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Issue. Articles

¹1(48) // 2016




1. Original researches


Comparative assessment of clinical, functional parameters and the parameters of echocardiography in patients with isolated COPD and COPD, combined with coronary heart disease, and the correlation of these parameters with the level of NT­-proBNP, as

O.O. Krakhmalova, D.M. Kalashnyk, O.M. Êîlesnikova, Yu.Ye. Kharchenko

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — to demonstrate direct correlation of neurohormones levels with the degree of myocardial dysfunction of  the right ventricle.
Materials and methods. The study involved two groups of patients: 75 patients with chronic obstructive pulmonary disease (COPD) and 83 patients with COPD, combined coronary heart disease. The level of brain natriuretic propeptide (NT­-proBNP) was determined by ELISA using a set Biomedica Medizinprodukte GmbH & Co KG, A, 1210 Vienna. Analysis was performed on Diciscan (ASYS/HITECH, Austria). Evaluation of the functional condition was performed using 6-­minute walk test, scales and Borg dyspnea MRS (before and after 6-­minute walk test). Parameters of cardiac hemodynamics and structural changes in the heart chambers were determined by echocardiography using ultrasonic scanner Philips IU­22 (US).
Results and discussion. Such parameters of diastolic RV function as the E/Atvf ratio, the mean right atrial pressure, and TAPSE — the marker of the RV myocardium contractility correlated with the level of NT-proBNP in the group of COPD patients. In the group of patients with COPD and CHD correlation was found between the level of NT-proBNP and pulmonary wedge pressure, cardiac output, RV/LVlat ratio, the area of RV, the mean right atrial pressure, TAPSE and RV fractional area change, %.
Conclusions. Based on the obtained results, it has been suggested that the NT­-proBNP levels may be non­invasive predictor of progression marker of right ventricular dysfunction in COPD, the formation of pulmonary hypertension and chronic cor pulmonale.

Keywords: COPD, brain natriuretic peptide, dysfunction of the right ventricle.

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Original language: Russian

2. Original researches


Insulin­like growth factor 1 and metabolic indexes in patients with comorbidity of hypertension and type 2 diabetes mellitus

L.V. Zhuravlyova, O.V. Pivovarov

Kharkiv National Medical University

Objective — tî study of the relationship of the indicators of carbohydrate and lipid metabolism and blood levels of insulin­like growth factor 1 (IGF1) in patients with arterial hypertension (AH) and patients with combined arterial hypertension and type 2 diabetes mellitus (DM 2).
Materials and methods. The study involved 120 subjects: the first group included 60 AH patients, the second group involved 40 patients with combined AH and  DM 2, the control group consisted of 20 healthy individuals. Examinations have been performed in compliance with the clinical protocols of medical care. IGF1 levels were determined by ELISA, with the use of reagents DRG kits.
Results and discussion. The authors presented the results of correlation-regression analysis of the indices of the status of carbohydrate, lipid metabolism and IGF1 blood levels in patients with isolated AH and combined course of AÍ and DM 2.
Conclusions. The obtained data confirmed the possibility of the use of IGF1 as a diagnostic marker for the prognosis of DM 2 development.

Keywords: insulin­like growth factor 1, arterial hypertension, type 2 diabetes mellitus, carbohydrate metabolism, somatomedins.

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Original language: Ukrainian

3. Original researches


Hypertension in women with pathologic menopause: definition and optimization of cardiovascular risk

O.I. Mitchenko, V.Yu. Romanov, G.Ya. Ilyushina  

SI «National Scientific Center “M.D. Strazhesko Institute of Cardiology”
of NAMS of Ukraine», Kyiv

