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ჩიტაძის ქ., 11, თბილისი, საქართველო

2015 წლის 12-16 ოქტომბერი

2015 October, 12-16

Tbilisi, Georgia, Chitadze St., 11

რეოლოგიის და მიკრეცირკულაციის საერთაშორისო სკოლა

International School of Rheology and Microcirculation

სკოლის ორგანიზატორი - მ. მანწკავა Head of School - Mantskava M.M.

ELECTRORHEOLOGICAL METHOD FOR STUDYING THE FLOW PROPERTIES OF BLOOD

1N. Antonova, 2P. Riha, 1I. Ivanov

1 Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria, 2Institute of Hydrodynamics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Тhe study presents an electrorheological method, based on the dielectric properties of dispersed systems in Couette flow, developed and used recently for identification and quantification of blood microstructural changes due to RBC aggregation-desaggregation and deformation processes at different shear rates and at different local structure of the flow field. The main advantage of this technique is that blood is subjected to a uniform shearing field in a Couette rheometric cell, and information about the mechanical properties of the fluid is obtained in parallel; furthermore, the resulting data could be directly related with results from different techniques using similar geometries and flow conditions. A concurrent measurement system with Contraves Low Shear 30 rotational rheometer, a device with data acquisition system and the program unit Rheoscan 100 were used and analyzed. Different unsteady flow conditions are simulated: rectangular (step-wise), trapezium-liked and triangular regimes of changes of shear rates. The relationship between the whole blood/RBC suspensions conductivity and time/shear rates was studied in parallel with the changes in the rheological behaviour under transient flow conditions. The time variation of blood/RBC suspensions conductivity at these unsteady flow conditions and the typical responses of the shear stresses under electric field of 2 kHz are presented. The results show that the blood conductivity is strongly dependent on the considered blood flow regimes. The results also show the conductivity dependences on shear rate, hematocrit and temperature.

NUMERICAL ANALYSIS OF BLOOD FLOW IN THE COMMON CAROTID ARTERY BIFURCATION WITH STENOSIS FOR UNSTEADY FLOWS

1N. Antonova, 2D. Xu, 3I. Velcheva, 4E. Kaliviotis, 1P. Tosheva

1Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria

2School of Civil Engineering, Tianjin University, Tianjin, China.

3University Hospital of Neurology and Psychiatry, Medical University, Sofia, Bulgaria

4Dept. Mechanical Engineering and Materials Science and Engineering, Limassol, Cyprus

Objective: To analyze numerically the time-varying blood flow in the common carotid artery (CCA) bifurcation on the basis of Navier-Stokes equations. For four different cases, including cases without stenosis and with one, two and three stenoses at different sites in the vicinity of the bifurcation. Materials and Methods: The cases studied were: a) without stenoses, b) with one stenosis upstream the bifurcation, c) with two opposite stenoses upstream the bifurcation and d) with an additional stenosis on the apex of the bifurcation. The blood flow in the arteries is modeled as incompressible viscous flow. The governing Navier-Stokes equations describing pulsatile, three-dimensional flow of an incompressible Newtonian fluid are approximated using a finite volume method. To create the complicated shape of the computation area a CAD system is applied with tetrahedral elements The mesh was generated via a geometry reconstruction and imported into a Computational Fluid Dynamics (CFD) solver. Results: The numerical results of the blood flow in the common carotid artery (CCA) bifurcation give a detailed picture of the axial and radial velocity distribution and presented as velocity and vorticity magnitudes. The structures of the flow around the bifurcation from the common carotid artery (CCA) to the internal carotid artery (ICA) and external carotid artery (ECA) are obtained considering characteristic time points for one pulse wave period For the case of carotid bifurcation without stenosis results for the axial velocity distribution are presented in six characteristic time points of the pulse wave: T=0 s, 0.1s 0.2s, 0.3s, 0.4s, 0.5s. The axial velocity distribution and wall shear stress (WSS) distribution and contours are presented. Discussion: The obtained velocity and WSS distribution around the bifurcation allow a prediction of the probably sites of stenosis growth. The recirculation zone behind the stenosis is the area of low WSS. Thus this area is the most probable one for monocytes and platelet aggregation and thrombosis formation. More specifically, it was observed that the appearance of stenotic regions upstream the bifurcation affect both the velocity and vorticity characteristics, whereas a stenosis on the apex of the bifurcation seems to have a small effect on the vorticity characteristics downstream the flow in the ECA and ICA.

REOLOGICAL DISORDERS DURING BLOOD LOSS

M.Mantskava, N.Momcelidze, L.Davlianidze

1. Beritashvili Center of Experimental Biomedicine, Tbilisi,

Georgia

Hemorrhagic shock appears to be the sequel of a variety of diseases, especially in abdominal surgery and in gynecological departments. In spite of this, the mechanism of development of microcirculational disorders as one of the basic links of shock pathogenesis has not been appropriately studied. In the past, shock was viewed only from the aspect of the alteration of general hemodynamics. In present day scientific literature, studies are often related only to the intravascular hemocoagulation. From the point of view of blood rheological properties, the crucial factors in the microcirculation system are: local hematocrit, erythrocyte aggregability, erythrocyte deformability and plasma viscosity. As regards the erythrocyte deformation, this rheological parameter may account for far graver results in organs, for the diameter of the capillary lumen is equal to or less than the erythrocyte size. Hemorheological shock appears to be a complex pathological process where the mechanism is unexplored. A particular link, which is involved in various stages of hemorheological shock, is blood rheology. The aim of our work was the study of red blood cell deformation (rheological marker) after different degrees of severity of experimental hemorrhagic shock. The study of erythrocyte deformability violation and a compulsory monitoring of this physical value deserve more attention of fundamental and applied sciences. Erythrocyte deformability depends on their elasticity and rigidity, therefore the determination of erythrocyte deformation index is particularly important for the treatment and prognosis of hemorrhagic shock. Experiments were carried out on adult rats of both sexes weighting 250-300 g., anesthetized with 4% solution chloral hydrate (0.15 ml/100 g,) administered intramuscularly. The conditions for conducting the work on animals corresponded to the European Convention on the protection of experimental animals, adopted in 1986 in Strasbourg and for the conduct of the experiments, the consent of I.Beritashvili Center of Experimental Biomedicine Ethics Committee was obtained. The modelling of hemorrhagic shock of different stages was performed in the group of anesthetized animals by means of standard blood discharge from the femoral artery (2.5 ml - first stage of shock; 5 ml - second stage of shock; 5ml - third stage of shock, n=12). Arterial pressure was measured in the tail vein with manometer MPX5050D (Motorola). The index of RBC deformability was determined by the nucleopore membrane filter method during hemorrhagic

shock and on the control group. Evaluation of erythrocytes deformability with the nucleopore membrane filter method, is based on assessing the velocity of the erythrocytes’ passage through very small pores (5 μm, which is the diameter of the smallest capillary) of the filter, at constant pressure (10 cm of water column) and temperature (37°C). Obtaining the pure erythrocytes was performed by centrifuging the blood sample at 3000 rpm for 15 min. The resulting plasma was aspirated with a micropipette and the remaining blood cells were added with bovine serum albumin (0.2 mg per 5 ml) and dissolved in the phosphate buffer. Then the blood was centrifuged a second time at 1000 rpm for 5 min. The precipitated erythrocytes, as well as thin layer of leukocytes and thrombocytes, were separated from the phosphate buffer. This procedure was repeated three times. Purified erythrocyte mass was diluted in the phosphate buffer, with hematocrit of 10%. Velocity of the erythrocyte passage through the filter (mm/min) was recorded. High quality polycarbonate filters (with 5 μm diameter pores) were used in the measuring procedures. The index of RBC deformability in the control group was 2.25±0,03%. The index of RBC deformability at the first, second and third stages of hemorrhagical shock is shown in table 1. Data show, that the index of deformability decreases with increase in the number of hemorrhagical shock’ stage (12% - one subgroup, 13% - second subgroup and 15% - third subgroup). The analysis of the data was performed using statistical programs “Origin 4.1” (Microsoft. Software, Ivc) and Microsoft Excel. All results were evaluated statistically and the significance of differences between mean values were assessed by Student’s Criterion. Acrisis of macro- and microcirculation shows an especially specific character after hemorrhagic shock. Hemorrhagic shock and the stages of its development depend on an adequate blood circulation, which is provided by the regulation of blood hemorheology. The blood circulating in the vessels is inhomogeneous, its parabolic profile is distorted with decreasing vessel calibre. The disturbance of various hemorheological functions, independent from hematological parameters takes place. Tissue hypoxia and hypoglycemia that attend the blood rheological disorders are undoubtedly especially hard for the organ tissue. It is s known that neural structures have no supply of carbohydrates and oxygen. Also that most operating compensatory reactions involved in the pathogenesis of shock in general and of hemorrhagic shock in particular are directed toward centralization of circulating blood volume and maintenance of relatively steady blood circulation. So far, under conditions of hemorrhagic shock, the changes developed in the blood circulation system must substantially differ in the peripheral organs (for instance, in the small intestinal mesentery studied by us earlier) and the central organs. This complex biomedical problem develops step by step from blood

loss and appears to be a consequence of shock situations. Analyzing the experimental data, we observed changes in erythrocyte deformation of the first, second and third stages of shock. The change in erythrocyte deformation occurs after the inclusion of compensatory reaction of the organism, and/ or deformation or deterioration appears to be the basis for the inclusion of this mechanism. The change and disorder of the feature of erythrocyte deformability takes place permanently from stage to stage. The change in elasticity and rigidity of erythrocytes causes a change in blood flow, which leads to a reduction in flow velocity in the microvessels up to the complete development of blood stasis, resulting in an occlusion of all open capillaries with a background of constant perfusion pressure. Microcirculation and blood hemorheology mainly depends on the erythrocyte component. When a red blood cell loses its flexibility, microcirculation becomes more difficult. It worsens even more when red blood cells stick together. Erythrocytes condition plays a particularly important role in blood loss. We investigated the hemorheological parameter, RBC deformability index, in healthy control and hemorrhagic shock conditions. Hemorheological features are modified and changed. Therefore, it is especially important to monitor the deformation of erythrocytes at a shock of any etiology. In the medicine of emergency situations, the tactics for the treatment of hemorrhagic shock is well known and widely used. However, at various stages of the shock, the laboratory- diagnostic methods of the research deserve special attention and completion. A correct diagnosis of hemorheological parameters is particularly important for correcting violations of the separate links of the homeostasis, which is an unavoidable cause of hypervolemia. While studying the deformability of erythrocytes, we monitored the rheological parameters that may promote the development of an algorithm of intensive therapy and a diagnosis of massive blood loss, as well as of hemorrhagic shock.

RHEOLOGY IN REYNAUD’S’ PHENOMENON, WHICH INDUCTION DISEASES.

