Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction In Patients With Resistant Hypertension and Type 2 Diabetes Mellitus.

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabolic, proinflammatory and profibrotic biomarkers, increased vascular wall stiffness, pronounced left ventricular hypertrophy, and with structural and functional alterations in kidneys.

Bone Remodeling Markers in Assessing of Sternal Reparative Regeneration in Patients With Carbohydrate Metabolism Disorders After Coronary Bypass Surgery.

Aim      To study time-related changes in bone remodeling markers in patients with ischemic heart disease (IHD) associated with type 2 diabetes mellitus (DM) and disorders of carbohydrate metabolism (CM). Also, a possibility was studied of using these markers for evaluation of breast bone reparative regeneration in early and late postoperative periods following coronary bypass (CB).Materials and methods           This study included 28 patients with IHD and functional class II-III exertional angina after CB. Patients were divided into 2 groups based on the presence (group 1) and absence (group 2) of CM disorders. Contents of osteocalcin (OC), C-terminal telopeptide (CTTP) of type 1 collagen, deoxypyridinoline (DPD), and alkaline phosphatase bone isoenzyme (ALPBI) were measured by enzyme immunoassay on admission (Т1) and at early (Т2) and late (Т3) postoperative stages. Sternal scintigraphy with a radiopharmaceutical (RP) was performed at stage 3 following sternotomy.Results The content of OC and CTTP was reduced in group 1 compared to the values in the group without CM disorders (р<0.005) at stages Т1 and Т2. There were no significant intergroup differences in concentrations of ALPBI and DPD throughout the study. Time-related changes in OC, CTTP, and DPD had some intergroup differences: the increase in biomarkers was observed in group 1 considerably later, at stage Т3 (р<0.005), while in group 2, it was observed at stage T2 after sternotomy. Scintigraphy revealed significant intergroup differences in the intensity of RP accumulation in sternal tissue.Conclusion      The intergroup differences in the content of biomarkers evidenced a disbalance among processes of formation and resorption of bone tissue and delayed remodeling processes in patients with IHD associated with type 2 DM and CM disorders. The study confirmed significance of comprehensive evaluation of time-related changes in markers for bone tissue metabolism and sternal scintigraphy for diagnosis and evaluation of sternal reparative regeneration following sternotomy in patients with IHD associated with type 2 DM and disorders of CM metabolism.

Research of spontaneous and stimulated functional activity of platelets in patients with different types of atrial fibrillation.

Platelet function testing is widely used to diagnose disorders of the cellular link of hemostasis. The study of platelet aggregation activity is relevant for the prevention of thromboembolic complications in atrial fibrillation and monitoring the effectiveness and safety of therapy. In this study, a comparative analysis of spontaneous and stimulated platelet aggregation in groups of patients with two types of atrial fibrillation was performed - paroxysmal and persistent. The effect of ß-adrenoblocker therapy on platelet aggregation activity in patients with atrial fibrillation was also studied. Platelet aggregation activity was studied using the method of G. Born in the modification of Z.A. Gabbasov on a two-channel laser analyzer "Biola". Collagen at a concentration of 2 mg / ml and adrenaline in a concentration range of 2.5-10 µg / ml were used as aggregation-promoting agents. It has been established that spontaneous aggregation potential and collagen-induced platelet aggregation depend on the type of atrial fibrillation, as well as on the presence or absence of ß-blockers in therapy. The response of platelets to stimulation with adrenaline depends, first of all, on the type of atrial fibrillation and the concentration of adrenaline in the reaction medium. The most significant changes were noted in the group of patients with a paroxysmal form atrial fibrillation, taking ß-blockers in therapy.

[Metabolic, inflammatory and imaging biomarkers in evaluation of coronary atherosclerosis severity in patients with coronary artery disease and diabetes mellitus type 2].

