[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.

[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 α (TNF-α), 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-α 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-a, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1ß 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.

[Serum markers of fibrosis and endothelial dysfunction in patients with alcoholism, with varying degrees of liver fibrosis].

In the serum of patients with alcoholism with varying degrees of severity of liver fibrosis were studied the content markers of fibrosis, endothelial dysfunction and proinflammatory cytokines. Concentration in blood indicators of fibrogenesis--collagen type 4, hyaluronic acid, TIMP-1, TIMP-2, YKL-40 and MMP-2 is considerably increased at the 4 degree of fibrosis and moderately increased at low and zero degrees of liver fibrosis. Similar results were obtained in respect of proinflammatory cytokines Il-6, IL-8, IL-12/p70 and IL-12/p40. The magnitude of endothelial dysfunc- tion, calculated based on its content in the blood markers--VEGF-A, MCP-1, s-VCAM, s-ICAM and endothelin, was maximal at 4 degrees of fibrosis and less pronounced at low degrees of fibrosis. Correlations between of the average degree of fibrosis, endothelial dysfunction, and blood levels of proinflammatory cytokines were installed. Close relation between the immune cells releasing stimulators of inflammation and fibrogenesis, perisinusoidal fat cells producing collagen, and endothelium secreting vasoconstrictors in the pathogenesis of alcoholic liver fibrosis and cirrhosis was installed.

[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.

[Mechanisms of the liver anti-endotoxin defence].

Current knowledge of immunocellular and lipoprotein mechanisms of the liver-induced anti-endotoxin tolerance has been summarized. The role of T regulatory cells, different macrophage phenotypes, high density lipoproteins, oxidized low density lipoproteins and their receptors as the key players in mechanism of tolerance to endotoxin has been discussed.

[Disorders in the immune status and hepatic pathologies in young heroin addicts]. / Narusheniia immunnogo statusa i patologiia pecheni u mologykh potrebitelei geroina.

The immunocytograms of 166 patients with opiomania, primarily of the heroin variation, aged 15 to 19, were examined. 18 healthy teenagers of the same age were in the control group. The sampling comprised both patients without any signs of infectious diseases (86 persons) and patients with viral hepatitis B and C. The deviations of the immune-cellular status comprised, in drug addicts, a deficit of T-helpers and NK-cells as well as an increased quantity of "zero" lymphocytes. An essential reduction in the level of T-suppressors (killers) was additional found in the group of drug-addicts with viral hepatices. The signs of cytolysis of hepatocytes were detected in young heroin addicts. The contents of lipid peroxides was significantly higher in the blood plasma of teenagers abusing the opium drugs; while the concentration of antioxidant factor was as follows: Vitamin E, sulfhydric proteins and urate were found to be decreased. A reliable correlation was found between the changes of the quantity of T-helpers, T-suppresses (killers) and 0-lymphocytes, on the one hand, and the activity of hepatic transaminases, on the other hand, (for AST = 0.65-0.70; p < 0.01). The disorders in the immune-cellular status persist for as long as three to four weeks after the refusal from drug consumption; it is noteworthy, that their severity can essentially go up. The activity of 5'-nucleotidase, involved in the transformation of receptor signals in T- and B-lymphocytes, was histochemically studied in immunocytes. The activity of the enzyme essentially went down in both populations of lymphocytes by the 7th day of abstinence; it remained at the mentioned level up to the 14th day (in patients with hepatitis) or up to 21st day (in patients without hepatitis). Therefore, the quantitative deficit of immunocytes in drug addicts was accompanied, during the abstinence period, by an inhibition of their functional activity.

[Quantitative changes in peripheral blood thrombocytes in chronic alcoholics and experimental alcoholic intoxication in animals]. / Kolichestvennye izmeneniia trombotsitov perifericheskoi krovi u bol'nykh khronicheskim alkogolizmom i pri éksperimental'noi alkogol'noi intoksikatsii zhivotnykh.

The time course of changes in peripheral-blood platelet count was examined in 129 alcoholics and 22 alcohol-intoxicated rats. The data obtained point to the existence of cause-and-effect relationships between the thrombocytopenia and thrombocytosis observed in various periods of abstinence on the one hand, and blood coagulation disturbances manifesting themselves in the forms of hemorrhages, thromboses and embolism, on the other.

[Bone marrow plasma cell reaction in alcoholic patients]. / Plazmakletochnaia reaktsiia kostnogo mozga u bol'nykh alkogolizmom.

A study of plasmocellular reactions of the bone marrow in alcoholism and alcoholic psychoses demonstrated an increase in the amount of plasmatic cells, a prevalence of mature plasmatic elements with distinctly marked basophilia and a reaction of clasmatosis. These facts indicate the functional preservation in alcoholism of the system of B cells, the derivatives of which are plasmatical elements; of an increase in the protein synthesis (including antibodies) as well as a prevalence of the so-called productive phase of immunogenesis over the adaptive.

[Effect on the whole alimentary starvation on DNA synthesis in cells precursors in human bone marrow]. / Sintez DNK v rodonachl'nykh kletkakh kostnogo mozga pri golodanii.

The rate of DNA synthesis in cells precursors of the bone marrow of 15 psychic patients was studied by tritiated thymidine autoradiography during different periods of whole alimentary starvation (duration 28 days) which was used with the aim of therapy. It was shown that starvation induced rapid, "leap", "uneven" block of DNA synthesis and decrease in mitotic index. It was found that DNA synthesis block was marked with different degree in different marrow cells. It was supposed that DNA synthesis block occured mainly during G1--S period of interphase. During the initial period of refeeding, intensification of DNA synthesis, which preceded to sharp increase in mitotic index, was observed.