Objective — to study the prevalence of gene polymorphisms of platelet receptors (T924C of thromboxane A2 receptor gene and C 807T of gene glycoprotein Ia) and their possible association with the risk of cardiovascular events in patients with coronary heart disease.
Materials and methods. The study involved 271 patients with chronic coronary heart disease (CHD). All patients were administered the standard drug therapy. The observation period was (27.8 ± 7.8) months. The overall and cardiovascular mortality, myocardial infarction, unstable angina, revascularization and acute cerebrovascular accident were endpoints of this study. Polymorphic sites T924C of thromboxane receptor gene TBXA2R (rs4523) and C 807T
of glycoprotein Ia gene (rs1126643) genotyping was performed by polymerase chain reaction followed by restriction fragment length analysis. The risk of cardiovascular complications in CHD patients, depending on the genotype was evaluated by the Kaplan—Meier method.
Results and discussion. The distribution of genotypes of TBXA2R gene T924C polymorphism in the patients group: TT genotype — 12.9 %; CT genotype — 46.1 %, the SS genotype — 40.9. The incidence of cardiovascular events in patients with TT and CC genotype was higher than TS-heterozygote genotype (χ2 = 6.11, p = 0.01 and (χ2 = 4.84,
p = 0,03 respectively). The patients groups with homozygous genotypes by widespread T and minor C alleles have not significant differences (χ2 = 0.68, p = 0.41). The relative number of patients with stable disease flow for 36 months in the group with the TT genotype of TBXA2R gene T924C polymorphism was significantly less than in the group with
(CC + CT) genotypes by Kaplan—Meir method (log-rank test = –2.04, p = 0.04). The prevalence of genotypes CC, CT and TT of ITGA2 gene C 807T polymorphism was 36.6, 44.9 and 18.5 % respectively. The incidence of end points in the groups of patients with different genotypes of ITGA2 gene C 807T polymorphism throughout the observation period did not differ significantly. Kaplan—Meir curves construction in groups of patients with different genotypes of ITGA2 gene C 807T polymorphic site revealed no significant differences (log-rank test = –0.24, p = 0.81). The combination of the ITGA2 gene C 807T polymorphism TT genotype and TBXA2R gene T924C polymorphism TT genotype increases the stability of connection with the endpoints probability (log-rank test = –3.48, p = 0.02).
Conclusions. It has been established, that TT genotype polymorphism T924C gene carriers had significantly worse TBXA2R 36-month prognosis for the stable course of the disease compared with the wild homozygotes and heterozygotes. It was revealed, that C 807T polymorphism ITGA2 gene was not associated with the risk of adverse cardiovascular events in patients with CAD at 36-month follow-up, but may increase the  risks in combination with TT genotype polymorphism T924C TBXA2R gene.

Keywords: polymorphism, platelet receptor genes TBXA2R and ITGA2, cardiovascular events, coronary heart disease.

List of references:
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In order to study a rate of glucocorticosteroid (GCS) therapy contraindications, serious adverse reactions and resistance in patients with newly diagnosed sarcoidosis, affecting lung parenchyma, we examined 185 patients. There have been established that on average one of 8 patients with newly diagnosed stage II—III sarcoidosis (12.4 %) required administration of immunosuppressive therapy due to apparent GCS therapy contraindications. Among patients already on GCS therapy the need in immunosuppressants increases due to serious adverse reactions, as well as due to GCS­resistance (32.4 % on average). Hence, every third patient requires use of immunosuppressants at different stages of treatment.
In 33 sarcoidosis patients with lung parenchyma lesions we evaluated the efficacy and tolerability of methotrexate. Use of methotrexate in patients with contraindications for GCS therapy allowed to achieve clinical cure at the end of 6th month of treatment, or regression in about 84 % of patients. In GCS­resistant sarcoidosis patients methotrexate monotherapy was mostly not effective (71 %), requiring further investigation of possible combining of methotrexate with other first­line drugs.
Serious adverse reactions of methotrexate resulted in its discontinuation were observed in 2 cases (drug­induced pulmonitis and 4­fold increase of blood ALT level). In general, immunosuppressive therapy of patients with pulmonary sarcoidosis using methotrexate 10 mg a week was tolerated quite well.

Keywords: pulmonary sarcoidosis, glucocorticosteroids, methotrexate, efficacy, tolerability.

