[An experience of the use of stem cells in the treatment of patients with myocardial infarction and low ejection fraction].

We present our own experience of assessment of effect of cell therapy on functional state of the myocardium in patients with lowered contractile capacity of the left ventricular myocardium. Intracoronary administration of stem cells in acute myocardial infarction is a safe method of treatment. It does not cause additional damage of the myocardium and does not provoke appearance of malignant arrhythmia. Cell therapy does not affect global left ventricular function. Data we have obtained demonstrate tendency to improvement of myocardial contractile function in dynamics in the majority of studied patients, including patients of the comparison group. This most probably indicates that the given process has been caused by restoration of blood flow to surviving cardiomyocytes after transluminal coronary angioplasty and improvement of function. Confirmation of participation of administered cells in myocardial contraction and improvement of perfusion requires further clinical investigations.

[Effect of cytarabine on expression of cell adhesion molecules and on endothelium-leukocyte interaction in vitro].

AIM: To characterize cytarabine effects on human endothelium expression of cell adhesion molecules (CAM) of various classes and interaction of cultured endothelial cells (EC) with blood leukocytes. MATERIAL AND METHODS: Primary cultures of EC of human umbilical vein were obtained by EC culturing for 24-72 h with cytarabine (10 mcg/ml). They were investigated with phase-contrast microscopy, immunohistochemistry and flow cytometry. RESULTS: Cytarabine effects manifested with EC-induced expression of cell surface P- and E-selectines and VCAM-1; ICAM-1 expression rapidly enhanced, leukocyte adhesion to endothelium also activates. CONCLUSION: Cytarabine, as a pathogenetic factor, induces proinflammatory alterations of the endothelium responsible for development of vascular complications in patients on cytostatic therapy.

[Space and time organization of perception in patients with chronic cerebral vascular insufficiency].

According to A.A. Ukhtomsky, chronotope is defined as a complex of time and space relations between subjects and events that surround human organism. Perception of chronotope by an individual is measured by individual minutes (IM), each minute being measuring in mind, and individual decimeters (ID) depicted by an individual as a line. In case of their simultaneous measuring, IM and ID chronotope is registered. Perception of chronotope has been studied in 31 women and 7 men with chronic cerebral vascular insufficiency and compared to the data obtained earlier in the group of young healthy people used as controls. In patients, giving short measure of time that was not treatment-depended, mismatch of spatial and temporal indices of chronotope measuring and influence of gender were observed.

[Damage of vascular endothelium in the treatment of acute leukemia: in vitro study]. / Povrezhdenie sosudistogo éndoteliia v protsesse lecheniia ostrykh leikozov: issledovanie in vitro.

AIM: Cytostatic drugs used in the treatment of hemopoietic malignancies affect cells of other organs and systems, vascular endothelium, in particular. This leads to cardiovascular complications. We studied effects of some drugs and their combinations on cultured human endothelial cells (EC). MATERIAL AND METHODS: Primary culture of umbilical human vein EC was used in the study. Cytosinearabinoside (cytozar, alexan, cytarabin) and daunorubicin were added in concentration from 1 ng/ml to 1 mg/ml; the action of the drugs was assessed by morphology of the cells, their viability, inclusion of bromodesoxyuridine by means of cloning, immunohistochemistry and flow cytofluorimetry. RESULTS: It is shown that in a wide range of concentrations cytosinearabinoside and daunorubicine cause specific structural-functional changes in the cells related to cytostatic and cytotoxic effects. CONCLUSION: The data of the study confirm that cardiovascular complications in the course of acute leukemia treatment are resultant from systemic damage to vascular endothelium.

[Effects of ozone on the lipid peroxidation--antioxidation system in blood serum of patients with chronic bronchitis]. / Vliianie ozona na sistemu "perekisnoe okislenie lipidov -- antiokislitel'naia aktivnost''" v syvorotke krovi u bol'nykh khronicheskim bronkhitom.

Biological effects of ozone on the lipid peroxidation (LPO)--antioxidation system was studied in blood serum of patients with various forms of chronic bronchitis. Breathing ozone was shown to intensify LPO processes and lead to a more considerable deviation of the parameters of non-enzymatic but not enzymatic antioxidants in patients.

