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001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p less then 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. Graphical abstract.Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction (AMI). The inflammatory response induced by ischemia and reperfusion (I/R) injury is considered one of the main mechanisms of MVO. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers an immunomodulatory effect in cardiac disease. The present study aimed to investigate whether immediate intravenous delivery of MSCs could be used as a potential therapeutic method to attenuate MVO formation. A cardiac catheterization-induced porcine model of myocardial I/R injury was established, and allograft MSCs were immediately delivered intravenously. Cardiac magnetic resonance (CMR) imaging was performed on days 2 and 7 after the operation to determine the infarct area, MVO, and cardiac function. The pigs with allograft MSCs showed decreased MVO and infarct size, as well as an improved left ventricular ejection fraction (LVEF). read more Histological analysis revealed decreased myocyte area, fibrosis, and inflammatory cell infiltration in the peri-infarct zone of pigs with allograft MSCs. Moreover, the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum were reduced in the allograft MSC group compared to the control group. Flow cytometry indicated decreased natural killer (NK) cells in the peripheral blood and ischemic heart tissue in the pigs with allograft MSCs. In summary, allograft MSCs delivered intravenously and immediately after myocardial I/R injury can attenuate MVO formation in a porcine model through a decline in the number of NK cells in the myocardium.Macroautophagy (hereafter called autophagy) is a highly conserved lysosomal pathway for catabolism of intracellular material in eukaryotic cells. Autophagy is also an essential homeostatic process through which intracellular components are recycled for reuse or energy production. The extremely regulated autophagy process begins with the formation of hallmarked double membrane bound organelles called autophagosomes which in turn fuse with lysosomes called autolysosomes and finally degrade the autophagic cargos. The multistages molecular machinery of autophagy is critically orchestrated by the action of a set of the autophagy proteins (Atg) and a supreme regulator, mTOR (mechanistic target of rapamycin). However, individual stages of autophagy are mechanistically complex and partially understood. In this review, the individual stages of autophagy are dissected, and the corresponding molecular regulation is discussed in view of current scientific knowledge of autophagy. This understanding of sequential events of autophagy machinery through this review may lead to great interest in the therapeutic potential for manipulating of autophagy in established diseases.How to prevent recurrences after a first venous thromboembolic (VTE) event in elderly patients is still an open issue, especially because of the high bleeding risk of anticoagulation in these patients. The placebo-controlled "Jason" study aims at assessing the efficacy and safety for secondary VTE prevention in elderly patients of oral Sulodexide (Vessel®) administration, a mixture of glycosaminoglycans (Alfasigma, Bologna, Italy) which proved effective against recurrences in a general population (SURVET study) without major bleeding (MB) complications. 1450 patients, aged ≥ 75 years, after at least 3 months of anticoagulation treatment for a first VTE episode, are double-blind randomized to receive for 12 months either sulodexide 500 lipasemic units (LSUs) twice daily, or sulodexide 250 LSU twice daily + indistinguishable placebo, or indistinguishable placebo. Primary outcomes for efficacy are the composite of death for VTE and recurrent VTE, and occurrence of MB for safety. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, and MB + clinically relevant non-MB. The first patient is scheduled to be randomized in May 2020. The study protocol has been approved by AIFA (Agenzia Italiana del Farmaco) and the Ethics Committee of the coordinating center. Written informed consent will be obtained from all patients prior to study participation. Jason study is an investigator-initiated trial, promoted by "Arianna Anticoagulazione" Foundation, Bologna, Italy, and supported by Alfasigma, Bologna, Italy. Study findings will be disseminated to participant centers, at research conferences and in peer-reviewed journals. Trial registration numbers NCT04257487; EudraCT (2019-000570-33).The history, electrocardiogram, age, risk factors, troponin (HEART) and global registry of acute coronary events (GRACE) scoring systems are commonly used to risk stratify patients with chest pain. This study investigated the application of these scores in predicting the short-term risk of a major adverse cardiac event (MACE) in patients with chest. A total of 509 patients were analyzed. All patients were followed up for 30 days after visiting our emergency department. At 30 days post-admission, the primary outcome (MACE) was recorded in 92 patients (18.1%), 88 (95.6%) of whom had experienced an acute myocardial infarction. Thirty-seven (40.2%) of the patients with a MACE underwent percutaneous coronary intervention and six patients (6.5%) died. The HEART and GRACE scores were both significantly higher in patients who developed a MACE than in those without (P less then 0.05). The HEART and GRACE scores had c-statistic values of 0.811 (95% CI 0.774-0.844) and 0.648 (95% CI 0.603-0.688), respectively. The Hosmer-Lemeshow statistic revealed that the HEART and GRACE scores had values of 8.
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