Aim . To study the association of the rs386000 polymorphic variant in the LILRA3 gene with the risk of developing obliterating atherosclerosis of the lower extremity arteries (OALEA). Material and methods . 1277 individuals of Slavic origin were examined (629 patients with OALEA and 648 healthy volunteers). Genotyping of the LILRA3 gene rs386000 was performed with a MassARRAY-4 genomic mass spectrometer. Polymorphic variants of the LILRA3 gene, that encodes the leukocyte immunoglobulin-like receptor A3, may be attractive objects for studying the mechanisms of atherosclerosis. Results . The study showed that the rs386000 polymorphic variant in the LILRA3 gene was associated with the risk of developing OALEA. However, this association was characterized by sexual dimorphism: in men, carriage of the rs386000-C allele (p=0.03) and the rs386000-C/C genotype (p=0.01) was protective against the risk of developing OALEA, while in women, this polymorphism did not influence the susceptibility to the disease. Single nucleotide polymorphism (SNP) annotation showed that carriage of the rs386000‑C allele was associated with an increased expression of the LILRA2, LILRB5, LILRA6, LILRP1 and TSEN34 genes and a decreased expression of the LILRA3 and LILRA5 genes in the blood. Conclusion . The present study revealed for the first time an association of the rs386000‑C allele of the LILRA3 gene with a reduced risk of developing OALEA. Further studies, including experimental studies, will determine the specific mechanisms mediating the involvement of the LILRA3 gene rs386000 polymorphism in the molecular mechanisms for the development of obliterating atherosclerosis, as well as the nature of the sex-specific association of the polymorphism.

Aim. To study the involvement of APOC1 rs445925 and rs4420638 single nucleotide polymorphisms (SNP) in the development of occlusive peripheral arterial disease (PAD) of lower extremities.Material and methods. The study included 1278 people, including 630 patients with occlusive PAD and 648 relatively healthy individuals. Genotyping of APOC1 rs445925 and rs4420638 SNPs was performed using the MassARRAY-4 genomic mass spectrometer. The analysis of the association of alleles, genotypes, haplotypes and diplotypes with the risk of occlusive PAD was performed using the statistical programs SNPStats, PLINK, v1.9 and STATISTICA 13.3. The adaptive permutation test was used to assess statistical significance of associations (Pperm).Results. The rs445925-A (Pperm=1,0×10-6) and rs4420638-G (Pperm=0,006) alleles, as well as the rs445925-G/A-A/A (Pperm=1,0×10-6) and rs4420638-A/G-G/G (Pperm=0,006) genotypes were associated with an increased risk of occlusive PAD. The rs445925 polymorphism was also associated with the blood cholesterol level in patients with occlusive PAD (Pperm=0,04). The rs445925A-rs4420638A and rs445925A-rs4420638G haplotypes, as well as three APOC1 diplotypes, showed a pronounced relationship with a predisposition to occlusive PAD. In particular, the rs445925G/A×rs4420638A/A (odds ratio (OR) 6,59, 95% confidence interval (CI) 4,20-10,35, P=2,4×10-19) and rs445925G/A×rs4420638A/G (OR 4,24, 95% CI 2,23-8,03, P=2,0×10-6) diplotypes were associated with an increased risk of occlusive PAD. The rs445925G/G×rs4420638A/A diplotype had a protective effect on the disease development (OR 0,26, 95% CI 0,20-0,35, P=1,3×10-20). Associations of haplotypes with the severity of peripheral arterial stenosis of various locations were also revealed (P<0,05).Conclusion. The study results established for the first time that APOC1 rs445925 and rs4420638 polymorphic variants are part of a genetic predisposition to occlusive PAD and have a significant effect on the severity of peripheral arterial stenosis. The molecular mechanisms underlying the identified genotypic associations can affect not only lipid metabolism disorders, but also the proliferation of immunocompetent cells, platelet activation and aggregation processes, inflammation and apoptosis.