T. Kotaria, M. Mantskava

Diagnostics and Correction Center of Foot Function „Terdi” Tbilisi, Georgia

Stress, being the general reaction of the organism to the physical and psychological effects, accompanies all the stages of somatic and psychic formation. Hemorrhagic shock occurring at blood loss appears to be powerful stress for the organism. The origin (emergence) and spread of stress reactions are characterized by the features of the macro-and microcirculation. In stressful situations the crisis of blood circulation affects the functions of hemorheological disorders, as well as appears to be a consequence of the shock. We were the first to combine these two problems. The dilemma has been built. Blood loss, being a cause of hemorrhagic shock development while spending adaptive energy would result in more slack development of stress stages, or the body who has received the stress from the outside, will be more subjected to hemorrhagic shock. The following specific objectives were set to answer this question: to ascertain the intensity of the transition from the lower grade of stress to higher due to the development of hemorrhagic shock and to investigate the hemorheological properties of blood at different stages of hemorrhagic shock and at different grades of stress. Experimental stress was induced by heating (hyperthermia). The erythrocyte aggregation increased as the blood volume quantity grew at the bleeding, i.e. with the increasing of shock stages by 10%, 25% and more than 110% compared to the control. When heated the erythrocyte aggregation increased with the transition of stress from one grade to another by 5%, 20% and 80% compared to the control and the increase of the amount of discharged blood was exacerbated at the first and second grades of the stress. During the third grade, even at low blood discharge the aggregation critically increased. The data obtained have shown that at hemorrhagic shock the stress developed according to the amount of blood loss, while in the stressful individuals of first and second grades, depending on the state of shock the aggregation increased analogously, but more intensely. The stress of third grade completely disturbed blood hemorheology even at the first stage of shock and induced lethality. The hemorrhagic shock, expending adaptive energy, stimulated the development of stress stages, but lethality occurred as a result of a critical blood loss. The organism receiving an external stress was more exposed to hemorrhagic shock and lethality. Our findings appear to be only the first experimental session of this problem. Further research in this direction may shed light on the development of hemorheological component of stress reactions. Probably, this will be the basis of the preventive measures at risk factors for the development of hemorrhagic shock of various etiologies, as well as in the evaluation of stressful situations of various nature.

HEMORHEOLOGICAL DISORDERS IN THE EXPERIMENTAL MICROCIRCULATORY STASIS

Momtselidze, 2. L. Gobejishvili, 1 M. Mantskava, [1G. Mchedlishvili]

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Department of Medicine, University of Louisville, Louisville, USA

Reinvestigation the microcirculatory alterations immediately responsible for blood rheological disorderes and blood stasis, which are related to red blood cell (RBC) aggregation in capillaries. Blood rheological disorders were produced by significantly intensified intravascular red blood cell aggregation in the intestinal mesentery of Wistar rats and in the cerebral cortex of chinchilla rabbits., either systemically (by intravascular administration of high molecular-weight dextran) or locally (by increase of high-molecular compounds in blood plasma inside individual or groups of capillaries). Under conditions where the microvascular lumina were not decreased and the aerteiolovenular pressure gradients got even higher, the significantly enhanced intrasvascular RBC aggregation resulted in the slowing down of blood flow in the microvessels to a full stop. A significant increase in microvascular RBC aggregation results in local hemorheological disorders, whith is, in all probability, related to derangement of the blood-flow structuring in microvessels. It became the basis for further study capillaries with stasis and tromb.

ERYTHROCYTE AGGREGATION IN HEMORRHAGIC SHOCK DURING STRESS

M. Mantskava, N. Momtselidze, L. Davlianidze

1. Beritashvili Center of Biomedicine, Tbilisi, Georgia

Stress, being the general reaction of the organism to the physical and psychological effects, accompanies all the stages of somatic and psychic formation. Hemorrhagic shock occurring at blood loss appears to be a powerful stress for the organism. The origin (emergence) and spread of stress reactions are characterized by the features of the macro-and microcirculation. In stressful situations the crisis of blood circulation affects the functions of hemorheological disorders, as well as appears to be a consequence of the shock. We were the first to combine these two problems. The dilemma has been built. Blood loss, being a cause of hemorrhagic shock development while spending adaptive energy would result in more slack development of stress stages, or the body who has received the stress from the outside, will be more subjected to hemorrhagic shock. The following specific objectives were set to answer this question: to ascertain the intensity of the transition from the lower grade of stress to higher due to the development of hemorrhagic shock and to investigate the hemorheological properties of blood at different stages of hemorrhagic shock and at different grades of stress. Experimental stress was induced by heating (hyperthermia). The erythrocyte aggregation increased as the blood volume quantity grew at the bleeding, i.e. with the increasing of shock stages by 10%, 25% and more than 110% compared to the control. When heated the erythrocyte aggregation increased with the transition of stress from one grade to another by 5%, 20% and 80% compared to the control and the increase of the amount of discharged blood was exacerbated at the first and second grades of the stress. During the third grade, even at low blood discharge the aggregation critically increased. The data obtained have shown that at hemorrhagic shock the stress developed according to the amount of blood loss, while in the stressful individuals of first and second grades, depending on the state of shock the aggregation increased analogously, but more intensely. The stress of third grade completely disturbed blood hemorheology even at the first stage of shock and induced lethality. The hemorrhagic shock, expending adaptive energy, stimulated the development of stress stages, but lethality occurred as a result of a critical blood loss. The organism receiving an external stress, was more exposed to hemorrhagic shock and lethality. Our findings appear to be only the first experimental session of this problem. Further research in this direction may

shed light on the development of hemorheological component of stress reactions. Probably, this will be the basis of the preventive measures at risk factors for the development of hemorrhagic shock of various etiologies, as well as in the evaluation of stressful situations of various nature.

HEMORHEOLOGICAL DISORDERS IN PATIENTS WITH FOOT GANGRENE

Mantskava M.

I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

The aim of the present study was to evaluate blood rheological disorders, in particular RBC enhanced aggregation, and compare changes in these parameters in patients with type 1 and 2 diabetes mellitus. For evaluation of RBC aggregability in the present study we applied the “Georgian technique”, which was developed and applied for several years in our laboratory. Its advantage is that it is a direct and quantitative method. In all the investigated patients, diabetes mellitus was complicated with the foot gangrenes. The patients were divided into two groups: with type 1 and with type 2 diabetes mellitus. We matched the RBC aggregability indices in both groups of diabetic patients and compared the obtained results with those in the healthy control group. We found that rheological disorders were considerably pronounced. The RBC aggregability index increased by 60 %in type 1 and by 55% in type 2 diabetic patients as compared to the control group. However, there were insignificant differences of the RBC aggregability changes between the two groups of patients. Therefore we conclude that blood rheological disorders are similar in both types of diabetes mellitus. The disturbed blood fluidity related to the increased RBC aggregability in the microcirculation promotes, in particular, the development of legs gangrene in both types of diabetes mellitus.

PHYSIOLOGICAL PREREQUISITES FOR APPLICATION OF HYPERTHERMIA IN CANCER TREATMENT

N. Mitagvaria, M. Mantskava, M. Devdariani, M. Nebieridze, L. Davlianidze,

N. Momtselidze, N. Saginadze, L. Gumberidze, I. Kvachakidze, N. Sikharulidze

I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

In the last decades of the 20th century in oncology clinics, a new therapeutic modality - hyperthermia, whose effectiveness has been established both in mono and (especially) in its combined use with radio- and chemotherapy have been implemented. Three types of use of this method are known – local, regional and whole body hyperthermia. In spite of already well-established efficiency of this new modality, the physiological mechanisms of its action is still not known. This presentation describes the distinctive features of normal and tumor cells, which have been identified by the German biochemist Otto Warburg back in the 30th years of the 20th century, and despite the fact that this discovery was awarded by the Nobel Prize, only after 70 years it appeared in the spotlight of clinicians and researchers. In studies conducted in our Department, concerning the possible physiological mechanisms of local and whole body hyperthermia effects, the results of which are presented in this report, we relied on a joint analysis of Warburg’s discovery, the role of Nitric Oxide, importance of rheological properties of blood and the phenomenon of “Hormesis”.

MICROFLOW DYNAMICS IN BRAIN STRUCTURES IN SLEEP-WAKE CYCLE

L. Davlianidze, M. Devdariani, M. Nebieridze, N. Mitagvaria

I. Beritashvili Center of Experimental Biomedicine, Georgia, Tbilisi

The triggering mechanisms responsible for the alteration of different phases in the sleep-wake cycle must be localized in the hypothalamus. In particular, the anterior hypothalamus and the preoptic region are considered to be the basic nervous substrates for the formation of slow-wave sleep (SWS), and the posterior hypothalamus, for behavioral wakefulness and paradoxical sleep (PS). Experiments were carried out on 15 adult cats of either sex with chronically implanted electrodes. Quantitative measurement of microflow in the anterior and the posterior hypothalamus, the preoptic region as well as in the sensorimotor cortex was made by the method of electrochemical hydrogen generation into tissue. In chronic experiments in cats recording of microflow in various areas of the hypothalamus in the sleep-wake cycle revealed that in paradoxical sleep (FS) the level of microflow significantly increases in the posterior hypothalamus, while in the anterior hypothalamus and the preoptic area its sharp reduction is observed. In deep slow-wave sleep (SWS), on the contrary, microflow increases in the anterior hypothalamus and the preoptic area whereas in the posterior hypothalamus it decreases. It is concluded that in one and the same phase of sleep a variety of microflow changes in various hypothalamic structures should be related to the functional changes occurring in the above structures, and on this basis the functional state of any one of these structures can be evaluated in different phases of the sleep-wake cycle.

FENTANYL EVOKES IN LOCAL BLOOD FLOW

1M. Devdariani, 1L. Davlianidze, 1N. Mitagvaria, 1M. Nebieridze, 2M.

Darbaidze

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2David Agmashenebeli National Defence Academy of Georgia

It is known that opioids can render significant influence on a level of cerebral blood flow. Such influences of Morphine, Fentanyl and Sufentanil on local cerebral blood flow (lCBF) are investigated both in experiments, and clinical examinations. In accordance with the data of some authors Fentanyl causes decrease of lCBF [3], and in accordance with others - its increase. There is also opinion, that opioids cannot cause any changes in lCBF. Taking into account above-mentioned the aim of this study was clarification of existing in literature discrepancies concerning effects of opioids on lCBF. The experiments were carried out on control and experimental groups of adult, mail white rats weighing 250-270g. Surgical intervention was done under Chloral- Hydrate (1 ml/100g, i/p) and local Novocain anesthesia. lCBF was measured by means of Hydrogen clearance method and the tissue oxygen tension (pO ) – by means of standard polarographic technique. Measuring electrodes were implanted in Parietal area of Neocortex, Dorsal Hippocampus, Nucleus Accumbens, Amygdala. EEG was registered from the Neocortex and Dorsal Hippocampus. Fentanyl (0,3 mg/kg in 0,5ml of solution) was administered i/p. The direct action of Fentanyl on smooth muscles cells of peripheral vessels is vasodilatatory reaction. Besides, opioids can lover (on the average on 11-12 of %) the systemic arterial pressure. This alteration is in range of autoregulatory reaction of cerebral vessels and accordingly should not cause any changes in intensity of CBF (if for any reason the mechanism of CBF autoregulation is not disturbed). The number of authors have observed that infusion of opioids caused suppression of EEG activity (the low amplitude fast waves were replaced by high amplitude delta-waves and EEG became similar to electrical activity at deep narcoses. It is also shown that the low dozes of Fentanyl alongside with depression of EEG-activity in some cerebral areas the local blood flow tends to decrease with simultaneous decrease of oxygen and glucose consumption. In regulation of adequate blood supply of the brain the significant role is played by well-known coupling “function- metabolism-blood flow”, that means that regulation of local blood flow intensity is depending on a level of functional and metabolic activity of the given area of nervous tissue. In view of the mentioned coupling and presented results it is possible to conclude, that the decrease of local blood flow in

parietal area of cerebral cortex should be caused by this mechanism of CBF regulation, i.e., should be a consequence of suppression functional-metabolic activity of these structures. At the same time, the increase of a level of local blood flow registered in Hippocampus, Amygdala and Nucleus Accumbens at first sight it is difficult to explain by the specified mechanism. However, it is known, that in limbic structures opioids can cause convulsive activity with so-called “hypermetabolism”. Decreased level of pO2 in Nucleus Accumbens and development of convulsive activity in Dorsal Hippocampus received in our experiments confirm these suggestions. Thus, we can conclude, that the changes of local blood flow in different brain areas induced by Fentanyl injection in all cases are caused by the metabolic mechanism of cerebral blood flow regulation, working on the basis of mentioned coupling: “function

- metabolism”.