Objective — to determine the cardiovascular risk (CVR) in women with essential hypertension (EH) on the background of postsurgical or early physiological menopause  and its possible correction due to hormone replacement therapy (HRT), that are prescribed to prevent postcastration menopausal symptoms.
Materials and methods. The study involved 112 women with essential hypertension (EH), II stage, grade 1—2, the average age (46.14 ± 1.60) years, formed 3 groups:
1 group with EH and postsurgical menopause  which was not prescribed HRT; 2 group with EH and postsurgical menopause which prescribed  lowest combined HRT; 3 group with EH and early physiological menopause. After a complex examination all patients underwent determine CVR using a SCORE (standard scale), SCOREHDL, SCOREBMI, SCORE with vascular ultrasound and scales PROCAM, FRAMINGHAM, DRS, IRIS.
Results and discussion. It is determined that calculation CVR by SCORE scale with using ultrasound of the carotid arteries improves detection of very high CVR to 83.8 % in 1 group, to 5.4 % in 2 group and to 13.1 % in 3 group. Determination of atherosclerotic plaques by ultrasound of carotid arteries in 5.4 % in 2 group forcing to cancel of HRT and the transition to the use of adaptive non-hormonal drugs. Calculation of the cardiometabolic risk by DRS and IRIS-II in all groups established high risk of developing and further progression type 2 diabetes with maximum in 1 group.
Conclusions. Hypertension in the background postsurgical and early physiological menopause without HRT is associated with a very high cardiovascular and cardiometabolic risk. Prescription of HRT can prevent as CVR and the development of diabetes.

Keywords: essential hypertension, postsurgical menopause, hormone replacement therapy, cardiovascular risk.

Original language: English

4. Original researches


Apelin 12 levels in patients with gastroesophageal reflux disease, combined with arterial hypertension

Î.Å. Gridniev

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — assessment of apelin 12 metabolism in patients with concomitant gastroesophageal reflux disease (GERD) and arterial hypertension.
Materials and methods. The study included 126 patients with arterial hypertension of stage 2, ²—²²² degrees, and GERD. The control group consisted of 20 healthy individuals. Determining the stage and grade of arterial hypertension were carried out according to the recommendations of the ESH/ESC 2013. Diagnosis of GERD was established according to the Montreal Consensus (2006). Patients selected in the study, had symptoms of heartburn two times a week or more. Anthropometric measurements, ambulatory blood pressure monitoring, echocardiography, daily intraesophageal pH monitoring, determination of malondialdehyde, SH­groups, glutathionperoxidase, apelin­12 were performed according to the standard procedures.
Results and discussion. It has been reveled that in patients with comorbid GERD and arterial hypertension, apelin 12 levels were significantly (p < 0.001) lower than in the control group: (755.15 ± 15.46) and (1133.42 ± 17.85) pg/ml respectively. The apelins 12 levels in male patients were significantly (p < 0.01) higher in comparison with female patients ((792.55 ± 21.29) and (710.41 ± 21.15) pg/ml, respectively) and had an negative correlation (r = – 0.23) with age, average systolic (r = – 0.63) and diastolic (r = – 0,62) blood pressure. The same negative correlation was established between apelin 12 levels and index of left ventricular mass (r = – 0.20). Apelin 12 level in patients with GERD duration of 5 years were significantly (p < 0.001) lower than that of patients with a disease duration of 5—10 years. However, the comparison of GERD duration in patients with 5—10 years duration and more than 10 years revealed that the patients with shorter history, had significantly (p < 0.01) lower levels. In patients with GERD and arterial hypertension, the inverse correlation has been established between apelin 12 levels and total number of reflux with pH of less than 4 per day (r = – 0.18), the total number of reflux with pH of less than 4 per day and duration of 5 minutes (r = – 0.21), the duration of the longest reflux with pH of less than 4 (r = – 0.29), DeMeester index (r = – 0.20).
Conclusions. It has been established that in patients with GERD and arterial hypertension, apelin 12 levels were significantly lower than in the control group/ At the same time, male patients with combination of GERD and arterial hypertension demonstrated apelin 12 levels, significantly higher than in women, they were decreasing with age of the patients. In patients with GERD and arterial hypertension, significant negative correlation between apelin 12 levels and mean systolic and diastolic blood pressure has been established; between apelin 12 levels and index of left ventricular mass, indicators of daily intraesophageal pH metry. It was found that patients with both GERD and arterial hypertension initially low level of apelin 12 increased to achieve GERD duration of 10 years, after which the level is reduced again.

Keywords: gastroesophageal reflux disease, arterial hypertension, ambulatory blood pressure monitoring, comorbidity.

