Elucidating the Therapeutic Potential of Bis(Maltolato)OxoVanadium(IV): The Protective Role of Copper in Cellular Metabolism.

Vanadium (V) is a trace mineral whose biological activity, role as a micronutrient, and pharmacotherapeutic applications remain unknown. Over the last years, interest in V has increased due to its potential use as an antidiabetic agent mediated by its ability to improve glycemic metabolism. However, some toxicological aspects limit its potential therapeutic application. The present study aims to evaluate the effect of the co-treatment with copper (Cu) and bis(maltolato)oxovanadium(IV) (BMOV) as a possible strategy to reduce the toxicity of BMOV. Treating hepatic cells with BMOV reduced cell viability under the present conditions, but cell viability was corrected when cells were co-incubated with BMOV and Cu. Additionally, the effect of these two minerals on nuclear and mitochondrial DNA was evaluated. Co-treatment with both metals reduced the nuclear damage caused by BMOV. Moreover, treatment with these two metals simultaneously tended to reduce the ND1/ND4 deletion of the mitochondrial DNA produced with the treatment using BMOV alone. In conclusion, these results showed that combining Cu and V could effectively reduce the toxicity associated with V and enhance its potential therapeutic applications.

The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes.

BACKGROUND: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. METHODS: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. RESULTS: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. CONCLUSION: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin) and inflammatory (TNF-α) mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

Ahorrando choques con terapias de estimulación durante la carga, una terapia para taquicardias ventriculares rápidas / Saving shocks with antitachycardia pacing during charging: treatment for fast ventricular tachycardias

Evitando choques con terapias de estimulación antitaquicardia durante la carga. Un nuevo tratamiento para taquicardias ventriculares rápidas. Se ha demostrado que las terapias de estimulación antitaquicardia en las taquicardias ventriculares rapidas pueden terminar 3 de 4 de estos episodios y comparado con los choques, terapia es segura, efectiva y produce una mejora significativa de la calidad e vida, se ha demostrado ademas que ellas tiene una baja incidencia en la aceleración de las taquicardias y en la presencia de sincopes. Este relato describe un caso en el que el uso de la terapias de ATP durante la carga de los capacitores evitó al paciente recibir choques sin minguan demora en la entrega del mismo si hubiera sido necesario, este paciente presentaba frecuentemente taquicardias ventriculares rápidas a 240 ms de cb, por ello la posibilidad e tratarlas con terapias de ATP efectivas y no dolorosas tuvo un gran impacto psicologico en su vida diaria.

Role of heart rate in cardiovascular diseases: how the results of the BEAUTIFUL study change clinical practice.

The BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary artery disease and left ventricULar systolic dysfunction) study assessed the morbidity and mortality benefits of the HR-lowering agent ivabradine. The placebo arm of the BEAUTIFUL trial was a large cohort of patients with stable coronary artery disease (CAD) and left ventricular systolic dysfunction. A subanalysis in the placebo group tested the hypothesis that elevated resting HR at baseline was a marker for subsequent cardiovascular death and morbidity. The primary aim of the study was to test whether lowering the HR with ivabradine reduced cardiovascular death and morbidity in patients with CAD and left ventricular systolic dysfunction. In the overall analysis, reduction in HR with ivabradine did not improve cardiac outcomes compared with placebo. The most important finding of the study was that patients with high baseline HR had an increase in serious cardiovascular events including death (34%), hospital admission secondary to congestive heart failure (53%), acute myocardial infarction (46%), or revascularization procedure (38%). In addition, in the subset analysis focusing on patients with baseline HR > or =70 bpm and left ventricular ejection fraction <40% the agent resulted in a 36% decrease in hospital admissions secondary to fatal and nonfatal myocardial infarction and a 30% decrease in coronary revascularization. The first practical implication from the study includes that baseline HR should be recorded in addition to other risk factors such as BP and lipid profile, in the follow-up of patients with CAD. Attempts should be made to achieve HR <70 bpm by cardiac rehabilitation and routine use of appropriately dosed beta-blockers. Despite the neutral results obtained in the BEAUTIFUL study, ivabradine could be administered to the subgroup of patients in whom HR <70 bpm is not achieved despite proper dosing of beta-blockers and in those in whom beta-blockers are contraindicated. Furthermore, in clinical practice, ivabradine may be helpful for patients with stable CAD who have a high HR while receiving beta-blockers. Future studies are needed to confirm the hypothesis that single reduction of HR can improve cardiovascular prognosis.