EFFECT OF PENTOXIFYLINE ON SOME FORMS OF ARTERIAL HYPERTENSION

1N. Momtselidze, 2N. Beritashvili

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Insurance Company “Imedi”, Tbilisi, Georgia

Is some hypotensive patients a high level of arterial pressure proved resistant to the effect of Ca-antagonists. However the addition of therapeutic doses of pentoxifyline caused a significant decrease of blood pressure. The arterial pressure changes were found to be correlated with the index of erythrocyte aggregability and deformability (investigated using a highly sensitive “Georgian technique” and nucleon (Raid) methods) in these patients. Our data support the pathogenetic link between blood pressure and hemorheological disorders. For an understanding of the mechanism of these events the direct effect of pentoxifyline on erythrocyte aggregability and erythrocyte deformability was investigated in vitro by using the blood samples of hypertensive patients. The obtained results showed that the effect of pentoxifyline was direct and that the dose - effect dependence was linear. From the obtained results we concluded that the beneficial effect of pentoxifyline in hypertensive patients resistant to Ca-blockers is attained by eliminating the immediate cause of blood rheological disorders, the enhanced erythrocyte aggregability.

CEREBRAL BLOOD FLOW STRUCTURING

1 N.Momtselidze, 2 L.Gobejishvili

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Department of Medicine, University of Louisville, Louisville, USA

Various manifestations of blood flow structuring were investigated in rabbit cerebral cortex capillaries, which possess the most narrow lumina of all parts of the body. Blood flow structuring in the capillaries was characterized by the presence of a stable and comparatively large parietal plasma layer, changed insignificantly under control and ischemic conditions, but disappeared when blood stasis developed inside the capillaries. The axial core of the blood flow in the capillaries which occupied almost two-thirds of the intracapillary volume under normal conditions, consisted of significantly deformed and nonagreggated erythrocytes did not change appreciably; only the blood plasma intervals between them increased significantly, demonstrating reduction of the local hematocrit. During primary blood stasis caused by enhanced intravascular erythrocyte aggregation. Typical Blood flow structuring became significantly disturbed: red cells filled the whole, or almost the whole, capillary lumina and did not leave visible space for plasma inside the microvessel lumina. Why? We concluded that, the deformation of the erythrocytes inside cerebral cortex capillaries was very pronounced. The erythrocytes were transported in the active capillaries separately, being considerably elongated. The degree of their deformation was changeable and adapted to the microvessels diameter: in the narrowest capillaries the coefficient of erythrocyte deformability, the length to width ratio, was found even more pronounced under the ischemic than under the control conditions despite a high degree of slowing of the flow. Investigation of erythrocyte deformation during their aggregation in capillaries with stases was impossible, since the individual erythrocytes were not clearly visible. Is a prior data. For further study blood flow’ structuring, we will plan ranked research. We are working on the design of these studies.

EFFECT OF MANGANESE SHORT-TERM ADMINISTRATION ON THE PREPUBERTAL

AND MATURED RAT’S LEARNING ABILITY

1I.L. Lazrishvili, 1T.Z. Bikashvili, 2A.A. Shukakidze, 1N.P. Mitagvaria, 1L.K.

Gelazonia

1I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Tbilisi State Medical University, Tbilisi, Georgia

Chronic manganese intoxication resulting in significant deficiency in memory and mental processes. The effect of short-term per os intoxication by different doses (10, 20mg/kg/day) Manganese Chloride (MnCl2.4H2O) on the process of learning of matured rats and 30-day-old off springs of dams which 15 days before pregnancy, during pregnancy and 30 days after delivery was received manganese chloride were studied. The number of errors (entering of dead-end sections) and the time, required for passing of multi-branch maze were used for evaluation of learning ability. The process of learning in newborns whose parent was exposed to MnCI2 .4H2O in the dose 10 mg/ kg was considerably hindered. They lagged behind the control pups by the level of maze test performance – have made more errors and spent more time for passing the maze. Low dose of Manganese did not significantly alter learning process of matured rats. Otherwise looked the process of learning of rats, which received intoxication by 20 mg/kg. Some of newborns could not learn at all correct maze passage and others, beginning from 6-th day of the maze learning session could overcome the maze test, while none of matured animals were able to become familiar with optimal trajectory for maze passing. One of the reason for such a significant difference in behavior between the prepubertal and adult animals might be that the neonates’ striatum is a vulnerable brain region in terms of manganese neurotoxicity. Whereas in mature brain other regions such as hippocampus, midbrain and olfactory bulb in addition to the striatum, have increased manganese concentrations, altered neurotransmitter levels and oxidative stress due to manganese exposure.

STRESS-FREE DISPLACEMENT CONTROL OF STRUCTURES

Y.Nyashin, V. Lokhov, F. Ziegler

Department TheoreticalMechanics and Biomechanics, Perm National Research Polytechnic University, Perm

The theorem on the unique decomposition of eigenstrain provides the tool to construct prescribed displacements inside and (or) at the surface of a linear elastic body in two novel ways (e.g., in connection with shape control). The first approach applies Maysel’s formula and renders the linear relationship between nodal displacements and impotent eigenstrain in discrete or discretized systems. The second, alternative approach can be applied to continuous systems as well, and allows controlling the shape of the body. Both approaches do not require the solution of the associated boundary value problem with prescribed eigenstrain, thus circumventing the possibly cumbersome (numerical) solution, which can present some difficulties with respect to its convergence.

ARTERIAL HYPERTENSUIN MANAGMENT NATIONAL GUEDELINE AND PROTOCOLS HYPERTENSION MANAGEMENT NATIONAL GUEDELINE AND PROTOCALS IMPLEMENTATION PROCESS ASSESSMENT IN GEORGIA: PP.20.278

B.Tsinamdzgvrishvili

Georgian Society of Hypertension, National Center of Cardiology, Tbilisi, Georgia

Insufficient hypertension control may be caused by the non-compliance of the patients or lack of motivation, but also by inadequate management of clinical practices. Aim: To assess the extent and approaches of implementation of the Hypertension Management Guideline and Protocols at primary healthcare level in Georgia. Methods: Interviewing of primary healthcare personal by the specially developed questionnaire. Results: 108 family doctors from Tbilisi and 2 regions of Georgia were interviewed. The response rate was 98%. The national hypertension guideline was widely adopted in clinical practice of urban healthcare system. There is a deficit of active involvement in the implementation process in the regions. 40% of questioned physicians are not adequately informed about the protocols. Adherence of the guideline is quite low in family doctors. Conclusion: The challenges in implementation of the guidelines in Georgian clinical practice seem to depend on the specifics of the healthcare setting and the strategy used.

DETERMINATION OF NONINVASIVE PARAMETERS OF LOW FREQUENCY MAGNETIC STIMULATION

FOR LIVE ORGANISM (THEORETICAL RESEARCH)

1N. Bukia, 1G. Kekelia, 1M. Butskhrikidze, 2M. Svanidze, 1L. Machavariani

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Tbilisi, Georgia

Introduction: All living organisms are under permanent effect of electromagnetic fields of various frequency that is caused both natural (sun and galactic radiation, atmospheric discharges) and artificially (radiation of various aerials and devices) created factors. Proceeding from this fact, determination of positive and negative effects of electromagnetic waves of various frequency on living organisms and results of this effect is one of the most topical problems of the modernity. Virtual absence of theoretical model of this effect produces a bottleneck during carrying out researches. Methods and results: Low-frequency magnetic fields are biologically active and almost without let of hindrance penetrate and pass through living tissue. One of the fundamental provisions on which represented project is based lies in the fact that dielectric polarization occurs under influence of magnetic field that causes change in dimension of bonded surfaces existing in it (in case of constant magnetic field this process is well known and called the effect of electrostriction) and change in current pressure in internal and external areas. This, in its turn, causes mechanical oscillations in the outer shell. At this time a part of low-frequency electromagnetic field energy transforms into mechanical energy of this outer shell (cell membrane is namely its outer shell). It should be noted that maximum displacement from equilibrium state (amplitude of oscillations) is inversely proportional to squared field oscillation frequency and is directly proportional to squared current strength passing inductance coil of oscillation circuit. That’s why we have to reckon with this effect only at low frequencies. Proceeding from the goals of the project experiments will be carried out using magnetic fields of 50-100 Hertz (1,5 m/Tesla) and 103-104 Hertz (1,5 Tesla) frequency. Ratio of squared current strength passing the coil to the squared external field oscillation frequency has to be the same for both frequency ranges (in this case, cell displacement from equilibrium state will be one and the same). From these reason, for low frequency magnetic stimulation we will use the coil with original design, which was made in the base of Tbilisi Technical University. By special manipulators we will be able to change the parameters of magnetic field. During experiment parameters of magnetic field (stimulus frequency,

number of stimuli, train duration, intertrain interval and stimulation sites) will be established. Conclusion: low frequency magnetic stimulation and the coil with original design help us to investigate influence of magnetic field on live organism.

Research was supported by FR/257/7-270/14.

INVESTIGATION OF BLOOD SURFACE TENSION AND ERYTHROCYTES’ DEFORMABILITY IN MICE WITH EHRLICH CARCINOMA AND THEIR POSSIBLE ROLE IN THE MECHANISMS OF PARANEOPLASTIC DISORDERS OF HEMORHEOLOGY AND MICROHEMOCIRCULATION

K. Gambashidze, T. Petriashvili, N. Bejitashvili,

N. Pkhaladze, D. Karkarashvili, N. Chelidze, M. Lomia

Tbilisi State Medical University, Department of Pathophysiology. Tbilisi Georgia

Paraneoplastic disorders accompanying cancer growth in most cases are early manifestations of the malignant tumor growth emphasizing its diagnostic value. However, on the other hand paraneoplastic disorders of microhemocirculation along with anemia could be discussed as one of the leading causes of generalized hypoxia developed in patients suffering with cancers. Any deviations and alterations developed in the body affecting blood surface tension and deformability of erythrocytes will be reflected on hemorheology and microhemocirculation respectively. For this reason we have found interesting to investigate blood surface tension and erythrocytes’ (RBC) membrane deformability in case of cancer growth to state their role in disorders of hemocirculation and suggest possible ways of their correction to improve blood supply of organs and tissues and decrease level of hypoxia, which in turn play dramatic role in disease progression. Material and methods: Experiments were conducted on 40 male lab. Mice (weight range 20-25 g) on 7th, 14th and 21st days after subcutaneous inoculation of Ehrlich carcinoma (1x106 cells). The surface tension of the blood in healthy and carcinoma- bearing mice were assessed with the use of maximum bubble pressure method (orbubble measure method using bubble pressure densitometer producing gas bubbles at constant rate, blowing them through a capillary, which is

submerged in the sample blood and its radius is already known) modified by P. A. Rebinder. RBC deformability was defined by means of filtration (computed photometry) method completely excluding subject initiate measuring of the time of RBC spread and passage through the filter (Filtrac

- 388). 1 ml blood and 20 unit heparin were centrifuged during 5 minute at 3000 rpm. 0.02 ml of RBC suspension was instilled on the filter. The time of RBC passage was registered and processed by computer. Results: The results of investigation have shown that blood surface tension in mice with Ehrlich carcinoma is increased significantly by 33,8%, 14,7%, 21.5% and RBC membrane deformability is reduced in parallel with increase in blood surface tension by 38,2%, 14,5% and 29,1% respectively compared to control data. RBC membrane disorders and reduced deformability could be explained by activation of peroxidation of lipids(POL)as a result of antioxidant deficiency and effects of toxic free radicals accompanying cancer growth. Increase in blood surface tension supposedly could be caused by hypoproteinemia, hyperfibrinogenemia, electrolyte imbalance, hypoxia and reduced elasticity of RBC membrane. Conclusion: At malignant tumor growth deformability of erythrocytes decreases and surface tension of the blood increases. Revealed disorders probably affect hemorheology and worsen fluidity of the blood, which in turn could be discussed as one of the important reasons of impaired microcirculation and local hemocirculation. We suppose that reducing blood surface tension using surface active agents (surfactants) and improving RBC deformability through increase in membrane protection against POL with the use of antioxidants will improve hemorheology, microhemocirculaton, blood supply and oxygenation of organs and tissues extremely suffering at malignant growth.