It is known that polymorphisms at gene encoding GUCY1A1 (α-subunit 1 of guanylate cyclase type 1) are associated with a predisposition to coronary artery disease and arterial hypertension, however, the relationship between these polymorphisms and the risk of peripheral artery disease (PAD) remains unexplored. This pilot study aimed to study the association of two polymorphisms such as rs7692387 and rs13139571 of the GUCY1A1 gene with the risk of peripheral artery disease. The study included 1277 unrelated individuals of Slavic origin, including 629 PAD patients and 648 relatively healthy volunteers. Genotyping of polymorphisms was done by the MassARRAY-4 system. We found that the rs7692387-A allele (OR=1.42, 95% CI 1.17-1.74, p=0.0005) and the rs7692387-G/A-A/A genotypes (OR=1.77, 95% CI 1.28-2.44, p=0.0005) were associated with an increased risk of peripheral artery disease, regardless of sex, age, body mass index, coronary artery disease, and hypertension. In addition, haplotype rs7692387A-rs13139571A (OR=1.52, 95%CI 1.17-1.98, p=0.002) was associated with an increased risk, while haplotype rs7692387G-rs13139571A (OR=0.26, 95%CI 0.12-0.58, p=0.0090), on the contrary, possessed a protective effect against disease risk. However, the observed associations occurred in cigarette smokers. Bioinformatics analysis showed that polymorphism rs7692387 is a functionally significant variant associated with increased GUCY1A1 expression and alternative polyadenylation in the tibial artery as well as a target for transcription factors and epigenetic regulation of gene expression. Thus, polymorphism rs7692387 of the GUCY1A1 gene represents a new genetic variant by which cigarette smoking, a major risk factor for peripheral artery disease, contributes to the disease development.

Acute pulmonary embolism (PE) is a relatively common vascular disease with potentially life-threatening complications. Right heart thrombi deteriorate the prognosis. Due to the known high lethality, such a clinical situation requires immediate diagnosis and treatment. With the existing different management options for intracardiac blood clots, the optimal one is still uncertain. The article describes the experience of therapeutic and diagnostic tactics in a patient with PE and thrombosis of two right chambers of the heart with a favorable outcome while the conservative approach was used.

Acute pulmonary embolism (PE) is a relatively common vascular disease with potentially life-threatening complications. Right heart thrombi deteriorate the prognosis. Due to the known high lethality, such a clinical situation requires immediate diagnosis and treatment. With the existing different management options for intracardiac blood clots, the optimal one is still uncertain. The article describes the experience of therapeutic and diagnostic tactics in a patient with PE and thrombosis of two right chambers of the heart with a favorable outcome while the conservative approach was used.

The influence of single nucleotide polymorphism (SNP) of genes encoding intracellular cholesterol transporters, such as rs1883025 of ABCA1 , rs217406 of NPC1L1 , and rs881844 of STARD3 , on blood lipid levels, carotid intima-media thickness (CIMT), and the risk of coronary heart disease (CHD) has been studied. SNP genotyping was performed using the MassARRAY 4 system. The effects of polymorphic genes on transformed values of blood lipids and CIMT were evaluated by linear regression analysis separately in men and women and adjusted for age and body mass index. SNP rs881844 of the STARD3 gene was associated with decreased risk of CHD in men (OR = 0.67, 95% CI 0.46–0.96, P = 0.02). In women, SNP rs1883025 of ABCA1 showed an association with decreased risk of CHD (OR = 0.65, 95% CI 0.44–0.95, P = 0.02). In men, SNP rs1883025 of the ABCA1 gene was associated with the levels of low density lipoprotein cholesterol ( P = 0.05), whereas SNP rs217406 was associated with triglyceride levels ( P = 0.02). Polymorphisms such as rs217406 of NPC1L1 and rs881844 of STARD3 in women and rs1883025 of ABCA1 in men were associated with CIMT. The present study has identified for the first time that rs1883025 of ABCA1 and rs881844 of STARD3 are associated with susceptibility to coronary heart disease and showed clear sex-specific differences in the associations between the genes and the studied phenotypes. Thus, polymorphic variants of genes encoding intracellular cholesterol transporters are potentially involved in the formation of the atherosclerotic process through the mechanisms that seem to be not directly related to the metabolism of cholesterol and cholesterol of low density lipoproteins.