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Original language: Russian

5. Original researches


Disorders of oxidative homeostasis, carbohydrate metabolism and their impact on the vessels and heart state in patients with comorbid pathology

Ya.K. Radzishevska

Kharkiv City Clinical Hospital N 27

Objective — to study the relationships between endothelial dysfunction, indices of oxidative stress (OS) and antioxidant defense (AOD), carbohydrate metabolism, the parameters of the heart and blood vessels in patients with arterial hypertension (AH) and concomitant type 2 diabetes mellitus (DM).
Materials and methods. The study involved 134 patients: 44 patients with essential hypertension stage II grade 2—3 without disorders of carbohydrate metabolism (group 1), 45 patients with essential hypertension stage II grade 2—3 with concomitant DM (group 2). The control group (group 0, healthy) — 45 healthy patients. The blood levels of conjugated dienes (DC), malondialdehyde (MD), superoxide dismutase (SOD), catalase (CAT), total antioxidant activity of red blood cells (AOARBC), glycated hemoglobin in the blood, the index HOMA, structural and functional parameters of the heart and blood vessels were measured. For the mathematical data processing software Statistica 6.1 was used.
Results and discussion. Disorders of antioxidant defense system in hypertensive patients in the condition of type 2 diabetes mellitus accession were revealed. They were accompanied by changes in the values of the correlations to the opposite in the groups of ultrasound parameters of macrocirculation and ultrasound parameters of the heart. CAT and AOARBC had the main diagnostic value. The ultrasound parameters of the diastolic heart function were more sensitive to the disorders of oxidative homeostasis. The deterioration of the antioxidant defense was accompanied by significant disorders of carbohydrate metabolism and had negative effects on ultrasound parameters of microcirculation. Increasing of insulin resistance index HOMA was accompanied by a significant increase of pulse wave velocity in the aorta.
Conclusions. The presence of type 2 diabetes mellitus in hypertensive patients was accompanied by disorders of the antioxidant defense system. This resulted in the changes of the structural and functional parameters of the heart and blood vessels. The feasibility of the use of antioxidants that activate antioxidant defense system in the treatment of hypertensive patients with concomitant type 2 diabetes mellitus was grounded.

Keywords: oxidative stress, hypertension, type 2 diabetes mellitus.

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Original language: Russian

6. Original researches


Effectiveness of the treatment of ANCA-­associated systemic vasculitis

O.V. Syniachenko1, M.V. Iermolaieva1, L.V. Sedaia1, T.B. Bevzenko2, E.D. Iegudina3

1 M. Gorky Donetsk National Medical University, Liman  
2 Scientific Practical Centre of Preventive and Clinical Medicine, State Administration, Kyiv
3 State Medical Academy, Dnipropetrovsk

Objective — to evaluate the efficacy of drug treatment of patients with systemic vasculitis associated with anti­neutrophil cytoplasmic antibody (ANCA-­SV), the degree of influence of the disease cardiovascular signs in it, as well as effects of the immunoproteins levels in the body, state of the vascular endothelial function and of the blood adsorption­rheological properties.
Materials and methods. The study involved 129 patients (47 % men and 53 % women) with ANCA-­SV, among whom there were 59 % subjects with microscopic polyangiitis (MPA), 20 % with Wegener’s granulomatous polyangiitis (GPA) and 21 % with eosinophilic polyangiitis (EPA) Churg­—Strauss.
Results and discussion. The «significant improvement» was confirmed with nearly similar frequency for all types of ANCA-­SV, but the lack of effect occurred in 4 % of the examined patients with EPA, 15 % with GPA and 25 % with MPA. The effectiveness of therapeutic measures in patients with MPA depended on the existence and extent of the articular syndrome, the severity of nephropathy, the use of glucocorticoids and antiplatelet agents. In patients with GPA it correlated with the endocardial and valve apparatus lesions, the severity of changes in large vessels, myocardial excitability disorders, the use of cytotoxic drugs and Tivortin, and in cases of EPA it depended on the duration of disease, renal function, myocardial contractility and the use of immunosuppressant with cytotoxic effect. The effect of treatment of ANCA-­SV was associated with the initial blood levels of immune-inflammatory proteins, the state of vascular endothelial function, and adsorption and rheological properties of serum, and the parameters of immunoglobulin-G and viscoelasticity modulus possess prognostic value in patients with EPA.
Conclusions. The best results of pathogenetic drug therapy were observed at EPA, the worse in patients with GPA, and the worst results were defined in subjects with MPA, they depended on the clinical and laboratory course of ANCA­SV and the use of the drugs of pathogenetic therapy.

