[The role of lipoprotein-associated enzyme paraoxonase 1 and its polymorphisms in the pathogenesis of endothelial dysfunction and somatic complications in patients with alcoholism: Review ].

A review of recent data on the role of the multifunctional enzyme, associated with high density lipoproteins - paraoxonase 1 (PON1) in maintaining healthy endothelial function by detoxifying both oxidized low density lipoproteins and homocysteine thiolactone. The additional contribution to the protection of the endothelium against damage makes organophosphatase activity of PON1 involved in the detoxification products of tobacco smoke. The reduction of antioxidant activity of PON1 promotes the differentiation of monocytes into macrophages and the development of inflammation. The reduction of thiolactonase activity of PON1 is accompanied by a decrease of methionine re-synthesis from homocysteine causing DNA- hypomethylation and alteratioin of the expression patterns of pro- and anti-atherogenic genes. Global hypomethylation of the genome is regarded as one of the three most important mechanisms of the increased risk of somatic complications of alcoholism. The accumulation of homocysteine thiolactone serving agonist of glutamate receptors and antagonist of dopamine receptors is a prerequisite to increased alcohol abuse. Clinical observations focusing on gene polymorphisms of PON indicate that three different genotypes of polymorphism PON1Q192R have unequal degrees atheroprotective properties.

Estimation of Functional Activity of Ionized Calcium for Complement System Reactivity Assessment.

We proposed a new indicator for evaluation of functional activity of Ca(2+) in human blood serum based on lysis of sheep erythrocytes with 10% human blood serum in the presence of 0.55 mM ethylene glycol tetraacetic acid at 37°C for 10 min. After incubation, the degree of sheep erythrocytes lysis inhibition is estimated: inhibition of complement hemolytic activity <30% is considered as high functional Са(2+) activity, inhibition by 31-70% corresponds to normal activity, and >71% indicates low activity. The comparative studies of complement activating function of heterophilic antibodies, complement system reactivity in the presence of 0.29 M NaCl, and functional activity of ionized Ca(2+) make possible estimation of the individual's immune status.

[Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n=45) and IHD (n=17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD - with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor (TNF-), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF- and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1 and factors of acute phase of inflammation did not reflect severity of CHF. Functional insufficiency of myocardium in IHD patients was best characterized by blood content of IL-6 while in ACMP patients - of BNP.

[A method of rapid determination of cholesterol in immune complexes].

A method of rapid determination of cholesterol in immune complexes (CIC). In the proposed method precipitate immune complexes containing multiple modified low density lipoproteins from human serum are prepared by treatment with a buffer containing 8.3 PEC 3350, and 3.3% PVP 12600, in a ratio of 1:1.2, incubated for 10 min at room temperature. The precipitate containing the CIC is separated by centrifugation at 3100 g for 5 min at 23 degrees C, dissolved in a buffer without PEG and PVP, the cholesterol is determined using an enzymatic kit and at a level of CIC more than 8.3 mg/dl ascertain higher level. The method improves the accuracy of the quantitative determination of CIC, conduct extensive screening tests to detect atherosclerosis as the pre-clinical stage and monitor the effectiveness of the therapy.

[Rapid assessment of the complement system reactivity].

The authors developed a new indicator of humoral immunity, which characterizes the complement system reactivity (CSR). Complement system reactivity has been investigated in haemolytic assay using sheep red blood cells, autologous heterophile antibodies and complement in a "load" as 0.29 M NaCl in the system. There has been made a study of blood sera of 10 healthy donors and 20 patients who undergo screening for chronic infections in clinical-diagnostic centers. Inhibition of complement--0.29 M NaCl at a level of 30-70% in healthy donors is taken as an indicator that characterizes normal complement system reactivity of a human serum. Investigations have revealed in 11 patients (55%) of the 20 examined people high complement system reactivity (lysis degree more than 70%), in 6 patients (30%)--normal complement system reactivity, and in 3 patients (15%)--low complement system reactivity (lysis degree less than 30%). Thus, the study of the complement system reactivity in a "load", in the presence of 0.29 M NaCl in the test sample, detects functional changes, both reinforcing and reducing complement activity.