List of references:
1. Gavrysyuk VK, Gumenyuk GL, Merenkova ЕО, Bychenko OV. Indications for use of glucocorticosteroids in management of patients with pulmonary sarcoidosis (Rus). Ukrayinskyy pulmonologychnyy zhurnal [Ukrainian Pulmonology journal] (Ukr). 2015;4:5-8.
2. Sarkoidoz organov dykhaniya [Pulmonary sarcoidosis] (Rus). Kyiv, 2015:192.
3. Unifikovanyy klinichnyy protokol pervynnoyi, vtorynnoyi (spetsializovannoyi) ta tretynnoyi (vysokospetsializovannoyi) medychnoui dopomogy «Sarkoyidoz». Nakaz MOZ Ukrayiny N 634 vid 08.09.2014 [Unified clinical protocols of primary, secondary (specialized) and tertiary (highly specialized) medical care "Sarcoidosis". Decree of MOH of Ukraine N 634 from 09.08.2014] (Ukr).
4. Baughman RP, Judson MA, Teirstein A et al. Presenting characteristics as predictors of duration of treatment of sarcoidosis. QJM. 2006;99:307-315.
5. Baughman RP, Drent M. The Treatment of Pulmonary Sarcoidosis. Pulmonary sarcoidosis. MA Judson Editor. Humana Press-​brand of Springer, 2014:41-64.
6. Baughman RP, Winget DB, Lower EE. Methotrexate is steroid sparing in acute sarcoidosis: results of double blind, randomized trial. Sarcoidosis Vasc Diffuse Lung Dis. 2000;17:60-66.
7. Cremers JP, Drent M, Bast A et al. Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide. Curr Opin Pulm Med. 2013;19:545-561.
8. Gibson GJ, Prescott RJ, Muers MF et al. British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment. Thorax. 1996;51:238-247.
9. Pietinalho A, Tukiainen P, Haahtela T et al. The Finish Pulmonary Sarcoidosis Study Group. Early treatment of study II sarcoidosis improves 5-year pulmonary function. Chest. 2002;121:24-31.
10. Rizzato G, Montemurro L, Colombo P. The late follow-up of chronic sarcoid patients previously treated with corticosteroids. Sarcoidosis. 1998;15:52-58.
11. Schutt AC, Bullington WM, Judson MA Pharmacotherapy for pulmonary sarcoidosis: a Delphi consensus study. Respir Med. 2010;104(5):717-723.
12. Veltkamp M, Grutters JC/ The pulmonary manifestations of sarcoidosis. Pulmonary sarcoidosis. MA Judson Editor. Humana Press-brand of Springer, 2014:19-40.

Objective — to study the state of right ventricular diastolic function, pulmonary hemodynamics and peripheral vascular innervation regulatory endothelial function in patients with chronic cor pulmonale (CCP) in the dynamics of complex treatment.
Materials and methods. The investigation involved 53 patients with chronic obstructive pulmonary disease (COPD), complicated with the progression of pulmonary hypertension (PH) with the man level of pulmonary pressure  more than 25 mm Hg. Besides, investigation included 40 patients with COPD with the disease, complicated with PH and right ventricular hypertrophy, and 20 healthy subjects.
Results and discussion. As a result of investigation, it was demonstrated that in COPD patients, complicated  with CCP, the imbalance of blood levels the stable nitric oxide metabolites and reduction of the ability of brachial artery vessels to the endothelial-dependent vasodilative activity. The patients demonstrated significantly manifested changes in the structure of the diastolic filling of cardiac right ventricle (RV). The reduction of filling indices at early diastole associated with the disorders of relaxation of the RV hypertrophic myocardium, that resulted in the slowdown of the declined intraventricular filling. The predomination of this anxiety affect in the structure of a personality was confirmed by the psychometric analysis.
Conclusions. The mostly pronounced reduction of the nitric oxide stable metabolites, endothelium dependent vasodilatation, affective symptoms were observed in COPD patients with right ventricular hypertrophy  in comparisons with the COPD patients with pulmonary hypertension. With this, the right ventricular dysfunction showed the direct correlation with the levels of NO stable metabolites (r = 0.32, р < 0.05). Ozone therapy and amlodipine against the background of basic therapy resulted in the significant correction the levels of stable NO metabolites, thus improving the endothelial-dependent vasodilatation  and right ventricular diastolic function, and  reducing the levels of mean pulmonary arterial pressure and affective symptoms in patients with COPD, complicated with the CCP.

Keywords: chronic obstructive pulmonary disease, pulmonary hypertension, chronic cor pulmonale, stable nitric oxide metabolites, psychometric analysis, ozone therapy, amlodipine.

