Mossmckenzie2766

Accumulation of dodine in tissues correlated with increase of dose. The maximum level of active substance accumulation in tissues were measured 96 hours after application of 1 mg/L dodine dose -in order- in gills, muscles and liver. The accumulations were statistically significant (p  less then  0.05) when compared with control group.Introduction Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and juvenile autoimmune hepatitis (JAIH). The pathophysiologic features of each disease vary, but generally include presence of autoantibodies, cytokine abnormalities, and/or T and B cell autoreactivity.Areas covered This article compares conventional therapy with newer biologics available for treatment of autoimmune liver diseases. Conventional therapy involves the use of immunosuppressive agents, or other treatment modalities for specific autoimmune liver diseases such as ursodeoxycholic acid and fibrates for PBC. Biologics were developed to target the production of autoantibodies by B cells, the presence of proinflammatory cytokines, adhesion molecules or T and B cell activation.Expert opinion Despite the promise of biologics being able to target specific cellular and humoral pathways, results have been generally poor, and safety has not been as expected. Cases of autoimmune hepatitis have also developed with the use of these biologicals. Reasons for the lack of success of biologics in treating autoimmune liver disease has led to a reevaluation of our understanding of underlying pathogenesis, demonstrating that while our knowledge of the immunity has improved over the past two decades, it is far from complete.The question of causation in psychiatry is one of the oldest and most difficult in this field. This paper is the first of two published in this journal. First, it traces the development of psychogenic and organogenic views of mental disorders from Pinel until the early twentieth century. This includes the debate as to how a disturbance of function might create a lesion even without a visible pathological trace. The second part of the paper discusses in detail the controversy between functional and organic causes of mental disease. These concepts evolved taking into account psychological factors and also the response of the uninjured parts of the nervous system to trauma of various kinds.OBJECTIVE Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Plinabulin chemical Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 181p/226 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 180/180/181 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.As far back as the ancient Egyptians and Greeks, physicians have observed and interpreted the arterial pulse to diagnose disease. In the last 20 years, advances in modern engineering have rendered quantitative pulse wave analysis widely available, reliable, and reproducible. To date, measurement of arterial stiffness has remained almost exclusively a research activity. However, ongoing technological improvements coupled with already strong and growing evidence of clinical value should facilitate integration of arterial stiffness measures into clinical practice in the near future. This brief review will highlight clinical areas where arterial stiffness measures are likely to be the most informative in clinical practice.OBJECTIVE Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM's ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis. Approach and Results Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM's in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM's procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor). CONCLUSIONS CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM's procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM's pathophysiology and its mechanistic influences on hemostasis or thrombosis.OBJECTIVE The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ3 and platelet-derived serotonin. CONCLUSIONS These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.BACKGROUND There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [ less then 3 mm] versus long overlap), strategy (provisional versus 2-stent), routine versus bail-out FKI, aget vessel revascularization and restenosis. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT03544294.BACKGROUND Intraseptal anomalous aortic origin of a coronary artery is considered a benign condition. However, there have been case reports of patients with myocardial ischemia, arrhythmia, and sudden cardiac death. The purpose of this study was to determine the clinical presentation, myocardial perfusion on provocative stress testing, and management of children with anomalous aortic origin of a coronary artery with an intraseptal course in a prospective cohort. METHODS Patients with anomalous aortic origin of a coronary artery and intraseptal course were prospectively enrolled from December 2012 to May 2019, evaluated, and managed following a standardized algorithm. Myocardial perfusion was assessed using stress imaging. Fractional flow reserve was performed in patients with myocardial hypoperfusion on noninvasive testing. Exercise restriction, β-blockers, and surgical intervention were discussed with the families. RESULTS Eighteen patients (female 6, 33.3%), who presented with no symptoms (10, 55.6%), nonexertional (4, 22.2%), and exertional symptoms (4, 22.2%), were enrolled at a median age of 12.4 years (0.3-15.9). Perfusion imaging was performed in 14/18 (77.8%) and was abnormal in 7/14 (50%); fractional flow reserve was positive in 5/8 (62.5%). All 4 patients with exertional symptoms and 3/10 (30%) with no or nonexertional symptoms had myocardial hypoperfusion. Coronary artery bypass grafting was performed in a 4-year-old patient; β-blocker and exercise restriction were recommended in 4 patients not suitable for surgery. One patient had nonexertional chest pain and 17 were symptom-free at median follow-up of 2.5 years (0.2-7.1). CONCLUSIONS Up to 50% of patients with intraseptal anomalous aortic origin of a coronary artery had inducible myocardial hypoperfusion during noninvasive provocative testing. Long-term follow-up is necessary to understand the natural history of this rare anomaly.Aortic aneurysms in children are rare and when present are usually caused by a connective tissue disorder. In this article, we present a case of multiple aortic aneurysms in an adolescent with a novel finding of a gene variation that is associated with aortic disease.