THE EFFECTIVENESS OF CILOSTAZOL IN PATIENTS WITH GENERALIZED ATHEROSCLEROSIS

The aim of the study is to investigate the effectiveness of cilostazol in patients with generalized atherosclerosis (GAS).A comprehensive examination of 65 male patients with proved GAS was performed (lesions of the lower extremities, carotid, mesenteric, coronary, cerebral arteries) and 28 healthy males (comparison group - CG) aged over 60 years. Patients with GAS consisted of 2 groups: GAS1 - patients in addition to basic therapy received cilostazol (C; 100 mg 2 times per day); GAS2 - placebo. Patients with GAS showed a significant deterioration in blood flow (decrease in its volumetric blood flow - FV, increase in peak systolic velocity - PSV) in all studied arteries, episodes of myocardial ischemia according to daily ECG monitoring, decreased cognitive function (CF). In patients with GAS1 on the background of taking C observed improvement (p<0,001) blood flow in the studied arteries (increase in FV and decrease in PSV), decrease in the number and duration of episodes of myocardial ischemia (p<0,01 and p<0,05, respectively), increase distances of painless and maximum walking distance (p<0,01), improvement of CF. The data obtained indicate the effectiveness of C as part of complex therapy in patients with GAS and expediency of further research in this direction to clarify the criteria for its appointment to such patients.The aim of the study is to investigate the effectiveness of cilostazol in patients with generalized atherosclerosis (GAS).A comprehensive examination of 65 male patients with proved GAS was performed (lesions of the lower extremities, carotid, mesenteric, coronary, cerebral arteries) and 28 healthy males (comparison group - CG) aged over 60 years. Patients with GAS consisted of 2 groups: GAS1 - patients in addition to basic therapy received cilostazol (C; 100 mg 2 times per day); GAS2 - placebo. Patients with GAS showed a significant deterioration in blood flow (decrease in its volumetric blood flow - FV, increase in peak systolic velocity - PSV) in all studied arteries, episodes of myocardial ischemia according to daily ECG monitoring, decreased cognitive function (CF). In patients with GAS1 on the background of taking C observed improvement (p<0,001) blood flow in the studied arteries (increase in FV and decrease in PSV), decrease in the number and duration of episodes of myocardial ischemia (p<0,01 and p<0,05, respectively), increase distances of painless and maximum walking distance (p<0,01), improvement of CF. The data obtained indicate the effectiveness of C as part of complex therapy in patients with GAS and expediency of further research in this direction to clarify the criteria for its appointment to such patients

Роль респираторных инфекций в обострениях бронхиальной астмы

Nineteen patients aged 18–65 years with moderate and severe exacerbations of atopic asthma were examined for respiratory viruses, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Interferon system, IL-4 and γ-IFN serum levels were also investigated. Viral infections (RS-virus, adenovirus, influenza types A (H1N1, H3N2) and B viruses, parainfluenza types 1 and 3 viruses) were diagnosed serologically or using PCR with direct detection of viral nucleic acids in 73.6 % of the patients. Diagnostic level of Mycoplasma pneumoniae antigen was found in 78.9 % of the patients, anti-Chlamydophila pneumoniae antibodies were detected in 31.6 %. Leukocyte interferon-producing function was decreased in all the patients.У 19 пациентов в возрасте 18–65 лет с атопической бронхиальной астмой во время тяжелых и среднетяжелых обострений проведено обследование на наличие респираторных вирусов, Mycoplasma pneumoniae и Chlamydophila pneumoniae, оценены состояние системы интерферона, уровни IL-4 и γ-IFN в сыворотке крови. У 73,6 % пациентов серологически или путем прямого выявления вирусных нуклеиновых кислот методом ПЦР подтверждено наличие вирусной инфекции (респираторно-синцитиальный вирус — РС-вирус, аденовирус, грипп А (H1N1, H3N2) и В, парагрипп 1-го и 3-го типа). У 78,9 % пациентов в сыворотке крови обнаружен антиген Mycoplasma pneumoniae в диагностически значимом титре, у 31,6 % пациентов — антитела к Chlamydophila pneumoniae. У всех пациентов отмечено выраженное снижение интерферон-продуцирующей способности лейкоцитов