List of references:
1. Boruta SA, Shakhnys ER, Omel'yanenko MH. Rol' dysfunktsyy эndotelyya, hypoksyy v formyrovanyy lehochnoy hypertenzyy u bol'nukh bronkhyal'noy astmoy. Pul'monolohyya. 2008;2:38-41.
2. Karoly NA, Rebrov AP. Эndotelyal'naya dysfunktsyya y ee klynycheskoe znachenye u bol'nukh khronycheskoy obstruktyv­noy bolezn'yu lehkykh. Klynycheskaya medytsyna. 2005;9:10-15.
3. Kokosov AN. Khronycheskye obstruktyvnue bolezny lehkykh: osobennosty klynycheskoy kartynu, klynyko-funktsyonal'naya dyahnostyka y pryntsypu lechenyya. Novue Sankt-Peterburh. vrach. vedomosty. 2004;4:8-19.
4. Kryukov NN, Drovyannykova LP, Volobuev AA. Vozmozhnosty medykamentoznoy terapyy hemodynamycheskykh y respyratornukh narushenyy u bol'nukh KhOBL. VII Natsyonal'nuy konhress po boleznyam orhanov dukhanyya: Sb. rezyume. M., 2004;1483:389.
5. Masyk AA, Kamusheva EP, Peretyahyn SP, Kulakova EP. Oput prymenenyya ozonoterapyy v lechenyy yshemycheskoy bolezny serdtsa. Ozon y metodu эfferentnoy terapyy v medytsyne. Tezysu dokladov 3-y Vserossyyskoy nauchno-praktycheskoy konferentsyy. N. Novhorod, 1998:101.
6. Mukharlyamov NM Mekhanyzmu ustoychyvosty k эmotsyonal'nomu stressu: preymushchestva yndyvydual'noho podkhoda. Vestnyk Rossyyskoy Akademyy Medytsynskykh Nauk. 1995;8:8-12.
7. Rakhymova DA, Sabyrzhanova ZT, Ybabekova Sh R. Otsenka эffektyvnosty razlychnukh rezhymov medykamentoznoy terapyy u bol'nukh khronycheskym lehochnum serdtsem. 5-y Konhress EARO. Yssuk-Kul', Kyrhyzyya. 2009;9:66-71.
8. Sabyrov YS, Sadukov AS, Marypov AM. Sostoyanye dyastolycheskoy funktsyy pravoho zheludochka u bol'nukh s vusotnoy lehochnoy hypertonyey. V kn.: Sbornyk tezysov III konhressa kardyolohov tyurkoyazuchnukh stran y II Mezhdunarodnoho sympozyuma po HM. Byshkek. 2002.
9. Senkevych N. Yu. Narushenye pokazateley hemodynamyky y KZh bol'nukh khronycheskoy obstruktyvnoy bolezn'yu lehkykh, oslozhnennoy khronycheskym lehochnum serdtsem. Pod red. AH Chuchalyna. M, 2001:71-91.
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Objective — to improve the efficacy of pharmacotherapy for patients with hypertensive disease (HD) and oncomitant chronic obstructive pulmonary disease (COPD) using an exogenous nitric oxide donor — L-arginine — by correction of structural changes in the heart as well as to improve pulmonary ventilation and quality of life in general.
Materials and methods. This study involved 102 patients with stage 2 arterial hypertension (AH) (2-nd and 3-rd degree) including 82 patients with HD and concomitant COPD, and 20 patients with essential hypertension of the identical stage and degree at the age of (65.5 ± 4.12). According to the treatment 82 patients with AH and COPD were divided into two groups, homogeneous by age, sex, duration of AH and COPD. Group I — the control group (CG) — included 40 patients receiving basic therapy only, group II — the main group (MG) — included 42 patients, who received L-arginine hydrochloride in addition to basic therapy.
Results and discussion. It has been observed that chronic obstructive disease burdened the course of hypertension by cardiorespiratory system rates deterioration.
In patients with HD and concomitant COPD, left ventricular (LV) was characterized by an increase in metric and volumetric indices — end-systolic dimension (ESD) increased by 17.8 %, and end-systolic volume (ESV) increased by 44.4 % compared to patients with isolated HD (p < 0.05). The size of the left atrium (LA) in COPD and AH was
(42.5 ± 2.13) mm, i.e. it was larger than that in patients with HD reflecting LV remodeling and indicating the development of diastolic dysfunction (p < 0.05).
The mean systolic pressure within the pulmonary circulation of patients with HD was 19 % higher than in healthy persons (p < 0.05) while in patients with comorbidity it was 128 % higher than that in healthy persons (p < 0.001).
According to the spirogram in patients with comorbidity the forced expiratory volume in one second was (48 ± 1.1) % compared to patients with HD ((70 ± 2.8) %, р < 0.01) indicating a moderate positive correlation with the indicator of physical functioning (r = 0.45, р < 0.05). Thus, in patients with AH and concomitant COPD, the bronchial patency was significantly impaired thereby increasing systolic pressure within the pulmonary circulation and creating a pathogenic basis for the development of cardiac remodeling as well as resulting in lower quality of life indices including general health, physical functioning, role limitations due to physical health and vitality.
3 months after basic therapy with L-arginine a number of positive effects in combination therapy was established: the decrease in blood pressure (BP) within the pulmonary circulation by 54 % (p < 0.001) due to treatment contributed to the increase in ventilation and gas exchange as indicated by increased lung capacity and, especially, increased Tiffeneau index, LV ESV reduced by 8.6 % (p < 0.05) indicating positive dynamics of LV contractile function.
Generally, under the influence of L-arginine the indicators of general health improved by 31.6 % (p < 0.05) while in the CG they improved by 17.6 % only (p < 0.05).
Conclusions. The addition of L-arginine to the combined therapy of patients with hypertension accompanied by COPD, resulted in the potentiation of antihypertensive therapy, improvement of bronchial patency and structural changes in the heart, as well as to the improvement of quality of life in general.

Keywords: chronic obstructive pulmonary disease, hypertensive disease, pulmonary hypertension, L-arginine, quality of life.

List of references:
1. Mostovyi YuM, Rasputina LV. Chronic obstructive pulmonary disease and arterial hypertension: peculiarities of clinical course, treatment strategy (Ukr). Ukrainskyi Pulmonolohichnyi Zhurnal [Ukrainian Pulmonology Journal] (Ukr). 2010;1:23-25.
2. Pertseva TA, Hashynova EYu. New possibilities in therapy for obstructive pulmonary disease (Ukr). Ukrainskyi Pulmonolo­hichnyi Zhurnal [Ukrainian Pulmonology Journal] (Ukr).2010;2:12-17.
3. Corsonello A, Incalzi RA, Pistelli R et al. Comorbidities of chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2011;17:21-28.
4. Chen H, De T Marco, Kobashigawa EA et al. Comparison of cardiac and pulmonary-specific quality-of-life measures in pulmonary arterial hypertension. Eur Respir J. 2011;3В:601-606.
5. Halpin DMG, Decramer M, Celli B et al. Exacerbation frequency and course of COPD. Int J COPD. 2012;7:653-661.
6. Feldman GJ Improving the quality of life in patients with chronic obstructive pulmonary disease. Int J COPD. 2013;В:89-96.
7. Burgel PR, Escamilla R, Perez T et al. Impact of comorbidities on COPD-specific health-related quality of life. Respir Med. 2013;107:233-241.
8. Jones PW, Quirk FH, Baveystock CM The St George’s Respiratory Questionnaire. Respir Med. 1991;5:25-31.
9. Tertemiz KC, Ellidokuz H et al. Mortality and factors affecting mortality in chronic obstructive pulmonary disease. Tuberk Toraks. 2012;6:114-122.
10. Berry CE, Drummond MB, Han MK et al. Relationship between lung function impairment and health-related quality of life in COPD and interstitial lung disease. Chest. 2012;142:704-711.

