[Changes in the receptor activity of ß2-adrenoreceptors of human T-lymphocytes under the effect of ß2-agonists].

Changes in the activity of ß2-adrenergic receptors of human T-lymphocytes under the effect of salbutamol (a short-acting ß2-agonist) have been evaluated with a new modified radioligand method utilizing [^(125)I]cyanopindolol and a specific ligand ICI 118551. In healthy volunteers, the receptor activity decreased after 30 min upon the inhalation of salbutamol and restored to the initial level after 2 h. At the same time, there were changes in the transcription level of the ADRB2 gene, which encodes the protein component of the ß2-adrenoreceptor. The dynamics of ß2-adrenergic receptor activity of T-lymphocytes after salbutamol treatment in patients with cardiorespiratory pathology significantly differed from that in healthy volunteers.

[Detection of Autoantibodies Against the 1-Adrenergic Receptor in the Sera of Patients via the Competitive cell-Based Enzyme Linked Immunosorbent Assay].

OBJECTIVE: This study aimed to assess the level of anti-1-adrenergic receptor autoantibodies in patients with ventricular arrhythmias with no signs of organic heart disease and with presence of cardiovascular pathology in comparison with a group of healthy volunteers. MATERIAL AND METHODS: The study included 44 patients with ventricular arrhythmias with no signs of organic heart disease ("idiopathic"), 34 patients with diagnosed dilated cardiomyopathy (DCM) of inflammatory origin, 35 patients with coronary heart disease and ventricular arrhythmias, 12patients with coronary heart disease with no ventricular arrhythmias, and 19 healthy volunteers (control group). The level of autoantibodies against the 1-adrenergic receptor was determined by the developed competitive cell-based enzyme-linked immunosorbent assay (ELISA) and by the standard ELISA using peptides corresponding to the second extracellular loop of the 1-adrenergic receptor. RESULTS: Elevated level of autoantibodies detected by a competitive cell-based ELISA was observed in 62% of patients with DCM compared to 21% of healthy volunteers (p=0.0006). In patients with "idiopathic" ventricular arrhythmias, the level of 1-adrenergic receptor autoantibodies was lower than in healthy subjects (p=0.003). Coronary heart disease patients with or without ventricular arrhythmias exhibited no differences from the control group. The number of significantly positive signals in peptide-based ELISA did not exceed 10% in any of the groups. No correlation between the data from competitive cell-based ELISA and peptide-based ELISA was found. CONCLUSIONS: This study demonstrated that competitive cell-based ELISA technique can be applied for detection of 1-adrenergic receptor autoantibodies. The results in DCM patients generally correspond to the expected. Decreased level of autoantibodies in patients with "idiopathic" ventricular arrhythmias indicates that this disease is related to changes in the immune system. Such relation is not observed in the case of coronary heart disease patients.

[Biomarkers in Heart Failure: Apelin Level Is Not Associated With Presence and Severity of the Disease].

We tested possibility of the use of apelin-12 as a biomarker of chronic heart failure (CHF). The study comprised 108 patients with I-IV functional class CHF of various etiology (ischemic heart disease, dilation cardiomyopathy) and 40 healthy volunteers. Blood samples were taken at hospital admission before prescription of pharmacological therapy. In all patients we carried out echocardiography with calculation of end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF). Blood plasma apelin-12 concentration was compared with CHF market NT-proBNP. Mean apelin-12 concentrations were 0.86 ± 0.22 hg/ml in healthy volunteers and 0.8±0.35, 0.81 ± 0.29, 0.68 ± 0.38, 0.82 ± 0.35 hg/ml in patients with CHF classes I, III, III, IV, respectively. There was no significant differences between appelin-12 concentrations in various classes of CHF. No correlations were found between apelin-12 and EF, EDV, ESV, sex, age, smoking, body mass index, and NT-proBNP level. Concentration of NT pro-BNP level correlated with CHF severity. Thus apelin-12 did not show itself as reliable biomarker of CHF.

[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

[The analysis of amount of matrix metalloproteinase 1 precursor, metalloproteinase 1 tissue inhibitor and cystatin C in the bronchoalveolar secretion of patients with nonspecific lung diseases].