AIM: To study interconnections between epicardial adipose tissue thickness (EATt), parameters of glucose metabolism/insulin, C-reactive protein (hsCRP), serum adipokines and severity of coronary artery disease (CAD) depending on the presence of diabetes mellitus type 2 (DM 2); to determine significant markers of CAD severity in patients with DM 2. MATERIALS AND METHODS: The study involved 106 patients with CAD (m/f 64/42, 60.96.8 years), including patients with DM 2 (group 1, n=35) and non-diabetic patients (group 2, n=71). Severity of CAD was evaluated according to angiography data with calculation of Gensini Score (GS). EATt was assessed via echocardiography. Serum levels of glucose/insulin metabolism parameters, lipid fractions, hsCRP and adipokines were evaluated. Clinical parameters, including GS, did not differ between groups. RESULTS: EAT thickness median was elevated in gr.1 (5.1 mm vs. 4.4 mm in group 2), while adiponectin levels were decreased (6.55 g/ml vs. 7.71 g/ml). Linear regression of body mass index and resistin levels on EATt was revealed in gr.1; in gr.2 EATt linearly increased with waist circumference increment when EATt6 mm. Linear regression of EATt on GS was revealed in gr.1 when EATt8 mm, while linear regression in the whole GS range was obtained for HDL-C and hsCRP levels. CONCLUSION: Study results demonstrate differences in mechanisms of deposition and functioning of epicardial and abdominal adipose tissue depending on the presence or absence of diabetic status. Patients with DM2 are characterized by the excessive EAT deposition and decrease of serum adiponectin levels compared to non-diabetic patients in the equal conditions. Independent markers of CAD severity in DM 2 are decreased HDL-C and increased hsCRP levels, but not EATt.

[Markers of endothelial dysfunction in patients with arterial hypertension exposed to occupational irradiation of low intensity].

Aim To study the association between concentrations of endothelial dysfunction (ED) markers and arterial hypertension (AH) in people who were exposed to long-term action of "low-dose" ionizing radiation.Material and methods The study subjects were men of middle age (45-55 years) who were workers of the Siberian Integrated Chemical Plant with the length of service on the shop floor of at least 5 years. The subjects were divided into the main group (n=96) consisting of workers with grade 1-2 AH and the control group (n=48) consisting of arbitrarily healthy workers. Both groups contained workers who had been exposed to long-term occupational low-intensity irradiation (γ-radiation) and those not exposed to this irradiation. The study evaluated risk factors for cardiovascular diseases, presence of concomitant diseases, blood biochemistry (concentrations of glucose, high-sensitivity C-reactive protein (hsCRP), total cholesterol, low-density lipoproteins, high-density lipoproteins, triglycerides, creatinine, and ED markers, including endothelin, angiotensin II, von Willebrand factor, C-type natriuretic peptide, tissue plasminogen activator, tumor necrosis factor α (TNF-α), and homocysteine, major clinical data, total dose of external irradiation, and the content of 239Pu in the body.Results AH was associated primarily with excessive body weight and severity of atherogenic dyslipidemia and homocysteinemia. Higher plasma concentrations of TNF-α and a tendency to increasing hsCRP in the AH group, as distinct from the control group of arbitrarily healthy men, indicated a proinflammatory shift. The ED markers were related with clinical data of AH patients and associated with the lipid profile and increased blood concentrations of inflammatory mediators. The radiation exposure did not change the ED marker array in AH patients, which did not allow recommendation of the studied plasma indexes for detection of vascular endothelial injury in workers with AH of the Siberian Integrated Chemical Plant.Conclusion The study results evidenced the absence of adverse effects of long-term occupational exposure to low-intensity radiation on the vascular endothelium as evaluated by ED markers. In men aged 45-55 years, AH was associated primarily with excessive body weight, homocysteinemia, and atherogenic dyslipidemia.

[Multiplex analysis on the luminex platform in complex estimation of cardiovascular biomarker dynamics in patients with acute myocardial infarction.]

