RalGPS2 is involved in tunneling nanotubes formation in 5637 bladder cancer cells.

RalGPS2 is a Ras-independent Guanine Nucleotide Exchange Factor (GEF) for RalA containing a PH domain and an SH3-binding region and it is involved in several cellular processes, such as cytokinesis, control of cell cycle progression, differentiation, cytoskeleton organization and rearrangement. Up to now, few data have been published regarding RalGPS2 role in cancer cells, and its involvement in bladder cancer is yet to be established. In this paper we demonstrated that RalGPS2 is expressed in urothelial carcinoma-derived 5637 cancer cells and is essential for cellular growth. These cells produces thin membrane protrusions that displayed the characteristics of actin rich tunneling nanotubes (TNTs) and here we show that RalGPS2 is involved in the formation of these cellular protrusions. In fact the overexpression of RalGPS2 or of its PH-domain increased markedly the number and the length of nanotubes, while the knock-down of RalGPS2 caused a strong reduction of these structures. Moreover, using a series of RalA mutants impaired in the interaction with different downstream components (Sec5, Exo84, RalBP1) we demonstrated that the interaction of RalA with Sec5 is required for TNTs formation. Furthermore, we found that RalGPS2 interacts with the transmembrane MHC class III protein leukocyte specific transcript 1 (LST1) and RalA, leading to the formation of a complex which promotes TNTs generation. These findings allow us to add novel elements to molecular models that have been previously proposed regarding TNTs formation.

Effects of transcatheter aortic valve implantation on left ventricular mass and global longitudinal strain: tissue Doppler and strain evaluation.

INTRODUCTION: Transcatheter aortic valve implantation is the option of choice for high surgical risk patients suffering from symptomatic aortic stenosis. We aimed to evaluate the influence of baseline global longitudinal strain on left ventricular mass regression after the procedure. METHODS: We enrolled 23 patients with pure symptomatic severe aortic stenosis who underwent CoreValve prosthesis (Medtronic, Minneapolis, MN) implantation. Everyone had echocardiography registration before the procedure and after six months in order to analyze two-, three-, and four-chamber peak longitudinal strain and global longitudinal strain. RESULTS: After the procedure New York Heart Association class, peak and mean aortic valve gradients (p<0.001 for all) improved. Interventricular septum and posterior wall thicknesses decreased (p<0.001 for both). Moreover, left ventricular mass index for body surface area changed from 190±44 to 143±30 g/m(2), (p<0.001). Finally, global longitudinal strain significantly increased (from 9.4±0.9 to 11.5±0.8%; p<0.001), as well as its components. Baseline global longitudinal strain correlated with left ventricular mass regression (r=0.560; p=0.005; 2-sided) and predicted it at linear regression analysis (B=23.707; p=0.005; adjusted R(2)=0.281). CONCLUSIONS: Global longitudinal strain and its components improved six months after the procedure. Moreover, baseline global longitudinal strain seemed to predict left ventricular mass regression in patients with pure aortic stenosis undergoing transcatheter aortic valve implantation. This finding could be related to the extent of myocardial fibrosis which is also responsible for lack of left ventricular mass regression and poorer prognosis.

The piezoresistive effect in graphene-based polymeric composites.

The strain-dependent electrical resistance of polyvinyl ester-based composites filled with different weight fractions of graphene nanoplatelets (GNPs) has been experimentally investigated. The GNP synthesis and nanocomposite fabrication process have been optimized in order to obtain highly homogeneous filler dispersion and outstanding electrical properties. The produced nanocomposites showed a low percolation threshold of 0.226 wt% and electrical conductivity of nearly 10 S m(-1) at only 4 wt% of GNPs. The piezoresistive response of thin nanocomposite laminae has been assessed by measuring the variation of the electrical resistance as a function of the flexural strain in three-point bending tests under both quasi-static monotonic and dynamic cyclic loading conditions. The obtained results showed higher strain sensitivity than traditional metal foil strain gauges or recently investigated carbon-based nanocomposite films.