Objective — to study the features of the changes of the indices of T- and B-cell immunity depending on the body mass index of the patients with comorbid course of the nonalcoholic fatty liver disease (NAFLD) in combination with the obesity (OB) and pathology of biliary tract (BT).
Materials and methods. The study involved 200 patients with NAFLD in combination with OB and BT pathology, who revealed signs of hepatic steatosis at the time of sonographic and morphological study of liver biopsy: 100 patients with nonalcoholic hepatic steatosis (NAHS) and OB, and 100 subjects with nonalcoholic steatohepatitis (NASH) and OB, from them 70 patients with the minimal activity of the process in terms of alanine transaminase and 30 patients with the moderate activity. Depending on the degree of increase in the body mass index, the patients with NAHS and OB and NASH and OB were divided into three subgroups: the first subgroup included patients with overweight, the second subgroup included the patients with the first degree obesity and the third subgroup included the patients with the second degree obesity. The control group consisted of 30 practically healthy persons. The indicators of T- and B-cell immunity were studied by using the serological methods.
Results and discussion. It has been established that in the patients with NAFLD in combination with OB and
BT pathology the disease runs against the background of the changes of T- and B-cell immunity (I—IV variants of the violation of the immune status in 98 % of patients with NAHS and 99 % with NASH). In patients with clinical forms of NAHS and more substantial with NASH, this reaction was mostly characterized by an increase in the number of blood circulating lymphocytes, and increased volume of B-lymphocytes and T-suppressors. The deepest decline of the immune protection was observed in the patients with OB of the I, and especially of II degree.
Conclusions. The patients with comorbid course of NAFLD in conjunction with OB and BT pathology were characterized by the observation of significant changes of T- and B-cell immunity which depended on the increase in the body mass index parameters and were more significant in the patients from NASH group.

Keywords: T-lymphocytes, B-lymphocytes, obesity, body mass index, nonalcoholic hepatic steatosis, nonalcoholic steatohepatitis.

List of references:
1.    Drapkyna OM, Popova YP. The role of obesity in the development of hypertension and non-alcoholic fatty liver disease. Ukrainskyi medychnyi chasopys. 2013;2:125-128.
2.    Yvashkyn VT. The immune system and liver damage in chronic hepatitis B and C. Ros.zhurn hastroэnterol hepatol koloproktol. 2009;6:4-10.
3.    Lefkovyts Y, Pernys B. Immunology. Research methods. 1983:188-212.
4.    Nakaz MOZ Ukraїni. N 826. Unіfіkovanij klіnіchnij protokol pervinnoї, vtorinnoї (specіalіzovanoї) medichnoї dopomogi Nealkogolnij steatogepatit [Unified clinical protocol of primary, secondary (specialized) medical care "Nonalcoholic steatohepatitis"]. 2014.
5.    Nakaz MOZ Ukraїni. N 271. Pro zatverdzhennya protokolіv nadannya medichnoї dopomogi xvorim za specіalnіstyu gastroenterologіya [On approval of protocols of medical care to patients in the specialty of Gastroenterology]. 2005.
6.    Petrov RV,  Khaytov RM, Pynehyn VV. The immune status of the person in mass surveys: methodological recommendations for researchers and physicians healthcare practice. Ymmunolohyia. 1992;6:51-63.
7.    Sochner AM, Belchenko YE, Burshtein AM. Limfozitatoxic test as a method of identifying subpopulations of T-lymphocytes with monoclonal antibodies. Labdelo. 1989;3:29-32
8.    Filippova OIu. Excessive body mass and obesity as a cause of progression of endogenous intoxication in patients with non-alcoholic fatty liver disease. Zaporozhskyi medychnyi zhurnal. 2016;3(96):63-66.
9.    Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711-725.
10.    Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014;28(4):637-653.
11.    Toouli J, Fried M, Ghafoor KA. Obesity World Gastroenterology Organisation Global Guideline. 2009:30.
12.    Sydorchuk A, Boychuk T, Sydorchuk R, Sydorchuk L.  Immune and metabolic disorders in obese patients with hepatic steatosis and hypertension associate with PPAR-GAMMA2 PRO12ALA and ACE I/D genes’ polymorphisms. United European Gastroenterology Journal. 2015;1:59.
13.    Tison  GH, Blaha MJ, Nasir K.  Relation of Anthropometric Obesity and Computed Tomography Measured Nonalcoholic Fatty Liver Disease (from the Multiethnic Study of Atherosclerosis). Am J Cardiol. 2015 May 21. pii: S0002-9149(15)01336-3.