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361

The Effectiveness of Cilostazol in Patients with Generalized Atherosclerosis

The aim of the study is to investigate the effectiveness of cilostazol in patients with generalized atherosclerosis (GAS).A comprehensive examination of 65 male patients with proved GAS was performed (lesions of the lower extremities, carotid, mesenteric, coronary, cerebral arteries) and 28 healthy males (comparison group - CG) aged over 60 years. Patients with GAS consisted of 2 groups: GAS1 - patients in addition to basic therapy received cilostazol (C; 100 mg 2 times per day); GAS2 - placebo. Patients with GAS showed a significant deterioration in blood flow (decrease in its volumetric blood flow - FV, increase in peak systolic velocity - PSV) in all studied arteries, episodes of myocardial ischemia according to daily ECG monitoring, decreased cognitive function (CF). In patients with GAS1 on the background of taking C observed improvement (p&lt;0,001) blood flow in the studied arteries (increase in FV and decrease in PSV), decrease in the number and duration of episodes of myocardial ischemia (p&lt;0,01 and p&lt;0,05, respectively), increase distances of painless and maximum walking distance (p&lt;0,01), improvement of CF. The data obtained indicate the effectiveness of C as part of complex therapy in patients with GAS and expediency of further research in this direction to clarify the criteria for its appointment to such patients

EPIGENETIC EFFECTS OF ENZASTAURIN – A NEW ASPECT IN THE MECHANISM OF ACTION OF AN ANTICANCER DRUG FROM PROTEIN KINASE INHIBITORS

The purpose of the study was to analyze the ability of five antitumor drugs from the pharmaceutical group of protein kinase inhibitors (gefitinib, imatinib, pazopanib, ponatinib and enzastaurin) to reactivate the expression of the epigenetically silenced GFP in HeLa TI cells, and to estimate the effect of epigenetically active drugs on: 1) acetylation and methylation of histones H3 and H4; 2) integral DNA methylation; 3) activity of HAT and HDAC1 enzymes; 4) expression levels of the genes encoding epigenetic regulation enzymes (DNMT1, DNMT3A, DNMT3B; SIRT1, HDAC1; SETD1A, SETD1B, SUV420H1, SUV420H2, SUV39H1, SUV39H2). Material and Methods. The epigenetic activity of antitumor drugs was determined using the HeLa TI test system, a population of HeLa cells with the retroviral vector containing the epigenetically silenced GFP. The level of integral DNA methylation was analyzed using MspI/HpaII methyl-sensitive restriction analysis. Histone modifications were analyzed by Western blotting with antibodies to acetylated and methylated histones H3 and H4. The total activity of HAT enzymes was analyzed using Histone Acetyltransferase Activity Assay Kit. Expression of the epigenetic enzyme genes was analyzed using real-time quantitative RT-PCR. Results. It was shown that only the enzyme inhibitor Cβ protein kinase enzastaurin had the ability to reactivate the expression of epigenetically silenced GFP in the HeLa TI cells. We showed that under the action of enzastaurin, the level of integral DNA methylation and expression of DNMT3A and DNMT3B DNA methyltransferase genes decreased. It was also found that enzastaurin reduced the expression levels of histone deacetylases HDAC1 and SIRT1, but did not affect the activity and expression levels of histone acetylases, the level of histone methylation (H3K4me3, H3K9me3, H3K27me3, H4K20me3), and the level of expression of the histone methyltransferases (SUV39H1, SUV39H2, SUV420H1, SUV420H2, SETD1A и SETD1B). Conclusion. The data obtained are important for clarifying the mechanisms of action of 5 protein kinase inhibitors, in particular with respect to enzastaurin, the protein kinase Cβ inhibitor, for which the ability to reactivate epigenetically silent genes due to the effect on DNA methylation and histone acetylation was demonstrated