Circulating free DNA in hypertensive patients with high cardiovascular risk

Aim. To evaluate the level of circulating free nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in hypertensive patients with high cardiovascular risk.Material and methods. The study included 70 patients, of which 51 were patients with hypertension (HTN) and 19 were healthy. The study of the level of circulating free nDNA and mtDNA was carried out using quantitative polymerase chain reaction (PCR). Additionally, demographic data, comorbidities, risk factors, heredity, results of complete blood count and biochemical blood tests, electrocardiography and echocardiography were analyzed.Results. The level of nDNA in HN patients was significantly higher than in healthy patients: Me (LQ; UQ) — 227 (110; 370) copies/mL and 88 (62; 116) copies/ml, respectively (p<0,0001). In hypertensive patients with a very high cardiovascular risk, the level of nDNA and mtDNA was significantly higher compared to healthy participants: 294 (154; 489) copies/ml versus 88 (62; 116) copies/ml, p<0,0001; 56731 (42531; 129375) copies/mL versus 35156 (18325; 54956) copies/mL, p=0,015.Conclusion. The level of circulating free DNA in hypertensive patients with very high cardiovascular risk is significantly increased, and therefore this parameter can be a cardiovascular risk marker

ASSESSMENT OF INDICES OF NONSPECIFIC RESISTANCE OF THE ORGANISM IN CONDITIONS OF NARROWING OF THE LUMEN OF THE TRACHEA IN AN EXPERIMENT

The narrowing of the lumen of the trachea due to cicatricial stenoses of the trachea is one of the urgent problems of the modern surgery.  The processes taking place in the trachea and lungs lead to a change in the state of the immune system. Assessment of the dynamics of  indices of nonspecific resistance is one of the methods for assessing  the severity of the course of the disease. We studied the indices of  nonspecific resistance of the organism in narrowing the lumen of the  trachea in an experiment in the early postoperative period.  The study was carried out on the basis of the scientific department  of experimental surgery with the vivarium of Irkutsk Scientific  Centre of Surgery and Traumatology, on 24 white male Wistar rats  with a body weight of 300–350 g. We simulated narrowing the lumen of the trachea by placing a silicone tube in the lumen of the trachea  for 14 days. The parameters of phagocytosis, the state of phagocytic activity of blood neutrophils, spontaneous NBT-test, induced NBT- test were studied. The animals were withdrawn from the experiment  on the 3rd, 7th and 14th day. We revealed that as a result of  narrowing of the lumen of the trachea with the original procedure,  the nonspecific resistance of the organism was violated with  inhibition of the phagocytic activity of leukocytes. There was  inhibition of phagocytic activity of leukocytes and depletion of the  functional reserve of leukocytes

Effect of single intake of exogenous hepatocytes growth inducer on the indices of non-specific resistance under conditions of postresection liver injury

HGF is one of the factors taking part in regeneration and recovery of liver after injury. The article is dedicated to the study of influence of single HGF intake on the indices of non-specific immune response in rats after 70% liver resection in the early postoperative period. Research was conducted on 42 six-months white male Wistar rats of 250-300 g. It was revealed that level of segmentonuclear neutrophils and lymphocytes in the group with HGF intake stand at normal level on the 2nd day and normalizes to the 11th day that testifies to the decrease of inflammatory response. Increased level of leukocytes and monocytes is registered in the group with HGF intake. Also integrity of non-specific resistance in the early postoperative period on the 2nd day is registered. Suppression of phagocytosis indices with preservation of functional activity of phagocytes was registered to the 11th day

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

ASSOCIATION OF THE GENE CYP11B2 WITH THE RISK OF ESSENTIAL HYPERTENSION AND ATHEROTHROMBOTIC COMPLICATIONS

Genetics of arterial hypertension is broadly discussed as of one of multifactorial diseases. Invention of an algoritm for risk stratification based upon genetic parameters, gives chance to select groups of higher essential hypertension (EH) risk with the aim of primary prevention. One of such prototypes was assessed, that inculdes 11 genetic markers, in 30 patients with known clinical parameters; 19 of those were with EH and 11 normotonics. Individual impact is assessed of each marker and comparison done for total risk in patients. As a result, there were no differences found in individual risk for patients with and without EH by 11 markers, between subgroups. There was protective effect found for the allele С rs1799998 of gene CYP11B2 (OR 0,247; CI=[0,081-0,754], p=0,01)

Hydrogels of Polycationic Acetohydrazone-Modified Phosphorus Dendrimers for Biomedical Applications: Gelation Studies and Nucleic Acid Loading

In this work, we report the assemblage of hydrogels from phosphorus dendrimers in the presence of biocompatible additives and the study of their interactions with nucleic acids. As precursors for hydrogels, phosphorus dendrimers of generations 1–3 based on the cyclotriphosphazene core and bearing ammonium or pyridinium acetohydrazones (Girard reagents) on the periphery have been synthesized. The gelation was done by the incubation of dendrimer solutions in water or phosphate-buffered saline in the presence of biocompatible additives (glucose, glycine or polyethylene glycol) to form physical gels. Physical properties of gels have been shown to depend on the gelation conditions. Transmission electron microscopy revealed structural units and well-developed network structures of the hydrogels. The hydrogels were shown to bind nucleic acids efficiently. In summary, hydrogels of phosphorus dendrimers represent a useful tool for biomedical applications