Efficacy of ranolazine in a patient with idiopathic dilated cardiomyopathy and electrical storm.

A case of idiopathic dilated cardiomyopathy with an arrhythmic storm refractory to the usual antiarrhythmic therapy will be reported. The idiopathic structural heart disease of the patient is a vulnerable anatomic substrate in itself, for electrical instability and reentry mechanism, because of heterogeneous areas of scarred myocardium and low left ventricle ejection fraction. In this case, the ranolazine administration was safe and effective for the prevention of further electrical storms.

Aortic valve stenosis and lipid-lowering therapy: the state of the art.

Aortic valve stenosis is the most common native valve disease and its most common cause in the United States and Europe is the calcification of a normal trileaflet. Recently, there is increasing evidence indicating that valve calcification has common underlying mechanisms with atherosclerosis. This connection raises interest in the potential efficacy of antiatherosclerosis medications in calcific valve stenosis (AS) therapy. Among them statins, are one of the most promising candidates, because of their pleiotropic effects. The aim of this review is to summarize and analyze the findings of contemporary studies and to discuss the rationale for statin usage in AS populations.

Stem cells and repair of the heart: cell-releasing epicardial scaffolds.

Cell transplantation represents the last frontier within the treatment of cardiac diseases. From the first paper published in 1992 that has documented the potentials of the transplantation of autologous skeletal muscle cells to treat the damage induced by acute myocardial infarction, innumerable techniques of implantation and types of cells used has been reported, greatly expanding this innovative and appealing field of search in cardiovascular medicine. Despite original promises and expectations, current evidences of stem cell transplantation are still weak and controversial. Therefore, alternative line of research are being explored, particularly in the field of techniques of cell implantation and engraftment. Besides direct implantation or myocardial colonization by bone marrow stimulation, epicardial application of cell-delivering systems (scaffold and patches) have gained popularity due to the possibility to apply selectively a cell-containing device which may gradually release the chosen cell type, alone or in combination with trophic substances. The scaffolds have proven to be successful in this respect and may represent a valid alternative to coronary, intra-myocardial, or venous injection of stem cells, or to stem cell stimulating factors. Finally these systems may be applied through minimally invasive procedures and act as external constraint to enhance ventricular reverse remodelling or limit further cardiac dilatation.

The importance of reducing heart rate in cardiovascular diseases: effects of Ivabradine.

Heart rate is a major determinant of cardiac output, myocardial oxygen consumption and coronary blood flow under physiological and pathological conditions. Experimental and clinical data have demonstrated that heart rate reduction is the main mechanism for reducing ischemia, improving left ventricular function, decreasing the risk of plaque rupture and post myocardial infarction mortality. Nowadays betablockers are the best class of drugs that can lower heart rate in patients with cardiovascular diseases, but sometimes their use is limited by some contraindications. Ivabradine is a new drug that reduces the firing rate of pacemaker cells in the sinoatrial node through a different mechanism with respect to betablockers. The purpose of this review is to investigate the main trials that support Ivabradine adoption in clinical practice.

Mitral valve prolapse and conduction disturbances: the forgotten association.

Various cardiac arrhythmias and conduction defects have been described in patients with mitral valve prolapse. We describe a case of a young woman affected by a mitral valve prolapse, involving the posterior mitral leaflet, with mild mitral regurgitation and an episode of syncope due to asystolia. It is hoped that this short communication will once again focus attention on the as yet unexplained association between mitral valve prolapse and various cardiac conduction disorders.

Tako-tsubo-like left ventricular dysfunction: transient left ventricular apical ballooning syndrome.