Introduction: Lower extremity varicose vein disease is one of the common problems in vascular surgery. Clinically, this disease is accompanied by a wide range of complaints and external symptoms, which eventually lead to a worse patients’ quality of life. The integrated approach is being applied to the disease treatment, which involves the use of various phlebotropic drugs as conservative therapy along with minimally invasive surgical correction and sclerotherapy.Objective: to improve the quality of phlebotropic therapy for patients with lower extremity varicose vein disease, based on the study of factors that shape the patient’s compliance with the effective treatment of clinical symptoms. The term «compliance» means the precise and informed implementation of the doctor’s recommendations during the treatment by the patient. Most often, «compliance» is assessed by the drug use index, which is the quotient of dividing the number of days on which the full dose of the drug was taken by the duration of the entire study period. Materials and methods: The analysis of 368 + 111 patients with lower extremity varicose vein disease was carried out. Of these, 111 patients turned out to be beyond the correct study of compliance (a phlebectomy was performed in a hospital). 368 patients were divided into the following groups: Group 1: the patients, who were assigned modern surgical treatment of varicose veins (endovenous laser coagulation, scleroobliteration); Group 2: the patients, who withdrew from assigned interventions. As it turned out, the different groups of patients differed in compliance.Results. The patients who were shown and performed surgical treatment – 320 (86.9%), can be considered highly compliant with the prescribed conservative therapy – the average value of the compliance index is 0.83, compared to the representatives who refused to perform the recommended surgical procedures recommended by them – 48 (13.1%), the compliance index is 0.78.In the course of the investigation, the factors shaping compliance with phlebotropic drugs were identified, a comparative assessment was carried out on the main indicators of the effectiveness of phlebotropic drugs.Conclusion. Thus, the compliance of the patients suffering from LEVVV during the treatment with phlebotropic drugs varies depending on the multiplicity and convenience of the form of the drug, on the effectiveness of the proposed phlebotropic therapy according to the influence on the complaints and symptoms, on the psychological readiness of the patient to entrust the result of the final treatment of the disease to the surgeon.

Aim. To analyze the associations of apolipoprotein E (APOE) gene polymorphisms (rs7412 and rs4420638) with the risk of coronary artery disease (CAD) and the effectiveness of lipid-lowering therapy with rosuvastatin.Material and methods. The study involved the analysis of deoxyribonucleic acid samples and phenotypic data of 1700 unrelated individuals of Slavic origin, natives of Central Russia. A pharmacogenetic testing included 205 patients with CAD. Patients were prescribed rosuvastatin with determination of lipid levels and intima-media thickness (IMT) after 6 and 12 months of follow-up.Results. Carriers of the minor T allele for rs7412 polymorphism of the APOE gene were characterized by a lower CAD risk and a higher baseline level of low-density lipoprotein cholesterol (LDL-C). Associations of this polymorphism depended on body mass index. An association with an increased CAD risk was typical for male carriers of the variant G allele for rs4420638 polymorphism of the APOE gene. When treating CAD patients with rosuvas-tatin, a more pronounced lipid-lowering effect on total cholesterol and LDL-C was characteristic of individuals homozygous for the minor T allele for rs7412 of the APOE gene after 1 month of therapy; decrease of the lipidlowering effect with respect to total cholesterol took place in carriers of the heterozygous A/G genotype of rs4420638 polymorphism of the APOE gene after 12 months of therapy. An association was found between the rs7412 polymorphism of the APOE gene and the changes of maximum IMT in CAD patients treated with rosuvastatin. It consisted of the absence of IMT regression in T allele carriers after 6 months of lipid-lowering therapy.Conclusion. Polymorphisms of the APOE gene are associated with parameters of cholesterol metabolism, the risk of CAD and the effectiveness of lipid-lowering therapy with rosuvastatin.

Objective: The definition of the conditions under which women with inherited thrombophilia can have a positive pregnancy outcome. Materials and Methods. We conducted a retrospective and partially prospective analysis of 100 women with various forms of hereditary thrombophilia with the purpose of studying the conditions of a positive outcome of pregnancy. Results. We learned that normal uncomplicated pregnancy is possible if the age of the pregnant geminimen 26 years or properly selected antithrombotic therapy. Later than the time of menarche and the presence of a large number of mutations, mainly homozygous forms are markers of phenotypic manifestation of hereditary thrombophilia, starting with the first pregnancy. Conclusion. Timely diagnosis of genetic mutations and polymorphisms of thrombophilia (pre-pregnancy), pregravid proper training and appropriate management of pregnant women with the use of antiplatelet and (or) anticoagulant therapy let to get a good results by reducing the performance of reproductive losses and complications of pregnancy.

Enhanced thrombogenesis in patients with diabetes mellitus (D) is related to genetically determined disorders of the blood coagulation system analogous to those associated with hereditary thrombophilia. The aim of this work was to elucidate the relationship between the functionally significant methylenetetrahydroxyfolatereductase (MTHFR) C677T (rs1801133) gene polymorphism and the development of diabetic angiopathy of lower extremities (DALE) in ethnic Russian men residing in Central Russia (mostly Kursk region). The study involved 434 subjects including 50 with DALE and 384 healthy volunteers. All of them were genotypedfor the MTHFR C677T gene polimorphim by real-time PCR with allele discrimination using TaqMan-probes. No significant differences in the frequency of alleles of MTHFR C677T gene polymorphism were documented between the general samples and sex-matched groups. Stratified sex-specific analysis showed that 677TT genotype is associated with increased risk of DALE in smoking men (OR 4.2; 95% CI 1.28-13.79, p=0.01). In non-smoking men the 677TTgenotype was unrelated to the development of this complication. It is concluded that the risk of DALE is determined by the close relationship between genetic (UTHFR gene) and exogenous (smoking) factors which suggests the multifactorial nature of this pathology.