Objective — to estimate the frequency of subclinical manifestations of atherosclerosis, leptin levels and postprandial hypertriglyceridemia (PPG) in patients with coronary heart disease (CHD) in combination with non-alcoholic fatty liver disease (NAFLD), depending on the body mass index.
Materials and methods. The study involved 31 men with CHD combined with NAFLD, the control group consisted of 17 patients with CHD without NAFLD. The study group was divided into 3 subgroups according to BMI (subgroup 1  involved patients who are overweight, the 2 — obesity 1 degree, the 3 — obesity grade 2). The atherosclerotic changes of the neck vessels, endothelial function, PPG, leptin levels were evaluated.
Results and discussion. In the group of CHD patients with NAFLD, the point plaques were found significantly more often (in 19 % cases) with the significantly more violated endothelial function (lower by47 %, p = 0.01), than in the control group. In patients with grade 2 obesity identified the highest leptin levels (43.6 ± 20.2, p < 0.05), which is 44 % higher than in the subgroup with obesity 1 degree (24.4 ± 14.6, p < 0.05) and 63 % greater than in the subgroup with overweight. The highest increase in triglycerides after the fat loading test were revealed in the subgroup 1 (70 %) and in the control group (125 %).
Conclusions. In patients with coronary heart disease combined with NAFLD, the determination of leptin and PPG levels can be used as an additional risk factor for the atherosclerosis progression.

Keywords: coronary heart disease, non-alcoholic fatty liver disease, subclinical atherosclerosis, leptin levels, postprandial hypertriglyceridemia.

List of references:


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19.    Singhal A, Farooqi I S, Cole T J et al. Influence of leptin on arterial dispensability: a novel link between obesity and cardiovascular disease?. Circulation. 2002;106:1919-1924.
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Objective — to investigate the prevalence of age-related peculiarities and  severity of comorbid diseases in patients with osteoarthritis (OA) and to evaluate L-arginine efficacy in the complex treatment.
Materials and methods. The study involved 120 patients with OA, to whom the age-related peculiarities of the clinical manifestations of the main and diseases were investigated with the use of relevant protocols, as well as the pro- and antioxidant properties of blood, plasma fibrinolytic and proteolytic activity, and changes in the application in treatment of L-arginine.
Results and discussion. In the age group of patients with OA up to 50 years old, the low comorbidity levels and moderate cardiovascular risk (CVR) were defined, in the group of 51—60 years the high comorbidity level and CVR against the background of severe OA manifestations were observed, and after 60 years the prevalence of comorbid processes was similar but the clinical severity and CVR was higher with more considerable systematic joints’ lesions.
In patients aged  up to 50 years, only moderate disturbances of pro- and antioxidant blood systems were defined, and in patients older than 50 and especially older than 60 years, these disturbances and disorders of blood plasma fibrinolytic and proteolytic activity were progressively increased.
The administration of L-arginine in the complex treatment had a beneficial effect on the regression of symptoms of comorbid vascular diseases, it considerably reduced the effects of oxidative stress and violation of fibrinolytic and proteolytic blood activity.
Conclusions. For patients with osteoarthritis with the increasing age and the duration of illness, have intrinsic peculiarities, such as increase of the spectrum and intensity of comorbid pathologies, of the cardiovascular risk level,  as well as progression of biochemical manifestations of the oxidative stress and violations of fibrinolytic and proteolytic blood activity. The four-weeks administration of L-arginine resulted in the significant improvement of the general results of treatment, mainly due to the beneficial effects on the comorbid vascular diseases, as well as on the manifestations of oxidative stress and violations of fibrinolytic and proteolytic blood activity.

Keywords: osteoarthritis, comorbidity, oxidative stress, fibrinolytic, proteolytic activity of blood, L-arginine.

List of references:
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Objective — to investigate the dynamics of lipid metabolism parameters in patients with type 2 diabetes mellitus (DM) who have had non-Q-myocardial infarction (non-Q-MI) against the background of treatment with alpha-lipoic acid (ALA).
Materials and methods. The study involved 44 patients (27 men and 17 women, mean age (61.76 ± 1.43) years) with type 2 DM who have had non-Q-MI. The ALA preparation in a daily dose of 600 mg during 4 months was added to the basic treatment of patients. The determination of lipid metabolism parameters was performed before treatment and after its completion.
Results and discussion. Comparison of the baseline lipid metabolism parameters of the patients of  the control group (CG) of practically healthy individuals showed significantly higher levels of total cholesterol (T-Chol) (p < 0.001), triglycerides (TG) (p < 0.001), low-density lipoproteins cholesterol (LDL-Chol) (p < 0.001), very low density lipoproteins cholesterol VLDL-Chol (p < 0.001), atherogenecity coefficient (AC) (p < 0.001), Apo B (p < 0.001) and the ratio of Apo B/Apo A-1 (p < 0.001) in postinfarction patients with type 2 DM. Thus, it was observed significantly lower concentrations of HDL-Chol (p < 0.001) and protein Apo A-1 (p < 0.001) in comparison with CG.
The analysis of lipid parameters in patients with type 2 DM with a history of non-Q-MI after 4 months of using ALA showed the significant decrease in the levels of T-Chol (p < 0.05), LDL-Chol (p < 0.05) and the ratio of Apo B/Apo A-1 (p < 0.05). In addition, the positive tendency to reduction in TG (p < 0.2), VLDL-Chol (p < 0.2) and Apo B (p < 0.1) and a tendency to increasing concentrations of Apo A-1 (p < 0.2) has been established. No effects of ALA on the HDL-Chol and LP (a) levels were observed.
Conclusions. The use of ALA during 4 months in patients with type 2 DM who have had non-Q-MI, positively influenced on the lipid metabolism, reducing the blood atherogenicity.

