Endothelium is a multilevel cellular structure that permeates all organs and systems of the body. A disorder of the regulation of the arterial tone underlies essential hypertension. However, its pathogenesis basis, despite intense efforts, remains unclear. The unfavorable role of emotional stress, hypodynamia, obesity and disorder of water-salt metabolism is obvious. However, the exact mechanisms and predictors of the development of arterial hypertension (HTN) are not currently defined. This opposes the prevention and detection of essential hypertension at an early stage. The investigation of endothelial function as a target and a predisposing factor for HTN development is promising and implies both scientific and applied clinical significance. Indeed, understanding of pathognomonic endothelial alterations for HTN development will clarify its pathogenesis and will help the development of the adequate treatment protocols. The paper reviews current data on the involvement of endothelial cells (EC) in the development of HTN. The role of lipid disorders in the physiological state of the endothelium is shown. The role of endothelial dysfunction in increasing production of active oxygen species and disorders in the nitric oxide metabolism is highlighted. The activity of the following enzyme is reviewed: NADPH (nicotinamide adenine dinucleotide phosphate) oxidase, cyclooxygenase, xantinoxydoreductase and endothelial NO synthase. The interaction of the endothelium and the extracellular matrix, as well as endothelium and smooth muscle cells, is also given according to the literature data. The role of ghrelin, produced by endothelium, in the regulation of vascular tone is highlighted. Methods of the EC assessment in vitro under hypoxia are presented. Based on the literature review, it is clear that the assessment of the endothelium under hypoxia is highly important, as well as the investigation of the influence of tissue and hemic hypoxia in vivo. These studies will help to establish the contribution of functional endothelial disturbances to the development of HTN.

Aim. To evaluate the prevalence of atherosclerosis, to define the type of atherosclerotic lesion of brachiocephalic arteries in patients with systemic sclerodermia (SSD); to reveal the main factors influencing that process.Material and methods. Totally 38 patients with SSD studied. We measured vessel stiffness on the area between carotid and femoral arteries; instrumental and laboratory characteristics of endothelial function, morphology of carotid arteries, lipid profile parameters, as glucose, uric acid, N-terminal brain natriuretic peptide (NT-proBNP), antinuclear autoantibodies spectrum, cytokines concentration and chemokines of serum.Results. The increase of intima-media thickness (IMT) was found in 79% (n=30/38) of the patients studied with SSD. In one of the patients there was occluded carotid artery. Different level of arterial stenosis (20- 70%) — in 52,6% (n=20/38) of patients. We also measured relation of IMT and several classic risk factors (RF) of atherosclerosis (age, glyciemia level). Among non-classical risk factors there was relation of IMT and levels of asymmetrical dimethyl arginine (ADMA), soluble adhesion endothelium molecule (sVCAM), uric acid, NT-proBNP, autoantibodies to centromeres proteines. In multiple regression analysis the most informative predictors of IMT were age, uric acid, sVCAM, granulocytic colony- stimulating factor (G-CSF) and interleucine-1 (IL-1). Conclusion. In SSD patients atherosclerosis develops partially through non-classic factors influence, primarily inflammatory mediators and common for SSD metabolic disruptions (uricemia). This can point on the specific interrelation of pathogenetic mechanisms of arterial wall involvement in SSD, and might require repeated assessment of IMT in SSD, using larger patients selection and additional investigation methods.