The multimarker approach more accurately reflects the key mechanisms of pathogenesis and biochemical interactions, compared with the use of individual indicators. It is a reason of steadily growing interest in the development and use of various combinations of biomarkers in assessing the prognosis and stratification of cardiovascular risk in patients with a wide range of cardiological profiles. Multiplex analysis technology on the Luminex platform is the best tool for the simultaneous quantitative determination of a complex of different biomarkers in a single. Using the MILLIPLEX® MAP Human Cardiovascular Disease Panel, a multiplefold increase of FABP, Troponin I, CK-MB, BNP, Nt-proBNP, BNP in the first 24 hours after MI, decreasing in 6 months with a high degree of confidence, was shown. There were no differences in the content of LIGHT between the stages of observation, as well as in comparison with the reference range. The content of LIGHT on the first day of MI showed strong positive associations with markers of damage of myocardium and myocardial stress. On the first day of MI, a significant increase in the content of ESM-1, decreasing in 6 months after MI to the reference values was found. Strong positive associations of ESM-1 with Troponin I and BNP levels were established. A significant increase of proinflammatory cytokine OSM on the first day of MI, decreasing in the late post-infarction period to reference values was shown. Correlation analysis revealed direct relationships of OSM with Troponin I, CK-MB, Nt-proBNP and BNP. The use of the MILLIPLEX® MAP Human Cardiovascular Disease Panel 1 diagnostic multimarker panel allowed for the simultaneous quantitative analysis of 11 biochemical parameters, associated with inflammation, atherogenesis, endothelial dysfunction, ischemia and myocardial necrosis. The results can be used to improve the effectiveness of complex diagnostics in patients with primary myocardial infarction with ST segment elevation.

HLA gene and haplotype frequencies in a Nagaybaks population from the Chelyabinsk Region (Russian South Urals).

A total of 112 Nagaybaks, a Turkic ethnoconfessional group living mainly in the Nagaybak district of the Chelyabinsk Region of Russian South Urals, were genotyped for HLA-A, -B, -DRB1, -DQA1 and -DQB1 loci using PCR-SSP (low-resolution) and HLA-A29 (high-resolution). All loci were in Hardy-Weinberg equilibrium (all p values >0.1 thus showing no locus-level deviations. The genotype data are available in the Allele Frequencies Net Database under the population name ''Russia, South Ural, Chelyabinsk Region, Nagaybaks" and the identifier AFND0003397.

[Myocardial and Arterial Stiffness Important Determinant of NT-ProBNP at Development of Heart Failure in Survivors of Myocardial Infarction].

AIM: To study diagnostic value of myocardial-arterial stiffness (MAS) as a determinant of N-terminal pro-brain natriuretic peptide (NT-proBNP) expression in patients with chronic heart failure (CHF) with ischemic or postinfarction left ventricular (LV) dysfunction. MATERIAL AND METHODS: We analyzed 6 months prognosis of 54 patients (mean age 61.7+/-8.6 years) with II-III NYHA class CHF divided into 2 groups: (I, n=18) with class II CHF and preserved LV ejection fraction (EF) (55+/-10.4%), (II, n=36) with class III CHF and low LF EF (30.4+/-6.8%). MAS was measured by echocardiography as ratio of arterial elasticity (Ea) and end-systolic elasticity of LV myocardium (Es). Serum NT-proBNP was measured by immunoenzyme assay. RESULTS: During 6 months follow-up one group II patient with initial NT-proBNP level 2020 rg/ml died. NT-proBNP level in group I was significantly lower than in group II (313 and 647 rg/ml, respectively). Ea/Es ratio was significantly higher (p=0.001) in group II. Multifactorial analysis demonstrated moderate correlation of NT-proBNP with Ea/Es ratio (r=0.50, p=0.0001) and negative correlation with LVEF (r=-0.45, =0.003) among patients with II-III class CHF. CONCLUSION: As correlation between symptoms and severity of clinical manifestations of ischemic or postinfarction cardiac dysfunction at development of CHF was not high it appears rational to consider MAS estimated by Ea/Es ratio as independent predictor of cardiovascular complications. Sufficiently close correlation between NT-proBNP and Ea/Es ratio allows to improve stratification of risk and to assess objectively prognosis of the disease using easier obtainable parameter Ea/Es in cases when possibility to measure NT-proBNP is not available.

[DISTRIBUTION OF TWO-LOCUS HAPLOTYPES OF MICROBIAL COMPONENT SENSOR GENES TLR1 AND TLR6 IN MAJOR POPULATIONS OF SOUTH URALS].

