Profibrinolytic effect of the epigenetic modifier valproic acid in man.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigenetically regulated mainly by histone deacetylase (HDAC) inhibitors. HDAC inhibitors, including VPA markedly upregulate t-PA gene expression in vitro.The trial had a cross-over design where healthy men (n = 10), were treated with VPA (Ergenyl Retard) 500 mg depot tablets twice daily for 2 weeks. Capacity for stimulated t-PA release was assessed in the perfused-forearm model using intra-brachial Substance P infusion and venous occlusion plethysmography. Each subject was investigated twice, untreated and after VPA treatment, with 5 weeks wash-out in-between. VPA treatment resulted in considerably decreased levels of circulating PAI-1 antigen from 22.2 (4.6) to 10.8 (2.1) ng/ml (p<0.05). It slightly decreased the levels of circulating venous t-PA antigen (p<0.05), and the t-PA:PAI-1 antigen ratio increased (p<0.01). Substance P infusion resulted in an increase in forearm blood flow (FBF) on both occasions (p<0.0001 for both). The acute t-PA release in response to Substance P was not affected by VPA (p = ns).Valproic acid treatment lowers plasma PAI-1 antigen levels and changes the fibrinolytic balance measured as t-PA/PAI-1 ratio in a profibrinolytic direction. This may in part explain the reduction in incidence of myocardial infarctions by VPA treatment observed in recent pharmacoepidemiological studies.The EU Clinical Trials Register 2009-011723-31.Swedish Heart-Lung Foundation Swedish Research Council Emelle Foundatio

Short- and long-term outcomes after heart transplantation in cardiac sarcoidosis and giant-cell myocarditis : a systematic review and meta-analysis

Heart transplantation (HTx) is a valid therapeutic option for end-stage heart failure secondary to cardiac sarcoidosis (CS) or giant-cell myocarditis (GCM). However, post-HTx outcomes in patients with inflammatory cardiomyopathy (ICM) have been poorly investigated. We searched PubMed, Scopus, Science Citation Index, EMBASE, and Google Scholar, screened the gray literature, and contacted experts in the field. We included studies comparing post-HTx survival, acute cellular rejection, and disease recurrence in patients with and without ICM. Data were synthesized by a random-effects meta-analysis. We screened 11,933 articles, of which 14 were considered eligible. In a pooled analysis, post-HTx survival was higher in CS than non-CS patients after 1 year (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.60-1.17; I-2 = 0%) and 5 years (RR 0.72, 95% CI 0.52-0.91; I-2 = 0%), but statistically significant only after 5 years. During the first-year post-HTx, the risk of acute cellular rejection was similar for patients with and without CS, but after 5 years, it was lower in those with CS (RR 0.38, 95% CI 0.03-0.72; I-2 = 0%). No difference in post-HTx survival was observed between patients with and without GCM after 1 year (RR 1.16, 95% CI 0.05-2.28; I-2 = 0%) or 5 years (RR 0.98, 95% CI 0.42-1.54; I-2 = 0%). During post-HTx follow-up, recurrence of CS and GCM occurred in 5% and 8% of patients, respectively. Post-HTx outcomes in patients with CS and GCM are comparable with cardiac recipients with other heart failure etiologies. Patients with ICM should not be disqualified from HTx. [GRAPHICS] .Peer reviewe

О причине возникновения неоднородности структуры экструзионных полимерных листов

Тез. докл. VII Междунар. науч.-техн. конф. (науч. чтения, посвящ. П. О. Сухому), Гомель, 23–24 окт. 2008 г

An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.

Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8+ T cells. Furthermore, loss of HIF-1α in CD8+ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8+ T cells accelerated tumorigenesis while also altering vascularization. Analyses of human breast cancer showed inverse correlations between VEGF-A expression and CD8+ T cell infiltration, and a link between T cell infiltration and vascularization. These data demonstrate that the HIF-1α/VEGF-A axis is an essential aspect of tumor immunity

An autonomous multi-agent evacuation scenario using sight and agent-to-agent communication.

This report simulates an evacuation scenario in a crowded building and attempts to optimize the flow of agents during the process. Each agent is autonomous and assumed to know the map. Agents also have the ability to communicate between themselves, as well as using sight to perceive the environment around them. The purpose is to design a set of rules making the agents evacuate efficiently, which then can applied in real world situation for training people in evacuation strategies. The model used is a time and space discrete setting, where agents move in a discrete graph, and have several exits to choose between. The number of agents is large, making crowd control an important factor. The simulation is run with a number of numerical algorithms such as path planning and logical reasoning. The algorithms are programmed into a simulation program allowing the evacuation to be shown in real time. The results shows the importance of agents communicating, and clear paths to emergency exits

An autonomous multi-agent evacuation scenario using sight and agent-to-agent communication.

This report simulates an evacuation scenario in a crowded building and attempts to optimize the flow of agents during the process. Each agent is autonomous and assumed to know the map. Agents also have the ability to communicate between themselves, as well as using sight to perceive the environment around them. The purpose is to design a set of rules making the agents evacuate efficiently, which then can applied in real world situation for training people in evacuation strategies. The model used is a time and space discrete setting, where agents move in a discrete graph, and have several exits to choose between. The number of agents is large, making crowd control an important factor. The simulation is run with a number of numerical algorithms such as path planning and logical reasoning. The algorithms are programmed into a simulation program allowing the evacuation to be shown in real time. The results shows the importance of agents communicating, and clear paths to emergency exits