Abstract. Some issues in etiology and pathogenesis of psoriasis are poorly studied. Therefore, a search for new potential markers is actual for diagnostics of psoriasis in less clear cases. In this study, an attempt was undertaken to evaluate contribution of some chemokines and appropriate receptors into pathogenesis of psoriasis. The main group consisted of the patients with psoriatic arthritis (n = 20) and psoriasis vulgaris (n = 9). A group of comparison consisted of patients with sclerodermia (n = 4), and a control group was represented by healthy persons (n = 9). The specimens were taken from visually normal and affected skin areas from psoriatic patients obtained by punch biopsy. Expression of the following chemokines was performed: CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/eotaxin, CCL24/eotaxin-2, CXCL8/IL-8 and their receptors (CCR1, CCR3, CCR5, CXCR1, CXCR2). In cases with PASI values 20, an increased expression of CCL11/eotaxin (p = 0.001), CCL24/eotaxin 2 (p = 0.001), CCL3/MIP-1α (р = 0.02), CXCR1 (p = 0.0001), CXCR2 (p = 0.001) was detected in visually healthy skin samples and affected skin of the patients, as well as higher expression of CCL4/MIP-1β (р = 0.03) in affected skin areas. A reverse correlation was revealed between expression of chemokines, i.e., CCL24/eotaxin 2 (r = –0,94, p = 0.005), CCL3/MIP-1α (r = –0,94, p = 0.005), CCL4/MIP-1β (r = –0,85, p = 0.03) and their receptors: ССR5 (r = –0,79, p = 0.005) and CXCR2 (r = –0,94, p = 0.005) in visually normal skin of the patients with psoriasis and PASI values < 10. A direct correlation was found between expression of mRNAs for CCL11/eotaxin (r = 0.69, p = 0.04) in visually healthy skin from psoriatic patients, and CCR5 (r = 0.82, p = 0.006) in affected skin of the patients with psoriasis and PASI values of 10 to 20. In the group of patients with PASI values over 20, no correlations were detectable. These data allow us of concluding aboutan important contribution of chemokine system to pathogenesis of psoriasis. (Med. Immunol., vol. 10, N 4-5, pp 337-346) .

Abstract. The aim of the study was to assess prevalence and risk factors for cryoglobulinemia associated with chronic hepatitis C in St.-Petersburg. Patients and methods. We studied 121 patients with chronic hepatitis C, including 53 men and 68 women with median age of 39±13 years. The median hepatitis duration was 3 years (range 0.5 to 34 years). In this group 25 (20,7%) had cirrhosis. Results. 37,2% (45/121) patients had circulating cryoglobulins. A low levels of crioglobulins (cryocrit 1-4%) were detected more frequently. Cryoglobulinaemic patients showed more frequent rates rheumatoid factors activity (р = 0,001), a higher levels of bilirubin (р = 0,003) and a γ-gamma-glutamyltransferase (р = 0,031). The presence of cryoglobulins was not correlated with HCV genotype (HCV 1a – 20,8% vs 20,7%, 1b – 29,2% vs 27,6%, 2 – 4,2% vs 6,9%, 3a – 20,8 vs 34,5%, mixt – 20,8% vs 6,9%, not identified – 4,1% vs 3,4%, in cryopositive vs cryonegative patients respectively, р = 0,7). By multivariate analysis hepatitis duration (Exp (B) = 1,07, 95% Cl 1,0-1,13, р = 0,049) and cirrhosis (Exp (B) = 6,2, 95% Cl 2,25-16,8, р < 0,001) could independently predict the presence of cryoglobulins. Conclusion. Our study demonstrates high prevalence of serum cryoglobulins in patients with chronic hepatitis C in St.-Petersburg and independent association between duration of hepatitis and advanced cirrhosis with development of cryoglobulinemia.

Abstract. Since decades, the aspects of chronic adenoiditis draw attention of specialists in ORL. From different data, prevalence of chronic adenoiditis is 20 to 56 per cent among children with diseases of upper respiratory ways. Chronic adenoiditis is relatively resistant to conventional therapy, and irreversible clinical course is revealed in more severe cases. The studies performed have shown that the patients with chronic adenoiditis exhibit signs of local immune deficiency that manifested into decreased local secretion of IL-4, IL-10 and GM-CSF, thus being considered as an indication for local immunocorrection procedures. To this purpose, we used Imunophan as a spray for intranasal application. Dynamics of clinical symptoms and local immune parameters showed that the efficiency of Imunophan treatment was dependent of both initial clinical features of the disorder, and on cytokine levels in oropharyngeal lavages. Therapeutic effect of Imunophan was more expressed in the patients with initial predomination of Th1 immune response and cell-type immune reactions in the area of inflammation. A set of certain clinical and laboratory data, i.e., absence of enlarged pharyngeal glands, predominance of local Th1 type response and cellular type of immune response may be used for monitoring before administration of local immunotherapy with Imunophan in the patients with chronic adenoiditis. (Med. Immunol., 2008, vol. 10, N 2-3, pp 261-268) .