REGULATION OF FUNCTIONAL CELLS COUNT IN PERIPHERAL BLOOD BY EXTRACELLULAR UBIQUITIN IN AN ANIMAL MODEL OF CYTOPENIA

1R. Sujashvili, 1I. Ioramashvili, 1K. Aptsiauri, 1N. Gvinadze, 2M.

Gamkrelidze

1I. Beritashvili Centre of Experimental Biomedicine, Tbilisi, Georgia

2University of Georgia, Medical School, Tbilisi, Georgia

Alterations in the ubiquitin proteasome system are correlated with a variety of human pathologies including autoimmunity, immunodeficiency, liver, hematopoietic, malignant, neurodegenerative etc. The exact role of the ubiquitin proteasome system in etiology of these diseases however, requires further investigation. Cellular ubiquitin is widely studied, but little data is available about extracellular ubiquitin possible pathways and role in regulation of various pathological processes. The present study aimed to investigate potential regulation of leucopoiesis by in vivo injected extracellular ubiquitin in the animal model of cytopenia induced by anticancer cytotoxic chemotherapy agent cyclophosphamide. The research was conducted on female Wistar rats divided into the control and two test groups. Animals of two test groups received an intraperitoneal injection of 100mg/kg LD 50-160mg/kg cyclophosphamide. One of the test groups was injected with 200 μk/ml extracellular ubiquitin 72 hours after cytostatic drug injection. Nucleated cells count was performed in peripheral blood smears stained with azure-eosin. The samples were studied under the light microscope Ampival, Zeiss. Statistical analysis was performed using the methods of Origin Pro, Image J. and Anova. Treatment of animals performed in accordance with regulations established by the Centre animal’s ethic committee (Protocol N06/13.10.2014). After the injection of cytostatic agent, animals in both groups developed clearly defined cytopenia. Change in nucleated cell/ total cell ratio in peripheral blood was observed with nucleated cell portion being increased at 24h point and gradually decreased by 96 h point. In the ubiquitin-injected test group, average total cell count in peripheral blood at 96 h point was by 20% lower as compared with the control group, with subsequent increase up to the normal values within the next period. Whereas, in the group of animals without ubiquitin injection elevation of cell count reached about 78% at the same hour point as compared to control values. The results demonstrate that extracellular ubiquitin acts as a regulator of hematopoiesis. It restores nuclear cell ratio and regulates total cell count in blood after chemically induces cytopenia. Hence, extracellular ubiquitin regulates regeneration of leucopoiesis and provides good potential to new therapies of hematological diseases.

OXYTOCIN ON THE FORMATION OF A FOOD-PROCURING REFLEX IN RATS

M. Butskhrikidze, N. Bukia

I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

Introduction: oxytocin affects the coagulation system of the blood. Coagulation/anticoagulation and rheology systems provide a liquid state of the blood Therefore, all studies (exsperimental and laboratory) with oxytocin is very interesting from the point of view of the microcirculation and hemorheology. Oxytocin-containing fibers are present in various CNS structures, namely in the terminal plate, amygdalar complex, some brainstem nuclei, septum, and hippocampus, i.e., the topography of target sites for oxytocin in the CNS is very wide. There is evidence that oxytocin can exert a regulatory action on the learning process; however, information in this respect is relatively limited. In our study, we examined the effect of course injections of oxytocin on the formation of long-term memory and behavioral phenomena in the process of development of a food-procuring conditioned reflex in rats. Perhaps the effects of oxytocin on long-term memory associated with the improvement of the rheological properties of blood.

Methods: Experiments were carried out on mongrel male albino rats (n= 20, body mass 220-300 g). Animals were divided into two equal groups (n= 10 in each), control and experimental ones. Rats of the experimental group were i.p. injected with 4 μg of oxytocin daily for 12 days of the experimental period, 15 min prior to each test. The food-procuring conditioned reflex was trained in an experimental chamber. Sources of a conditioning visual signal was light bulbs (60 W). After switching on the conditioning signal for 5 sec, the door of the starting compartment was opened, and the animal was able to move freely. In the case of approach to the “correct” feedbox with the conditioning signal (a flashed lamp above), the rat received a food reward. In the course of the test, we estimated the number of correct responses (level of differentiation) and durations of the food-procuring reaction and its separate components. The characteristics of motor activity and emotional state of the rats were studied under conditions of the standard open field test. Results: It was found that course injections of oxytocin (4 μg daily, 15 min prior to the test for 12 days) relatively slightly influenced the process of development of the food-procuring conditioned reaction (animals reached the 80% critical level of correct differentiations practically simultaneously), but rats injected with oxytocin demonstrated smaller manifestations of anxiety, more rapid food-procuring activity, and higher intensity of motor/research activities in the open field. Conclusion: In general, food-procuring behavior under the action of oxytocin develops more effectively at the expense of formation of

a more favorable emotional/autonomic background. Here it should be noted that the emotional/autonomic background is directly proportional to the improvement of the rheological properties. It should be parallel study blood rheological and coagulation properties for a detailed study positive influence of oxytocin on physiological and pathphysiological processes.

HEMORHEOLOGICAL, MICROVASCULAR AND HEMODYNEMIC PROFILES

IN PATIENTS WITH ISCHEMIC HEART DISEASE

1T. Urdulashvili, 2N. Narsia

1Medical Centre “Medisoni”, Tbilisi, Georgia

2 Tbilisi State Medical University, Tbilisi, Georgia

Since many of the cardiovascular disorders are related to the patients’ blood disturbances. The aim of the present study was evaluation how the increased erythrocyte aggregability is related to the severity of ischemic heart disease as compare to the increased arteriolar resistance. We investigated 64 patients with chronic coronary disease and hypertension. The control group consisted of 20 healthy subjects. Erithrocyte aggregability was investigated with the “Georgian technique” that provided us with the direct and quantitative data. The tone of the resistance arteries was investigated in the same patients with Doppler technique under conditions of the stardantly induced post ischemic hyperemia. Echocardiografically we studied the standard characteristics of left ventricular function (systolic and diastolic volume, its mass and ejection function). ECG by standard leads and the blood pressure were investigated in all patients. We found that the erythrocyte aggregability was positively correlated with the severity of the disease and left ventricular mass. The erythrocyte aggregability index was increased by 110 per cent as compare to the control group. There as a negative relationship between erythrocyte aggregability and left ventricular ejection function. As to the arteriolar resistance index, it was increased by 105 per cent as compare to the control. Therefore significant association exists between erythrocyte aggregability, intracardial hemodynemics and left ventricular hypertrophy. These disturbances represent early signs of left ventricular remodeling and affect prognosis of the patients. They can be considered as predictors of the disease and may, probably, contribute to development of the atherosclerotic diseases in the patients.

DETERMINATION OF NONINVASIVE PARAMETERS OF LOW FREQUENCY MAGNETIC STIMULATION

FOR LIVE ORGANISM (THEORETICAL RESEARCH)

1N. Bukia, 1G. Kekelia, 1M. Butskhrikidze, 2M. Svanidze, 1L. Machavariani

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Tbilisi, Georgia

Research was supported by FR/257/7-270/14.

ASSOTIATIOM OF SOLUDATE CD14 WITH INFLAMATORY MARKERS AND DISEASE SEVERUTY IN TYPE 2 DM

Gobejishvili, S. P. L. Mokshagundam, D. Mokshagundam, V. Vatsalya,
Kong and Sh. Barve

School of Medicine, University of Louisville, Louisville, Kentucky, USA

The role of the gut microbiome in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and its complications has been gaining increasing recognition. Increased gut permeability and microbial translocation are postulated to play a significant role in mediating the effect of the gut microbiome on diabetes through their effects on inflammatory pathways. Soluble CD14 (sCD14) is useful marker of microbial translocation and macrophage activation. The serum sCD14 levels increase during the systemic response to bacterial invasion and endotoxin. The association between multiple markers of inflammation and several micro and macrovascular complications of T2DM has been well recognized. However, individuals with T2DM often have multiple complications, both micro and macrovascular, concurrently. The Diabetes Clinical Severity Index (DCSI) is a useful and validated tool that incorporates multiple complications to assess individual’s risk of adverse outcomes. Methods: 17 subjects with T2DM between 25 - 80 yrs were recruited for the study from a diabetes specialty clinic. Clinical documentation from charts was used to calculate DCSI. Blood samples were drawn in the fasting state for measurements of gut permeability markers (endotoxin and sCD14) and inflammatory markers (IL-6, IL-8, TNF, MCP-1, PAI-1). To assess the relationship between gut permeability markers, inflammation markers, and DCSI, multiple linear regressions were used. Results: There were 9 male and 8 female subjects recruited (Age - 61.1 +/- 10.4 years, BMI 36.1 +/- 7.1, and A1c 9.1 +/- 1.9 %). sCD14 showed significant association with IL-6 (R2 = 0.276, p = 0.021) and IL-(R2 = 0.287, p = 0.019). The DCSI score was 1.94

+/- 1.4. DCSI measure did not show any significant association with MCP-1 (p = 0.102) with MCP-1 as the contributing variable in the regression model. However, this association augmented to significant level when sCD14 and PAI-1 were included as covariates (R2 = 0.364, p= 0.022). Similarly, DCSI showed significant association with IL-8 (p = 0.046) when CD14 with TNF-a was included in the analysis, and IL6 showed nearly significant association with DCSI (p = 0.078) when sCD14 and TNF were included in the analysis. Discussion: The complex associations between sCD14, inflammatory markers and DCSI suggest a pathway wherein microbial translocation leading to immune activation and inflammation lead to poor outcomes in diabetes. The precise sequence of events and the nature of these interactions need further elucidation. The earliest step is likely to be microbial translocation due to increased gut permeability. Understanding the nature of these interactions and developing interventions that could favorably alter these pathways will likely lead to better outcomes in T2DM.

PDE4 INHIBITION ATTENUATES ALCOHOL INDUCED OXIDATIVE STRESS BY INCREASING ANTIOXIDANT ENZYME EXPRESSION

Gobejishvili, D. Avila, C. McClain and Sh. Barve

School of Medicine, University of Louisville, Louisville, Kentucky, USA

Alcohol metabolism leads to generation of free radicals and oxidative stress with a resultant formation of lipid peroxidation products. Increased oxidative stress and generation of lipid peroxidation products critically contribute to the development of alcoholic liver disease (ALD). Chronic alcohol also leads to decreased antioxidant capacity of liver, e.g. glutathione and nuclear factor erythroid 2–related factor 2 (Nrf2) dependent enzymes. cAMP increasing agents have been shown to effectively mitigate oxidative stress both in vivo and in vitro. Hence, we hypothesized that compromised cAMP levels by alcohol might contribute to decreased antioxidant capacity of liver and restoring cAMP signaling could prevent alcohol induced oxidative stress. To test this hypothesis, we employed two approaches to block degradation of cAMP by phosphodiesterases (PDEs): genetic (by using PDE4B knockout mice) and pharmacological inhibitor of PDE4, Rolipram. C57Bl/6 wild type (WT) and Pde4b knockout (pde4b-/-) mice were pair-fed control or ethanol liquid diets

for 4 weeks. One group of WT mice received Rolipram, a PDE4 specific inhibitor, during alcohol feeding. Liver cAMP levels were measured by cAMP ELISA kit, liver tissue was stained with F4/80 and 4HNE antibody. Hepatic antioxidant enzymes superoxide dismutase 1 and 2 (SOD1/2), Catalase (Cat) and glutathione peroxidase (GPx) were analyzed by Western blot. Activation of NRF2 was evaluated by examining nuclear NRF2 levels. Alcohol feeding resulted in a significant increase in hepatic PDE4 expression and decrease in cAMP levels. Liver 4HNE and F4/80 staining were significantly increased in alcohol fed WT mice demonstrating increased oxidative stress, but was significantly attenuated by PDE4 inhibition. Alcohol reduced nuclear NRF2 levels in wild type mice but not in Rolipram treated and PDE4B knockout mice. Catalase levels did not seem to be affected by alcohol, but SOD1 and GPx1/2 were decreased in alcohol fed wild type mice; SOD2 levels were not changed. PDE4B knockout and Rolipram treated alcohol fed mice had higher levels of SOD1/2, and GPx1/2. In summary, these data indicate that alcohol effect of hepatic cAMP levels contribute to compromised antioxidant capacity of the liver which could be prevented by PDE4 inhibition.