Influence of the preimplantation QRS axis on responses to cardiac resynchronization therapy.

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine whether measurement of the QRS axis can help to predict outcome in patients undergoing cardiac resynchronization therapy. METHODS: The study included 78 patients who had undergone successful cardiac resynchronization device implantation. Patients were classified as having either a normal QRS axis (i.e., between -30 degrees and +120 degrees) or a left QRS axis deviation (i.e., between -30 degrees and -90 degrees). Patients were regarded as responders if they fulfilled all of the following criteria: their functional class improved by at least one grade, their left ventricular ejection fraction increased by at least 5%, they did not need hospitalization for worsening heart failure, and they were still alive at 12-month follow-up. RESULTS: After adjustment for age, preimplantation left ventricular ejection fraction, etiology and mitral regurgitation, a statistically significant interaction was found between the QRS axis and lead location (P=.026). There was a better response with an anterior lead location if the patient had a left QRS axis deviation. CONCLUSIONS: A significant interaction was found between the lead location and the preimplantation QRS electrical axis, such that there was a better response to resynchronization therapy when the lead was implanted in the anterior interventricular vein if the patient had a left QRS axis deviation.

Influencia del eje eléctrico QRS preimplante en la respuesta a la terapia de resincronización cardiaca / Influence of the preimplantation QRS axis on responses to cardiac resynchronization therapy

Introducción y objetivos. El objetivo del estudio es evaluar si el eje QRS puede ayudar a predecir el resultado en pacientes sometidos a terapia de resincronización cardiaca. Métodos. Se ha incluido a 78 pacientes a los que se implantó con éxito un dispositivo de resincronización. Los pacientes se clasificaron en eje normal (QRS entre -30° y +120°) y eje izquierdo (QRS entre -30° y -90°). Se consideró respondedores a los pacientes que cumplían todos los criterios siguientes: mejorar al menos un grado en su clase funcional, aumentar al menos un 5% la fracción de eyección del ventrículo izquierdo, no requerir hospitalización por insuficiencia cardiaca y seguir vivos a los 12 meses de seguimiento. Resultados. Tras ajustar por edad, fracción de eyección preimplante, etiología e insuficiencia mitral, hemos encontrado una interacción estadísticamente significativa (p = 0,026) entre el eje eléctrico y la localización del electrodo, con mejor respuesta en la localización anterior cuando el eje QRS era izquierdo. Conclusiones. Se objetiva una interacción entre la localización del electrodo y el eje eléctrico QRS preimplante, de tal forma que se observa una mejor respuesta a la terapia de resincronización en pacientes a quienes se implanta el electrodo en la vena interventricular anterior y el eje está desviado a la izquierda (AU)

Introduction and objectives. The aim of this study was to determine whether measurement of the QRS axis can help to predict outcome in patients undergoing cardiac resynchronization therapy. Methods. The study included 78 patients who had undergone successful cardiac resynchronization device implantation. Patients were classified as having either a normal QRS axis (i.e., between -30° and +120°) or a left QRS axis deviation (i.e., between -30° and -90°). Patients were regarded as responders if they fulfilled all of the following criteria: their functional class improved by at least one grade, their left ventricular ejection fraction increased by at least 5%, they did not need hospitalization for worsening heart failure, and they were still alive at 12-month follow-up. Results. After adjustment for age, preimplantation left ventricular ejection fraction, etiology and mitral regurgitation, a statistically significant interaction was found between the QRS axis and lead location (P=.026). There was a better response with an anterior lead location if the patient had a left QRS axis deviation. Conclusions. A significant interaction was found between the lead location and the preimplantation QRS electrical axis, such that there was a better response to resynchronization therapy when the lead was implanted in the anterior interventricular vein if the patient had a left QRS axis deviation (AU)