The chronic hepatitis C is characterized by the increase of inflammatory disorders and progression of fibrosis of liver The corresponding immunologic mechanisms of hepatic lesions are still undiscovered. The actual review presents the analysis of scientific publications and genuine research data concerning the role of chemokines in pathogenesis of chronic hepatitis C. The chemokines are small cationic proteins enhancing transit and precipitation of migrating cells (leucocytes mainly) in tissues and organs. The significant role of chemokines in tissue homeostasis, in case of inflammation, wound healing and cell proliferation is demonstrated. The particular kinds of chemokines are produced by different types of cells and impact target cells through their specific receptors. According the data of various studies, chemokines and chemokine receptors of CC-families and CXC-families are involved in fibrosing processes and anti-inflammatory activation of hepatic-biliary system under chronic hepatitis C. The diversity of producers and targets of chemokines in liver is very pronounced: hepatocytes, stellar cells, endothelium cells, macrophages (Kupffer cells), dendritic cells, lymphocytes and monocytes. The review considers pathogenesis of chronic hepatitis C from the standpoint of participation of chemokines and chemokine receptors at different stages of cellular transit. The most important cellpopulations involved into pathologic changes under chronic hepatitis C are characterized. The decrease of expression of such gens as CCR1, CCR2, CCR3, and CCR5 in blood leucocytes deserves additional studies to establish their diagnostic values as a marker of disorders of immune system in patients with chronic hepatitis C.

The chronic hepatitis C is characterized by the increase of inflammatory disorders and progression of fibrosis of liver. The corresponding immunologic mechanisms of hepatic lesions are still undiscovered. The actual review presents the analysis of scientific publications and genuine research data concerning the role of chemokines in pathogenesis of chronic hepatitis C. The chemokines are small cationic proteins enhancing transit and precipitation of migrating cells (leucocytes mainly) in tissues and organs. The significant role of chemokines in tissue homeostasis, in case of inflammation, wound healing and cell proliferation is demonstrated. The particular kinds of chemokines are produced by different types of cells and impact target cells through their specific receptors. According the data of various studies, chemokines and chemokine receptors of CC-families and CXC-families are involved in fibrosing processes and anti-inflammatory activation of hepatic-biliary system under chronic hepatitis C. The diversity of producers and targets of chemokines in liver is very pronounced: hepatocytes, stellar cells, endothelium cells, macrophages (Kupffer cells), dendritic cells, lymphocytes and monocytes. The review considers pathogenesis of chronic hepatitis C from the standpoint of participation of chemokines and chemokine receptors at different stages of cellular transit. The most important cell populations involved into pathologic changes under chronic hepatitis C are characterized. The decrease of expression of such gens as CCR1, CCR2, CCR3, and CCR5 in blood leucocytes deserves additional studies to establish their diagnostic values as a marker of disorders of immune system in patients with chronic hepatitis C.

Abstract. Pathogenesis of chronic hepatitis C (CHC) remains to be determined. Mechanisms of liver parenchyma damage in patients with CHC are complex and different. Cytokines play the role of intermediaries in the process of fibrosis development and chronic inflammation. In the present study levels of 27 cytokines in the blood plasma of 14 patients with CHC were tested using multiplex analysis. The liver biopsy was performed in all patients to define the activity of inflammation (histological activity index) and the degree of fibrosis. Nineteen samples of blood plasma obtained from healthy individuals were served as a control group in this study. The following cytokines were measured: IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, FGF-2, G-CSF, GM-CSF, IFNγ, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, PDGF-BB, TNFα and VEGF. In patients with CHC elevated levels of plasma IL-1ra, IL-6, IL-7, IFNγ, IL-12 (p70), IL-4, IL-9, IL-8, IP-10, eotaxin, MCP-1, MIP-1β, TNFα, G-CSF and GM-CSF were found in compare with the control group. At the same time levels of FGF-2 and PDGF-BB were reduced in patients with CHC in compare with controls. Differences in the production of IL-1ra, IL-6, IL-7, IFNγ, IL-12 (p70), IL-4, IL-9, IL-8, IP-10, eotaxin, MCP-1, MIP-1β, TNFα, G-CSF and GM-CSF were depend on the genotype of HCV (3a or 1b), histological activity index in liver tissue and the degree of liver fibrosis. The revealed changes of cytokine production in patients with CHC characterize different orientation of regulatory violations confirming that CHC is an immunopathological process.

Introduction: Mechanism of BA onset and progression at different ages are still poorly understood. System of chemokines in upper airways is a tempting object of investigation BA pathogenesis. Methods: We examined 70 patients with asthma. The patients age ranged from 16 to 74 years. Were studied 31 men and 39 women. The control group used brush-biopsy 17 healthy volunteers with no history of atopic diseases. Were studied mRNA of eotaxin, eotaxin-2, MIP-1α, MIP-1β, RANTES, CCR1, CCR3, CCR5, CXCR1, and CXCR2. Results: A study in patients with asthma was revealed a significant increase in eotaxin mRNA expression (p = 0.045), eotaxin-2 (0.036), MIP-1α (0.0003), MIP-1β (0.002) and CXCR1 (0.004) compared with healthy volunteers. At the same time CCR1 gene expression in patients with asthma was reduced compared with control. To study the age dynamics of the asthma patients were divided into 4 groups: first group - 16-25 years (n = 14), the second group - 26-39 years (n = 14), the third group - 40-53 years (n = 21) and the fourth group - 54-74 years (n = 21). Eotaxin-2 had wave-like dynamics depending on patents age. MIP-1α was lowest in the second and third groups, and in the first and fourth - were significantly higher. The values of MIP-1β - the lowest in the first group with increasing age became more and peaked in the fourth group. mRNA of CCR1 and CXCR1 was significantly decreased in the second group compared to the first, meanwhile in the third and fourth ones levels of mRNA of both receptors increases depending on the age of the patients. Conclusion: The state of chemokines and relative receptors gene expression in upper airways reflects age features of BA pathogenesis.

We studied the levels of IL-1, IL-6 and TNFin patients with coronary artery disease (CAD) and with concomitant anxiety and depression. We found a significant growth these parametres in patients with CAD and with concomitant anxiety and depression as compared with patients with CAD without anxiety and depressive disorders. The level of IL-6 was significant decreased in patients with isolated anxiety and depression as compared with patients with CAD and anxiety and depression. Our results support cytocines hypothesis of depression in patients with CAD and concomitant anxiety and depression.

The aim of this study was to evaluate some patterns in expression of CC-chemokines (MIP-1alpha, MIP-1beta, MCP-1, RANTES) and their receptors (CCR1, CCR2, CCR3, CCR5) in peripheral blood leukocytes and liver biopsy samples from 21 patients with chronic hepatitis C. 10 healthy subjects were included in the control group. In patients with chronic HCV-infection significant increase of MCP-1 mRNA in liver tissue was observed as the disease progressed. Moreover, content of MCP-1 mRNA was significantly higher in liver as compared with blood. Level of MCP-1 mRNA in liver was directly related with histological changes. Levels of mRNA of CCR1, CCR2, CCR3, and CCR5 in blood of patients with minimal histological manifestations of chronic HCV-infection were significantly lower than in patients with more marked lesions. Expression of CCR1 and CCR5 mRNA in blood was directly correlated with histological activity index and degree of fibrosis. Conducted study demonstrates that progression of chronic hepatitis C is realized through local activation of MCP-1 mRNA synthesis leading to systemic response which manifested by increase of expression of CCR1, CCR2, CCR3, and CCR5 in peripheral blood leukocytes.

Infectious endocarditis can be caused by various microorganisms. Diagnostics of local infection by microbiological methods is not always effective. For that reason we performed a study aimed for direct detection of potential infectious agents by polymerase chain reaction in patients' heart valve tissue. DNA of infectious agents was revealed in 72% of heart valve tissue samples from patients with septic endocarditis; in studied samples, along with bacterial DNA, herpesviruses' DNA was detected. Obtained results confirm the presence of infection, which allows to perform specific diagnostics of infectious complications after implantation of prosthetic cardiac valves.

The increase of quantity of coronary artery bypass graft surgery is interfaced to necessity of active introduction of the methods which improve the nearest and remote results of these interventions. The mediated role of chemokine system is supposed in mechanisms of development and progressing of atherosclerosis in a shunting material. The researches which were performed during the last years allow to consider that ω-3 polyunsaturated fat acids as additional means for improvement of outcomes of surgery treatment of coronary artery disease. In our research it was shown that the administration of OMACOR in a dose 2,0 g daily within 14 days before coronary artery bypass graft surgery leads to maintenance increase of мRNA CCR1, CCR3 and CCR5 in the aorta and the great saphenous vein. The expression of chemokine receptors ССR1 in blood against OMACOR comes nearer to the level in healthy individuals.