THE LOCAL CEREBRAL BLOOD FLOW IN THE DORSAL HIPPOCAMPUS OF RATS DURING INITIAL AND DEEP STAGES OF INFORMATIONAL PATHOLOGY OF BEHAVIOR

1. Kvachakidze, L. Gumberidze, N. Sikharulidze

I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

Introduction, materials and methods: The local cerebral blood flow (LCBF) was studied by the hydrogen clearance technique in the dorsal hippocampus (DH) of rats with initial and deep stages of informational pathology of behavior (IPB). The initial stage of IPB was induced by the negative emotional stress developed during the short period of delayed testing (indirect version, 2-3s delay), in I group of animals, while the deep stage of IPB was produced by the chronic negative emotional stress developed during the long period of testing delayed reactions (indirect version, 2-3s delay) in II group of animals, under conditions of the time storage between the signals (30s) and the existence of high level of motivation. Results: A significant increase in the LCBF level was observed in I experimental group in comparison with the control one, while in II experimental group was demonstrated a significant decrease in the LCBF level in comparison with the control group. Conclusion: It is supposed,

that this alteration of LCBF in I group may be caused by the strengthening of DH functional activity as result of short time negative emotional stress, thus being a form of the cerebral self-regulation activity. In II group 1) the decrease in the LCBF may be of a secondary character as a result of suppression of functional activity of the DH by exposure to the chronic negative emotional stress; 2) It is not inconceivable that the LCBF decrease is of a primary character and may account for dysfunction of this structure facilitating the emotional stress and its acquisition of pathogenic properties, thus being an important factor of the IPB formation.

INTENSIFIED RBC AAGGREGATION AS INITIATING FACTOR OF MICROCIRCULATORY DISORDERS

N. Beritashvili

Insurance Company “Imedi”, Tbilisi, Georgia

Recent proof of a considerable increase of RBC (red blood cell) aggregability in patients with arterial hypertension, ischemic stroke, etc. was an evidence of its key role in rising blood viscosity during development of these pathologies. In rats’ (intestinal mesenteries) and rabbits’ (brain cortex) experiments we analyzed the role of RBC intravascular aggregation in the disturbance of blood rheological properties in capillaries. The RBC aggregation was produced systemically (following intravascular administration of high molecular dextran) or locally (intensified exudation from individualcapillaries). Systemic increase of RBC aggregation leads to elevation of the arterial pressure. As to the local intensified aggregation, it results in considerable slowing down of blood flow till full stasis in appropriate capillaries. In this latter case the systemic arterial pressure does not change and the microvascular diameter does not decrease at any point all along the microvessels. This furnished ample evidence that intensified RBC aggregation is a factor that causes disturbance of blood rheological properties (by increasing the resistance to blood from in the narrow microvessels) and represents itself an essential factor of blood rheological disorders in the microcirculation.

HEMOSTASIS - INFRINGEMENT AND ITS CORRECTION IN OPERATIONS AMPULLAR COLON CANCER

2M. Skoblo, 2A. Pirumyan, 1A.Pogosyan,1 I. Dudarev, 2 I. Efrosinina, 1E.

Lebedeva

1Medical University “Rostov State Medical University” Ministry of Health, Russian

2MBUZ “Hospital №6” «coloproctological city center” Rostov-on-Don, Russia

Evaluation of the activation of the hemostatic system to determine the risk of thrombotic and hemorrhagic complications and make a plan of correction data breaches. Objective. To study the intraoperative changes and their correction in the hemostatic system during operations ampullar colon cancer. Material and methods. The study included 47 men and 37 women aged 54-79 years (mean age 58,3 ± 1,6 years) with a verified ampullar colon cancer and did not have a history of thrombotic complications. Operations (front low resection of the colon with anastomosis - 33 operations bryushnopromezhnostnye eksetrpatsii rectum - 51 operation) was carried out under spinal anesthesia with bupivacaine 15-20 mg and sedation in medozalamom dozerovke (0,25- 0,35mg/ kg body weight). General criteria for inclusion in the study were the following signs: the absence of localized and systemic inflammation, diabetes, lack of taking drugs that affect blood clotting. The control group included 30 patients. The study group included 54 patients who in the course of surgery corrects hemostasis. Fencing material produced just before skin incision (I stage), at the time of surgical exposure on the fabric (II stage) and immediately after the closure of the wound (III stage). Screening parameters: activated partial thrombin time (APTT), prothrombin time (PT). Blood for researches by a method immuno-fermental analysis (IFA) centrifuged. ELISA determined the content of thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP), D-dimer and plasminogen activator (u-PA). Statistical analysis was performed using software STATISTICA

7. Patients in the study group operation on / in 200.0 ml of 0.9% sodium chloride solution was administered tranexamic acid at a dose of 1 g. Results. The lack of significant differences in the “screening” in terms of the data confirms their insensitivity, and thus not informative in the diagnosis of disease and hypercoagulable fibrinolysis. Investigation of concentration of plasminogen activator produced only in the control group, and was designed to determine the presence or absence of the ejection of fibrinolysis activator during handling on the rectum. TAT complex is a marker of activation of the

hemostatic system and is the reaction product of thrombin and antithrombin

III. A statistically significant increase in the concentration of TAT in the II and III stages indicates an increase in coagulation potential during surgery. To study the fibrinolytic system to determine the level of the complex plasmin-a- 2-antiplasmin. This active complex is not formed in the inhibition of plasmin by binding it to a-2-antiplasmin. It should be noted that the concentration of the complex in these patients higher than those in healthy individuals. This may indicate the presence of both reactive (secondary in response to hypercoagulability) and strengthen primary fibrinolysis. The presence of the latter suggests a higher initial level of urokinase plasminogen activator. The sharp increase in the complex in the postoperative period, most likely due to the release of i-RA, the level of which increased significantly in the postoperative period. The mechanism of receipt of the enzyme in blood, is as follows and includes a lasting effect on the tumor tissue directly with possible permanent contact yawning blood vessels and possible entry into the blood released from malignant cells plasminogen activator. D-dimer is a product lysis crosslinked fibrin by plasmin, and thus is a measure that reflects the state of both the coagulation and fibrinolytic link, in the study group was lower (0.178 ± 0,014mkg / ml), which testifies to the state of the system kompensirorvannom homeostasis background of the treatment. Conclusions. Patients with ampullary cancer of the large intestine is an increase in the capacity of the blood coagulation system. This is due to the prevalence of the process, and the presence of comorbidities. The fibrinolytic system is activated as a secondary (response to elevated blood clots) and primary (higher level and RA-23 ± 1,3%, p <0.05). The operation is accompanied by the release of plasminogen activator, leading to a sharp activation of fibrinolysis. To reduce the activity of the fibrinolytic system is expedient intraoperative administration of tranexamic acid.

ALTERATIONS IN CUTANEOUS MICROCIRCULATION AND BLOOD RHEOLOGICAL PROPERTIES IN PATIENTS WITH DIABETES MELLITUS TYPE 2 ESTIMATED THROUGH THE CHANGES OF OSCILLATIONS IN SKIN TEMPERATURE AFTER COLD TEST

1N. Antonova, 1V. Kostova, 2I. Velcheva, 3S. Podtaev, 2N. Chaushev

1Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria 2University Hospital of Neurology and Psychiatry, Medical University, Sofia, Bulgaria

3Research Center “FM Diagnostics”, Perm, Russia

Diabetes mellitus has high social and economic importance and accompanied with vascular degenerative complications, leading to the change in the mechanical properties of vessels of the microcirculation (capillaries, arterioles, venules and the like). It is one of the major risk factors of cardiovascular diseases.

The aim of the study is to evaluate the dynamics of changes of the skin temperature oscillations during cold test in patients with diabetes mellitus type 2 and to estimate the mechanisms of regulation corresponding to the myogenic, neurogenic and endothelial regulation of vascular tonus in these patients group. Skin temperature was measured on the palm surface of the distal phalanx of the second (index) finger with two closely-spaced sensors and were continuously measured under basal conditions (10 min), during contralateral hand immersion in cold water (3 min) and thereafter (10 min) in patients with type 2 diabetes and in control group of healthy persons by a Microtest device (Russia).The wavelet transformation analysis was used to study the localized variations of the low amplitude oscillations of skin temperature in accordance with myogenic (0.05 - 0.14 Hz), neurogenic (0.02

0.05 Hz), and endothelial (0.0095 - 0.02 Hz) control mechanisms and their association with skin blood flow changes during indirect cold test in 10 patients with diabetes mellitus type 2 and 10 healthy age and sex matched controls. Dynamics of changes of oscillations in skin (cutaneous) temperature were evaluated through the root mean square values of the amplitudes obtained by the wavelet analysis in the frequency range corresponding to the mechanism of myogenic, neurogenic and endothelial regulation of vascular tonus. The measured average amplitudes in three frequency ranges were estimated by a box plot diagram. The aim was to study in parallel the rheological properties in patients with Diabetes mellitus and to compare them with a control group of healthy subjects. A rotational viscometer Contraves Low Shear 30 (Switzerland) was used to measure whole blood viscosity at shear rates of 0,

0237s-1 to 128,5s-1 in both groups. The basic hemorheological constituents: hematocrit (HT), whole blood (WBV) and plasma viscosity (PV) were also investigated. Increased blood viscosity in patients versus controls was correlated with the amplitudes of myogenic, neurogenic and endothelial vasomotor reactivities, determined by the wavelet analysis .

ELECTRON MICROSCOPIC STUDY OF RAT NEURONAL POROSOME COMPLEX IN NORM AND PATHOLOGY

1,2M.G. Zhvania, 1,3N.J. Japaridze

1Ilia State University, Tbilisi, Georgia

2I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

3New Vision University, Tbilisi, Georgia

In all cells, cellular cargo destinated for secretion is packaged in membranous vesicles that transiently dock and establish continuity at the base of cup-shaped membranous structures called “porosomes” and neurons are not exception. Via porosomes vesicles release intravesicular contents to the outside of the cell during secretion. It is suggested that in each type of secretory cell special content of secretory vesicles, different speed of release and different volume of content release dictates specific size of porosomes. In earlier atomic force microscopic and electron microscopic studies, it was shown that in the neurons, reprensenting fast secretory cells, 40-50 nm synaptic vesicles are docked at roughly 10 nm in diameter neuronal porosomes. Recent EM 3D tomography in rat brain also reveals the presence of 12-17 nm permanent presynaptc densities in which 35-50 nm synaptic vesciles are found docked. Moreover, the inside-out ultrahig-resolution atomic force microscopic study of presynaptic membrane preparations of isolated synaptosomes displays the presence of the inverted cup-shaped 10-17 nm neuronal porosomes. Neuronal porosomes possess a central plug, that is absent in porosomes in other kinds of secretory cells. This plug interacts with proteins at the periphery of the structure, conforming to an eight fold symmetry; each of them is connected with spoke-like elements to the central plug that is involved in the rapid opening and closing of the neuronal porosome to the outside. The central plug has been further examined in various conformations: fully pushed outward, halfway retracted, and completely retracted into porosome cup – has been demonstrated. Recently we described the morphology of porosome

in different brain structure of various mammals (rat, cat, dog). In this electron microscopis study we evaluate if rat porosome structure/size is altered as a result of pathological and other conditions, specifically as a result of chronic restraint stress. Finally, to further understand the structure of the neuronal porosome complex, and the bare protein backbone of the complex for future single-particle cryo-EM studies, we evaluated the size of this complex from high-detegent solubilized synaptosome membrane preparations. For to assess the effect of hypokinetic stress on porosome structure, conventional electron microscopic methods were used. For to evaluate the isolated neuronal porosome complex, it was immunoisolated from synaptosomes, using SNAP- 25 specific antibody conjugated to protein A-sepharose. For all cases the morphometric analysis of porosome diameter and depth was made. The one- way ANOVA was performed on the diameter and depth. The results revealed that the parameters of porosome, especially diameter, are very heterogenous. However despite the dynamic nature of neuronal porosome, the ranges of dimension (diameter 12-16 nm, depth - 5-20 nm) remain the same in normal conditions and after influence of chronic restraint stress or white noise. Results of studies of isolated complex demonstrate, that althouight the eigth

–fold symmetry of the immunoisolated porosome is maintained, and the central plug is present, there is a loss in the average size of the porosome, possibly due to a loss of lipids, proteins or both from the complex. In view of this, proteomics and lipidomics on the isolated neuronal porosome using our current procedure using elevated detergent for synaptosome solubilization, will be carried out to determine whether there is loss of lipids, proteins, or both from the structure.As a result of the injection of manganese ions, may cause histopathological changes induced in some visceral organs.

