Another off-label novel oral anticoagulant to HIT cardiac surgery patients

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Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling

Nutritional excess and hyperlipidemia increase the heart’s susceptibility to ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular response to nutritional status and may play a role in ischemic injury. To explore the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR signaling in hypercholesterolemic swine (HC) that are also susceptible to increased cardiac ischemia-reperfusion injury. Yucatan pigs were fed a high-fat/high-cholesterol diet for 4 weeks to induce hypercholesterolemia, and mTOR signaling was measured by immunoblotting and immunofluorescence in the non-ischemic left ventricular area. Total myocardial mTOR and raptor levels were markedly increased in the HC group compared to the normocholesterolemic group, and directly correlated with serum cholesterol levels. mTOR exhibited intense perinuclear staining in myocytes only in the HC group. Hypercholesterolemia was associated with hyperactive signaling upstream and downstream of both mTOR complexes, including myocardial Akt, S6K1, 4EBP1, S6 and PKC-alpha, increased levels of cardiac hypertrophy markers, and a trend toward lower levels of myocardial autophagy. Hypercholesterolemia can now be added to the growing list of conditions associated with aberrant mTOR signaling. Hypercholesterolemia produces a unique profile of alterations in cardiac mTOR signaling, which is a potential target in cardiac diseases associated with hypercholesterolemia and nutritional excess

Phosphorylation and translocation of heat shock protein 27 and αB-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass

ObjectivesCardiac surgery using cardioplegia and cardiopulmonary bypass subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function. Research in animal and cell models demonstrates that acute myocardial ischemia/reperfusion injury causes phosphorylation of heat shock protein 27 and αB-crystallin. Phosphorylation of heat shock protein 27 and αB-crystallin is implicated in the regulation of both beneficial and detrimental responses to ischemic injury. The phosphorylation status of these proteins in human myocardium after ischemic insults associated with cardioplegia and cardiopulmonary bypass is unknown.MethodsRight atrial appendage and chest wall skeletal muscle samples were collected from patients before and after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass-induced changes in phosphorylation and localization of heat shock protein 27 and αB-crystallin were determined using immunoblot and confocal microscopy with total and phospho-specific antibodies.ResultsCardioplegia and cardiopulmonary bypass increased the phosphorylation of heat shock protein 27 on serine 15, 78, and 82, and αB-crystallin on serine 59 and 45, but not serine 19. The majority of heat shock protein 27 and αB-crystallin localized to I-bands of cardiac myofilaments and shifted to a detergent insoluble fraction after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass–induced phosphorylation of specific heat shock protein 27 and αB-crystallin residues were associated with additional subcellular locations. Increases in phosphorylation of heat shock protein 27 and αB-crystallin were negatively correlated with cardiac function after surgery.ConclusionCardiac surgery using cardioplegia and cardiopulmonary bypass is associated with phosphorylation and myofilament translocation of heat shock protein 27 and αB-crystallin in human myocardium. Phosphorylation of specific heat shock protein 27 and αB-crystallin serine residues is associated with distinct localization. Understanding the human myocardial small heat shock protein response may have significant implications for surgical myocardial protection

Development of a digital research assistant for the management of patients\u2019 enrollment in oncology clinical trials within a research hospital

Clinical trials in cancer treatment are imperative in enhancing patients\u2019 survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients\u2019 accrual in clinical trials. We developed a specific platform, called \u201cDigital Research Assistant\u201d (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients\u2019 records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients\u2019 records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient\u2019s data and clinical trial\u2019s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

Localization and Distribution of Binging Sites for Atrial Natriuretic Factor in the Rat: A Light and Electron Microscope Radioautographic Study

Note:Studies were undertaken to localize in vivo binding sites for atrial natriuretic factor (ANF) in rats by light and electron microscope radioautography. ANF binding sites were identified in the brain, kidney, eye and small intestine. In the brain, they were present in the circumventricular organs, blood vessels and choroid plexus. In the renal cortex, they were mainly localized in epithelial visceral cells. In addition, ANF inhibited the decrease in the size of isolated glomeruli induced by Angiotensin II. ANF binding sites in the renal medulla corresponded mainly to the descending vasa recta, and to papillary collecting tubules in the renal papilla. In the eye, ANF binding sites were present at the base of "pigmented" cells of the ciliary processes. In the small intestine, they were localized in fibroblast like cells of the lamina propria, at the base of mature enterocytes and to a lesser extent in the capillaries. Such detailed map of ANF binding sites may be very helpful in our understanding of the mechanisms and implications of circulating ANF in physiological and pathophysiological states where this hormone seems to play a major role in the homeostasis of body fluid volume and blood pressure.Nous avons entrepris des études microscopie photonique et électronique radioautographiques en dans le but de révéler les sites de liaison in vivo du facteur natriurétique auriculaire (FNA) chez le rat. Nous avons pu démontrer la présence de ces sites de liaison dans le cerveau, les reins, les yeux ainsi que l'intestin grêle. Dans le cerveau, les sites de liaison sont situés au niveau des organes circumventriculaires, des vaisseaux sanguin et du plexus choroide. Dans le cortex rénal, ils se retrouvent principalement localises sur les cellules épithéliales viscérales. En outre, nous avons pu démontrer que le FNA inhibe la contraction des glomérules isoles en réponse a l'angiotensine II. Dans la médullaire rénale; les sites de liaison du FNA sont localises sur les vasa recta descendants et les tubules collecteurs. Dans l'œil, ils se trouvent à la base des cellules "pigmentées" du procès ciliaire. Les sites de liaison de l'intestin grêle se partagent entre les fibroblastes de la lamina propria et la base des entérocytes. Cette carte détaillée des sites de liaison du FNA devrait s'avérer d'une grande utilité pour la compréhension du rôle physiologique du FNA circulant et de ses implications physiopathologiques

Another Off-label Novel Oral Anticoagulant To Hit Cardiac Surgery Patients

1502E20E2

Angiogenic Gene Therapy in the Treatment of Ischemic Cardiovascular Diseases

Encouraging preliminary data suggest that gene therapy may soon be an option for the treatment of patients with advanced coronary artery disease that is not amenable to conventional treatment. A critical consideration in developing cardiovascular gene transfer as a therapy is the ability to deliver the vector, viral or plasmid, to the desired tissue in a safe fashion. Attempts at developing non-viral direct DNA therapy delivered through the intravenous route are currently underway and with the use of advanced technology the possibility of making gene therapy a simple outpatient procedure does not seem out of the realm of possibility. Several clinical trials are currently underway that should help characterize the risk–benefit profile of various products, the optimal dose that should be administered, and the patient population likely to derive greatest benefit

Angiogenic Gene Therapy in the Treatment of Ischemic Cardiovascular Diseases

Encouraging preliminary data suggest that gene therapy may soon be an option for the treatment of patients with advanced coronary artery disease that is not amenable to conventional treatment. A critical consideration in developing cardiovascular gene transfer as a therapy is the ability to deliver the vector, viral or plasmid, to the desired tissue in a safe fashion. Attempts at developing non-viral direct DNA therapy delivered through the intravenous route are currently underway and with the use of advanced technology the possibility of making gene therapy a simple outpatient procedure does not seem out of the realm of possibility. Several clinical trials are currently underway that should help characterize the risk–benefit profile of various products, the optimal dose that should be administered, and the patient population likely to derive greatest benefit