A vascularis intervenciókat követő restenosis vizsgálata klinikai és kísérletes tanulmányokban

Restenosis following endovascular interventions is the main limitation of their long-term success. The incidence of restenosis varies according to the method (stenting, endarterectomy) and the treated vascular region, but the pathomechanism and risk factors are similar. The current article reviews of the author's previous studies in this field. In clinical studies, we compared the restenosis rate after carotid artery stenting and carotid endarterectomy. We also analyzed the complement activation profile after these interventions. In another study, we investigated the role of two polymorphisms of the estrogen receptor alpha in the occurrence of carotid restenosis after either carotid artery stenting or carotid endarterectomy. In an animal model of carotid endarterectomy, we studied the role of the nitrite-oxide-cyclic guanosine monophosphate signaling and the effect of the phosphodiesterase-5 inhibitor therapy in neointimal hyperplasia. Our results suggest that higher incidence of restenosis following carotid endarterectomy can be correlated with the more highly expressed complement activation after this type of carotid intervention. Polymorphisms in the estrogen receptor alpha gene could contribute to the restenosis formation, especially in women. Neointimal hyperplasia can be attenuated by increased cyclic guanosine monophosphate signaling

Access to and clinical use of cardiac implantable electronic devices and interventional electrophysiological procedures in the European Society of Cardiology Countries: 2016 Report from the European Heart Rhythm Association.

AIMS: The aim of this analysis was to provide comprehensive information on the access to and use of cardiac implantable electronic device (CIED) and catheter ablation therapy in the European Society of Cardiology (ESC) area. METHODS AND RESULTS: The European Heart Rhythm Association (EHRA) has been collecting descriptive and quantitative data on invasive arrhythmia therapies since 2008. This year 50 of the 56 ESC member countries provided data for the EHRA White Book. Up-to-date information on procedure rates for the last 5 years together with information on demographics, economy, vital statistics, local healthcare systems, and training activities is presented for each country and the 5 geographical ESC regions. Our analysis indicated that considerable heterogeneity in the access to arrhythmia therapies still exists across the ESC area. In 2015, the CIED implantation rates per million population were highest in the Western followed by the Southern and Northern European countries. The catheter ablation activity was largest in the Western followed by the Northern and Southern areas. Overall, the procedure rates were 3-10 times higher in the European than in the non-European ESC countries. Economic resources were not the only driver for utilization of arrhythmia therapies as in some Eastern European countries with relative low gross domestic product the procedure rates exceeded the average values. CONCLUSION: These data will help the healthcare professionals and stakeholders to identify and to understand in more depth the trends, disparities, and gaps in cardiac arrhythmia care and thereby promote harmonization of cardiac arrhythmias therapies in the ESC area

Signaling via PI3K/FOXO1A pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells

Vascular derivatives of human embryonic stem cells (hESC) are being developed as sources of tissue-specific cells for organ regeneration. However, identity of developmental pathways that modulate the specification of endothelial cells is not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward endothelial lineage and on proliferation, maturation, and cell death of hESC-derived endothelial cells (hESC-EC). During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodeling-related genes. PI3K inhibitor LY294002 activated FOXO1A and induced formation of CD31(+) hESC-EC. In contrast, differentiating hESC with silenced FOXO1A by small interfering RNA (siRNA) showed lower mRNA levels of CD31 and angiopoietin2. LY294002 decreased proliferative activity of purified hESC-EC, while FOXO1A siRNA increased their proliferation. LY294002 inhibits migration and tube formation of hESC-EC; in contrast, FOXO1A siRNA increased in vitro tube formation activity of hESC-EC. After in vivo conditioning of cells in athymic nude rats, cells retain their low FOXO1A expression levels. PI3K/FOXO1A pathway is important for function and survival of hESC-EC and in the regulation of endothelial cell fate. Understanding these properties of hESC-EC may help in future applications for treatment of injured organs

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.

BACKGROUND: Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. METHODS: Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 +/- 6.8 years) received NAC IV (N = 13) or IA (N = 15). RESULTS: The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. CONCLUSIONS: In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92