Keywords: systemic vasculitis, treatment, blood adsorption­-rheological properties.

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Original language: Russian

7. Original researches


Changes of the structural and functional status of the cardiac left parts and cardiac hemodynamics under the influence of therapy with angiotensin converting enzyme inhibitors and angiotensin­II receptor blockers in patients with decompensated chroni

V.N. Seredyuk

SHEI «Ivano-Frankivsk National Medical University»

Objective — to study of influence of angiotensin converting enzyme (ACE) inhibitor enalapril and angiotensin­II receptor blocker (ARB) candesartan and their combination on the structural and functional status of the left part of heart and cardio­hemodynamics in patients with decompensated chronic pulmonary heart disease (CPHD) with arterial hypertension (AH).
Materials and methods. The study involved of 295 patients (212 males, 83 females) with decompensated CPHD with AH II stage and chronic heart failure (CHF) I—IIB stage. The structural and functional condition of left cardiac parts was assessed with two dimensional echocardiography (EchoCG) and impulse Doppler­EchoCG (equipment Logiq­-500, Germany; Logiq E, China).
Results and discussion. It has been established, that at the decompensated CPHD with AH and stage I  CHF, efficacy of the ACE inhibitor and  ARB against the basic therapy background was comparable in terms of the dynamics of the metric, volumetric indices and left ventricular (LF) hemodynamics. In patients with the decompensated CPHD with AH and stage IIA and IIÂ CHF, the combined therapy with enalapril and candesartan, resulted in the more pronounced regression of remodeling and improvement of the left cardiac functional state in terms of the  of the dynamics of the metric, volumetric indices and hemodynamics, as compared to the monotherapy with enalapril against the basic therapy background.
Conclusions. The authors worked out the differentiated approaches to the treatment of decompensated CPHD with AH. For the treatment of decompensated CPHD with AH and stage I  CHF, it is advisable to add to the basic therapy either ACE ­inhibitor Enalapril, or ARB Candesartan. In cases of the severe decompensation of chronic pulmonary heart (HF IIÀ—²²B stages) with AH, the combination ACE ­inhibitor Enalapril and ARB Candesartan proved to be more effective. With this, this treatment is more effective at II A stage of HF with AH.

Keywords: angiotensin converting enzyme inhibitors, angiotensin­II receptor blockers, decompensated chronic pulmonary heart disease, arterial hypertension.

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Original language: Ukrainian

8. Original researches


Some peculiarities of secondary dyslipidemiain patients at high cardiometabolic risk

