ENDOTHELIAL DYSFUNCTION AND PATHOGENETIC PHENOTYPES OF LOCALIZED SCLERODERMA.

There are several pathogenetic models of localized scleroderma. At the same time, studies examining the role of endothelin-1, vascular endothelial growth factor (VEGF-A) and cell adhesion molecule-1 (VCAM) are limited. Objectives - to learn the nature of disorders of vascular, proliferative, adhesive functions of the endothelium on the content of endothelin-1, VEGF-A and VCAM-1 in localized scleroderma. The study included 78 patients with localized scleroderma and 35 healthy individuals (mean age - 44.2±17.6 years, 73 women (64.6%), 40 men (35.4%). All patients underwent clinical, laboratory, enzyme-linked immunosorbent assay examination (endothelin-1, VEGF-A, VCAM-1). In the local form of scleroderma, there are the number of disorders of vascular, proliferative and adhesive functions of the endothelium, with an increase in endothelin-1 (p<0.05), VEGF-A (p<0.05) and VCAM-1 (p<0.05) content. In idiopathic atrophodermia, the level of endothelin-1 was probably higher (p<0.05). The vasospastic type of pathogenesis of localized scleroderma was established in patients under 20 years of age (p<0.05) and in patients older than 70 years (p<0.05). U-shaped age dependence of pathogenesis was noted: high content of VEGF-A in patients under 20 years of age (p<0.05) and after 35 years (p<0.05). Higher levels of VCAM-1 were found in women compared to men (p<0.05). The analysis of the age dependence of the content revealed a U-shaped dependence of VCAM-1 - the highest content in patients under 20 years (p<0.05) and in patients 55-70 years (p<0.05). The level of biomarkers of endothelial dysfunction in patients with localized scleroderma - endothelin-1, VEGF and VCAM is associated with different phenotypes of the disease course - vasospastic, proliferative or adhesive.

Relationship between the Contents of Cyclins, Cyclin-Dependent Kinases, and Their Inhibitors in Whole Blood Mononuclear Leukocytes during the Postclinical Stage of Community-Acquired Pneumonia under the Influence of 1-GHz Microwaves.

The contents of cyclins A1, B1, E1, and D1, cyclin-dependent kinases 2 and 4 (CDK2 and CDK4), cyclin-dependent kinase 2C inhibitor (p18), and cyclin-dependent kinase 1C inhibitor (p57) in whole blood mononuclear cells of practically healthy donors and convalescents from community-acquired pneumonia were measured after cell exposure to low-intensity electromagnetic radiation of 1 GHz. The level of cyclins A1, D1, and B1, p57, and p18 proteins, and CDK2 was reduced in convalescents, while the content of cyclin B1 was elevated in both groups. A strong correlation was found between the content of cyclin B1 and the levels of cyclin A1 and CDK2 in convalescents. Single exposure of whole blood cells to 1-GHz microwaves was accompanied by an increase in the content of the analyzed factors (particularly, cyclins A1 and E1). These data indicate that radiation induced activation of the synthetic phase of the cell cycle.

[PROINFLAMMATORY CYTOKINES AND SIGNALING PATHWAYS IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE].

Aim: To determine content of mononuclear ells (MNC) in peripheral blood of patients with coronary heart disease (CHD) and factors responsible for their functional state and cytokine production. Materials and methods: Concentration of proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3, STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin 1ß, 2, 4 and y-interferon levels were measured in blood sera. Results: In patients with angina of effort and unstable angina, the JNK level was 59,8% and 53,1% higher than the normal one respectively (р=0,013) and (р=0,012). The level of the nuclear transcription factor was 26,9% (р=0,015) and 27,9% (р=0,017), JAK2 31,5% (р=0,022) and 48,6% (р=0,018), STAT3 49,6% (р=0,025) and 55,3% (р=0,02), STAT5B 21,5% (р=0,018) and 30,2% (р=0,011) lower. These changes were associated with a 13,1% (р=0,047) and 51,4% (р=0,019) rise in the STAT6 level, 30,1% (р=0,025) and 79,4% (р=0,003) FAK level, 7,6% (р=0,09) and 15,2% (р=0,039) АКТ1 level, 65,3 (р=0,02) and 76,2% (р=0,017) p70S6K level. Conclusion: Results of the study suggest persistent pro-inflammatory activation of whole blood cells in CHD patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK signal pathway in MNC and decreased STAT3 level determining cell sensitivity to IL-10. The elevated intracellular level of ERK and JNK us responsible for high responsiveness of MNC to pro-inflammatory cytokines.

