a problem Urgency.

the Stress and illness inseparably linked among themselves, also is available a considerable quantity of data confirming a hypothesis that stressornye influences directly positively correlate with frequency of diseases [P.

DeVito, 1994], especially at the teenagers which organism is most sensitive to stressornym vozdejsvijam [D.R.Baldwin, S.M.Harris, L.N.Chambliss, 1997]. About 25 % of the population of the USA test negative influences of constant stress and about 50 % of the patients who have addressed to the doctor in America are subject to the problems bound to consequences of stress [G.S.Jr. Everly, 1989]. The live organism aspires to receive and support the optimal conditions of the life. When environment conditions are not optimum, individuals adapt to existing circumstances [K.V.Sudakov, Belova T.I., Yumatov E.A., 1985; K.V.Sudakov, 1981]. In norm dynamic balance of interaction of counteracting processes, "homeostasis" is constantly supported. Extreme adjustment of physiological processes is referred on minimisation of consequences of influence of factors of external and internal medium of an organism. Now it is established, that emotional stress, as well as the stress caused by an infection, a virus both other pathogenic microorganisms and xenobiotics, can practically provoke any disease. When to an organism excessive demands or threats are made, the adaptive answer starts to have stereotypic nonspecific character - a condition known as "stress", the general adaptic syndrome [Selye G, 1960, 1972, Selye H., 1956, 1976]. Under nespetsifichnostju stress relative independence of reactions of character of stimulation was understood. At the same time the stress, acting as a nonspecific component, is in indissoluble unity with specific reactions of an organism on influencing agents, changes at all levels - organizmennom, organnom, fabric, cellular and molecular. As one of the basic targets stressornyh influences consider cardiovascular functions and activity of the central nervous system. Reaction to stress in
appreciable degree depends on individual reactance of the person and animals, from their individual condition nejroreguljatornyh mechanisms [K.V.Sudakov, 1976, 1998; H. Selye, 1970]. Stressornye organism reactions are genetically determined and generated as a result of evolution as the mechanism of the active adaptation [D.K.Beljaev, 1979]. The emotional excitation originally developing at level of gipotalamo-LIMBIKO-reticular structures of a brain, is generalised extends in an ascending direction on a cortex of the big hemispheres, and in descending - on various internal organs.

the Formation of "congestive" excitation occurring to obligatory participation monoaminergicheskih of systems of a brain, is a basis of emotional stresses. At depression of fastness central nejrohimicheskih mechanisms there is the dysregulation of cardiovascular functions interfaced to disturbance of an exchange of biologically active substances and underlying pathological syndromes, developing at stress [K.V.pike perch, 1997; G. Aguilera, C. Rabadan-Deihl X. Luo, A.Kiss, 1996; W.F. Ganong, 1996]. Metabolic shifts in the course of stress include change of secretion of adrenaline and Noradrenalinum cerebral substance of adrenals and the sympathetic nervous terminations accordingly. The cores

as neuroendocrinal links of stress are considered: simpato-adrenalovoe, gipotalamo - a gipofizo-epinephral axis through which the brain influences each cell of an organism during influence of menacing stimulus.

The role of simpato-adrenal system in development adaptativnyh organism reactions, is shown for the first time in L.A.Orbeli's works (1938) and V.Kennona (1927) still before G.Sele has formulated the concept about stress. G.I.Kassil and E.M.Matlina (1973) was allocated with three stages of development adaptativnyh processes: a phase quickly coming adaptativnoj activation, a phase of long and steady activation and the third phase - a phase of weakening and progressing attrition of functions. Transition to the third phase reflects transition to irreversible changes and L.S.Shtern, 1960] can end with formation of a pathological syndrome or a shock with full attrition of simpato-adrenal system [. Besides, stress, as is known, zakachivaetsja a condition immunosupressii (intensifying humoral and suppression of cellular immunity). Stress-reaction of immune system it is caused by differential effect of hormones of stress, glucocorticoids and catecholamins, on reguljatornoe parity 4 +/8 + cells and production of various types of cytokines. On the other hand, the acute stress, as is known, stimulates proinflammatory activity [K.G.Gurevich, 2002; B.Netterstrom,

A.M.Hansen, 1999].

Key and subcellular systems, it is close vzaimosvjazannnami with the friend with

the friend on which action various stressornyh agents is referred are:

- system of energy balance and stability of cellular membranes;

- system of a homeostasis intracellular micro-and macrocells;

- system of activation of is free-radical processes in a cell and system of antioxidatic protection;

- system of a plastic exchange.