[Peripheral blood morphology during chronic bronchitis complicated by the effect of ozone]. / Morfologiia perifericheskoi krovi pri khronicheskom bronkhite, oslozhnennom deistviem ozona.

In workers afflicted with chronic bronchitis (ChB) after breathing ozone leukocytosis gives place to leukopenia against development of lympho-, monocyto- and neutropenia. In contrast to the workers, in citizens who have not previously contacted ozone chronic obstructive bronchitis is characterized by leukocytosis with less expressed lympho- and neutropenia. Changes in peripheral blood in ChB patients (development of leuko-, lympho-, monocyto- and neutropenia) grow drastically in 5-8 years of ozone inhalation.

[On some basic issues and factorial structure of ecological pulmonology]. / Nekotorye obshchie voprosy y faktorial'naia struktura ékologicheskoi pul'monologii.

Consideration is given to the place occupied by diseases of respiratory organs in the general structure of morbidity. In many ways, growth in their number has been determined by amplification of anthropogenic factors. This is manifested in emergence of new eco-dependent diseases and syndromes including more difficult course of pulmonary pathology. One of the prioritized disciplines of the modern pulmonology is ecological pulmonology which lies in the domain of medical ecology and is central to the concept of eco-dependent human diseases. A factorial structure of ecological pulmonology built on the etiological principle is proposed to facilitate inquiry into the origin and course of various forms of eco-dependent pathology of the lung.

[Alterations in actin cytoskeleton and rate of reparation of human endothelium (the wound-healing model) under the condition of clinostatting]. / Izmeneniia aktinovogo tsitoskeleta i skorosti reparatsii mekhanicheski povrezhdennogo monosloia éndoteliia cheloveka v usloviiakh klinostatirovaniia.

Effects of long-term simulation of hypogravity on actin cytoskeleton and cell migration were investigated in cultured human endothelium cells (EC). In control, F-actin resided predominantly on the periphery of cell forming an array of parallel bundles with "dense bodies" along the edge. A small number of actin cable fibers was found in the center. Already after 1-2 hrs of clinostatting at 5 RPM the cell cytoskeleton showed actin filament thinning and displacement toward the cell edges. In subsequent 6-18 hrs, almost all actin fibers had left the center part of EC and had ranged themselves in a continuous F-actin line in the intercellular contact area. In most cases, these changes resulted in the so-called "ruff-edge". Since both the disappearance of cable fibers and formation of the "ruff-edge" add to the cell migration activity, this parameter was studied with the would-healing model. According to our data, 24-48 hrs of exposure to hypogravity stimulates cell migration and expedites 2-3 times reparation of mechanically damaged monolayer. The results suggest that effects of hypogravity on cultured human EC are likely to be consequent to alterations in the activity of protein kinase C and/or adenylate cyclase involving many members of the cellular metabolism.

[Morphological and functional study of human endothelium response to hyperthermia in vitro]. / Morfologicheskie i funktsional'nye osobennosti otveta éndoteliia cheloveka na gipertermiiu in vitro.

Effects of hyperthermia (+42.5 degrees C) on the endothelial monolayer organization, actin cytoskeleton and cell viability have been examined in culture of human aortic endothelial cells (EC). Short-lasting hyperthermia (1-4 hrs) provoked disappearance of stress fibers, redistribution of actin filaments to the area of cell-to-cell contacts, shape changes and reorganization of the monolayer. It also stimulated formation of intercellular contacts in a preconfluent EC culture. The cAMP content was elevated one hour after heat treatment and then lowered to negligible values (comparing to the basal cAMP level). Long-lasting hyperthermia (6-72 hrs) resulted in EC injury, and damage of endothelial monolayer accompanied by increased Chromium-51 release and almost complete blockade of [3H]-thymidine incorporation into DNA. Addition of cAMP elevating drugs (forskolin, 8-Br-cAMP or isobutylmethylxanthine) into the cell culture medium prevented heat-induced decrease in cAMP concentration, stimulated EC spreading, protected EC from injury, and promoted integrity of endothelial monolayers. Obtained results indicate that long-lasting hyperthermia can be regarded as an additional factor of endothelium injury involved in development of vascular pathology.

