[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.

[Oxidative stress in the of alcoholic liver disease].

Parameters reflecting oxidative stress (OS) have been studied in 37 patients with alcoholic liver disease (ALD) during admission to the hospital and 2 weeks after the beginning of therapy. The patients were divided into 3 groups: alcoholic hepatitis (AH), alcoholic cirrhosis with hepatic insufficiency (the group C with Child-Paquet) and terminal stage patients (they subsequently died). All patients were characterized by a significant increase in plasma products of lipid peroxidation (conjugated diene and malondialdehyde) and decrease of the ceruloplasmin level. The coefficient K OS significantly exceeded normal values both on admission and after the 2-week course of traditional treatment. This suggests an important role of the OS with ALD.

[A simple method for quantification of modified low-density lipoproteins].

A simple method for quantification of modified low-density lipoproteins (mLDL) in the blood serum containing 8.9% polyvinylpyrrolidone solution 12600 +/- 2700 has been developed. The results show that 10 min incubation of serum in a buffer containing 8.9% PVP leads to complete aggregation mLDL. Atherogenicity of aggregated mLDLs is experimentally confirmed by two independent tests (mLDLs bind and activate the complement system of a guinea pig (pro-inflammatory effect) and cause platelet hyperaggregation (thrombogenic effect)). The proposed method is simple and involves only two steps: mixing the serum with a solution of PVP and recording the turbidity. The method allows to register the presence of mLDL directly in serum without its prior fractionation.

[Effects of morphine withdrawal on the indices of free radical homeostasis and nitric oxide system in rat liver and thymus]. / Vliianie sindroma otmeny morfina na pokazateli svobodnoradikal'nogo gomeostaza i sistemu oksida azota v pecheni i timuse krys.

Indices of oxidative stress, nitric oxide (NO) metabolism as well as the activity of caspase-3, an important enzyme of apoptotic cell death, were measured during the morphine withdrawal syndrome in liver and thymus of rats. Male Wistar rats were administered with morphine hydrochloride (i.p., at increasing doses from 10 to 100 mg/kg, twice a day, for 6 days). Thirty-six hours after the last administration the withdrawal syndrome was monitored using the specific autonomic and locomotor indices. During this period, weights of body and thymus significantly decreased. Oxidative stress in liver was accompanied by an increase in aspartate aminotransferase and gamma-glutamyl transferase in blood serum. No signs of oxidative stress could be demonstrated in thymus. The activity of the Ca(2+)-dependent isoform of nitric oxide synthase (NOS) in liver increased, while, the activity of the Ca(2+)-independent NOS diminished, the total activity of NOS in liver and thymus remained unchanged. The concentration of nitrates/nitrites in blood was decreased, in thymus increased, and in liver unchanged. Caspase-3 activity changed neither in liver, nor in thymus. The results are discussed from the perspective of possible antioxidant and antiapoptotic role of NO during morphine withdrawal syndrome.

[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.

[Lipid peroxidation, peroxyl radical-scavenging system of plasma and liver and heart pathology in adolescence heroin users]. / Perekisnoe okislenie lipidov, sistema antiperoksil'noi zashchity plasmy krovi i patologiia pecheni i serdtsa u podrostkov, zloupotrebliaiushchikh geroinom.

Chronic opiate intoxication has been shown to cause various pathologic changes in the liver almost in 100% of cases. Earlier it has been demonstrated that acute or chronic morphine intoxication evokes activation of lipid peroxidation in the liver, heart, and brain cells. The aim of the present work was to assess parameters reflecting cytolysis in the liver and heart, and the plasma content of factors contributing to the peroxyl radical-scavenging system of the blood of teenagers using heroin. Blood samples were obtained from 20 male patients from 14 to 16 years old, with a mean duration of regular heroin use of 1.7 years. The control group included 13 healthy teenagers which denied the previous drug use. Mean plasma ALT and myocardial isoform of LDH activities were significantly higher (1.7- and 1.4-times respectively) in the heroin users than in the control group. The mean plasma level of lipid peroxides in the heroin users is increased by 20% compared to the control individuals. In teenagers using heroin a high level of correlation was observed between the plasma content of lipid peroxides and myocardial LDH activity (r = 0.76; P < 0.01). The effect of heroin use on the content of the plasma peroxyl radical-scavenging factors--vitamin E, ascorbic acid, and protein SH-groups--was not found. It has been concluded that heart injury during heroin use in teenagers may be associated with activation of lipid peroxidation reactions in the myocardium.

[Some features of enkephalin metabolism in the rat brain after administration of bestatin]. / Nekotorye pokazateli metabolizma énkefalinov v golovnom mozge krysy posle vvedeniia bestatina.

The effect of a single bestatin dose on enkephalin content, activities of enkephalin convertase, enkephalinase A and aminopeptidases as well as on the level of specific binding of (3H) (D-Ala-2,D-Leu-5)enkephalin in rat midbrain (including hypothalamus) and striatum has been studied. Using ANOVA and correlation analyses, the relationship between the changes in these parameters has been established. The different responses of the enkephalin system of rat brain seem to be due not only to differences in the ratios of the "enkephalinase" and "aminopeptidase" pathways of enkephalin catabolism but, also, to structural peculiarities of enkephalin-containing conduction tracts.

[Role of aminopeptidases in enkephalin catabolism: comparative study of the regional distribution of aminopeptidases and enkephalinase A in the rat brain]. / K voprosu o roli aminopeptidaz v katabolizme énkefalinov: sravnitel'noe issledovanie regional'nogo raspredeleniia aminopeptidaz i énkefalinazy A v golovnom mozge krysy.

In order to elucidate the role of aminopeptidases in enkephalin catabolism in rat brain, the local distribution of two types of cerebral cellular membrane aminopeptidases (puromycin-sensitive and puromycin-insensitive ones) and of the enkephalin system marker, enkephalinase A, was studied. It was found that the distribution patterns of the former enzymes differ essentially from that of enkephalinase A. Study of coupling between the enzymatic activities in different regions of rat brain revealed a strong correlation between the activities of puromycin-insensitive aminopeptidase and enkephalinase A in midbrain (including hypothalamus). It was supposed that in midbrain the role of aminopeptidase M in intrasynaptic inactivation of enkephalins is much more conspicuous than in other regions of rat brain. The puromycin-sensitive aminopeptidase activity does not seem to play a role in enkephalin catabolism.