AIMS/OBJECTIVES: This review examines the 'tako-tsubo-like' syndrome or transient left ventricular apical ballooning. The aim of this review is a complete evaluation of epidemiology, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome. METHODS: We have evaluated the data from literature for a comprehensive consideration of multiple aspects of this syndrome. RESULTS/FINDINGS: Transient left ventricular apical ballooning typically affects women, and the clinical presentation is comparable to acute coronary syndrome with chest pain or sudden dyspnoea, changes in ECG and elevated cardiac enzymes in the absence of significant coronary stenosis, with complete resolution of wall-motion abnormalities in a period of days or weeks. This syndrome is triggered by marked psychological or physiological stress. Several pathophysiological mechanisms have been proposed, such as cathecolamine-mediated cardiotoxicity, abnormalities in coronary microvascular function and multivessel coronary vasospasm. The highest incidence of transient left ventricular apical ballooning is in the Japanese population, but it has been recently identified also in the USA and Europe. Treatment is empirical and supportive. The prognosis is generally favourable, although some deaths have been reported, usually the result of irreversible cardiogenic shock, refractory ventricular arrhythmias, or other catastrophic cardiovascular event. CONCLUSIONS/INTERPRETATIONS: We conclude by emphasising the importance of a more deeper knowledge of this syndrome for general physicians and cardiologists and it should be often considered as a possible diagnosis occurring in emergency department and in patients admitted in the Chest Pain Units with a diagnosis of coronary acute syndrome.

A quadricuspid aortic valve associated with severe aortic regurgitation and left ventricular systolic dysfunction.

We report a case of a quadricuspid aortic valve associated with severe aortic regurgitation and left ventricular systolic dysfunction.

Coronary artery fistula: diagnostic role of transthoracic and transesophageal echocardiography.

Congenital coronary artery fistulas (CAFs) are rare. Some patients develop symptoms of congestive heart failure secondary to a large left-to-right shunt or myocardial ischemia from coronary artery steal in the first few years after birth. After the second decade the frequency of symptoms and complications increase. We report a case of CAF originating from the circumflex artery and draining into the coronary sinus, associated with left main coronary aneurysm. Transtho-racic and transesophageal echocardiography approach showed the origin, course, and drainage site of the CAF. This case represents a typical sample of this rare anomaly and puts into evidence the essential role of echocardiography to define and complete the angiographic diagnosis.

Cardiac arrest in a patient with a mobile right atrial thrombus in transit and amyloidosis.

Primary amyloidosis is a rare disorder in which insoluble fibers are deposited in tissue and organs, impairing their function. Cardiac involvement occurs in up to 50% of patients with primary amyloidosis. We describe a case of a 75-year-old admitted to our department after he had a sudden cardiac arrest due to massive bilateral thrombotic occlusion of the pulmonary arteries. The echocardiogram revealed many atrial thrombi swirling inside the right atrium and protruding into the tricuspid valve partly occluding it. Severe concentric hypertrophy of the left ventricle was also present with a preserved ejection fraction. The right ventricle was dilated, hypertrophic and ipokinetic with a severe tricuspidal insufficiency that permitted estimation of a severe pulmonary hypertension. All these characteristics were highly suggestive for an infiltrative form of hypertrophic cardiomyopathy. The final diagnosis was amyloidosis.

Brain cancer mimicking an acute coronary syndrome.

The authors report the case of a 62-year-old woman admitted to hospital for episodes of chest pain with ischemic abnormalities at ECG without enzyme release. Coronography confirmed a normal coronary tree with mild ascending aortic dilatation. Subsequent diagnostic and clinical examinations resulted normal. Episodes of chest pain and dyspnea persisted over the following days. Administration of nitrates, calcium antagonist, diuretic, antidepressant agents for suspected syndrome X led to partial improvement of clinical symptoms. The patient was discharged from the hospital. A few days later she was referred to the neurology department because of an episode of transient dysarthria, hyposthenia and paresthesis localized to the right lower and upper limbs associated with chest pain. A brain computed tomography showed an expansive solid mass. Nuclear magnetic resonance imaging and stereotaxis biopsy confirmed the etiology of the lesion to be a glioblastoma. The patient died soon thereafter from respiratory and cardiocirculatory arrest.