[Effect of an angiotensin-converting-enzyme inhibitor on the plasma concentration of cytokines and vasoactive molecules in patients with coronary heart disease and hypertension]. / Vliianie ingibitora angiotenzinprevrashchaiushchego fermenta na kontsentratsiiu v plazme krovi tsitokinov i vazoaktivnykh molekul u bol'nykh ishemicheskoi bolezn'iu serdtsa i arterial'noi gipertoniei.

AIM: To investigate the plasma concentrations of cytokines and vasoactive molecules in patients with coronary heart disease (CHD) in the presence of hypertension in relation to the angiotensin-converting-enzyme (ACE) inhibitor level reflecting the degree of renin-angiotensin-aldosterone system (RAAS) inhibition. SUBJECTS AND METHODS: 72 patients with NYHA functional class (FC) II-III angina pectoris and 40 healthy persons at the age of 47-65 years were examined in a controlled cohort study. Enzyme immunoassay was employed to determine the serum concentrations of interleukins (IL) (IL-2, IL-12, IL-17A, and IL-24), the vasoactive molecules of bradykinin, serotonin, ACE, angiotensin-II (AT-II), NO, and endothelin-1 (ET-1), and plasma renin activity. In addition, the plasma level of the tetrapeptide N-acetyl-Ser-Asp-Lys-Pro was used as a marker for ACE inhibition. RESULTS: The patients with CHD occurring in the presence of hypertension compared with the apparently healthy individuals displayed decreased ET-1 and NO production along with elevated levels of serotonin, AT-II, as well as IL-17A and IL-12. The found changes were accompanied by reduced renin activity. Thus, the individuals with low ACE inhibitor levels showed more pronounced production of the proinflammatory cytokine IL-17A, as well as high plasma concentrations of ACE and NO. The high ACE inhibitor level that reflects patient adherence to appropriate antihypertensive therapy is associated with the reduced production of IL-2 and with the minimum serum levels of ACE, AT-II, and NO, being characterized by the high production of IL-12 and serotonin at the same time. CONCLUSION: In patients with CHD and hypertension, the high plasma enzyme inhibitor concentration that reflects the activity of appropriate antihypertensive therapy, by contributing to the strengthening of the mechanisms of relaxation of blood vessels, is associated with the risk for proinflammatory activation of whole blood cells and platelets. The mean ACE inhibitor levels that reflect moderate RAAS suppression and are characterized by a relatively low proinflammatory activation of mononuclear cells may be more preferable than the maximum ones, from the point of view of slowing the progression of the subclinical inflammatory process of the vascular wall and preventing possible CHD exacerbations. This determines the feasibility of estimating the plasma level of an ACE inhibitor to control the depth of inhibition of RAAS activity.

[The state of receptor-dependent signal pathways in the agranulocytes from the peripheral blood of the reconvalescent patients following community-acquired pneumonia under the influence of microwave radiation]. / Sostoyanie retseptorzavisimykh signal'nykh putei v agranulotsitakh perifericheskoi krovi rekonvalestsentov vnebol'nichnoi pnevmonii pod vliyaniem mikrovolnovogo izlucheniya.

The present article reports the study of the influence of low-intensity microwave radiation on the state of the JAK/STAT-signaling pathways in the mononuclear cells and the intercellular levels of the molecules maintaining the functioning of this pathway. The experiments on the model of intercellular interactions in the whole blood cell culture obtained during the convalescence phase of community-acquired bacterial pneumonia were designed to elucidate the effects of the cell-cell interactions in the culture exposed to electromagnetic radiation with a frequency of 1000 MHz and power flux density 0.1 mcW/cm2 on the intracellular levels of total and phosphorylated species of JAK-kinases, STAT-factors and SOCS-proteins. It is concluded that sensitivity of intracellular signaling systems to the effects of low-intensity microwave radiation manifests itself in the form of increased intracellular concentrations of Janus kinases and SOCS proteins with a simultaneous decrease in the level of STAT factors.

Cardiomyocyte Autophagia and Morphological Alterations in the Left Ventricular Myocardium during Acute Focal Ischemia.

In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensification of cardiomyocyte autophagia, which attained maximum on postligation day 1.

[The laboratory detection of intra-cellular factors of anti-viral defense under community-acquired pneumonia in evaluation of effects of low-intensity microwave radiation].