AIM: Evaluate the fraction of various TLR1-TLR6 haplotypes in populations of Russians Bashkir and Nagaybak of Chelyabinsk Region. MATERIALS AND METHODS: Potential donors of stem cells from Chelyabinsk Region Station of Blood Transfusion registry were included into the study and split into 3 populations: Russians (81), Bashkir (78) and Nagaybak (84). Genotyping by 2 polymorphisms of TLR1 and TLR6 genes was carried out in all the 3 groups. Point polymorphism of TLR1 gene 1805T>G was determined by polymorphism analysis of length of restriction fragments, and polymorphism of TLR6 gene 745C>T by PCR using sequence-specific primers. RESULTS: TLR1 1805*G-TLR6 745*T haplotype occurs in population of Russians (42%) and relatively rare--among Bashkir (17%). An inverse picture is observed for TLR1 1805*T-TLR6 745*C haplotype: a more frequent spread among Bashkir (65%) and relatively rare occurrence in Russians (23%). Frequencies of the mentioned haplotypes, that occupy intermediate position compared with corresponding parameters for populations of Russians and Bashkir, were detected for Nagaybak, that, probably, reflects complex pathways of settling of their ancestors and effects of other non-adaptation factors. CONCLUSION: Frequencies of TLR1-TLR6 two-locus haplotypes in major populations of South Urals were determined for the first time. Further studies in this field will allow better understanding of features of immune response and sensitivity to infections in various populations.

[Correlation of Endothelial Dysfunction With Course of Essential Arterial Hypertension in Adolescence].

AIM: to study laboratory parameters of endothelial dysfunction (ED) and their correlation with risk factors (RF) of cardiovascular diseases at early stages of essential arterial hypertension (AH) in adolescents. MATERIAL AND METHODS: We examined 299 adolescents aged 12-18 years with EAH. According to results of 24-hour blood pressure (BP) monitoring all patients were divided into three groups: (1) 98 adolescents with "white coat hypertension", (2) 108 adolescents with liable AH (LAH), (3) 93 patients with stable AH (stAH). Control group consisted of 27 healthy adolescents. Examination included 24-hour BP monitoring, measurement of some laboratory parameters of ED (Von Willebrand factor [vWF], nitric oxide metabolites, urine catecholamines), and assessment of cardiovascular RF. RESULTS: Mean vWF values in groups (2) and (3) were clinically significantly different from control. Increase of vWF activity by 1 unit was associated with increase of mean nocturnal pulse pressure by 0.36 mm Hg (p = 0.048). Markers of ED were related to family history of AH, overweight and low birth weight.

[Comparative Randomized Study of the Effects of Long-Term Therapy With Rosuvastatin and Combination of Atorvastatin and Ezetimibe on Carbohydrate Metabolism and Adipokines Levels in Patients With Coronary Artery Disease and Diabetes Mellitus].

OBJECTIVE: This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT). METHOD: A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n = 16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n = 15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l)/22.5) was calculated. RESULTS: During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group 1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p < 0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% 16.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p < 0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r = 0.37, p = 0.04) in the entire group of patients (n = 31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r = -0.57, p = 0.034). CONCLUSIONS: In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.

[THE INFLUENCE OF HYDROGEN SULFIDE ON COLLAGEN-INDUCED AGGREGATION OF HUMAN PLATELETS].

Study the impact of hydrogen sulfide on collagen-induced platelet aggregation from healthy donors and patients with type 2 diabetes. In healthy individuals, in contrast to patients with type 2 diabetes, NaHS significantly inhibited platelet aggregation. Activators of cAMP signaling (forskolin and phosphodiesterase inhibitor) significantly reduced platelet aggregation in both groups of examinees. NO-synthase inhibitors increased platelet aggregation in healthy volunteers, but not in patients with type 2 diabetes. The presence of H2S donor did not alter the extent of platelet aggregation at high concentrations of cAMP or decreased production of nitric oxide. It is assumed that the antiplatelet effect of H2S is not associated with the effect on the signal system, mediated cAMP or nitric oxide. Change H2S-dependent regulation of platelet aggregation in patients with type 2 diabetes is caused by disorders have been reported with this disease: the increase of intracellular calcium ion concentration, oxidative damage to proteins, hyperhomocysteinemia, glycosylation of key proteins involved in this process.

