1,720,994 research outputs found
Endothelin-1 potentiates nuclear calcium transients via IP3-dependent calcium release from perinuclear calcium stores
Letter regarding article by von Lewinski et al, "Insulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium" - Reply
Letter regarding article by von Lewinski et al, "Insulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium" - Reply
Insulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium
Background - Insulin has been shown to exert positive inotropic effects in several in vitro and in vivo models, but signal transduction and substrate dependency remain unclear. We examined inotropic responses and signal transduction mechanisms of insulin in human myocardium. Methods and Results - Experiments were performed in isolated trabeculae from end- stage failing hearts of 58 nondiabetic and 3 diabetic patients undergoing heart transplantation. The effect of insulin ( 0.3 and 3 IU/ L) on isometric twitch force ( 37 degrees C, 1 Hz) was tested in the presence of glucose or pyruvate as energetic substrate. Furthermore, intracellular Ca2+ transients ( aequorin method), sarcoplasmic reticulum ( SR) Ca2+ content ( rapid cooling contractures), and myofilament Ca2+ sensitivity ( semiskinned fibers) were assessed. In addition, potential signaling pathways were tested by blocking glycolysis, PI- 3- kinase, protein kinase C, diacylglycerol kinase, insulin- like growth factor- 1 receptors, or transsarcolemmal Ca2+ entry via the Na+/Ca2+ exchanger. Insulin exerted concentration- dependent and partially substrate- dependent positive inotropic effects. The phosphatidylinositol- 3- kinase inhibitor wortmannin and the Na2+/Ca2+ exchanger reverse- mode inhibitor KB- R7943 completely or partially prevented the functional effects of insulin. In contrast, insulin- like growth factor- 1 receptor blockade, protein kinase C inhibition, and diacylglycerol kinase blockade were without effect. The inotropic response was associated with increases in intracellular Ca2+ transients, SR Ca2+ content, and increased myofilament Ca2+ sensitivity. Conclusions - Insulin exerts Ca2+- dependent and - independent positive inotropic effects through a phosphatidylinositol3- kinase - dependent pathway in failing human myocardium. The increased [ Ca2+] (i) originates at least in part from enhanced reverse- mode Na+/Ca2+ exchange and consequently increased SR- Ca2+ load. These nongenomic functional effects of insulin may be of clinical relevance, eg, during insulin- glucose- potassium infusions
Extended myectomy for hypertrophic obstructive cardiomyopathy after failure or contraindication of septal ablation or with combined surgical procedures
Background: Surgical correction of hypertrophic obstructive cardiomyopathy in severely symptomatic patients has been proven to be effective over the long term. The introduction of catheter-based procedures restricts surgical therapy to a subset of patients not suitable for septal ablation or requiring concomitant cardiac surgery. Methods: Between 8/2001 and 8/2003, 25 patients (58 15 years) underwent extended transaortic septal myectomy with partial excision and mobilization of the papillary muscles. Concomitant surgical procedures were performed in 40% (CABG n = 9, aortic valve replacement n = 2). In 24%, prior septal ablation was ineffective. Intraventricular gradient was 80 29 mm Hg at rest and 143 +/- 35 mm Hg during exercise. Mitral regurgitation affected 72% of patients, and 88% were NYHA functional class III or IV. Results: No hospital death, no postsurgical ventricular septal defect, and no complete atrioventricular block occurred. Severe nonfatal complications occurred in 24% of patients. Intensive care was necessary for 1.8 +/- 1.7 days; total hospital stay was 11.8 +/- 3.8 days. Early follow-up was complete in 100% (15 +/- 6 months, total of 376 months) with no late deaths, no relevant mitral regurgitation, or intraventricular gradients. Functional status was markedly improved (NYHA class 1 40%, class II 56%, class III 4%). Conclusions: Early results of extended surgical myectomy and reconstruction of the subvalvular mitral apparatus in hypertrophic obstructive cardiomyopathy remain excellent with respect to mortality, Morbidity, and functional capacity even when restricting surgery to patients earlier supposed to be at high risk
Early results of extended myectomy in hypertrophic obstructive cardiomyopathy in the era of interventional septal ablation
Early results of extended myectomy in hypertrophic obstructive cardiomyopathy in the era of interventional septal ablation
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