V.A. Chernyshov, O.V. Chyrva, I.A. Valentinova

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Khark³v

Objective — to rectify the variants of dyslipidemia (DLP) phenotypes as well as the state of lipid exchange and contribution of separate risk factors (RF) to the atherogenicity of lipid blood spectrum in patients (pts) at high cardiometabolic risk (CMR).
Materials and methods. The retrospective investigation of the history cases involved results of examination of 1029 pts (410 (39.8 %) females and 619 (60.2 %) males aged to 30—69 years old (average age is (57.3 ± 0.24) years old) with essential hypertension (EH) of II—III stages. In all cases EH was combined with metabolic RF, such as body mass excess (BME), abdominal obesity (AO), type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and secon­dary DLP revealed in 937 (91.1 %) pts). Among the CMR components, smoking was analyzed separately, and it occurred in 192 (18.6 %) of cases. Calculation of cardiovascular risk (CVR) was performed with the use of PROCAM, Framingham and SCORE scales in 693 (67.3 %) pts without cardiovascular events. The risk of type 2 DM development was assessed by DRS scale, and the risk of its vascular complications was evaluated by IRIS II scale. The data of pts examination before treatment prescription were selected from the history cases. The analysis of blood lipid spectrum was performed based on the following values: total cholesterol (C), triglycerides (TG), high­density lipoprotein cholesterol (HDL­C), non­HDL­C, low­density lipoprotein cholesterol (LDL­C), a coefficient of atherogenicity and lipid ratios TG/HDL­C and LDL­C/HDL­C. In addition such anthropometric data as waist circumference, body mass index as well as the results of glycosylated hemoglobin evolution have been taken into consideration.
Results and discussion. In the structure of secondary DLP there was a prevalence of isolated hypercholesterolemia (HC) (49.7 % of pts) compared with isolated hypertriglyceridemia (HTG) (15.3 % of persons) and hypoalfacholesterolemia (6.8 % of cases). Combined DLP included all isolated variants occurred in 17.7 % of pts although combination only HC with HTG registered more frequently (19.3 % of pts). Correlation analysis confirmed that non­HDL­C and lipid ratio LDL­C/HDL­C could be additionally considered in CVR calculation with PCOCAM and Framingham scales. Lipid ratio TG/HDL­C was assumed to be associated with insulin resistance through hyperglycemia.
Conclusions. In pts with metabolic RF such as BME, AO and NAFLD secondary DLP increases risk of type 2 DM calculated by DRS scale through metabolic abnormalities in TG and HDL. Risk of vascular complications of type 2 DM assessed by IRIS ²² scale increases when blood HDL­C concentration is decreased and lipid ratio TG/HDL­C is increased. In persons with BME elevation in blood TG and decrease in HDL­C were additionally associated with smoking.

Keywords: dyslipidemia, cardiometabolic risk, risk factors.

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Original language: Ukrainian

9. Original researches


Evaluation of effects of metoprolol succinate on the parameters of quality of life, clinical status, indices of hemodynamics and heart rhythm in patients with chronic heart failure against the background of obesity

Yu.Ch. Gasanov, Yu.S. Rudyk, T.V. Lozyk

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — to determine efficacy of the long­term use of metoprolol succinate in patients with chronic heart failure (CHF) against the background of obesity on the basis of assessment  of psychosocial aspects (quality of life), the clinical condition, central hemodynamics and heart rate variability.
Materials and methods. The prospective study has been performed to analyze efficacy of metoprolol succinate in CHF patients against the background of obesity, which involved 55 patients of both genders with II—­III stages CHF, aged 32—87 (60 [56; 75]) years, 41 males and 14 females). From them 10 (18.2 %) patients had initially normal weight as per body mass index, 18 (32.7 %) patients had excessive body mass, and obesity of the 1st degree was defined in 18 (32.7 %) participants, of the 2nd degree — in 7 (12.7 %) patients, the 3rd degree — in 2 (3.7 %) subjects. Clinical signs were evaluated with the use of clinical symptoms estimation scale, exertion tolerance was assessed in 6­minutes walk test, quality of life was evaluated with Minnesota questionnaire.  Doppler­ and echocardiographic investigations were used to assess central hemodynamics, Holter ECG monitoring to define the cardiac rhythm variability.
Results and discussion. During observations’ period,  the frequency of survival rate was 98.2 %. Generalized incidence of clinically significant side effects of metoprolol succinate (bradycardia, dizziness, weakness, and the like) was 9 %, with a statistically significant difference in the rate of side effects in the different groups has been established. Clinical characteristics of clinical symptoms estimation scale showed overall significant improvement (4 [3, 6] points against the output 6 [5, 9] points, p = 0.01). The increase of  the distance in 6­minutes walk test was confirmed (280 [247; 370] m vs. 230 [160 352] m, p < 0.01). It has been noted that individuals with the higher BMI values had a tendency
(r ≈ 0.15) to the progressive reduction of tolerance to physical activity with increasing of weight category, both for the initial state and after treatment. All cardio hemodynamic parameters were improved, with significant changes gained in left ventricular (LV) ejection fraction, LV end-diastolic volume, LV end-systolic volume. Definite differences in the profiles of the dynamics of the cardiac rhythm variability have been revealed in each group.
Conclusions. The efficacy of metoprolol succinate in the complex treatment of patients with heart failure was not homogeneous in terms of clinical, psychosocial, hemodynamic and rhythmographic  characteristics. It depended on the categories of patients’ weight: in addition to the improvement of clinical and functional parameters, good tolerance and low incidence of deaths due to progression of heart failure in all weight groups, the contradictory information was obtained in the assessment the quality of life, functional tests, and indices of rhythmography.