Keywords: type 2 diabetes mellitus, non-Q-myocardial infarction, alfa-lipoic acid, lipids metabolism.

List of references:
1.    Kurmambaev Y, Chukanova G, Dworacka M. Influence of alfa-lipoic acid on 1,5-anhydruglucitol plasma level and fasting glycaemia in experimental type 2 diabetes mellitus (Rus). Sovremennaya meditsina: aktualnye voprosy [Modern medicine: current issues] (Rus). 2015;8-9(42):6-12.
2.    Khaidarova FA, Khojayeva NV, Rakhmanova KhA, Akhmedova MS. Antioxidants role in therapy of diabetic peripheral sensomotor polyneuropathy (Rus). Мezhdunarodnyi nevrologicheskii zhurnal [International neurological journal] (Ukr). 2010;8(38):24-28.
3.    Carling D., Mayer FV., Sandrs MJ., Gamblin SJ. AMP-activated protein kinase: nature’s energy sensor. Nat Chem Biol. 2011;7(8):512-518.
4.    Gomes MB, Negrato CA. Alpha-lipoic acid as a pleiotropic compound with other potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr. 2014;6:80. doi: 10.1186/1758-5996-6-80.
5.    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996;3(2):213-219.
6.    Hotta Y, Nakamura H, Konishi M et al. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. Endocrinology. 2009;150(10):4625-4633. doi: 10.1210/en.2009-0119.
7.    Jones W, Li X, Qu ZC et al. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free radical biology & medicine. 2002;33(1):83-93.
8.    Khabbazi T, Mahdavi R, Safa J, Pour-Abdollahi P. Effects of alpha-lipoic acid supplementation on inflammation, oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. J Ren Nutr. 2012;22(2):244-250. doi: 10.1053/j.jrn.2011.06.005.
9.    Koh EH, Lee WJ, Lee SA et al. Effects of alpha-lipoic acid on body weight in obese subjects. Am J Med. 2011;124:851-858. doi: 10.1016/j.amjmed.2010.08.005.
10.    Kralisch S, Fasshauer M. Fibroblast growth factor 21: Effects on carbohydrate and lipid metabolism in health and disease. Current Opinion in Clinical Nutrition and Metabolic Care. 2011;14:354-359. doi: 10.1097/MCO.0b013e328346a326.
11.    Lee WJ, Song KH, Koh EH et al.  Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochemical and Biophysical Research Communications. 2005;332:885-891.
12.    Masharani U, Gjerde C, Evans JL, Youngren JF, Goldfine ID. Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. J Diabetes Sci Technol. 2010;4(2):359-364.
13.    McCarty MF, Barroso-Aranda J, Contreras F et al.  The ‘‘rejuvenatory” impact of lipoic acid on mitochondrial function in aging rats may reflect induction and activation of PPAR-c coactivator-1a. Medical Hypotheses. 2009;72(1):29-33. doi: 10.1016/j.mehy.2008.07.043.
14.    Morakinyo AO, Awobajo FO, Adegoke OA. Effects of alpha lipoic acid on blood lipids, renal indices, antioxidant enzymes, insulin and glucose level in streptozotocin-diabetic rats. Biology and Medicine. 2013;5:26-33.
15.    Okanovic A, Prnjavorac B, Jusufovic E, Sejdinovic R. Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus. Med Glas (Zenica). 2015;12(2):122-127. doi: 10.17392/798-15.
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17.    Seo EY, Ha AW, Kim WK. α-Lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet. Nutr Res Pract. 2012;6(3):195-200. doi: 10.4162/nrp.2012.6.3.195.
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Objective — to study the peculiarities of endothelial dysfunction biochemical and instrumental markers in patients with gouty arthritis (GA).
Materials and methods. The study included 26 patients with GA, the control group consisted of 10 healthy individuals. The mean age of the patients was (60.8 ± 12.2) years, the duration of gout 7.0 [3.0—10.0] years. In all patients, the following markers were determined: von Willebrand Factor (vWF), Interleukin-1β (IL­-1), endothelin-­1 (ET­-1), the level of nitrite and nitrate in blood plasma, the total activity of NO-­synthase, FMD, NMD.
Results and discussion. The concentration of vWF in GA patients was significantly higher than the control group (75.7 [61.4—90.5] vs. 49.2 [30.4—62.2] %, p = 0.007) and in these patients was an increase in the level of IL-1 (1.58 [0.82—2.55] pg/ml, p = 0.02). The increase of ET-1 levels (1.58 mmol/ml vs. 0.339 mmol/ml in the control, p < 0.0001). NO-­synthase activity increased to 6.0 nmol/min ⋅ mg (versus 1.4 nmol/min ⋅ mg in the control group, p < 0.0001), and the NO2– concentration was increased to 10.9 mmol/l (reference value — 4.15 mmol/l. p < 0.0001), and of NO3– — to
17.5 mmol/l (reference value — 6.93 mmol/l, p < 0.0001). FMD and NMD in patients with GA did not differ significantly from the control group, showing a tendency to decrease.
Conclusions. Endothelial dysfunction in patients with GA is expressed predominantly in the significant increase in the synthesis of pro-inflammatory IL-­1, markers of endothelial damage vWF and ET-1 and the compensatory increase in NO-synthesis in the background of a slight decrease in reactivity of the brachial artery.