AS A RESULT OF THE INJECTION OF MANGANESE IONS, MAY CAUSE HISTOPATHOLOGICAL CHANGES INDUCED IN SOME

VISCERAL ORGANS

1,2T. Bagashvili, 1N. Papuashvili, 2T. Jorbenadze, 1G. Andronikashvili,

1T.Gurashvili, 1K. Gogeshvili

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Faculty Medicine, Tbilisi, Georgia

Dose of magnesium in the body determines activation of catalyzing enzymes by the exchange reactions of organic substances, the genital glands and the normal functioning of the musculoskeletal system, nerve cell membranes, and in general, the stability of the nervous system, blood cleaning and much more.

However, the small or overdose toxic quantity of manganese ions have negative impact on organism. The actuality of the problem is caused by proliferation of “secondary Parkinson” (in other words “manganism”), and the wide use of the surrogate drugs the CNS stimulators - Metkatinin (“Jeff”) by the drug addicts and drug users. By intravenous injection of the potassium permanganate-containing aqueous solutions in adult white rats the valid and chronic model of manganese encephalopathy had been created, which by its physiological and behavioral parameters is maximally close to the changes seen in ephedronic drug users. We set the goal to study the possible histopathological changes in some visceral organs (heart, lung, liver, lymph nodes), in the tissue building of which it was expected that the changes should be provoked. A single intravenous dose of potassium permanganate solution (2-3 injections per day) was in accordance with the per unit body weight calculations of the white rat and this drug, which in average was in accordance with 1 kg of body weight of epedronic drug users / drug addicts during Methcathinone (,,Jeff”) intravenous injection (toxic dose). At the end of the experiment, after the euthanasia of animals being under anesthesia we were getting visceral organs and as a result of the review fixation of the material for the micro morphological studies was carried out in 10% of formalin solution.After appropriate treatment it has evolved in paraffin. Slices prepared on a rotary microtome were stained with hematoxylin and eosin. Histo-morphological microscopic study confirmed some of the significant changes in visceral body tissue building.Dissociation and fatty degeneration of the hepatocytes has been observed in liver remedies (before noting liver in macroscopic formalin solution it was significantly increased in size and relatively of the soft consistency); the number of alveolar widening

had been detected in pulmonary remedies, some districts of the alveolar layer septum had been ruptured, some of the bronchial tubes had been widened, hyperplasia of some peribronchialis lymph node had been detected; the picture of fiber separation in the slice taken from the heart muscle tissue had been sharply outlined, and in lymph node preparation - lymph node hyperplasia.Thus, the histopathology research of visceral organs presented by us has shown that the changes in the tissues construction of the organs are in full correlation with the neurological and pathologic behavioral parameters developed both in the organisms of the animals or the humans suffering from the drug addiction. This type of research is of great theoretical and practical significance for studying ethio-pathogenesis of drug abuse and addiction and for recommending preventive measures.

LET’S TRY USE PYTHON (COMPUTER LANGUAGE) IN RHEOLOGY

G. Kuchava

Interdisciplinary informatics Department of Georgian Technical University, Tbilisi, Georgia

Python programming language is using everywhere ininformation technologies today. Where can we use it?

Google Inc. use it in his searching engines.

-We can release videos on YouTube by Python.

-Business giants, like: Intel, Cisco, Hewlett-Packard, Seagate, Qualcomm and IBM are using Python for testing assembled machines and devices.

-Python is using for develop animation movies by big corporations like:Industrial Light & Magic, Pixar.

-It is using by trading market companies, like: JPMorgan Chase, UBS, Getco & Citadel.

-It is using for science calculations by NASA, Los Alamos, Fermilab, JPL.

-Python has fundamental and basic methods of computer functions, which allows to do manipulations on pictures and do text indexing, It needs a lot of parts of medicine, For example: cancer surveillance.

We think, that it will be innovation, if we use Python in medicine and in rheology. We will be able to describe processes in veins, arteries and lymphatic ways by python.Python is one of the most popular programming language. It has simple syntax, its allows programmers to express concepts

in fewer lines of code than would be possible in languages such as C++ or Java. Python supports multiple programming paradigms, including object- oriented, imperative and functional programming or procedural styles. It features a dynamic type system and automatic memory management and has a large and comprehensive standart library. Python interpreters are available for installation on many operating systems. This subject is new and it’s difficult to say which kind of success we will win. But it needs big attention.

EFFECT OF GLUCOSE ON FORMATION OF THREE DIMENSIONAL AGGREGATES OF RED BLOOD CELLS

B. Gregorzewski, A. Szolma-Chodor, M. Bosek

Department of Biophysics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland

The influence of increased glucose concentration in blood on its rheological properties is still important issue. The formation of three dimensional aggregates of erythrocytes after incubation of the cells in glucose media is experimentally investigated. The blood was obtained from healthy donors. Erythrocytes were removed from the blood and were incubated in glucose at concentration 0.0.1, 1, 2 and 3g/dl for 1 hour. The incubated erythrocytes were three times washed and were suspended in solution of dextran at 3g/dl concentration as well as resuspended in autologous plasma. The suspensions were filled in glass container. Images of the aggregates formed in container were obtained every 1s. The duration of every measurement was 30 min. The Fourier based analysis of these data allowed the aggregate size and their sedimentation velocity estimation. Analysis of aggregate velocity dependent on their size gives an insight into their rheological properties.

CONCERNING HEMORHEOLOGICAL DISTRURBANCE IN SEPSIS (CHALLENGES IN EXPERIMENTAL HEMORHEOLOGY)

N. Nemeth

Department of Operative Techniques and Surgical Research, Institute of Surgery, faculty of Medicine, University of Debrecen, Debrecen, Hungary

Despite the modern diagnostic and treatment possibilities, sepsis still means serious challenge in the clinical practice, and of wich pathphysiology has not been elucidated completely yet. Besides macro0hemodynamic changes, septic process is knows to be associated with serve micricirculatory disturbance caused by altered vascular resistance, tissue flow redistribution. Opening arterio-venous shunts, vasoplegia, endothelial activation, edema formation, congestion and hemorrhage, disseminated intravascular coagulation, alterations of blood and plasma viscosity, red blood cell deformability and aggregation, and leukocyte deformability. It is known from numerous clinical and experimental data that red blood cell aggregation markedly increases in developed sepsis, together with the rise of fibrinogen concentration as well as with decreased deformability, so contributing to microcirculatory deterioration. Concerning these microrheological disturbances main questions are the magnitude, the dynamics and the irreversibility. Sepsis is a process, starting with colonization and infection, leading to bacteremia. If the bacteremia is associated with systemic inflammatory response syndrome (SIRS), it means sepsis that can progress in severe sepsis, septic shock, multiorgan dysfunction and death. Most of the available hemorheological findings are from developed sepsis. There is a lack of data on the very microrheological changes, like during bacteremia, the developing SIRS and the early hours of the sepsis. In a fulminant sepsis model in gs (E.coli i.v. administration with an increasing concentration) we found an early tendency of impairment in red blood cell deformability and a controversial decreasing red blood cell aggregation values (declining all aggregation index, values,

elongating t ) during the early hours (4-6) of the sepsis process. The in

vitro effect of these bacteria on erythrocytes’ microrheological parameter was similar. Further studies are needed to clarify he early microrheological changes of bacteremia and the developing sepsis.

CAN LEVEL OF EDUCATION, ACCREDITATION AND USE OF DATABASES IN CARDIAC REHABILITATION BE IMPROVEDRESULTS FROM THE EUROPEAN CARDIAC REHABILITATION INVENTORY SURVEY

N.Pogosova

Rusian National Society for Cardiovascular Prevention and Rehabilitation, Moscow, Russia

Introduction: Professional skills, education and accreditation, along with clinical outcomeassessment, are considered important factors to achieve comprehensive delivery and quality of cardialic rehabitation (CR). This study assessed professional educational programmes, accreditation and use of databases in CR across the European countries.Materials and methods: Questions on professional education, accreditation and clinical databases from the European Cardialic Rehabitation Inventory Survey, which is a postal questionnaire survey, conducted from November 2007 to January 2009 among national CR-related organizations in Europe; 28 countries responded (72%) to this survey.Results: Among the participating countries, 32% had guidelines on professional CR skills, 61% had formal educational programmes and 29% had accreditation systems for professional CR skills. One hundred and seventy-four ad-hoc educational and scientific activities were registered during 2005–2007. Forty-three percent of the countries had established CR programme accreditation systems, primarily aimed at phase

One in three (35%) countries had established clinical CR databases with a further 25% planning to do so.Conclusion: More than half of the European countries had developed formal CR educational programmes. Furthermore, many ad-hoc CR-related meetings and conference activities take place across Europe. Although only a quarter of countries had developed accreditation systems aimed at professionals, programme accreditation was somewhat more widespread with over a third having programme accreditation systems. Clinical databases were underdeveloped. A greater focus on education, accreditation and database implementation is needed to promote CR availability and the quality of CR services for the benefit of cardiac patients across Europe

PHYTO-PREPARATION “STEPALOL E”

M.Nikolaishvili

1. Beritashvili Center of Biomedicine, Tbilisi, Georgia

It contains grape seed oil and vitamin E. The application of the phyto- preparation “Stepalol E” in the experiment shows anti-inflammatory. It is used to improve physiological activity of digestive, urinary and cardiovascular systems, remove scars after surgery, maintain skin elasticity, and eliminate cellulite, as well as during mild forms of gingivitis and parodontitis, also as an antioxidant during tumor pathologies. It is useful to young children and breastfeeding mothers. It decreases breast tumor in size, also has a perfect effect on parodontitis and cures it in 10 days. Treatment is conducted with the application of 15 % solution. 5% solution should be taken 3 times a day during a month, then they should have interval for a month and then continue to take it again.

DETERMINING COMBINED PESTICIDES IN THE LOPOTA RIVER, KAKHETI, GEORGIA

I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

M. Nikolaishvili, N. G. Jiqia

The results and quantity of chemical usage show that chemical method of plant protection has been the main source of agricultural development as an effective and remarkable method, and the pesticides appear to be a progressive means of pest control. In recent years, combined preparations of pesticides have been widely used. Therefore, we decided to study the quantitative distribution of waste products of some combined preparations decis, belophos and DDT in the water of the Lopota River as well as in the soil of its shoreline and bottom sediments. As it was found, they were in great amount in the water just near the villages of Napareuli and Saniore. There was no DDT in the Lopota River, but as for the soil, increased combined action of Decis and belophos was observed near the villages of Lapankuri, Napareuli and Saniore caused by abnormal use of the combined pesticides. They were in a slightly increased amount in the bottom sediments of the river near the villages of Lapankuri, Napareuli and Saniore, while DDT was observed as a trace in the soil and bottom sediments.

