[CYP2C8, PTGS-1, 2 gene polymorphisms prevalence associated with sensitivity to non-steroidal anti-inflammatory drugs among North Caucasus ethnic groups].

AIM: Find the prevalence of CYP2C8*3 (rs10509681; rs11572080), PTGS-1 (rs10306135; rs12353214) and PTGS-2 (rs20417) alleles and genotypes in four ethnic groups among Laks, Avars, Dargins and Kumyks. MATERIALS AND METHODS: The study involved 400 volunteers from four ethnic groups living in Republic of Dagestan: 100 participants from each group. Carriage of polymorphic markers was determined by reverse transcription polymerase chain reaction. RESULTS: Minor allele frequency of the CYP2C8 (rs10509681) was 5.5% in Avars, 10% in Dargins, Laks and Kumyks 6.5% both; CYP2C8 (rs11572080) was 5.5% in Avars, 9.5% in Dargins, 6.5% in Laks, 8.5% in Kumyks; PTGS-1 (rs10306135) in Avars 10.5%, in Dargins 13.0%, in Laks 9.5% and Kumyks 7.5%; PTGS-1 (rs12353214) in Avars 9.0%, in Dargins 4.5%, in Laks 7.5%, in Kumyks 8.0%; PTGS-2 (rs20417) in Avars 1.0%, in Dargins 2.5%, in Laks 3.5%, in Kumyks 5.0%. There were no significant differences between groups. CONCLUSION: The study of CYP2C8 and PTGS-1 and 2 gene polymorphisms is promising for predicting the effectiveness and safety of non-steroidal anti-inflammatory drug therapy, due to the high prevalence of these polymorphisms in ethnic groups in the North Caucasus.

[Effect of infectious factors on the activation of proinflammatory cytokines in chronic heart failure].

The results of recent studies favor the immunological theory of the pathogenesis of chronic heart failure (CHF). In this connection, of particular interest is a search for possible causes of cytokine hyperactivation in patients with CHF of ischemic etiology, one of which may be viral infection. The aim of the study was to evaluate the impact of herpesvirus simplex (HVS), cytomegalovirus (CMV), Chlamydia pneumoniae on the activation of cytokines in patients with CHF of ischemic etiology. Ninety patients with CHF of ischemic etiology were examined. After comprehensive study, the patients were divided into 2 groups: 1) Functional Class (FC) I-II CHF and 2) FC III-IV CHF Increases in the levels of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma and in the content of IgG and IgM to CMV and IgM to HVS were ascertained in patients with CHF of ischemic etiology. There were statistically significant correlations of the level of proinflammatory cytokines, CMV, and HVS with the FC of CHF and the echocardiographic indicators reflecting left ventricular systolic function.

[Molecular diagnosis of heritable unconjugated hyperbilirubinemias].

There is considerable evidence suggesting that genetic damages to human uridine diphosphate glucuronyltransferase (UDPGT) gene located on clhromosome 2q37 are responsible for hereditary unconjugated hyperbilirubinemias (HUHB). The Crigler-Najjar syndrome of types I and II is characterized by structural mutations on one of 5 exons of HUHB gene, resulting in the synthesis of defective catalytically inactive isoforms of the enzyme. In Gilbert's syndrome, genetic alterations are located at the promoter of the gene and accompanied by the nucleotide insert of thymine adenine (TA). Promoter prolongation impairs the binding of IID transcription factor and leads to the decreased production of the enzyme UDPGT 1,1. Examination of the molecular epidemiology of gene mutations of UDPGT 1,1 that is typical of Gilbert's syndrome ascertained a great difference in the indices, from 2 to 16% in the Asian and European populations, respectively. In addition to polymerase chain reaction, high performance liquid chromatography may be used for the diagnosis of genetic alterations in Gilbert's syndrome.

[Subpopulation blood lymphocyte composition in blood of patients with chronic hepatitis C during therapy with interferon]. / Subpopuliatsionnyi sostav limfotsitov krovi bol'nykh khronicheskim gepatitom C v dinamike interferonoterapii.

The number of lymphocytes expressing CD3, CD4, CD8, CD16, CD25, and CD19 antigens was studied in patients with chronic hepatitis C before and after 12-week therapy with interferon-alpha (IFN-alpha). The percentage of cells expressing CD4+, CD16+, and CD25+ antigens decreased significantly in untreated patients, while the percentage of CD8+ and CD19+ lymphocytes was increased (p < 0.05) vs. the control. After 3-month therapy with IFN-alpha the counts of CD4+ and CD25+ increased significantly in patients with chronic hepatitis C (p < 0.05 and p < 0.01, respectively) in comparison with the initial values. The treatment led to a significant (p < 0.05) decrease in the number of CD8+ cells in the blood. The number of cells expressing CD19+ decreased, but remained high in comparison with the control. These results indicate that cellular immune response is inadequate in patients with chronic hepatitis C. Time course of subpopulation composition of T lymphocytes during effective treatment with IFN-alpha indicates an important role of T-cellular component of immunity in the antiviral defense mechanisms in chronic HCV infection.