The proteinases and their inhibitors participate in the inflammatory process. The damage of lung tissue can be a result of proteinase activity. This activity is regulated by such inhibitors as metalloprvteinase 1 tissue inhibitor and cystatin C. The comparative analysis was applied concerning matrix metalloproteinase 1 precursor; metalloproteinase I tissue inhibitor and cystatin C--indicators of conditions of the "proteolysis-antiproteolysis" system in the bronchoalveolar secretion of patients with chronic obstructive lung disease, bronchial asthma and pneumonia. In the group of patients with chronic obstructive lung disease, in contrast with other groups, the significant increase of proteinase inhibitors was not detected on the tenth day of treatment after exacerbation of disease. This fact testifies the ongoing proteolytic activity and chronic inflammation under chronic obstructive lung disease.

[The study of peculiarities of immunotropic action of statins in chronic heart failure of various etiology].

AIM: To study features of statin therapy in patients with heart failure (HF) of different etiology on immune system. MATERIAL AND METHODS: The basic markers of immune activation in 43 patients with chronic heart disease (CHD) and HF in New York Heart Association (NYHA) class I to IV were studied. Mine age was 48 +/- 8 years (from 33 to 64 years). 43 patients with dilated cardiomyopathy (DCM) and HF were also observed. Mine age was 43 +/- 10 years (from 22 to 61 years). Parameters of systolic and diastolic left ventricle (LV) function were measured. Also non invasive methods for evaluation of endothelial function were used. Concentrations of hsCRP, IgG, IgA, IgM were measured using commercially available kits. IL 6, IL 8, sIL 2R, IL 18, IL 10, IFN Y, endothelin levels were measured using enzyme linked immunosorbent assay method. RESULTS: Statin therapy has immunomodulation effect in patients with heart failure any etiology. This effect depends on etiology of HF. In CHD patients the decreasing of IFN Y, IL 8, sIL 2R, hsCRP and increasing of IL 18, IL 6 levels were observed. In DCM patients the decreasing of IL 8, IL 18, sIL 2R and increasing of IL 10 were observed. There was significant clinical improving in patients with DCM and HF after statin therapy. But there were no changes of endothelial function in patients with CHD and DCM. There were no changes of LV function in patients with CHD. So statin therapy may reduce level of proinflammatory mediators but not fully control inflammation process in patients with HF of different etiology.

[Comparative dynamics of markers of inflammation and NT-proBNP in different variants of treatment of patients with ACS].

STUDY AIM - assessment of dynamics of markers of inflammation (CRP, Il-6, Il-10, TNFa, CD40L, fibrinogen) and N - N in acute coronary syndrome (ACS) as well as analysis of effect of various methods of treatment on level of these parameters. Patient aged 30 - 70 years were included in the study: 52 patients with ACS with ST-segment elevation (STEACS) and 61 - without ST-segment elevation (NSTEACS). Initial level of markers of inflammation (Il-6, CRP) in STEACS was lower than in NSTEACS. Initial level of antiinflammatory Il-10 was significantly higher in patients in the STEACS group (72.6 +/- 39.1 and 6.6+4.2 pg/ml, < 0.01). At admission the highest values of N - N were noted in the group of NSTEACS (761.5 pg/ml compared with 451.1 pg/ml in STEACS, =0.04). During period of hospitalization elevation of N - N occurred in the group of STEACS while its lowering occurred in the group of NSTEACS. In STEACS patients with early restored coronary blood flow dysfunction of the myocardium was less pronounced (lower level of N - N ). In patients with NSTEACS during period of hospitalization levels of CRP, Il-6 fibrinogen lowered. In invasively treated patients with NSTEACS levels of CRP and fibrinogen lowered to a greater extent than in conservatively treated.

[Immunity in chronic bronchitis patients with significant residual changes after prior pulmonary tuberculosis].