[From chronobiology to chronotopobiology]. / Ot khronobiologii k khronotopobiologii.

Based on the data available in the literature and his own findings, the author presents a concept of the spatial-temporary organization of biological systems. Experimental evidence is provided for this concept with emphasis on its theoretical and medical values. A role of spatial and temporary organization in the activity of the biological system is shown separately. It is emphasized that the spatial-temporary organization of biological system is not the sum of properties of components of its spatial and temporary organizations and has its own features. The author proposed to single out a section of theoretical biology dealing with the study of the spatial-temporary organization of biological systems and to call it chronotopobiology.

[Spatial and temporary changes in sensitivity of murine proliferative system and energy exchange to typhoid fever infection]. / Prostranstvennye i vremennye izmeneniia chuvstvitel'nosti sistem proliferatsii i énergeticheskogo obmena u myshei k vozdeistviiu briushnotifoznoi infektsii.

The authors studied the spatial and temporary organization of the proliferative system and energy exchange in the small intestinal epithelium, as well as spatial and temporary changes in the sensitivity of these systems in mice to typhoid fever infection (cultured Salmonella typhi, 4446) at day and night. The small intestinal epithelial systems were found to show a spatial and time organization and a close correlation between their temporary and spatial changes after infection. The temporary organization of the proliferative system in the esophageal epithelium is more sensitive to infection in the day-time and that of the small intestinal epithelial proliferative system is more marked at night. Thus, these changes are tissue-specific. Typhoid fever infection causes a negative effect on the proliferative system of the small intestine at night and on its energy exchange in the day-time, which shows the system-specific response of the temporary organization of a biological process within the same organ. The changes in the spatial proliferative and energy exchange parameters in the small intestinal epithelium, which have been caused by the infection of animals, depend on the time of a day.

[Chrono-ecological analysis of population health and ways of its recreation]. / Khronoékologicheskii analiz sostoianiia zdorov'ia naseleniia i sposoby ego rekreatsii.

Reported are results of multiyear observation of the structure of individual and population health in Vladikavkaz, and the authors' concept of health recovery and protection through application of modern high technologies of active chronoadaptation to extreme living conditions. The proposed methods of active chronoadapation, i.e. phytocorrection and phytopro-phylaxis, reflexocorrection, bioradiological correction, bioresonance chronolasercorrection can be also of interest for aerospace medicine.

[Gravitation sensitivity of human endothelium]. / Gravichuvstvitel'nost' éndoteliia cheloveka.

Experiments on the effects of hypogravity (clinostatting) on growth and formation of monolayer of cultivated endothelium cells of the human umbilical vein demonstrated sensitivity of endothelium to the gravitational stimulus as it responded by a significant reduction of the proliferative activity of cells in culture. The most favorable conditions for cultivating endothelium cells under extended (15-d) hypogravity in vitro were determined.

[Coculture of human endothelium and smooth muscle cells: functional heterogeneity of endothelial cells from zones with different susceptibility to atherosclerosis]. / Sovmestnoe kul'tivirovanie éndotelial'nykh i gladkomyshechnykh kletok aorty cheloveka: funktsional'naia geterogennost' éndoteliia v zonakh s razlichnoi predraspolozhennost'iu k aterosklerozu.

Using co-culture technique and 3H-thymidine radioautography we have studied effects of human aortic endothelial cells (EC), isolated separately from zones of low (LP) and high (HP) probability of atherosclerosis of grossly normal and atherosclerotic aortas, on 3H-thymidine incorporation by human intimal smooth muscle cells (SMCs). It was found that EC activity depended on a zone of probability, from which the cells were isolated, and on the degree of atherosclerotic lesion. The first-passage ECs from grossly normal LP zones inhibited 3H-thymidine incorporation, compared to control, incubated without Ecs, SMCs (63.5 +/- 27.5%). Cells from HP zones of the same vessels were less active or stimulated SMC proliferation (99.4 +/- 42.9%). EC cultures obtained from both LP and HP zones of atherosclerotic vessels had, as a rule, no effect or increased 3H-thymidine incorporation by SMCs (100.3 +/- 19.8 and 124.1 +/- 20.1%). In contrast to morphologically heterogeneous primary and first-passage cultures obtained from high seeding density, EC monolayers obtained with a split 1:10 were composed predominantly of small mononuclear cells. These cultures effectively inhibited SMC DNA synthesis independently of a zone of probability and a degree of atherosclerotic lesion of aorta (60.4 +/- 10.0 and 51.5 +/- 12.7%). The obtained data suggest that EC morphological heterogeneity is accompanied by functional changes of cells and may be involved in atherosclerotic plaque formation.