Keywords: gout, endothelial dysfunction, flow mediated vasodilation.

Objective — to evaluate the effectiveness of prolonged complex treatment of postimplantational atrial fibrillation (AF) atn nonischemic cardiac pathology in patients of older age categories with a cardiac pacemaker (CP) against the background of liposomal preparations administration, to determine the patients’ mortality and quality of  life, and dynamics of metabolic and inflammatory factors and the components of the vascular endothelial function.
Materials and methods. The examinations involved 387 patients aged 65 to 80 years with implanted CP, form them
46 (12 %) subjects (30 males and 16 females) suffered from nonischemic postimplantational AF. The time of AF onset since the CP implantation was up to 12 months. The patients-participants of the study had no signs of the coronary arteries stenotic atherosclerosis; the main indications for the cardiac pacemaker implantation were atrioventricular block of II or III degree, «tachy­brady» syndrome with syncopes, the presence of binodal block.
Results and discussion. The prolonged use of liposomal drugs, as the components of complex treatment programs, enabled significant reduction of the frequency and the duration of AF paroxysms after the CP implantation in patients of older age categories due to positive pathogenic effects which are directed to metabolic and inflammatory changes and vascular endothelial dysfunction. Phosphatidylcholine and quercetin promoted the improvement of the state of cardiovascular system and quality of life of elderly patients with postimplantational AF, and to gain the overall effectiveness of both immediate and remote results of treatment, to slowdown the rates of the progression of chronic heart failure, and to reduce the frequency of patients’ admissions and mortality.
Conclusions. Liposomal drugs are highly effective in patients of older age groups with postimplantational AF and they should be administered in addition to the main drug treatment (amiodarone, beta­blockers, angiotensin-converting enzyme inhibitors, sartans, statins).
Prospects for further research: The evaluation of liposomal drugs’ efficacy in the elderly patients with nonischemic cardiac pathology is advisable before the pacemaker implantation. Further investigations of the pathogenetic action of these therapeutic agents in this category of patients are required to define the lipids’ metabolism, the activity of anti­inflammatory cytokines, the rheological properties of blood, synthesis of vasodilators’ in the body, associated with the vascular endothelial function, etc.

Keywords: atrium, fibrillation, age, treatment, effectiveness.

List of references:
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2. Diaduk AY, Bahryi AЕ. Serdechno-sosudystue zabolevanyia u pozhylukh. K.: Liudy v belom, 2013:170.
3. Zharinov OI, Levchuk NP. Klinichni kharakterystyky ta liku­vannia khvorykh iz persystentnoiu fibryliatsiieiu peredserd. Sertse i sudyny. 2013;4;122-130.
4. Kovalenko VM Diahnostyka ta likuvannia fibryliatsii peredserd. K.: Morion, 2015:158.
5. Skychbyk VA, Melen Iu. P. Fibryliatsiia peredserd: suchasni pidkhody do profilaktyky tromboembolichnykh uskladnen. Liky Ukrainy. 2015;186(1):14-16.
6. Aydin U, Yilmaz M, Duzyol C et al. Efficiency of postoperative statin treatment for preventing new onset postoperative atrial fibrillation in patients undergoing isolated coronary artery bypass grafting: a prospective randomized study. Anat J Cardiol. 2014;12(1):10-14.
7. Crosato M, Calzolari V, Franceschini E et al. Implanting cardiac rhythm devices during uninterrupted warfarin therapy: a prospective, single center experience. J Cardiovasc Med. 2015;16(7):503-506.
8. Dagres N, Liodromitis EK, Lekakis JP et al. Ranolazine for the prevention or treatment of atrial fibrillation: a systematic review. J Cardiovasc Med. 2014;15:254-259.
9. Korantzopoulos P, Liub T. RDW as a marker of postoperative atrial fibrillation. Int J Cardiol. 2015;191(3):109-116.
10. Kosiuk J, Koutalas E, Doering M. et al. Comparison of dabigatran and uninterrupted warfarin in patients with atrial fibrillation undergoing cardiac rhythm device implantations. Case-control study. Circ J. 2014;78(1):2402-2407.
11. Krishnamoorthy S, Khoo CW, Lim HS, Lip GY Predictive value of atrial high-rate episodes for arterial stiffness and endothelial dysfunction in dual-chamber pacemaker patients. Eur J Clin Invest. 2014;44(1):13-21.
12. Matusik P, Woznica N. Atrial fibrillation before and after pacemaker implantation (WI and DDD) in patients with complete atrioventricular block. J Pol Merkur Lekarski. 2010;28(67):345-349.
13. Perez-Vizcaino F, Duarte J. Flavonols and cardiovascular disease. Mol Aspects Med. 2010;31(6):478-494.
14. Quirino G, Giammaria M, Corbucci G et al. Diagnosis of paroxysmal atrial fibrillation in patients with implanted pacemakers: relationship to symptoms and other variables. Pacing Clin Electrophysiol. 2009;32(1):91-98.
15. Ruiz-Esparza G.U, Flores-Arredondo J.H, Segura-Ibarra V. The physiology of cardiovascular disease and innovative liposomal platforms for therapy. Int J Nanomedicine. 2013;8(1):629-640.
16. Schiener M, Hossann M, J. Viola R. et al. Nanomedicine-based strategies for treatment of atherosclerosis. Trends Mol Med. 2014;20(5):271-281.
17. Silva R, Pereira T, Martins V. Effectiveness of atrial antitachycardia pacing in the treatment of paroxysmal atrial fibrillation in patients with pacemakers. Rev Port Cardiol. 2014;33(2):781-788.
18.    Xue-Jun R, Zhihong H, Ye W. et al. A clinical comparison between a new dual-chamber pacing mode-AAIsafeR and DDD mode. Am J Med Sci. 2015;339(2):145-147.
19.    Yedlapati N, Fisher J.D. Pacemaker diagnostics in atrial fibrilla­tion: limited usefulness for therapy initiation in a pacemaker practice. Pacing Clin Electrophysiol. 2014;37(9):1189-1197.
20.    Zannad F, McMurray JJ, Drexler H et al. Rationale and design of the eplerenone in mild patients hospitalization and survival study in heart failure. Eur J Heart Fail. 2013;12:617-622.