To study the immunological features in chronic bronchitis (CB) patients with great residual changes (GRC) after prior pulmonary tuberculosis, the authors examined two groups: 1) 40 CB patients with GRC after prior pulmonary tuberculosis (a study group) and 2) 30 CB patients without a history of pulmonary tuberculosis. The examination revealed that CB patients with GRC after prior pulmonary tuberculosis were found to have higher T lymphocytes, lower B lymphocytes on an exacerbation of the disease. The phagocytic properties of neutrophils were altered as their high phagocytic activity, decreased oxygen-dependent microbicidal activity of phagocytes with their stimulation. The humoral response remained to be slightly pronounced in CB bronchitis with GRC. The low serum levels of TBC active products may suggest the low activity of lipid peroxidation processes in the study group patients. After prior pulmonary tuberculosis, antioxidative activity preserves to be high in CB patients with GRC.

[Effect of therapy with rosuvastatin on lipid spectrum, factors of inflammation and endothelial function in patients with ischemic heart disease].

Rosuvastatin (10 mg) was given for 3 months to 30 men (mean age 57+/-9 years) with total cholesterol (CH) above 5.2 mmol/l. Questioning, physical examination, registration of ECG, measurement of levels of total, low density lipoprotein (LDL), high density lipoprotein (HDL) CH, and triglycerides (TG), assessment of endothelium-dependent brachial artery dilation were carried out at baseline and in 3 months. It was noted that 3 months therapy with rosuvastatin exerted positive effect on blood lipid spectrum: lowering of concentration of total CH (-31%, baseline 6.52+/-0.92, after therapy 4.47+/-0.96 mmol/l, p<0.0001), TG (-39%, baseline 2.73+/-1.56, after therapy 1.67+/-0.71 mmol/l, p<0.001), LDLCH (-44%, baseline 4.11+/-0.85, after therapy 2.40+/-0.90 mmol/l, p<0.0001), elevation of HDLCH (+6%, baseline 1.15+/-0.27, after therapy 1.22+/-0.34 mmol/l, p=0.08). Target LDL CH level (<2.6 mmol/l) was achieved in 23 patients (77%). Significant lowering of concentration of C-reactive protein (CRP) (-56%) and interleukin 6 (-25%) was also established. Before beginning of therapy mean flow dependent dilation was 6.1+/-1.64%, after therapy -- 10.4+/-5.0% (p<0.05). Treatment of men with ischemic heart disease with rosuvastatin (10 mg for 3 months) led to achievement of target values of LDLCH in 77% of them, to significant lowering of concentrations of CRP and interleukin 6, and to improvement of endothelial function.

[Diagnostic and prognostic value of antioxidant enzyme assay in erythrocytes of patients with end stage renal disease treated with hemodialysis].

Anemia is one of the main complications seen in patients with end stage renal disease (ESRD) treated with hemodialysis. We hypothesized that oxidative stress and decrease of antioxidant defense enzyme activity may be major causes underlying functional insufficiency of erythrocytes. Blood samples of 16 patients with ESRD undergoing hemodialysis were investigated. All patients received Recormon for treatment of anemia. In spite of effective hemodialysis procedures cleared patient blood the erythrocyte activities of superoxide dismutase (SOD), glutathione peroxidase (GP) were lower than in healthy controls and hemodialysis procedure insignificantly influenced enzyme activities. After 6 months repeated study of the erythrocyte enzymes revealed further decrease of SOD and GP activities.

[Determination of the low protein concentration in biological fluids. Methodological aspects (the use of mathematical analysis)]. / Metodicheskie aspekty laboratornogo opredeleniia nizkikh konsentratsii belka v biologicheskikh zhidkostiakh (opyt primeneniia matematicheskogo analiza).

We investigated the effect of albumin/globulin ratio on the analytic error of protein determination. Several methods were used: Bradford, Lowry, pyrogallol-red, biuret, and sulfosalicylic acid. Reagents used in Lowry method exhibit higher affinity to globulins, whereas reagents used in other methods have higher affinity to albumins. Although the biuret method demonstrated equal efficiency in determining concentrations of various proteins low sensitivity of this method limits its clinical applicability. For other methods there was non-linear dependence of the analytic error on protein composition in the sample. Combination of two methods for protein determination (using one calibrator) completely removes the analytic error.