[Correlation of Endothelial Dysfunction With Course of Essential Arterial hypertension in Adolescence].

AIM: to study laboratory parameters of endothelial dysfunction (ED) and their correlation with risk factors (RF) of cardiovascular diseases at early stages of essential arterial hypertension (AH) in adolescents. MATERIAL AND METHODS: We examined 299 adolescents aged 12 - 18 years with EAH. According to results of 24-hour blood pressure (BP) monitoring all patients were divided into three groups: (1) 98 adolescents with "white coat hypertension", (2) 108 adolescents with liable AH (LAH), (3) 93 patients with stable AH (stAH). Control group consisted of 27 healthy adolescents. Examination included 24-hour BP monitoring, measurement of some laboratory parameters of ED (Von Willebrand factor [vWF], nitric oxide metabolites, urine catecholamines), and assessment of cardiovascular RF. RESULTS: Mean vWF values in groups (2) and (3) were clinically significantly different from control. Increase of vWF activity by 1 unit was associated with increase of mean nocturnal pulse pressure by 0.36 mm Hg (=0,048). Markers of ED were related to family history of AH, overweight and low birth weight.

[Comparative Randomized Study of the Effects of Long-Term Therapy With Rosuvastatin and With Combination of Atorvastatin and Ezetimibe on Carbohydrate Metabolism and Adipokynes Levels in Patients With Coronary Artery Disease and Diabetes Mellitus].

OBJECTIVE: This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT). METHOD: A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n=16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n=15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l) / 22.5) was calculated. RESULTS: During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p<0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% [6.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p<0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r=0.37, p=0.04) in the entire group of patients (n=31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r=-0.57, p=0.034). CONCLUSIONS: In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.

[Comparative characteristics of HLA system gene distribution in patients with lung tuberculosis of the Russian population of Chelyabinsk region].

AIM: Study of distribution of genes and HLA system haplotypes A, B, DRB1, DQA1, DQB1 in healthy individuals and patients with lung tuberculosis, members of the Russian population of Chelyabinsk region for isolation of risk markers for the development of various forms of tuberculosis. MATERIALS AND METHODS: The study group consisted of 86 patients with lung tuberculosis of the Tuberculosis Dispensary No. 3 of Chelyabinsk of Russian nationality. 239 healthy donors of Chelyabinsk Hemotransfusion Station of Russian nationality composed the comparison group. HLA-typing was carried out by multi-primer polymerase chain reaction--PCR SSP, HLA II genotyping--by DNA technology (Russia) kits, HLA class I--by methods described in the article by Downing J.M.G. et al. (2004). Result detection was carried out by electrophoresis. RESULTS: In lung tuberculosis patients high frequency of detection of HLA haplotype DRB1*16-DQA1*01:02-DQB1*05:02/4 was established. In patients with fibrous-cavernous form B*08 and DRB1*03 gene frequency of detection increased and DRB1*07 and DQA1*02:01 genes did not occur. During focal form high frequency of HLA B*15 and HLA DRB1*15 alleles was determined compared with infiltrative form. HLA A*01-B*08-DRB1*03-DQA1*05:01-DQB1*02:01 haplotype only occurred ingroups of patients with more severe forms of tuberculosis. CONCLUSION: Markers of sensitivity to clinical phenotypes of tuberculosis were isolated.

System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

[The cerebral sodium uretric peptide (see text symbol) patients with chronic cardiac insufficiency under decreased and preserved ejection fraction].

The concentration of cerebral sodium uretic peptide was analyzed in patients with chronic cardiac insufficiency and in healthy volunteers. The study established that concentration of cerebral sodium uretic peptide was higher in patients with chronic cardiac insufficiency as compared control group and reflected severity of pathologic process. In patients with decreased ejection fraction the levels cerebral sodium uretic peptide were higher as compared with patients with preserved ejection fraction. According data of the present study the existing threshold of concentration of cerebral sodium uretic peptide has a lower diagnostic sensitivity to exclude chronic cardiac insufficiency (100 pg).