[Role of staphylococcus aureus hemolytic toxin-alpha in pathogenesis of infectious endocarditis: studies in vitro]. / Rol' alpha-gemoliziruiushchego toksina staphylococcus aureus v patogeneze infektsionnogo éndokardita (issledovanie in vitro).

AIM: To study effects of alpha-toxin (AT) Staphylococcus aureus on human platelets and endothelial cells. MATERIALS AND METHODS: Concentrations of intracellular calcium in human platelets and endothelial cells were estimated by fluorescence, phosphoinositide metabolism in the endothelial cells was studied using 3H-myoinositole. RESULTS: AT induced a dose-dependent increase of intracellular calcium in blood and vascular cells, stimulates dose-dependent formation of inositol phosphates in endothelial cells. CONCLUSION: AT action on the platelets and endothelial cells results in a significant receptor-independent rise in concentration of intracellular calcium, activation of phosphoinositide metabolism, death of cells. These data support the hypothesis that the platelet and endothelial cell damage is mostly due to the passive Ca2+ influxvia pores formed by AT in cellular membrane.

[Morphologic and functional characterization of human aortic endothelium. III. Growth in culture and colony formation at low seeding density]. / Morfologicheskie i funtsional'nye osobennosti éndoteliia aorty cheloveka. III. Rost v kul'ture i formirovanie kolonii pri nizkoi plotnosti posadki.

In human aortic endothelial cell (HAEC) cultures, obtained separately from aortic zones of low (LP) and high (HP) probability of atherosclerosis, proliferative characteristics of cells and HAEC ability to form colonies at clonal seeding density were studied. It has been found that the population doubling time is significantly higher in endothelial cell (EC) cultures from HP-zones, compared to that in cultures from LP-zones of the same vessels. In cultures from both LP- and HP-zones only a few percent of EC had a proliferative potential enough to form cell colonies. The number of formed colonies was always lower in EC cultures from HP-zones, and decreased depending on atherosclerotic lesions and cell donor age. The obtained data suggest that the decline of EC proliferative potential, mostly in HP-zones (even without visible signs of atherosclerotic lesions) is due to a decrease in the number of cells with a high mitotic activity, i.e. "cambial" cells.

[Induction of cell adhesion molecules, E-selectin, VCAM-1 and ICAM-1, in a co-culture of human endothelial and smooth muscle cells]. / Induktsiia molekul kletochnoi adgezii, E-selektina, VCAM-1 i ICAM-1 v sovmestnoi kul'ture éndotelial'nykh i gladkomyshechnykh kletok cheloveka.

Using immunofluorescence and flow cytometry, we studied the surface expression of cell adhesion molecules, E-selectin, VCAM-1 and ICAM-1, in human umbilical vein endothelial cells (HUVEC) co-cultured with human aortic intimal smooth muscle cells (SMC). It was found that inactivated HUVEC constitutively expressed only ICAM-1. After 3-4 h of co-culturing with SMC in the Transwell system we observed the appearance of E-selectin and VCAM-1, and the increase of ICAM-1 content on the cell surface. In all the cases, the maximum expression of these molecules (85-100% of positively stained cells) was detected within 18-24 h after co-culturing. Similar effect was exerted by SMC-conditioned culture medium, whose action well compared with that of a direct addition of interleukin-1 to EC at a concentration of 5-10 u/ml. The obtained data suggest that the cytokines secreted by SMC may participate in the regulation of endothelial cell adhesion molecule expression, and influence cell accumulation in sites of inflammation, immune disorders, etc.