Keywords: chronic heart failure, obesity, treatment, metoprolol succinate, quality of life, cardiac rhythm variability, hemodynamics.

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Original language: Ukrainian

10. Original researches


Quality of life and the risk of osteoporosis in patients with chronic obstructive pulmonary disease

N.P. Masik

National Pirogov Memorial Medical University, Vinnytsya

Objective — to study the q uality of life in patients with COPD with the definition of the risk of osteoporosis.
Materials and methods. Examinations involved 696 patients, aged (55.40 ± 14.98) years. Form them,  391 men with the mean age (54.09 ± 14.04) years, and 305 women mean age (56.98 ± 15.88) years old. Concomitant diseases were diagnosed in 347 (49.86 %) patients.
Quality of life was measured using a questionnaire SF­12 and EuroQol-­5D. Assessment of risk factors for osteoporosis was performed using minute test (one­minute osteoporosis risk test), proposed by the International Association of osteoporosis.
Results and discussion. The specific feature of the clinical course in these patients was association of COPD symptoms with signs of the musculoskeletal system lesions (pain in the spine, joints, muscles reduced height, thoracic kyphosis). Thus, 46.80 % of patients with COPD notified about pain/discomfort, and 19.15 % of the patients complained on the significant vertebral pain.
In patients with severe COPD course, the twofold increase was observed in the frequency of deteriorated physical status, deterioration of general health and social activity. The reduction of mental status parameters was noted in 85.10 % COPD patients with stage I and 65.96 % patients with stages II, which might indicate a lack of adaptation to the disease, and 48.94 % of patients with stage IV. Impaired physical activity was diagnosed in 59.94 %, altered mental status — in 79.83 % of COPD patients with comorbidities. Using minute test for osteoporosis risk assessment enables the detection of patients with structural and functional disorders of bone tissue.
Conclusions. COPD resulted in the limitation of all components of the normal life of patients, that is, reduction of quality of life, the intensity of the changes as determined by the characteristics of clinical symptoms, the degree of bronchial obstruction, duration and severity of illness, presence of comorbidities, age and sex of the patients. The presence of vertebral pain syndrome in patients with COPD requires further examination of the patient.

Keywords: chronic obstructive pulmonary disease, quality of life, osteoporosis, risk factors.

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Original language: Ukrainian

11. Original researches


The relationship of gene polymorphism of serotonin receptors 5ÍÒ2A A1438­G with anxiety and depressive disorders in patients with rheumatoid arthritis

L.O. Protsiuk, M.A. Stanislavchuk

National Pirogov Memorial Medical University, Vinnytsya

Objective — to study the distribution of A1438­G gene of serotonin receptor 5HTR2A polymorphism in patients with rheumatoid arthritis (RA) and the relationship of anxiety and depressive disorders with different variants of polymorphic areas of promotor region of 5­HTR2A A1438­G gene.
Materials and methods. The distribution of genotype rate of serotonin receptor 5­HT2A A1438­G gene was studied in 100 patients with RA, who underwent standard examinations. Different variants of polymorphic areas of A1438­G gene was determined by isolating genomic DNA with phenol­chloroform method using the kit for DNA/RNA isolation from blood serum or plasma. Polymorphic areas of T102C gene were amplified with polymerase chain reaction. Anxiety level was assessed by Spielberger State­Trait Anxiety Scale. Depressive status and depression severity was evaluated by Hamilton Depression Rating Scale.
Results and discussion. During the study, heterozygous variant AG was found in 47 % of RA patients and occurred significantly more often compared to homozygous variants ÀÀ (17 %; χ2 = 20.7; ð < 0.01); the GG genotype occurred significantly more often compared to homozygous variants ÀÀ (36.0 % and 17%; χ2 = 9.3; ð < 0.01). In the patients with ÀG and GG genotype significantly more common occurrence high and moderate level of state anxiety (ð < 0.01), while the high and moderate level of trait anxiety was detected significantly more frequently among patients with ÀG and ÀÀ genotype (ð < 0.01—< 0.001). We found a significant increase in the frequency of depressive disorders of mild in patients with the AA genotype compared to patients with AG (ð < 0.05) and GG (ð < 0.01) genotypes.
Conclusions. In the patients with GG genotype in areas of promotor region A1438­G gene on the background of higher rates of state and trait anxiety significantly more often showed signs of severe depressive disorders, while in patients with the AA genotype the signs of mild depression. G allele carries state can be considered as a poor prognostic factor in development and progression anxiety and depressive disorders.