16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

HLA gene and haplotype frequencies in Russians, Bashkirs and Tatars, living in the Chelyabinsk Region (Russian South Urals).

We have characterized the HLA-A, -B, -DRB1, -DQA1 and -DQB1 profiles of three major ethnic groups living in Chelyabinsk Region of Russian South Urals, viz., Russians (n = 207), Bashkirs (n = 146) and Tatars (n = 135). First field level typing was performed by PCR using sequence-specific primers. Estimates included carriage and gene frequencies, linkage disequilibrium and its significance and related values. Population comparisons were made between the allele family frequencies of the three populations and between these populations and 20 others using a dendrogram. Chelyabinsk Region Russians demonstrate all the features typical of a Caucasoid population, but also have some peculiarities. Together with Tatars, Russians have high frequencies of allele families and haplotypes characteristic of Finno-Ugric populations. This presupposes a Finno-Ugric impact on Russian and Tatar ethnogenesis. However, this was not apparent in Bashkirs, the first of the three populations to live in this territory, and implies admixture with populations of a Finno-Ugric origin with precursors of Russians and Tatars before they came to the South Urals. The Bashkirs appear close to Mongoloids in allele and haplotype distribution. However, Bashkirs cannot be labelled either as typical Mongoloids or as Caucasoids. Thus, Bashkirs possess some alleles and haplotypes frequent in Mongoloids, which supports the Turkic impact on Bashkir ethnogenesis, but also possess the AH 8.1 haplotype, which could evidence an ancient Caucasoid population that took part in their ethnic formation or of recent admixture with adjacent populations (Russians and Tatars). Bashkirs showed no features of populations with a substantial Finno-Ugric component, for example Chuvashes or Russian Saami. This disputes the commonly held belief of a Finno-Ugric origin for Bashkirs. Tatars appeared close to many European populations. However, they possessed some characteristics of Asiatic populations possibly reflecting a Mongoloid influence on Tatar ethnogenesis. Some aspects of HLA in Tatars appeared close to Chuvashes and Bulgarians, thus supporting the view that Tatars may be descendents of ancient Bulgars.

[Consistence of the radial artery as a conduit used in aortocoronary bypass surgery, a possibility of preventing shunt spasm].

AIM: To develop a new procedure to evaluate the functional consistence of the radial artery (RA) as a conduit used in aortocoronary bypass surgery (ACBS), to verify the prognostic value of the changed diameter of RA, and to prevent its spasm. SUBJECTS AND METHODS: The study enrolled 34 patients aged 59.4 +/- 8.6 years with coronary artery stenoses, who underwent ACBS using a RA conduit. While preparing them for surgery, endothelium-dependent vasodilation (EDVD) of RA, i.e. the magnitude of a change in its diameter (deltaD) was assessed; RA tone and nitric oxide (NO) concentrations were estimated during surgery; RA EDVD was re-estimated in 12 lercanidipine-treated patients with deltaD < 8%. RESULTS: The patients were primarily divided into 2 groups: 1) deltaD > or = 8% (RA spasm intra- and postoperatively); 2) EDVD deltaD < 8% (RA spasm). Significant differences between Groups 1 and 2 were intraoperatively recorded in vascular wall tone (U = 1.0; Z = -2.3; p = 0.02) and NO concentrations (p = 0.0); a relationship was found between these parameters. After lercanidipine treatment, the degree of deltaD = 4.36 +/- 1.89% increased to 11.32 +/- 2.22% (p = 0.0) and RA tone dropped from -1.68 to -3.9 mm in Group 2a with the baseline decreased vasodilating activity of RA. CONCLUSION: Ultrasound assessment of the vasodilating activity of RA provides adequate evidence about its arterial wall tone during surgery. deltaD < 8% is prognostically unfavorable and serves as a contraindication to the use of RA as a conduit during ACBS. The administration of lercanidipine allows effective correction of the dilatory capacities of an arterial conduit.