The study was carried out to investigate intro-cellular concentration of factors of antiviral defense of cells of whole blood of re-convalescents of community-acquired pneumonia and healthy individuals under effect of low intensity SHF-radiation of whole blood in vitro with frequency of 1000 MGz. The technique of enzyme-linked immunosorbent assay was applied for analyzing lysates of mononuclears of whole blood exposed to impact of low intensity SHF-radiation with frequency of1000 MGz on concentration of mitochondrial antiviral signal protein MAVS, RIG-I-like receptor type III - helicase LGP2, RIG-I-like receptor - helicaseMDA5, trans-membrane protein 173 (Tmem 173), interferon-regulated factors (IRF) 3,7 and 8, sub-units p50 and p65 of nuclear factor of transcription NF-kB, phosphorylated on serine in position form 32 of inhibitor of nuclear factor of transcription (IkB-a) and also its total concentration. Besides, spontaneous production of interferon - a/ß by cells of whole blood was evaluated in cellular supernatant. The capacity of single 20 minutes of SHF-radiation effect to increase intracellular level of important regulative proteins, primarily MDA5, during the phase of convalescence of community-acquired pneumonia was established. Besides, radiation stimulates increasing of intracellular level of MAVS and Tmem173. The capacity of radiation was established to increase phosphorylation of inhibitor of nuclear factor NF-kB and level of components p50 and p65 of NF-kB. The capacity of SHF-radiation effecting production of interferon-ß by cells of hole blood is demonstrated. In healthy individuals, radiation contributes into decreasing of intercellular content of MAVS in more degree as compared with levels of MDA5 and Tmem173. At that, radiation of culture of cells of whole blood stimulates increasing of production of interferons.

Broadband observations of the naked-eye gamma-ray burst GRB 080319B.

Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet.

[Indexes of activity of specialized department for the treatment of foot lesions in patients with diabetes mellitus]. / Polaznyky diial'nosti spetsializovanoho viddilennia z likuvannia urazhennia stopy u khvorykh na tsukrovyi diabet.

Experience of treatment of 2524 patients with diabetes mellitus (DM) for the 1990-2001 yrs period was summarized. Of all the patients 48-52% are presenting the citizens of Darnitskiy and Kharkivskiy regions of city of Kyiv. For the 1990-1994 yrs period general lethality had constituted 7.5-9.1%, postoperative mortality--9.2-13.5%, while after 1996--4.3-1.9 and 5.4-1.1% accordingly. Improvement of results of treatment was promoted by conversion in 1996 to conduction of operative interventions using spinal or epidural anesthesia. From 2000 we are planning performance of two-, three- or multistage treatment of patients because there exists possibility to preserve the foot, using several stages to excise nonviable tissues and to perform plastic operations. Right from the moment when conversion to multistaged operations happened, new demands occurred for quality of local measures of struggle against infection and for application of technology for preservation of viability in the skin-free foot tissues. Analysis of the case records of 62 patients with DM, to whom in other medical institutions operation for purulent-necrotic affection of the foot was performed, witnesses the necessity of spreading of the experience of the specialized division work among surgeons and endocrinologists.

[Immunological disturbances in psoriatic patients exposed to radionuclides and corrective complex therapy with dibazol and hepatoradioprotective diet]. / Imunni porushennia u khvorykh na psoriaz pid vplyvom radionuklidiv ta koryhuiucha kompleksna terapiia dybazolom i hepatoradioprotektornoiu diietoiu.

In an inpatient setting, 67 and 70 patients with psoriasis living in contaminated and uncontaminated with radionuclides territories respectively were studied in the time-related course of some qualitative indices of immunity. Significant deviations from the norm were recordable, especially in those patients residing in the contaminated with radionuclides tcrritiry. Combined treatment involving the use of dibazol and hepatoradioprotective diet in the experiment group of psoriatic patients proved to be significantly more effective than in patients of the control group who were treated by the generally accepted method.

[Correction of lipid peroxidation intensity and glutathione system by derivatives of polygalacturonic acid after exposure to nitrogen dioxide]. / Korrektsiia proizvodnymi poligalakturonovoi kisloty intensivnosti perekisnogo okisleniia lipidov i sistemy glutationa pri vozdeistvii dioksida azota.

Influence of intraperitoneal administration of polygalacturonic acid derivatives at a dose of 100 mg/kg on the glutathione system and lipid peroxidation in the rat lung after treatment with NO2 was studied. A considerable decrease of lipid peroxidation intensity by these derivatives was caused not only by ability of these compounds to the chelate formation and absorption of free radicals, but also by the substantial activation of the glutathione system.

[Prediction of bleeding from esophageal and gastric varices in patients with liver cirrhosis]. / Prognozirovanie krovotecheniia iz varikozno-rasshirennykh ven pishchevoda i zheludka u bol'nykh s tsirrozom pecheni.

A course of the disease was studied in 190 patients with hepatic cirrhosis and portal hypertension without bleeding as well as in 107 patients with bleeding from esophageal and gastric varices. The Wald's consecutive analysis with derivation of a summary diagnostic coefficient on the basis of 13 clinical signs was used. Effectiveness of the method was assessed by means of retrospective analysis of 150 case records and long-term results of treatment of 30 patients. The method permits to predict the development of gastroesophageal bleeding in 95.4% of cases.