reduces myocardial infarction by activation of the adenosine A1 receptor at the onset of the reperfusion period. This protective effect would be also mediated by the activation of nitric oxide synthase during reperfusion.Es conocido que la adenosina está involucrada en el mecanismo del precondicionamiento isquémico clásico, actuando a través de los receptores A1 y A3. El objetivo de nuestro estudio fue evaluar si el precondicionamiento isquémico remoto (rIPC) activa los receptores de adenosina A1 antes de la isquemia o en la reperfusión reduciendo el tamaño del infarto de miocardio. Corazones aislados de rata fueron sometidos a 30 minutos de isquemia y 60 minutos de reperfusión (I/R). En el siguiente grupo, se realizó un protocolo de rIPC. El tamaño del infarto se midió con trifenil de tetrazolio. El rIPC disminuyó significativamente el tamaño del infarto. Este efecto fue abolido cuando se administraron DPCPX (bloqueante del receptor A1) y L-NAME (inhibidor de la síntesis de óxido nítrico) durante la reperfusión. En conclusión, demostramos en el corazón aislado de rata que el rIPC reduce el tamaño de infarto de miocardio mediante la activación del receptor de A1 de adenosina al inicio de la reperfusión miocárdica. Este efecto protector también estaría mediado por la activación de la enzima óxido nítrico sintasa durante la reperfusión.

Storage in the yolk platelets of low MW DNA produced by the regressing follicle cells.

The present work was carried out to clarify the nature and origin of the yolk DNA present in vitellogenic oocytes of the lizard Podarcis sicula. Morphological and biochemical evidences indicate that it has an intrafollicular origin, from the apoptotic bodies resulting from follicle cells regression at the end of previtellogenesis. This conclusion is reinforced by the observation that the oocyte membrane, in in vitro experiments, is unpermeable to exogenous DNA. Biochemical evidences reveal that the yolk DNA has a low (200bp) molecular weight and this suggests that it is produced by the endonucleases typically involved in apoptotic DNA laddering. Indeed, immunocytochemical analyses demonstrate that follicle cells contain significant amounts of DNAse I. In immunoblots, carried out during different periods of the ovarian cycle, the enzyme shows a MW of about 33, 66 or 100 kDa thus indicating that its activity in the follicle of Podarcis is modulated by dimerization and/or binding to regulatory factors

Storage in the yolk platelets of low MW DNA produced by the regressing follicle cells.

The present work was carried out to clarify the nature and origin of the yolk DNA present in vitellogenic oocytes of the lizard Podarcis sicula. Morphological and biochemical evidences indicate that it has an intrafollicular origin, from the apoptotic bodies resulting from follicle cells regression at the end of previtellogenesis. This conclusion is reinforced by the observation that the oocyte membrane, in in vitro experiments, is unpermeable to exogenous DNA. Biochemical evidences reveal that the yolk DNA has a low (200bp) molecular weight and this suggests that it is produced by the endonucleases typically involved in apoptotic DNA laddering. Indeed, immunocytochemical analyses demonstrate that follicle cells contain significant amounts of DNAse I. In immunoblots, carried out during different periods of the ovarian cycle, the enzyme shows a MW of about 33, 66 or 100 kDa thus indicating that its activity in the follicle of Podarcis is modulated by dimerization and/or binding to regulatory factors

Improving depressive symptoms in patients with schizophrenia using bilateral bipolar-nonbalanced prefrontal tDCS: Results from a double-blind sham-controlled trial

Background: Treating depressive symptoms in patients with schizophrenia is challenging. While transcranical Dicrect Current Stimulation (tDCS) improved other core symptoms of schizophrenia, conflicting results have been obtained on depressive symptoms. Thus, we aimed to expand current evidence on tDCS efficacy to improve depressive symptoms in patients with schizophrenia. Methods: A double-blind RCT was performed with patients randomized to 2 mA active-tDCS or sham-tDCS (15 daily sessions) with a bilateral bipolar-nonbalanced prefrontal placement (anode: left Dorsolateral prefrontal cortex; cathode: right orbitofrontal region). Clinical outcomes included variations of Calgary Depression Scale for Schizophrenia total score (CDSS) and of Depression-hopelessness and Guilty idea of reference-pathological guilt factors. Analysis of covariance was performed evaluating between-group changes over time. The presence/absence of probable clinically significant depression was determined when CDSS > 6. Results: As 50 outpatients were included (both groups, n = 25), significant improvements following active-tDCS were observed for CDSS total score (p = 0.001), Depression-hopelessness (p = 0.001) and Guilty idea of reference-pathological guilt (p = 0.03). Considering patients with CDSS>6 (n = 23), compared to sham, activetDCS significantly improved CDSS total score (p < 0.001), Depression-hopelessness (p = 0.001) but Guilty idea of reference-pathological guilt only marginally improved (p = 0.051). Considering response rates of clinically significant depression, important reductions of CDSS score were observed (78 % of the sample scored <= 6; activetDCS, n = 23; sham-tDCS, n = 16; p = 0.017). Early wakening item did not significantly change in any group. Limitations: The study lacks a follow-up period and evaluation of tDCS effects on psychosocial functioning. Conclusions: Bilateral bipolar-nonbalanced prefrontal tDCS is a successful protocol for the treatment of depressive symptoms in patients with schizophrenia