Keywords: rheumatoid arthritis, polymorphism, serotonin receptor 5­HT2A A1438­G gene, depression.

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Original language: Ukrainian

12. Original researches


Tissue inhibitor of matrix metalloproteinase­-1, periodontopathogenic microflora and polymorphism 896A / G gene TLR4 — predictors of atherosclerotic lesions in patients with coronary heart disease

O.V. Skochko1, T.V. Mamontova2, O.A. Shlykova2, M.V. Mikityuk2, L.E. Vesnina2, I.P. Kaydashev1

1 Ukrainian Medical Stomatological Academy, Poltava
2 Research Institute for Genetic and immunological Research Institute for Genetic and Immunological Grounds of Pathology and Pharmacogenetics, Ukrainian Medical Stomatological Academy, Poltava

Objective — to study the main markers of inflammation, representative periodontopathogenic microflora and polymorphism Asp299Gly gene TLR4 in patients with coronary heart disease (CHD), and to assess their relationship with pathogenetic mechanisms of atherosclerotic lesion of the neck vessels.
Materials and methods. The study included 63 people with coronary heart disease aged 45 to 68 years. All patients underwent a standard physical examinations, evaluation of the state of the vascular flow, assessment of the quality of life (QoL). The following measurements were performed: concentration of inflammatory markers (human tissue inhibitor of metalloproteinase 1 (TIMP­1), interleukin (IL) 2, 6, C­reactive protein (ÑRP), the DNA of periodontopathogenic microflora in periodontal liquid by polymerase chain reaction (PCR), polymorphism Asp299Gly of TLR4 gene by PCR.
Results and discussion. The reduction of QoL in patients with CHD was defined, mainly due to the physical functioning, namely, patients reported the appearance of pain/discomfort, loss of mobility and fatigue, which limited the implementation of physical activity and daily work. The development of atherosclerotic lesions one of the vascular pools were discovered in 52 % of cases, the two of the vascular pools — in 31.7 % of cases. In the blood vessels the localization of atherosclerotic plaques were found, predominantly in right oral carotid artery in 44.44 % of cases and left in 34.92 % of cases. There were detected a hemodynamically significant stenosis of the neck blood vessels in 4.77 % of cases. It was registered a high level of systemic inflammation in patients with CHD, as evidenced by increased concentration of TIMP­1 is more than 2 times and concentration of CRP (39.68 % patients), indicating a high degree of cardiovascular complications risk. It were found a disorder in oral cavity hygienic condition, the development of inflammation in the gingival mucous and persistence in the periodontal liquid specimens of periodontopathogenic microflora, namely
P. gingivalis, A. actinomycetemcomitans, P. intermedia and B. forsythus. There was a significant relationship between the presence of polymorphism 896A/G gene TLR4 (rs4986790) and an increased risk of CHD. Unfavorable course of atherosclerotic lesions in the carotid neck vessels and increased risk of CHD are associated with the presence of allele G of TLR4 gene in these patients.
Conclusions. CHD patients reported worsening in QoL, increased concentration of inflammatory markers (TIMP­1, IL­2 and CRP), persistence periodontopathogenic microflora in the oral cavity, the relationship of polymorphism 896A/G of TLR4 gene with the risk of CHD, which should be considered when predict the development of atherosclerosis and CHD.

Keywords: coronary heart disease, quality of life, tissue inhibitor of matrix metalloproteinase-1, periodontopathogenic microflora, polymorphism 896A/G gene TLR4.