Objective: The definition of the conditions under which women with inherited thrombophilia can have a positive pregnancy outcome. Materials and Methods. We conducted a retrospective and partially prospective analysis of 100 women with various forms of hereditary thrombophilia with the purpose of studying the conditions of a positive outcome of pregnancy. Results. We learned that normal uncomplicated pregnancy is possible if the age of the pregnant geminimen 26 years or properly selected antithrombotic therapy. Later than the time of menarche and the presence of a large number of mutations, mainly homozygous forms are markers of phenotypic manifestation of hereditary thrombophilia, starting with the first pregnancy. Conclusion. Timely diagnosis of genetic mutations and polymorphisms of thrombophilia (pre-pregnancy), pregravid proper training and appropriate management of pregnant women with the use of antiplatelet and (or) anticoagulant therapy let to get a good results by reducing the performance of reproductive losses and complications of pregnancy.

We studied a prevalence of genetic polymorphisms in folate cycle and hemostasis system in pregnant women with reproductive losses in their anamnesis, living in Kursk region. The retrospective analysis was based on 50 case histories of women, suffering from thrombophilia, who had in their anamnesis from 1 to 4 reproductive losses in the first and/or the second trimester. There was a high occurrence in heterozygous mutations in the MTHFR and PAI-1 genes, and absence of defects in the FII and FV genes. To prevent any development of pregnancy complications, being from genetic mutations in the MTHFR and PAI-1, it is necessary to develop the pathogenetic tactics to conduct pregnant women, suffering from hereditary thrombophilia.

The main purpose of our study is to estimate the frequency of thromboembolic complications in hospitalized patients of the Regional of Kursk Region and Municipal Healthcare Agency Clinical Emergency Hospital of Kursk within the period from 2007 to 2011. We analyzed 1139 autopsy protocols of patients who had died in the Regional of Kursk Region and 3040 autopsy protocols of patients who had died in the Emergency of Kursk within the period from 2007 to 2011. The analysis was carried out according to the following parameters: the number of cases per 100 autopsies and separation of a specific group of massive pulmonary embolism and mortality on the first day of hospitalization. It was found out that there had been a statistically significant decrease in the analyzed parameters from 2007 to 2011 in the Regional of Kursk Region. Probably this was a result of the internal protocol of thromboprophylaxis introduced in 2010. In the Emergency these parameters still tend to increase. The reason of the increase requires the additional analysis.

The main purpose of our study is to estimate the frequency of thromboembolic complications in hospitalized patients of the Regional Clinical Hospital of Kursk Region and Municipal Healthcare Agency "Clinical Emergency Hospital" of Kursk within the period from 2007 to 2011. We analyzed 1139 autopsy protocols of patients who had died in the Regional Clinical Hospital of Kursk Region and 3040 autopsy protocols of patients who had died in the Clinical Emergency Hospital of Kursk within the period from 2007 to 2011. The analysis was carried out according to the following parameters: the number of cases per 100 autopsies and separation of a specific group of massive pulmonary embolism and mortality on the first day of hospitalization. It was found out that there had been a statistically significant decrease in the analyzed parameters from 2007 to 2011 in the Clinical Regional Hospital of Kursk Region. Probably this was a result of the internal protocol of thromboprophylaxis introduced in 2010. In the Clinical Emergency Hospital these parameters still tend to increase. The reason of the increase requires the additional analysis.

Study of 297 patients with preparative methods of nontoxic nodular goiter and cytological diagnose "adenomatosis" with the use of artificial neural network (ANN) were analyzed. Malignant pathology could be supposed with 95.5% accuracy when we applied experience of trained ANN. Clinical, instrumental and cytologic criteria, which make possible to prognosticate degree of malignant process in thyroid gland parenchyma, were determined. Painless elastic nodules with sonographically iso- o hyperechogenic structure, with clear outline and cytologically determined adenomatosis in combination with colloid can be interpreted as benign lesion of thyroid gland.

297 results of the complex examination and surgical management of the patients with nodular nontoxic goiter and "adenomatosis" as a cytological decision were analyzed. On the basis of clinical-sonographic and morphologic criteria we could determine the integrated probability of malignant disease in each particular case.