SIMULATION OF BONE REMODELING UNDER LOAD

V.A. Lokhov, Y.I. Nyashin, A.A. Kichenko, V.M. Tverier

Department of Theoretical Mechanics and Biomechanics, Perm National Research Polytechnic University, Perm, Russia

During ontogenesis of the human body, the development and operation of its musculoskeletal system are affected to the ever-changing loads of different nature. Such changes are distant in time and implications primarily reflect in the organization of structure of the bone tissue. Trabecular bone is heterogeneous porous anisotropic material whose mechanical properties are largely determined by its internal architecture. Determination of changes in the trabecular microstructure in vivo is often not possible, so that there is a need to predict the long-term response the structure to the external intervention by methods of mathematical modeling. Structural features of trabecular bone are described by the tensor structure. The presentation shows the output of the defining relation that allows us to describe the stress- strain state of the trabecular bone in view of its structure. Also, it gives the evolutionary relations describing the adaptation processes in the bone. The initial boundary value problems on the restructuring of the trabecular bone, which can be used to study the history of the formation of bone structures in time for different types of loading are developed. An algorithm for solving a number of examples is elaborated and shows the evolution of the trabecular bone at the change of the stress-strain state. We consider the local area of the bone tissue in a state of homeostasis. At the initial time, we set a single change in the loading conditions, resulting in a restructuring of the trabecular microstructure. The classic example is reproduced and various options for a new stress state are discussed. The results show the influence of different types of load change on the formation of structures. It coincides with the Wolf’s law.

The work is supported by RFBR, project No. 15–01–04884–а.

ELECTROMAGNETIC FIELD, AS A STRESS FACTOR FOR 25 TO 35 YEARS

OFFICES WORKING FEMALE’S PSYCHO-EMOTIONAL STATE

Dondoladze K., ZurabashviliD., Nikolaishvili M., Zenaishvili S.

The research was executed in Mental Health and Drug Abuse Prevention Center, Tbilisi, Georgia.

The electromagnetic field affects the human mental condition. Individuals who spend more than 56 hours a week under the electromagnetic field, are more vulnerable to mental health disorders compared to those who have less time in the presence of EMF. Frequent headaches, dizziness, giddiness, attention and concentration impairment, anxiety, increased aggression, excessive weight, endocrine and metabolic disorders frequency and severity is different for persons who are in EMF constantly, often and rarely.

BIOMECHANICS AND МEDICINE OF THE XXI ENTURY

Y.I. Nyashin, V.A. Lokhov

Department of Theoretical Mechanics and Biomechanics, Perm National Research Polytechnic University, Perm, Russia

Development of medicine in the XXI century rests on four directions started from letter “p”: predictive medicine, personalized medicine, prophylactic medicine, participatory medicine. For realization of these directions in medicine, it is necessary to broadly use the last advantages of science, in particular computer sciences. One from these perspective advantages in this direction is development of International project “Virtual Physiological Human (VPH)”. According to this conception, human organism is considered as complex multiunit biomechanical system. This system contains all subsystems of human organism (system of breathing, cardiovascular, nervous, maxillofacial, biliary systems, locomotive apparatus, etc.). The target of development of conception “VPH” consists in detail research of all subsystems of human organism and establishment of quantitative and qualitative relations between them. Development of this conception allows us to accelerate significantly and improve diagnostics, to find the optimal method of healing of every individual patient, including conduction of virtual operation. We can open new real possibilities for realization of directions of medicine designated as four “p”. In suggested research, we pay special attention to analysis of structure and physiological peculiarities of the maxillofacial system of human in dynamics of its development, beginning from birth and further during all human life. We analyze the influence of the biomechanical pressure on processes of phylogenesis and ontogenesis. In particular, we describe the development of different elements of the system in norm and at different pathologies. Particularly important element of research in the framework of given problem is analysis of relation of pathological changes in the maxillofacial system and in other human systems. In conclusion, we conduct analysis of relation of pathologies in the maxillofacial system and disturbances of intracerebral blood circulation including insult to the brain. This work obtained in framework of state (project № 1873).

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beritaSvilis eqsperimentuli biomedicinis centri SoTa rusTavelis erovnuli samecniero fondi
1. Beritashvili Center of Experimental biomedicine Shota Rustaveli National Science Foundation

www.lifescience.org.ge www.rustaveli.org.ge

რეეოლლოოგგიიისს დდა მმიიკკრროოცციირრკკუულლააცციიიის უაახხლლეესსიი მმეეთთოოდდეებბიი, მმოონნააცცეემმეებბიი, დაასსკკვვნნეებბი

რეეოოლლოოგგიიიის დდაა მმიიკკრროოცციი

რრკკუულლ

ააცციიიის სსააეერრთთააშშოორრიისსოო

სკკოოლლიისს მმსსმმეენნეელლეებბიისსაათთვვიის

(თთბბიილლიისსიი,, სსააქქაარრთთვვეელლოო,, 22001155 წწლლიისს 1122--1166 ოოქქტტოომმბბეერრიი))

RHEOLOGYCAL AND МICROCIRCULATION METHODS, NEW DATA, CONCLUSIONS

for participants of International School of Rheology and Microcirculation

(2015 October, 12-16 Tbilisi, Georgia)

beritaSvilis eqsperimentuli biomedicinis centri SoTa rusTavelis erovnuli samecniero fondi
1. Beritashvili Center of Experimental biomedicine Shota Rustaveli National Science Foundation

www.lifescience.org.ge www.rustaveli.org.ge

რეეოოლლოოგგიიიისს დდა მმიიკკრროოცციირრკკუულლააცციიიის უაახხლლეესსიი მმეეთთოოდდეებბიი, მმოონნააცცეემმეებბიი, დდაასსკკვვნნეებბი

რეეოოლლოოგგიიიის დდაა მმიიკკრროოცციირრკკუულლააცციიიისს სსააეერრთთააშშოორრიისსოო სსკკოოლლიისს მსსმმეენნეელლეებბიისსაათთვვიის

RHEOLOGYCAL AND МICROCIRCULATION METHODS, NEW DATA, CONCLUSIONS

for participants of International School of Rheology and Microcirculation

(2015 October, 12-16 Tbilisi, Georgia)

THIS BOOK CREATED by M.Mantskava

ACKNOWLEDGEMENTS. Authors and co-authors of all abstracts and scientific essays.

ISBN 978-9951---------

ELECTRORHEOLOGICAL METHOD FOR STUDYING THE FLOW PROPERTIES OF BLOOD

1N. Antonova, 2P. Riha, 1I. Ivanov

1 Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria, 2Institute of Hydrodynamics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

NUMERICAL ANALYSIS OF BLOOD FLOW IN THE COMMON CAROTID ARTERY BIFURCATION WITH STENOSIS FOR UNSTEADY FLOWS

1N. Antonova, 2D. Xu, 3I. Velcheva, 4E. Kaliviotis, 1P. Tosheva

1Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria

2School of Civil Engineering, Tianjin University, Tianjin, China.

3University Hospital of Neurology and Psychiatry, Medical University, Sofia, Bulgaria

4Dept. Mechanical Engineering and Materials Science and Engineering, Limassol, Cyprus

REOLOGICAL DISORDERS DURING BLOOD LOSS

M.Mantskava, N.Momcelidze, L.Davlianidze

1. Beritashvili Center of Experimental Biomedicine, Tbilisi,

Georgia

RHEOLOGY IN REYNAUD’S’ PHENOMENON, WHICH INDUCTION DISEASES.

T. Kotaria, M. Mantskava

Diagnostics and Correction Center of Foot Function „Terdi” Tbilisi, Georgia

HEMORHEOLOGICAL DISORDERS IN THE EXPERIMENTAL MICROCIRCULATORY STASIS

Momtselidze, 2. L. Gobejishvili, 1 M. Mantskava, [1G. Mchedlishvili]

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Department of Medicine, University of Louisville, Louisville, USA

ERYTHROCYTE AGGREGATION IN HEMORRHAGIC SHOCK DURING STRESS

M. Mantskava, N. Momtselidze, L. Davlianidze

1. Beritashvili Center of Biomedicine, Tbilisi, Georgia

Stress, being the general reaction of the organism to the physical and psychological effects, accompanies all the stages of somatic and psychic formation. Hemorrhagic shock occurring at blood loss appears to be a powerful stress for the organism. The origin (emergence) and spread of stress reactions are characterized by the features of the macro-and microcirculation. In stressful situations the crisis of blood circulation affects the functions of hemorheological disorders, as well as appears to be a consequence of the shock. We were the first to combine these two problems. The dilemma has been built. Blood loss, being a cause of hemorrhagic shock development while spending adaptive energy would result in more slack development of stress stages, or the body who has received the stress from the outside, will be more subjected to hemorrhagic shock. The following specific objectives were set to answer this question: to ascertain the intensity of the transition from the lower grade of stress to higher due to the development of hemorrhagic shock and to investigate the hemorheological properties of blood at different stages of hemorrhagic shock and at different grades of stress. Experimental stress was induced by heating (hyperthermia). The erythrocyte aggregation increased as the blood volume quantity grew at the bleeding, i.e. with the increasing of shock stages by 10%, 25% and more than 110% compared to the control. When heated the erythrocyte aggregation increased with the transition of stress from one grade to another by 5%, 20% and 80% compared to the control and the increase of the amount of discharged blood was exacerbated at the first and second grades of the stress. During the third grade, even at low blood discharge the aggregation critically increased. The data obtained have shown that at hemorrhagic shock the stress developed according to the amount of blood loss, while in the stressful individuals of first and second grades, depending on the state of shock the aggregation increased analogously, but more intensely. The stress of third grade completely disturbed blood hemorheology even at the first stage of shock and induced lethality. The hemorrhagic shock, expending adaptive energy, stimulated the development of stress stages, but lethality occurred as a result of a critical blood loss. The organism receiving an external stress, was more exposed to hemorrhagic shock and lethality. Our findings appear to be only the first experimental session of this problem. Further research in this direction may

HEMORHEOLOGICAL DISORDERS IN PATIENTS WITH FOOT GANGRENE

Mantskava M.

I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

PHYSIOLOGICAL PREREQUISITES FOR APPLICATION OF HYPERTHERMIA IN CANCER TREATMENT

N. Mitagvaria, M. Mantskava, M. Devdariani, M. Nebieridze, L. Davlianidze,

N. Momtselidze, N. Saginadze, L. Gumberidze, I. Kvachakidze, N. Sikharulidze

I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

MICROFLOW DYNAMICS IN BRAIN STRUCTURES IN SLEEP-WAKE CYCLE

L. Davlianidze, M. Devdariani, M. Nebieridze, N. Mitagvaria

I. Beritashvili Center of Experimental Biomedicine, Georgia, Tbilisi

FENTANYL EVOKES IN LOCAL BLOOD FLOW

1M. Devdariani, 1L. Davlianidze, 1N. Mitagvaria, 1M. Nebieridze, 2M.

Darbaidze

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2David Agmashenebeli National Defence Academy of Georgia

- metabolism”.

EFFECT OF PENTOXIFYLINE ON SOME FORMS OF ARTERIAL HYPERTENSION

1N. Momtselidze, 2N. Beritashvili

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Insurance Company “Imedi”, Tbilisi, Georgia

CEREBRAL BLOOD FLOW STRUCTURING

1 N.Momtselidze, 2 L.Gobejishvili

1I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Department of Medicine, University of Louisville, Louisville, USA

EFFECT OF MANGANESE SHORT-TERM ADMINISTRATION ON THE PREPUBERTAL

AND MATURED RAT’S LEARNING ABILITY

1I.L. Lazrishvili, 1T.Z. Bikashvili, 2A.A. Shukakidze, 1N.P. Mitagvaria, 1L.K.

