A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Culture-dependent and culture-independent characterization of microorganisms associated with Aedes aegypti (Diptera: Culicidae) (L.) and dynamics of bacterial colonization in the midgut

In this work we show that the lumen of Aedes aegypti midgut is highly colonized by bacteria that were identified by culture-dependent and culture-independent methods. rDNA sequences obtained were compared with those from GenBank and the main bacterial genera identified were: Serratia, Klebsiella, Asaia, Bacillus, Enterococcus, Enterobacter, Kluyvera and Pantoea. All genera were identified in midgut except Enterobacter that was observed only in eggs. Asaia and Pantoea were also identified in eggs and ovary, respectively. In addition two yeast genera were observed in A. aegypti: Pichia isolated from midgut and Candida identified in midgut and ovary. The genus Serratia was dominant in all isolation assays representing 54.5% of the total of microorganisms. Thirty-nine and 24 bacterial clones were successfully obtained from midguts 24 and 48 h after blood feeding (ABF), respectively. The majority of clones obtained were from Serratia sp. (48.7% and 50% for 24 and 48 h ABF, respectively). Light microscopy showed that bacteria were located preferentially in the posterior midgut, around the blood meal and associated with peritrophic matrix. Scanning electron microscopy images showed a high number of bacteria in midgut during blood digestion and the peak of bacterial enumeration was reached 48 h ABF, stage in which lumen was almost totally occupied by bacteria that were also interacting with epithelial microvilli. Our results show the dynamics of microbial colonization and their distribution in midgut during blood digestion. (C) 2010 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Interventional treatment in diabetics in the era of drugeluting stents and compliance to the ESC guidelines: Lessons learned from the Euro Heart Survey Programme

Aims: The objective of the study is to determine the demographics and the in-hospital outcome of diabetic and non-diabetic patients treated with percutaneous coronary interventions (PCI) in Europe, to report the type of equipment and technology used for PCI procedures in diabetics and to clarify whether the treatment of diabetic patients complies with current European Society of Cardiology (ESC) guidelines. Methods and results: A total of 14,458 patients treated with PCI were enrolled from 29 member countries of the ESC between June 2005 and January 2006. Data were collected on patient characteristics and treatment, using new Cardiology Audit and Registration Data standards. In total, 3,603 patients (24.9%) were diabetic. Diabetics were older, more often female and had a higher body mass index than non-diabetics. Diabetics had higher rates of hypercholesterolaemia and hypertension, while current smokers were more frequent in the non-diabetics. Diabetics also had significantly higher rates of previous cardiovascular events. Clopidogrel was administered only in 48.1% of diabetic patients before PCI, while IIb/IIIa inhibitors were 22.9% during PCI. At discharge, there was a major adjustment of treatment with increases in the use of Beta-blocker (80.4%), angiotensin converting enzyme inhibitor (ACEI, 71.3%) and statins (89.8%) compared with on admission (Beta-blocker 60.9%, ACEI 55.0%, statin 63.1%). Inhospital mortality was higher in diabetics (1.8% vs 1.2%) although the in-hospital MACCE rate was not significantly different (3.6% vs 3.0%, p=0.09). Conclusions: Diabetic patients treated with PCI were older with more comorbidity. According to ESC guideline, the under-usage of clopidogrel, GP IIb/IIIa inhibitors should be improved. PCI is now taken as a good opportunity to adjust the use of appropriate medication. © Europa Edition. All rights reserved

Stress neuropeptide levels in adults with chest pain due to coronary artery disease: potential implications for clinical assessment

: Substance P (SP) and neuropeptide Y (NPY) are neuropeptides involved in nociception. The study of biochemical markers of pain in communicating critically ill coronary patients may provide insight for pain assessment and management in critical care. Purpose of the study was to to explore potential associations between plasma neuropeptide levels and reported pain intensity in coronary critical care adults, in order to test the reliability of SP measurements for objective pain assessment in critical care

A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration