[Effectiveness of physical rehabilitation methods based on the impact of eccentric load in upper limb injuries]. / Effektivnost' fizicheskikh metodov reabilitatsii, osnovannykh na vozdeistvii ekstsentricheskikh nagruzok, pri travmakh verkhnikh konechnostei.

The rehabilitation of patients after upper limb injuries is becoming increasingly relevant in current medical practice considering that this pathology is often occurred in professional athletes, elderly people, people with active lifestyle. OBJECTIVE: To study the effectiveness of isolated therapeutic exercises (TE) with eccentric muscle loads when using rubber cable compared to traditional TE to restore functional capabilities of patients after upper limb injuries. MATERIAL AND METHODS: The study included 38 patients with upper limb injuries diagnosed by orthopedic surgeon. Patients were randomly enrolled into group of isolated TE with eccentric muscle loads (group A, 20 patients, mean age 40.2±10.8 years) and group of traditional exercises (group B, 18 patients, mean age 38.6±12.3 years). The study consisted of anamnesis taking, clinical examination, functional tests applying (isometric dynamometry, joint mobility tests, functional scales and questionnaires). The rehabilitation effectiveness was assessed by comparing the indicators before and after treatment course. RESULTS: There has been a significant improvement in muscle strength, movement amplitude and decrease of pain syndrome in patients rehabilitated by eccentric muscle loads. A comparison with a control group using traditional TE methods confirmed the superiority of eccentric exercises in reducing recovery time and improving functional performance. CONCLUSION: The study confirmed the high effectiveness of eccentric muscular loads in the rehabilitation of patients after upper limb injuries. The method has shown significant improvement in clinical and functional indices, which allows to recommend it for inclusion in standard rehabilitation protocols. Further researches may extend application of this approach and reveal the TE effectiveness in other types of traumas and orthopedic injuries.

[Acute and chronic rhinosinusitis age characteristics]. / Vozrastnye osobennosti techeniya ostrogo i khronicheskogo rinosinusita.

Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on Pelargonium sidoides roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8+ lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1ß chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, Pelargonium sidoides increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on Streptococcus pneumoniae, Staphylococcus aureus, Neisseria, Moraxella catarrhalis and Haemophilus influenza. Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on Pelargonium sidoides in ENT organs inflammation treatment, for both adults and children over 1 year old.

Implication of integrin α5ß1 in senescence of SK-Mel-147 human melanoma cells.

Downregulation of α5ß1 integrin in the SK-Mel-147 human melanoma culture model sharply inhibits the phenotypic manifestations of tumor progression: cell proliferation and clonal activity. This was accompanied by a 2-3-fold increase in the content of SA-ß-Gal positive cells thus indicating an increase in the cellular senescence phenotype. These changes were accompanied by a significant increase in the activity of p53 and p21 tumor suppressors and components of the PI3K/Akt/mTOR/p70 signaling pathway. Pharmacological inhibition of mTORC1 reduced the content of SA-ß-Gal positive cells in the population of α5ß1-deficient SK-Mel-147 cells. A similar effect was observed with pharmacological and genetic inhibition of the activity of Akt1, one of the three Akt protein kinase isoenzymes; suppression of other Akt isozymes did not affect melanoma cell senescence. The results presented in this work and previously obtained indicate that α5ß1 shares with other integrins of the ß1 family the function of cell protection from senescence. This function is realized via regulation of the PI3K/Akt1/mTOR signaling pathway, in which Akt1 exhibits a non-canonical activity.

[Integrin α3ß1 signaling in regulation of the SK-Mel-147 melanoma cell senescence]. / Signaling integrina α3ß1 v regulirovanii stareniia kletok SK-MEL-147 melanomy cheloveka.

Using a model of the human SK-Mel-147 melanoma cell line, it was shown that blocking the expression of integrin α3ß1 by transduction of cells with α3-specific shRNA did not affect their proliferation, but sharply increased the proportion of SA-ß-Gal-positive cells, a phenotypic feature of cell senescence. These findings were accompanied by a significant increase in the activity of the Akt and mTOR protein kinases and the expression of p53 and p21 oncosupressors. Pharmacological inhibition of mTORC1 reduced the number SA-ß-Gal-positive cells in the SK-Mel-147 cell population depleted of α3ß1. Based on our recent data on a non-canonical function of Akt isomers in the regulation of SK-Mel-147 cell senescence caused by deficiency of α2ß1 receptor, we investigated the role of Akt isomers in senescence induced by the α3ß1 knockdown. It appeared that in the cell population with downregulated α3ß1, inhibition of Akt1 reduced the number SA-ß-Gal positive cells to the level of control cell population, while inhibition of Akt2 had no visible effect. Our results demonstrate that the laminin-specific integrin α3ß1, like the collagen-specific receptor α2ß1, is involved in tumor cell protection from senescence, and senescence induced by α3ß1 depletion, like that caused by α2ß1 deficiency, is based on a signaling mechanism employing a non-canonical function of the Akt1 isoform.

Implication of Integrin α2ß1 in Proliferation and Invasion of Human Breast Carcinoma and Melanoma Cells: Noncanonical Function of Akt Protein Kinase.

Blocking the expression of integrin α2ß1, which was accomplished by transduction of α2-specific shRNA, resulted in significant inhibition of proliferation and clonal activity in human MCF-7 breast carcinoma and SK-Mel-147 melanoma cells. Along with these changes, deprivation of α2ß1 caused a sharp decrease in melanoma cell invasion in vitro. Analysis of integrin-mediating signal pathways that control cell behavior revealed a significant increase in activity of Akt protein kinase in response to depletion of α2ß1. The increase in Akt activity that accompanies a suppressive effect on cell invasion contradicts well-known Akt function aimed at stimulation of tumor progression. This contradiction could be explained by the "reversed" (noncanonical) role played by Akt in some cells that consists in suppression rather than promotion of invasive phenotype. To test this suggestion, the effects of Akt inhibitors on invasive activity of SK-Mel-147 cells were investigated. If the above suggestion is true, then inhibition of Akt in cells depleted of α2ß1 should result in the restoration of their invasive activity. It appeared that treatment with LY294002, which inhibits all Akt isoforms (Akt1, Akt2, Akt3), not only failed to restore the invasive phenotype of melanoma cells but further attenuated their invasive activity. However, treatment of the cells with an Akt1-specific inhibitor significantly increased their invasion. Thus, the stimulating effect of α2ß1 integrin on invasion of melanoma cells is realized through a mechanism based on inhibition of one of the Akt isoforms, which in these cells exhibits a noncanonical function consisting in suppression of invasion.

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and ß-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

Hyperexpression of Integrin α5ß1 Promotes Resistance of MCF-7 Human Breast Carcinoma Cells to Doxorubicin via ERK Protein Kinase Down-regulation.

In MCF-7 human breast carcinoma cells, α5ß1 integrin hyperexpression, which was accomplished by transduction of a full-length α5 integrin cDNA, increased by about 50-70% the number of cells, survived during 48-72 h cell treatment with doxorubicin. Up-regulation of α5ß1 reduced the level of the apoptogenic p53 protein and p21 cell cycle inhibitor, but enhanced the activity of Akt and mTOR protein kinases. In addition to these findings, we observed a significant decrease in the activity of both isoforms of phosphokinase Erk1/2, which is known to play a key role in cell viability pathways, including pathways alleviating stress damages caused by distinct antitumor drugs. Diminished Erk activity accompanying the rise of drug resistance can be explained by an "atypical" function of this kinase, which, in the cells studied, promotes an enhanced rather than reduced sensitivity to doxorubicin. To verify this suggestion, the effect of a specific Erk inhibitor, PD98059, on the resistance to doxorubicin of control and α5 cDNA-transduced MCF-7 cells was investigated. The data showed that suppression of Erk activity increased the resistance of control cells (transduced with an "empty" vector) to a level higher than that demonstrated by the α5 cDNA-transduced cells. The highest level of resistance was observed in α5ß1-trancduced cells treated with PD98059. Akt and mTOR kinase inhibitors had little if any effect on doxorubicin resistance of α5 cDNA-transduced MCF-7 cells. The data show for the first time that integrin α5ß1 can stimulate drug resistance of tumor cells through a mechanism based on the inhibition of protein kinase Erk. From a more general view, the results of this investigation suggest that signal protein kinases can perform in tumor cells "non-canonical" functions, opposite to those, which are the basis for using kinase inhibitors in targeted cancer therapy. It follows that if a protein kinase is supposed to be used as a target for such therapy, it is important to explore its features in the particular tumor prior to the onset of treatment.

[Protective action of fish muscle extracts against cellular senescence induced by oxidative stress]. / Zashchitnoe deistvie ékstraktov iz myshts ryb ot indutsirovannogo okislitel'nym stressom kletochnogo stareniia.

Muscle extracts of some fish species, i.e. pike (Esox lucius), sterlet (Acipenser ruthenus), pink salmon (Oncorhynchus gorbuscha) and, to a lesser extent, perch (Perca fluviatilis) and Russian sturgeon, (Acipenser gueldenstaedtii) prevent the development of premature senescence of the human embryonic fibroblasts induced by the sublethal concentration of H2O2. Muscle extracts of other fish species tested, i.e. coho salmon (Oncorhynchus kisutch) and zander (Sander lucioperca), have not demonstrated this feature. Cell proliferation increased after the action of the senescence-inhibiting muscle extracts. Possible mechanisms of the action of nature biologically active compounds that interfere with the development of stress-induced cell senescence are discussed.

Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools.

Melanoma progression is associated with increased invasion and, often, decreased levels of microphthalmia-associated transcription factor (MITF). Accordingly, downregulation of MITF induces invasion in melanoma cells; however, little is known about the underlying mechanisms. Here, we report for the first time that depletion of MITF results in elevation of intracellular GTP levels and increased amounts of active (GTP-bound) RAC1, RHO-A and RHO-C. Concomitantly, MITF-depleted cells display larger number of invadopodia and increased invasion. We further demonstrate that the gene for guanosine monophosphate reductase (GMPR) is a direct MITF target, and that the partial repression of GMPR accounts mostly for the above phenotypes in MITF-depleted cells. Reciprocally, transactivation of GMPR is required for MITF-dependent suppression of melanoma cell invasion, tumorigenicity and lung colonization. Moreover, loss of GMPR accompanies downregulation of MITF in vemurafenib-resistant BRAFV600E-melanoma cells and underlies the increased invasion in these cells. Our data uncover novel mechanisms linking MITF-dependent inhibition of invasion to suppression of guanylate metabolism.

[Implication of integrin alpha5beta1 signal pathways in proliferation and apoptosis of MCF-7/Dox human breast carcinoma cells]. / Razlichiia mezhdu integrinom al'fa5beta1i retseptorom EGRF v signal'nykh putiakh, kontroliruiushchikh proliferatsiiu i apoptoz kletokMCF-7/Dox kartsinomy molochnoi zhelezy cheloveka.

In MCF-7/Dox human breast carcinoma cells, down-regulation of integrin alpha5beta1 and inhibition of epidermal growth factor receptor (EGFR) markedly reduced rates of cell proliferation. Mitotic cycle analysis showed that alpha5beta1 down-regulation resulted in cell cycle arrest at the S phase, followed by a significant increase in the population of apoptotic cells (subG1 population). Inhibition of EGFR activity also caused cell cycle arrest at the S-phase but without any increase in the subG1 population. Down-regulation of alpha5beta1 and EGFR inhibition resulted in a significant decrease of cell content of the active (phosphorylated) forms of FAK and Erk protein kinases. The data obtained suggest that alpha5beta1 integrin is implicated in cell growth control via inhibition of apoptotic cell death and through EGFR activation.

PO-59 - Hemorheologic disturbances as thrombosis risk factor in patients with some myeloproliferative neoplasms.

INTRODUCTION: In today's antithrombotic prevention we forget that hemorheologic abnormalities are part of Virchow's triad. Isn't this one of reasons that venous thromboembolism (VTE) including catheter-related thrombosis (CRT) retain high frequency despite of modern antithrombotic therapy? AIM: The aim was to investigate rheological behavior of blood in patients with some myeloproliferative neoplasms. MATERIALS AND METHODS: The study included 16 adults with Polycythemia Vera (PV), 42 young with acute lymphoblastic leukemia (ALL), and 67 healthy donors as control group. Of patients 38% had thrombosis. We measured plasma viscosity, and whole blood viscosity (WBV) by shear rate from 300 to 5 s-1. Then indices were calculated for erythrocyte aggregation, and deformability, and non-Newtonian behavior of blood. Hematocrit, erythrocytes count, erythrocyte indices, leukocyte count, fibrinogen and B-type natriuretic peptide (BNP) were analyzed simultaneously. RESULTS: Increased WBV revealed totally in PV-patients but not by all shear rates in ALL-patients. Unlike donor, in patients WBV values had no equivalence under sequential one sample measurements with a decrease and then an increase of shear rates. We speculated this difference becomes diagnostic meaning like one and by its size. WBV dependent on leukocytes count, on MCH and mainly on MCV. Forty percent of patients had elevated BNP assuming subclinical cardiac dysfunction. The latter explains discoordinated changes in shear stress values required for fully reversible erythrocyte aggregation. As a result, residual units like "erythrocyte-erythrocyte" and/or "erythrocyte-leukocyte" interferes blood stream and violates mechanically blood flow in small vessels. Moreover in PV-patients but not in ALL-patients we found loss of non-Newtonian behavior of blood later than in control group. Both myeloproliferative neoplasms lead to increased erythrocyte aggregation but not impair deformability of red blood cells. In total these facts explains chronic hypoxia in these patients. CONCLUSIONS: Patients with some myeloproliferative neoplasms has abnormal blood flow properties. Revealed hemorheologic disturbances could be as a trigger to start of VTE or to growth of blood clot in the area of permanent venous catheter. These non-hemocoagulation conditions leaded for thrombus formation makes hemorheologic therapy looking attractive for antithrombotic management. The choice of targeted methods requires to continue this study.

[The significance of the rehabilitative potential for the combined medical rehabilitation of the patients presenting with acute cerebral circulation problems]. / Rol' reabilitatsionnogo potentsiala v kompleksnoi meditsinskoi reabilitatsii patsientov s ostrymi narusheniyami mozgovogo krovoobrashcheniya.

This article outlines the current WHO concepts of the process of rehabilitation with special reference to the consideration and the analysis of the concept of rehabilitation potential, its structure, levels, and functions of each level. The main stages and the aim of the comprehensive medical and psychological rehabilitation of the patients presenting with acute cerebrovascular accidents (ACVA) are discussed. The importance of the recoverable and reusable resources at the biological and psychological levels that may play the role of compensatory functions in the patients suffering from acute cerebral circulation disorders is emphasized. The three main stages of the rehabilitation process for the ACVA patients («diagnostic¼, «therapeutic¼, and «verifying¼) are described. The necessity of the development of the systemic strategy for medical and psychological rehabilitation of the post-stroke patients is substantiated taking into account the criteria for allocating them to the groups of either early or late rehabilitation and the group of patients suffering from the consequences of acute cerebral circulation disorders. It may allow to achieve the optimal level of the patients' well-being, in accordance with the rehabilitation potential currently attainable for the patients undergoing acute cerebrovascular accidents.

[Influence of the Potassium Channels Activator Nicorandil to the Quality of Life in Patients With Ishemic Heart Disease and Stable Angina Pectoris].

The aim of the study to assess the influence of medicamentous therapy to the quality of life of ischemic heart disease patients with stable angina pectoris by activator potassium channels nicorandil in comparison with traditional therapy by isosorbide dinitrate. The study included 84 ischemic heart disease patients. Authors consider quality of life as an estimated category of state of the subject in an illness situation. The dynamic of physical and psychological components of quality of life are compared in ischemic heart disease patients under the treatment by nicorandil and isosorbide dinitrate. Indicators of quality of life, defined on the basis of a questionnaires of SAQ and GHQ supplementing an illness picture, are an multiple-factor criterion of an assessment of a condition of this category of patients. The benefits of nicorandil in influence on quality of life indicators were revealed in the study.

[Gas chromatography-mass spectrometric studies of volatile emissions from plants for the assessment of the effectiveness and chemical safety of the implementation of environment improving phytotechnologies].

The chromato-mass-spectrometric studies of volatile emissions of fresh-cut roses have revealed the persistence of wide range of organic compounds. The most large content was consist of terpene hydrocarbons. The contribution of oxygen-containing components (alcohols, ethers, aldehydes and ketones) varied in wide ranges in dependence on the content of the feeding solution. The significant part of plants ' volatiles has no hygienic norm. Among the substances released into the air space ofpremises with volatile emissions ofplants, a significant part has not hygienic standards. Purposeful change in composition of the mixture of volatile organic compounds released by the plants, in the combination with chemical-analytical control of the content of these substances by gas chromatography-mass spectrometry in terms of ecological and hygienic aspects may be useful in the development, use and determination of the optimal conditions of the implementation of environment improving phytotechnologies and evaluation of the efficacy and safety of their impact on public health.

[T-LYMPHOCYTES AND TISSUE GROWTH FACTORS].

Lympnoici regulation, in aciaition to ensuring tne protection of tne antigen, is aimecl at maintaining a qualitative, quantitative, structural and functional integrity of the body. T-lymphocytes and growth factors are involved in cell proliferation, differentiation, and tissue and organ regeneration. Lymphocyte's, sensitivity to homeostasis changes and their morphogenetic function are connected with a large number of receptors to bioactive substances and with their ability to syn- thesize and secrete hormones and tissue growth factors. At the same time tissue growth factors are involved in the development of thymocytes, in the differentiation of T helper and cytotoxic lymphocytes. Growth factors modulate the functions of Thl, Th2, Treg, Thl7, Th9. The important aspects of the interaction of T cells and EGF, TGF-P, FGF, VEGF, PlGF, HGF/SF in normal and pathological conditions are shown in this review.

[INFLUENCE OF TOTAL RNA SPLENIC LYMPHOID CELLS ON ERYTHROPOIESIS IN EXPERIMENTAL POLYCYTHEMIA].

Total RNA, isolated from rat spleen's lymphoid cells during the period of hematopoietic tissue's reparative regeneration, has a remarkable activating effect on the processes of erythroblastic islet formation in vivo and in vitro. Total RNA, isolated from normal rat spleen's lymphoid cells, restores depressed erythropoiesis in erythroblastic islets up to physiological level.

[ESPECIALLY CHRONIC RHINOSINUSITIS ASSOCIATED WITH GASTROESOPHAGEAL REFLUX DISEASE].

OBJECTIVE: to study the clinical and laboratory features of chronic rhinosinusitis (CRS) associated with gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: The study involved 87 patients with complaints of difficulty in nasal breathing and 30 healthy volunteers with no pathology ENT and GERD. The diagnosis of CRS met the criteria EPOS 2012. Diagnosis of GERD was performed based on the recommendations of the Montreal consensus. All investigated conducted a survey for the presence of esophageal and extraesophageal manifestations of GERD, fibroesophagogastroduodenoscopy, LOR examination with the use of endoscopes, rhinoscopy, laryngoscopy, computed tomography of the paranasal sinuses, pH-metry mucous secretions of the nose and pharynx using visual test - strips, microbiological examination of discharge from the middle of the nose stroke. Association of CRS with GERD with GERD compared with impaired nasal breathing inflammatory and non-inflammatory genesis in the absence of GERD and healthy volunteers accompanied by a large variety and frequency of symptoms, endoscopic signs of laryngitis back, reducing the pH of the pharynx, the change in quantitative and qualitative characteristics of the microflora of the nasal mucosa and paranasal sinuses.

[Comparative Assessment of Effects of Isosorbide Dinitrate, Isosorbide-5-Mononitrate and Nicorandil on the Frequency of Angina Attacks and Vasoregulating Endothelial Function in Patients With Ischemic Heart Disease].

AIM: to compare effects of isosorbide dinitrate, isosorbide-5-mononitrate and nicorandil on frequency of angina attacks and vasoregulating endothelial function in patients with ischemic heart disease (IHD). MATERIAL AND METHODS. In 117 patients with stable II-III functional class angina we analyzed frequency of angina attacks, exercise tolerance, data of 24-hour Holter ECG monitoring and brachial artery Doppler study. RESULTS. Patients with IHD had impaired endothelium-dependent vasodilation in the form of reduced endothelial response to increase of "shear stress" during test with reactive hyperemia. Long-term therapy with isosorbide dinitrate, isosorbide-5-mononitrate, and nicorandil was associated with normalization of endothelium-dependent vasodilation of the brachial artery. This effect was more pronounced during therapy with nicorandil.

Implication of α2ß1 integrin in anoikis of MCF-7 human breast carcinoma cells.

Silencing of α2ß1 integrin expression significantly promoted anchorage-dependent apoptosis (anoikis) and drastically reduced clonal activity of MCF-7 human breast carcinoma cells. Depletion of α2ß1 enhanced the production of apoptotic protein p53 and of inhibitor of cyclin-dependent protein kinases, p27, while downregulating antiapoptotic protein Bcl-2 and multifunctional protein cMyc. Blocking the expression of α2ß1 had no effect on activity of protein kinase Akt, but it sharply increased the kinase activity of Erk1/2. Pharmacological inhibition of Erk1/2 had a minor effect on anoikis of control cells, while it reduced anoikis of cells with downregulated α2ß1 to the level of control cells. The data show for the first time that integrin α2ß1 is implicated in the protection of tumor cells from anoikis through a mechanism based on the inhibition of protein kinase Erk.

[Comparative Assessment of Effects of Isosorbide Dinitrate, Isosorbide-5-Mononitrate and Nicorandil on the Frequency-of Angina Attacks and Vasoregulating Endothelial Function in Patients With Ischemic Heart Disease].

AIM: to compare effects of isosorbide dinitrate, isosorbide-5-mononitrate and nicorandil on frequency of angina attacks and vasoregulating endothelial function in patients with ischemic heart disease (IHD). MATERIAL AND METHODS: In 117 patients with stable II-III functional class angina we analyzed frequency of angina attacks, exercise tolerance, data of 24-hour Holter ECG monitoring and brachial artery Doppler study. RESULTS: Patients with IHD had impaired endothelium-dependent vasodilation in the form of reduced endothelial response to increase of "shear stress" during test with reactive hyperemia. Long-term therapy with isosorbide dinitrate, isosorbide-5-mononitrate, and nicorandil was associated with normalization of endothelium-dependent vasodilation of the brachial artery. This effect was more pronounced during therapy with nicorandil.