Gelazonia

1I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

2Tbilisi State Medical University, Tbilisi, Georgia

STRESS-FREE DISPLACEMENT CONTROL OF STRUCTURES

Y.Nyashin, V. Lokhov, F. Ziegler

Department TheoreticalMechanics and Biomechanics, Perm National Research Polytechnic University, Perm

ARTERIAL HYPERTENSUIN MANAGMENT NATIONAL GUEDELINE AND PROTOCOLS HYPERTENSION MANAGEMENT NATIONAL GUEDELINE AND PROTOCALS IMPLEMENTATION PROCESS ASSESSMENT IN GEORGIA: PP.20.278

B.Tsinamdzgvrishvili

Georgian Society of Hypertension, National Center of Cardiology, Tbilisi, Georgia

DETERMINATION OF NONINVASIVE PARAMETERS OF LOW FREQUENCY MAGNETIC STIMULATION

FOR LIVE ORGANISM (THEORETICAL RESEARCH)

1N. Bukia, 1G. Kekelia, 1M. Butskhrikidze, 2M. Svanidze, 1L. Machavariani

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Tbilisi, Georgia

Research was supported by FR/257/7-270/14.

K. Gambashidze, T. Petriashvili, N. Bejitashvili,

N. Pkhaladze, D. Karkarashvili, N. Chelidze, M. Lomia

Tbilisi State Medical University, Department of Pathophysiology. Tbilisi Georgia

REGULATION OF FUNCTIONAL CELLS COUNT IN PERIPHERAL BLOOD BY EXTRACELLULAR UBIQUITIN IN AN ANIMAL MODEL OF CYTOPENIA

1R. Sujashvili, 1I. Ioramashvili, 1K. Aptsiauri, 1N. Gvinadze, 2M.

Gamkrelidze

1I. Beritashvili Centre of Experimental Biomedicine, Tbilisi, Georgia

2University of Georgia, Medical School, Tbilisi, Georgia

OXYTOCIN ON THE FORMATION OF A FOOD-PROCURING REFLEX IN RATS

M. Butskhrikidze, N. Bukia

I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

HEMORHEOLOGICAL, MICROVASCULAR AND HEMODYNEMIC PROFILES

IN PATIENTS WITH ISCHEMIC HEART DISEASE

1T. Urdulashvili, 2N. Narsia

1Medical Centre “Medisoni”, Tbilisi, Georgia

2 Tbilisi State Medical University, Tbilisi, Georgia

DETERMINATION OF NONINVASIVE PARAMETERS OF LOW FREQUENCY MAGNETIC STIMULATION

FOR LIVE ORGANISM (THEORETICAL RESEARCH)

1N. Bukia, 1G. Kekelia, 1M. Butskhrikidze, 2M. Svanidze, 1L. Machavariani

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Tbilisi, Georgia

Research was supported by FR/257/7-270/14.

ASSOTIATIOM OF SOLUDATE CD14 WITH INFLAMATORY MARKERS AND DISEASE SEVERUTY IN TYPE 2 DM

Gobejishvili, S. P. L. Mokshagundam, D. Mokshagundam, V. Vatsalya,
Kong and Sh. Barve

School of Medicine, University of Louisville, Louisville, Kentucky, USA

PDE4 INHIBITION ATTENUATES ALCOHOL INDUCED OXIDATIVE STRESS BY INCREASING ANTIOXIDANT ENZYME EXPRESSION

Gobejishvili, D. Avila, C. McClain and Sh. Barve

School of Medicine, University of Louisville, Louisville, Kentucky, USA

THE LOCAL CEREBRAL BLOOD FLOW IN THE DORSAL HIPPOCAMPUS OF RATS DURING INITIAL AND DEEP STAGES OF INFORMATIONAL PATHOLOGY OF BEHAVIOR

1. Kvachakidze, L. Gumberidze, N. Sikharulidze

I.Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

INTENSIFIED RBC AAGGREGATION AS INITIATING FACTOR OF MICROCIRCULATORY DISORDERS

N. Beritashvili

Insurance Company “Imedi”, Tbilisi, Georgia

HEMOSTASIS - INFRINGEMENT AND ITS CORRECTION IN OPERATIONS AMPULLAR COLON CANCER

2M. Skoblo, 2A. Pirumyan, 1A.Pogosyan,1 I. Dudarev, 2 I. Efrosinina, 1E.

Lebedeva

1Medical University “Rostov State Medical University” Ministry of Health, Russian

2MBUZ “Hospital №6” «coloproctological city center” Rostov-on-Don, Russia

hemostatic system and is the reaction product of thrombin and antithrombin

ALTERATIONS IN CUTANEOUS MICROCIRCULATION AND BLOOD RHEOLOGICAL PROPERTIES IN PATIENTS WITH DIABETES MELLITUS TYPE 2 ESTIMATED THROUGH THE CHANGES OF OSCILLATIONS IN SKIN TEMPERATURE AFTER COLD TEST

1N. Antonova, 1V. Kostova, 2I. Velcheva, 3S. Podtaev, 2N. Chaushev

1Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria 2University Hospital of Neurology and Psychiatry, Medical University, Sofia, Bulgaria

3Research Center “FM Diagnostics”, Perm, Russia

0.05 Hz), and endothelial (0.0095 - 0.02 Hz) control mechanisms and their association with skin blood flow changes during indirect cold test in 10 patients with diabetes mellitus type 2 and 10 healthy age and sex matched controls. Dynamics of changes of oscillations in skin (cutaneous) temperature were evaluated through the root mean square values of the amplitudes obtained by the wavelet analysis in the frequency range corresponding to the mechanism of myogenic, neurogenic and endothelial regulation of vascular tonus. The measured average amplitudes in three frequency ranges were estimated by a box plot diagram. The aim was to study in parallel the rheological properties in patients with Diabetes mellitus and to compare them with a control group of healthy subjects. A rotational viscometer Contraves Low Shear 30 (Switzerland) was used to measure whole blood viscosity at shear rates of 0,

ELECTRON MICROSCOPIC STUDY OF RAT NEURONAL POROSOME COMPLEX IN NORM AND PATHOLOGY

1,2M.G. Zhvania, 1,3N.J. Japaridze

1Ilia State University, Tbilisi, Georgia

2I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

3New Vision University, Tbilisi, Georgia

AS A RESULT OF THE INJECTION OF MANGANESE IONS, MAY CAUSE HISTOPATHOLOGICAL CHANGES INDUCED IN SOME

VISCERAL ORGANS

1,2T. Bagashvili, 1N. Papuashvili, 2T. Jorbenadze, 1G. Andronikashvili,

1T.Gurashvili, 1K. Gogeshvili

1I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

2I. Javakhishvili Tbilisi State University, Faculty Medicine, Tbilisi, Georgia

LET’S TRY USE PYTHON (COMPUTER LANGUAGE) IN RHEOLOGY

G. Kuchava

Interdisciplinary informatics Department of Georgian Technical University, Tbilisi, Georgia

Python programming language is using everywhere ininformation technologies today. Where can we use it?

Google Inc. use it in his searching engines.

-We can release videos on YouTube by Python.

-Business giants, like: Intel, Cisco, Hewlett-Packard, Seagate, Qualcomm and IBM are using Python for testing assembled machines and devices.

-Python is using for develop animation movies by big corporations like:Industrial Light & Magic, Pixar.

-It is using by trading market companies, like: JPMorgan Chase, UBS, Getco & Citadel.

-It is using for science calculations by NASA, Los Alamos, Fermilab, JPL.

EFFECT OF GLUCOSE ON FORMATION OF THREE DIMENSIONAL AGGREGATES OF RED BLOOD CELLS

B. Gregorzewski, A. Szolma-Chodor, M. Bosek

Department of Biophysics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland

CONCERNING HEMORHEOLOGICAL DISTRURBANCE IN SEPSIS (CHALLENGES IN EXPERIMENTAL HEMORHEOLOGY)

N. Nemeth

Department of Operative Techniques and Surgical Research, Institute of Surgery, faculty of Medicine, University of Debrecen, Debrecen, Hungary

elongating t ) during the early hours (4-6) of the sepsis process. The in

CAN LEVEL OF EDUCATION, ACCREDITATION AND USE OF DATABASES IN CARDIAC REHABILITATION BE IMPROVEDRESULTS FROM THE EUROPEAN CARDIAC REHABILITATION INVENTORY SURVEY

N.Pogosova

Rusian National Society for Cardiovascular Prevention and Rehabilitation, Moscow, Russia

One in three (35%) countries had established clinical CR databases with a further 25% planning to do so.Conclusion: More than half of the European countries had developed formal CR educational programmes. Furthermore, many ad-hoc CR-related meetings and conference activities take place across Europe. Although only a quarter of countries had developed accreditation systems aimed at professionals, programme accreditation was somewhat more widespread with over a third having programme accreditation systems. Clinical databases were underdeveloped. A greater focus on education, accreditation and database implementation is needed to promote CR availability and the quality of CR services for the benefit of cardiac patients across Europe

PHYTO-PREPARATION “STEPALOL E”

M.Nikolaishvili

1. Beritashvili Center of Biomedicine, Tbilisi, Georgia

DETERMINING COMBINED PESTICIDES IN THE LOPOTA RIVER, KAKHETI, GEORGIA

I.Beritashvili Center of Biomedicine, Tbilisi, Georgia

M. Nikolaishvili, N. G. Jiqia

SIMULATION OF BONE REMODELING UNDER LOAD

V.A. Lokhov, Y.I. Nyashin, A.A. Kichenko, V.M. Tverier

Department of Theoretical Mechanics and Biomechanics, Perm National Research Polytechnic University, Perm, Russia

The work is supported by RFBR, project No. 15–01–04884–а.

ELECTROMAGNETIC FIELD, AS A STRESS FACTOR FOR 25 TO 35 YEARS

OFFICES WORKING FEMALE’S PSYCHO-EMOTIONAL STATE

Dondoladze K., ZurabashviliD., Nikolaishvili M., Zenaishvili S.

The research was executed in Mental Health and Drug Abuse Prevention Center, Tbilisi, Georgia.

BIOMECHANICS AND МEDICINE OF THE XXI ENTURY

Y.I. Nyashin, V.A. Lokhov

Department of Theoretical Mechanics and Biomechanics, Perm National Research Polytechnic University, Perm, Russia

ი.ბერიტაშვილის ექსპერიმენტული ბიომედიცინის ცენტრი შოთა რუსთაველის ეროვნული სამეცნიერო ფონდი

I.Beritashvili Center of Experimental biomedicine Shota Rustaveli National Science Foundation

www.lifescience.org.ge www.rustaveli.org.ge

M.Mantskava, N.Momcelidze, L.Davlianidze

T. Kotaria, M. Mantskava

Mantskava M.

L. Davlianidze, M. Devdariani, M. Nebieridze, N. Mitagvaria

Y.Nyashin, V. Lokhov, F. Ziegler

B.Tsinamdzgvrishvili

N. Nemeth

N.Pogosova

M.Nikolaishvili

Beritashvili Center of Experimental biomedicine Shota Rustaveli National Science Foundation

Beritashvili Center of Experimental biomedicine Shota Rustaveli National Science Foundation

RHEOLOGYCAL AND МICROCIRCULATION METHODS, NEW DATA, CONCLUSIONS

M.Mantskava, N.Momcelidze, L.Davlianidze

T. Kotaria, M. Mantskava

Mantskava M.

L. Davlianidze, M. Devdariani, M. Nebieridze, N. Mitagvaria

Y.Nyashin, V. Lokhov, F. Ziegler

B.Tsinamdzgvrishvili

N. Nemeth

N.Pogosova

M.Nikolaishvili