ASSOCIATION OF COMBINATIONS OF ALLELIC VARIANTS OF CYP2C19 AND VEGFR2 GENES WITH CORONARY ATHEROSCLEROSIS IN ACUTE CORONARY SYNDROME IN THE NORTH AND IN SIBERIA

Purpose: to study associations of homozygous allelic variants of VEGFR2*C/*C and CYP2C19*17/*17 genes with atherosclerotic lesion of coronary arteries in patients with acute coronary syndrome (ACS) in the North (Surgut) and in large cities of the Siberian Federal District of Russia (Irkutsk and Kemerovo). 257 consecutive patients with ACS upon admission to the cardiological hospitals of Surgut, Irkutsk and Kemerovo has been included in the study. All examined patients underwent coronarography and determination of allelic variants of VEGFR2*C/*C and CYP2C19*17 /*17 genes. In patients from Surgut has been determened the direct associations of the combination of allelic variants of VEGFR2*C/*C + CYP2C19*17/*17 with indicators of severe coronary atherosclerosis (lesion of the left coronary artery trunk (LCA), LCA stenosis more than 50 %, proximal or medial lesion of the three major arteries more than 70 % (PLA) and the presence of PLA or stenosis of the LCA trunk more than 50 %). Such associations were not found in patients from Kemerovo and Irkutsk. The multivariate analysis determined the direct effect of combination of allelic variants of the VEGFR2*C/*C and CYP2C19*17/*17 genes on the presence of PTA or stenosis of the LCA trunk more than 50 % in patients with ACS from Surgut regardless of males gender, ages and smoking (Exp B) = 21.065, 95 % CI (2.003; 221.524), p = 0.011). Thus, the combination of allelic variants of VEGFR2*C/*C and CYP2C19*17/*17 genes directly affects the presence of severe coronary atherosclerosis in patients with ACS from Surgut

Regional aspects of associations of the CYP2C19 gene polymorphism with coronary atherosclerosis in acute coronary syndrome

Aim. To study the associations of allelic variants of the CYP2C19 gene with atherosclerotic lesions of the coronary arteries in patients with acute coronary syndrome (ACS) in the North of Siberia (Surgut) and in large cities of the Siberian Federal Okrug (SFO).Material and methods. During the study 296 patients with ACS were examined at admission to cardiology hospitals in large cities of the North (Surgut, 114 patients) and SFO (Irkutsk and Kemerovo, 182 patients). All patients underwent coronary angiography and genetic research (identification of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles).Results. In patients with ACS living in the North of Russia allelic variant CYP2C19*17 (*17/*17) is positively associated with the severity of lesion of left coronary artery (LCA) (χ2=9,81; p=0,002), as well as with at least 50% stenosis, more than 70% lesion of the proximal or middle part of the three main arteries, or more than 50% lesion of LCA trunk (χ2 =6,52; p=0,011), and previous myocardial infarction (χ2=8,15; p=0,004). Among patients with ACS living in cities of the Siberian Federal Okrug, the allelic variant CYP2C19*17 (*17/*17) is directly associated with diabetes mellitus (χ2=5,48; p=0,019) and less than 45% left ventricular ejection fraction (χ2=4,20; p=0,040). Regression analysis showed that in patients with ACS living in the northern region of Russia, only the allelic variant CYP2C19*17 (*17/*17) correlated with at least 50% stenosis of LCA trunk (Exp (B): 11,623, 95% CI: 1,893; 71,342; p=0,008). It did not correlate with the male sex, age, smoking and diabetes (p>0,05).Conclusion. The results show the presence of direct associations of CYP2C19*17 alleles with prognostically unfavorable coronary atherosclerosis in ACS patients living in the North of Siberia

THE “PROTOCOL” STUDY: PRELIMINARY RESULTS

Aim. To reveal the association of gene polymorphism CYP2С19*2 and recurrent early stent thrombosis in coronary vessels, and paradoxal response to clopidogrel intake in patients — the inhabitants of Siberian Region — after acute coronary syndrome.Material and methods. Totally 105 patients studied, hospitalized for stenting of coronary arteries in acute coronary syndrome, never received clopidogrel previously. The polymorphism of studied СУР2С19: *2, *3, *17 alleles, as assessment of platelet aggregation with ADP before and after clopidogrel intake, as of endpoints on safety and efficacy during 30 days (thrombotic complications, bleeding).Results. Within the selected patients there was no any significant association of any CYP2С19*2 and/or CYP2С19*3 alleles and paradoxic laboratory reaction. There was significant association of the CYP2C19*17 gene carriage and bleedings. When comparing the groups of patients having or not having complications related to clopidogrel (thrombotic or bleedings), there was significant difference in residual platelet aggregation.Conclusion. The results of the study might be strongly significant for the decisions making on double antiplatelet therapy and on the tactics of drugs preference