Впервые была изучена клинико-иммунологическая эффективность интравагинального применения ликопида (вагинальные свечи, 10 мг по 1 свече ежедневно) в ходе монотерапии хронических инфекционно-воспалительных и дисбиотических заболеваний нижнего отдела женской репродуктивной сферы 30 пациенток репродуктивного возраста. Полное клиническое выздоровление было отмечено у 12 пациенток (40%), у 13 пациенток иммунотерапия выявила наличие ранее не диагностированных инфекционных заболеваний: хламидиоз, микоуреаплазмоз, вирус простого герпеса. Препарат хорошо переносится, не обладает аллергическими или другими побочными эффектами. Локальная иммунотерапия ликопидом приводила к нормализации вагинального микробиоценоза. Для оценки состояния местного иммунитета нижнего отдела женской половой сферы и влияния на него ликопида был изучен иммуноглобулиновый и цитокиновый состав вагинального секрета. В ходе исследования было выявлено выраженное влияние препарата на показатели гуморального звена местной иммунной системы нижних отделов женского репродуктивного тракта. При изучении динамики цитокинов в вагинальном секрете были выявлены различия, связанные с характером течения патологического процесса: при нормализации вагинального микробиоценоза происходило повышение концентрации IL-6, с параллельным снижением G-GSF (р < 0.05). У пациенток с отсутствием эффекта терапии (5 человек) отмечено достоверное повышение уровня IL-6, G-GSF и TNF-a (р < 0.05). В группе с обострением хронических инфекционнызх процессов местная терапия приводила к снижению концентрации IL-6, G-GSF и TNF-a. Ликопид при местном введении не влиял на локальный уровень IL-8 ни в одной из обследованных групп. Таким образом, местная терапия ликопидом является эффективным способом лечения хронических инфекционно-воспалительных и дисбиотических заболеваний нижнего отдела женской репродуктивной сферы.

33 patients with complaints of hyposalivation (21 in a 33 with syaloadenopatya and 12 in a 33 with syalosis out of the acute stage of disease) were examined. Complex examination of the saliva glands, analysis of the haemokynes in the various mediums of organism and thyoles compounds in the blood plasma was carried out. Tendency to increase in contents of haemokynes in the mixed saliva and in the tissue samples (from low in the syaloadenopatya to expressed in the syalosis) was revealed. Reduction of thyosulfide index in the blood plasma of these patients was determined. Use of antioxidant remedy in complex treatment of syaloadenopatya and syalosis was substanciated in this paper.

Abstract. Uterine leiomyoma (UL) is a hormone-dependent benign tumor of uterus. Social significance of UL is stipulated by its high rate among fertile females. Scarce data exist about the impact of cytokines in UL progression. Th1/Th2 paradigm is one of crucial points in modern immunology. Evaluation of cytokines involved into either type of immune response is of special significance for studying the diseases accompanied by the changes of extracellular matrix, e.g., leiomyomas. In present study, we analyzed peritoneal fluids from UL patients, with multiplex detection of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF, IFN-γ and TNF-α (Th1/Th2 panel), by means of a Bio-Plex® instrument (Bio-Rad, USA). Twenty-seven patients were observed in our study (20 patients with UL, and 7 myoma-free women (a group of comparison). The mean age of the patients was 43.5±0.6 years. The duration of UL ranged from 0 to 18 years. As a result, the levels of IL-10, GM-CSF, IFN-γ and TNF-α in patients with long-existing UL (over 5 years) were significantly higher (p<0,05) than in group with a disease story of <5 years. IFN-γ values in peritoneal fluid patients with UL did inversely correlate with uterine size. Moreover, the levels of IFN-γ in patients with smaller uterine volume (<8 weeks of pregnancy) were increased in relation to the group with larger tumor size. IL-10 contents were increased in the patients with adenomyosis, rapid and slow growth of UL, and in both types of tumor (simple and proliferative). Increased IL-5 levels were observed in the patients with single tumor nodules (as related to the patients bearing multiple nodes, and comparison group). Furthermore, intramural and subserosal location of nodes was characterized by increased levels of IL-5. In the patients free of adenomyosis, IL-5 value was increased against the comparison group. The changes in IL-2, IL-4, IL-12 and IL-13 levels in patients with UL were not statistically significant.