Objective — to create a simplified model for assessment of the long-term unfavorable outcome for the patients  after Q-wave myocardial infarction (MI), to whom troponin diagnostics was not performed.
Materials and methods. The registry STIMUL (ST Elevation Myocardial Infarction in Ukraine and Its Mortality Rate) included 1103 patients with acute coronary syndrome (ACS) with ST segment elevation, admitted in the cardiological in-hospital departments (3 sites) on the 1st day of the acute MI. The data processing was performed with the use of software Microsoft Excel and SAS 9.1 for Windows 2000. The difference with < 0,05 was considered as statistically significant.  
Results and discussion. Due to the fact that troponin diagnostics was performed only in 17.1 % of patients, the simplified scale of the stratification of two year mortality was created, that did not require the detection of the cardio-specific markers. The possibility of lethal outcome prognosis with the use of simplified model for the two year after the previous Q-wave MI remained significant (с­statistic 0.9 % (р <0.001). However, the detection of cardiospecific markers increased the informational value of the model by 10.7 %.  
Conclusions. The simplified scoring system for predicting of the two year mortality can be applied for patients after Q-wave myocardial infarction, to whom troponin diagnostics was not performed. With this,   the exclusion of troponin detection from the scale declined the informational value of the model by 10.7 %.  

 

Keywords: Q-wave myocardial infarction, registry, troponin I, simplified score, two year mortality.

List of references:
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Objective — to improve the diagnosis of nosocomial pneumonia (NP) based on the investigation of the indicators of blood serum cytokine profile in NP patients against the background of traumatic brain injury (TBI), and in patients with isolated TBI.
Materials and methods. The study involved 40 patients with NP against the TBI background and 45 patients with isolated TBI. The control group included 35 relatively healthy people.
Results and discussion. The increase of cytokine level was revealed in the in the comparison group vs. healthy individuals was statistically significant (p < 0.0001), but significantly lower than in the main group. Increase of all cytokines in the main group was significantly higher than in the comparison group (p < 0.0001).
Conclusions. The significant increase in the serum levels of TNF-α, IL-6, IL-8, IL-10 was established in patients with NP against after the TBI. The quantitative changes in the serum interleukins levels in NP patients against the background TBI allow the use of these markers as additional laboratory criterion in the specifying of NP diagnosis in patients with TBI.

Keywords: nosocomial pneumonia, traumatic brain injury, diagnosis, cytokines.

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This article presents generalized data on the relationship between subclinical hypothyroidism (SH) and non­alcoholic fatty liver disease (NAFLD) and the risk of origin cardiovascular complication from comorbid condition of the patients. The role of early predictors of cardiovascular complications has been examined, that can develop in patients with SH  and NAFLD, that is adipocytokines, dyslipidemia, some inflammatory marker (CRB), vascular ageing marker: telomerase activity and dysfunction marker — vascular endothelial factor. It gas been shown that investigation of patients with hormonal and metabolic predictors and vascular markers SH combined with NAFLD, will expand the understanding of the mechanisms of cardiovascular risk formation and will help to make the early diagnostics, individuate approach to the cardiovascular prophylaxis in this category of patients.

Keywords: cardiovascular risk, non­alcoholic fatty liver disease, subclinical hypothyroidism, risk factors.

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25. Targher G. Relationship of hepatic steatosis and alanine aminotransferase with coronary calcification. Clin Chem Lab Med. 2011;49(4):741.
26. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363(14):1341-1350.
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The author presents review of recent data that reveal the mechanisms of miRNAs action, methods of determining, the role of individual miRNAs representatives in aging, cardiovascular biology, diseases of lung, liver and gastrointestinal tract, diabetes mellitus and pathology of kidney. The review includes peculiarities of about 70 miRNA representatives, as well the evaluation of the use of miRNAs as biomarkers for internal diseases prognosis, that can contribute to the individual approach and improvement of a patient’s outcomes.

Keywords: microRNA, methods of determining, aging, diseases of lung, heart, liver, kidney, gastrointestinal tract, diabetes mellitus.

List of references:


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