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Original language: Russian

13. Point of view


Principles of glucocorticosteroid therapy of patients with pulmonary sarcoidosis

V.K. Gavrysiuk, G.L. Gumeniuk, E.Î. Merenkova, O.V. Bychenko

SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of NAMS of Ukraine», Kyiv

The issue of the indications for the use of glucocorticosteroids (GCS) in patients with bronchopulmonary lymph nodes and lung sarcoidosis (stage II) remains disputable. Usually, corticosteroid therapy in this group of patients is administered in case of the presence of clinical symptoms and/or disturbances of lung function or hypercalcemia.
The authors performed analysis of the rate and the character of clinical symptoms, lung function disturbances and hypercalcemia for 146 cases of pulmonary sarcoidosis with lung lesions. As a result, clear indications for corticosteroid therapy were established in the vast majority (90%) of patients.
A comparative analysis has been held for the outcomes of three months follow-up of patients with stage II asymp­to­matic sarcoidosis (52 subjects) without therapy, and results of 3-moths GCS therapy of stage II symptomatic sarcoidosis patients (86 subjects).
In asymptomatic stage II sarcoidosis patients after three months follow­up period, the rate of spontaneous regression was observed in only 32.7 % of cases; no changes — in 30.8 %; and progression — in 36.5 %.
In symptomatic stage II sarcoidosis patients or those with pulmonary function/diffusion disturbances after three months corticosteroid treatment, the regression was achieved in the majority of patients (80.2 %); stabilization —
in 15.1 %; and progression only in 4.7 % of patients.
A significant number of progressing pulmonary sarcoidosis cases when corticosteroid therapy have not been started, confirmed the need for urgent administration of glucocorticosteroids at the first visit regardless of the presence or absence of clinical symptoms, lung function disturbances or hypercalcemia.

Keywords: pulmonary sarcoidosis, glucocorticosteroids, indications for use, dose and regimens.

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Original language: Russian

14. MEDICINES in therapy


The role of metabolic therapy in patients after myocardial infarction

S.A. Serik, V.I. Strona, Yu.G. Gorb

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Khark³v

Objective — to study the effects of therapy with meldonium on clinical and hemodynamic status, exercise tolerance and performance of daily monitoring of the electrocardiogram in patients after myocardial infarction (MI).
Materials and methods. The study involved 47 patients with previous non-Q wave MI, which took place not earlier than 6 months ago. Patients of group 1 (n = 29) received additionally to standard therapy meldonium (MetaMax, Darnitsya, Ukraine), at a dose of 500 mg 2 times a day. Patients of group 2 (n = 18) received only standard therapy. The efficacy of the therapy was assessed by the dynamics of hemodynamic parameters, level of exercise tolerance in 6­minute walk test, data daily monitoring of the electrocardiogram, indices of myocardial contractility after 6 weeks of observation.
Results and discussion. In the patients group treated with the combined therapy with meldonium, the total number of ST­segment depression episodes, the total daily duration of ischemia mainly due to reduction of the duration of episodes of silent myocardial ischemia decreased. Left ventricular ejection fraction and 6­minute walk test distance increased more significantly in the patients group treated with meldonium. Changes of left ventricular diastolic function were not observed in both groups.
Conclusions. Addition of meldonium to the treatment of patients with stable angina and heart failure after recent (within 6 months) myocardial infarction contributes to the reduction of the daily duration of myocardial ischemia, primarily due to the decrease of the duration of painless episodes, and favors the increase of exercise tolerance and the improvement of left ventricular systolic function.

Keywords: metabolic therapy, myocardial ischemia, left ventricular systolic function, meldonium.

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Original language: Ukrainian

15. Reviews


Frequency, possible mechanisms of development and new biomarkers of idiosyncratic drug­induced liver injury

S.M. Tkach1, K.S. Puchkov2, T.L. Cheverda2

1 Ukrainian Research Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of Ministry of Public Health of Ukraine, Kyiv
2 O.O. Bogomolets National Medical University, Kyiv

The article presents recent data of epidemiology of idiosyncratic drug­induced liver injury (DILI), possible mechanisms of its development and new biomarkers, such as glutamate dehydrogenase, HÌGB­-1 and microRNA-­122.
It has been concluded that determination of these biomarkers can provide useful information regarding diagnosis and prognosis of some DILI and will allow better to know its pathogenetic mechanisms.

Keywords: idiosyncratic drug­induced liver injury, epidemiology, mechanisms of development, new biomarkers.

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Original language: Russian