[Cytokine system in patients with chronic hepatitis C during treatment with interferon-alfa]. / Sistema tsitokinov u bol'nykh khronicheskim gepatitom C pri lechenii interferonom-al'fa.

AIM: To study changes in serum levels of interleukine-1 beta (IL-1b), IL-6, TNF-alpha (TNFa), HM-HMF and TFR-1 beta (TFR-1b), expression of surface antigens CD14 and CD95 on blood monocytes from patients with chronic hepatitis C (CHC) treated with interferon-alpha (INFa). MATERIAL AND METHODS: Examinations covered 25 CHC patients and 25 healthy controls. Concentrations of proinflammatory cytokines and growth factors in blood serum were measured with ELISA (kits by "R&D systems", USA). CD14 and CD95 antigen expression on monocytes of venous blood were studied using flow cytoflowmeter (Partes, USA) before and after a 12-week course of INFa. RESULTS: Before INFa treatment CHC patients had significantly elevated serum concentrations of TNFa, HM-KSF and TFR-1b. Coexpression of antigens CD14+ and CD95+ was found on 61% of blood monocytes. Three-month INFa treatment lowered levels of TNFa, GM-KSF and CD95+ expression on monocytes as well as TFR-1b concentration in the serum which correlated with a positive trend in the standard clinicolaboratory and virusological indices in the examinees. CONCLUSION: Changes in serum indices of proinflammatory cytokines and growth factors, in expression of CD95 on blood monocytes from CHC patients treated with INFa show an important role of cytokines system activation and mechanisms of programmed cell death in pathogenesis of chronic HCV infection.

[Cytokine production in patients with chronic viral hepatitis C during treatment with interferon-alpha]. / Produktsiia tsitokinov u bol'nykh khronicheskim virusnym gepatitom C na fone terapii interferonom-alpha.

Serum content of proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) and growth factors (GM-CSF, TGF-1 beta) and expression of CD14 and CD95 antigens on peripheral blood monocytes before and after 12-day therapy with alpha-interferon were studied in 25 patients with chronic viral hepatitis C (VHC). The concentrations of TNF alpha, GM-CSF, and TGF-1 beta were significantly increased (p < 0.05) and coexpression of CD14+ and CD95+ antigens on monocytes was increased by 61% in VHC patients in comparison with the control. After 3 months of therapy with alpha-interferon, the content of TNF alpha, GM-CSF, and TGF-1 beta essentially decreased and that of IL-6 increased; this was paralleled by improvement of clinical and laboratory parameters and decrease of coexpression of CD14+ and CD95+ antigens on blood monocytes. Modulation of the functions of immunocompetent cells and changed production of cytokines are apparently one of the mechanisms of inhibitory effect of alpha-interferon on HCV infection. Study of proinflammatory cytokines and growth factors in the serum and expression of CD14 and CD 95 antigens on monocytes can serve as additional tests for evaluating the efficiency of interferon therapy in patients with VHC.

[Cytokine regulation of liver inflammation and fibrosis during chronic hepatic diseases]. / Reguliatsiia vospaleniia i fibroza pecheni tsitokinami pri ee khronicheskikh porazheniiakh.

Serum concentrations of antiinflammatory cytokines and growth factors were measured in 30 patients with chronic viral hepatitis (HCV), mainly HCV RNA, and 10 patients with liver cirrhosis (LC), classes B and C according to Child-Pew. Serum concentrations of tumor necrosis factor-alpha (TNF alpha), granulocytic-macrophagal colony-stimulating factor (GM-CSF), and growth-transforming factor-1 beta (TGF1 beta) were increased in 63.86 and 80% patients with HCV and LC, respectively, and differed significantly (p < 0.05) from the control. The level of TNF alpha positively correlated with the concentration of alanine aminotransferase (r = 0.14). A positive correlation between TGF1 beta and histologic activity index was detected (r = 0.16). Increased levels (p < 0.05) of IL-5, TNF alpha, and TGF1 beta were detected in LC patients in comparison with the control. Patients with LC concomitant with anemia had higher (though not significantly) concentrations of TNF alpha in comparison with patients without anemia. Increased levels of proinflammatory cytokines and growth factors in the sera of patients with HCV and LC indicate activation of immunocompetent cells, including mononuclear phagocytes. These data are in line with experimental findings, indicating an important role of the studied cytokines in the development of hepatic inflammation, fibrosis, and cytopenic syndromes.