More often depending on a kind stressornogo the agent one of the listed systems is starting, but further the special importance for character adapatatsionnoj reactions of the damaged cell get others. Very often two or several of the mentioned systems are bound among themselves on type " vicious ".

attempts to lower environmental contamination level as one of the major constantly present stressornyh factors, to raise an overall performance of protective systems (pharmaceutical by) Now are undertaken. Especially important it for children and teenagers - they are very sensitive to foreign chemical substances as mechanisms of protection at them are not developed yet to the full. Thus, complex research of intimate mechanisms of development and advance stressornyh syndromes, rising of risk of failure of adaptation and development of conditions of preillness and illness is one of the major problems of teenage medicine.

the Purpose of the present work is revealing of early criteria of diagnostics of premorbidal conditions of an organism of teenagers, identification biopower and nejrotransmitternyh the systems (subsystems) responsible for formation of fastness of reserve systems of an organism to stressornym to influences at teenage age.

For achievement of this purpose in work following problems have been put:

- to study interrelation between a condition simpato-adrenal and serotoninergicheskoj regulations and a redox potential of a cell under the influence of emotsialno-information stress and a hypokinesia;

- to study interrelation between a condition simpato-adrenal and serotoninergicheskoj regulations and a redox potential of a cell at chastobolejushchih teenagers;

- to study interrelation between a condition dofaminergicheskoj systems and activity of system of power maintenance at teenagers with a bronchial asthma;

- to study interrelation between a condition simpato-adrenal and serotoninergicheskoj regulations and a cell redox potential, activity of immune and endothelial systems at a bronchial asthma;

- to study a role of augmentation of activity NADN - and NADFN-OKSIDAZ-DEPENDENT formation of active forms of oxygen in the gljukortikoid-induced apoptosis of lymphocytes at chastobolejushchih acute respiratorno-virus diseases of teenagers and at teenagers with a bronchial asthma;

- to study interrelation between a condition simpato-adrenalovoj and serotoninergicheskoj regulations and a redox potential of a cell under the influence of stratification of emotsialno-information stress and a bronchial asthma;

- to study resistances of a liver, kidneys, easy, a cerebral tissue, heart and to influence of various doses of serious metals and toxic bonds on the basic intracellular target - respiratory a chain of mitochondrions at preadolescent not purebred white rats.

Scientific novelty. In work the new direction - the doctrine about biomarkers which is an actual and important direction in sovrmennoj to a biomedical science, pediatrics and ecological pediatrics is developed. As biological markers quantitatively defined biological parametres which are indicators of health of the teenager, risk of development of disease, influence stressornyh agents, effects of environment, diagnostics of disease, metabolic processes, epidemiologii etc. are surveyed. It is shown, that the system of power maintenance and various links nejrohimicheskih systems are the basic targets of implication indiviudalnyh reactions of an organism of teenagers on various stressornye influences and, apparently, take part in formation of personal features of an organism. Thus the greatest value dofaminergicheskoj systems is bound with ekstraversiej, and defects in serotoninergicheskoj systems to development of depressions. It is shown, that between a condition kateholaminoergicheskoj systems and mechanisms of development of stress, expression stressornoj reactions teenagers at emotsialno-information stress, allergic reaction have a close interrelation. And degree disbalansirovanija kateholaminergicheskoj systems directly is interfaced to degree of expression of stress-reaction, irrespective of its aetiology. At action stressornogo the factor in indemnification phase
kateholaminergicheskaja and biopower systems work odnonapravleno, thus their compounded functioning defines degree of expression of stress-reaction so that it was adequate stressornomu to influence. In a phase of failure of compensatory possibilities kateholaminergicheskaja and biopower systems can function as antagonists and to close a vicious circle in formation of pathological changes, to promote development got mitohondrialnoj to a pathology.

It is shown, that cytotoxicity of serious metals, the majority of chemical agents is caused by three interconnected mechanisms: oppression mitohondrialnogo respirations of cells of a brain, cardiomyocytes, hepatocytes, nefrotsitov owing to change of a membrane potential of mitochondrions and disturbance of activity of enzymes respiratory a chain and cycle Krebsa.

the Knowledge of pathogenetic mechanisms of cytotoxic action endoekologicheskih factors will allow to develop highly reliable, accessible clinics of test system of early diagnostics of an endogenous intoxication and to plan ways endoekologicheskoj aftertreatments, resistance risings adaptativnyh systems of an organism of teenagers that will provide appreciable depression of a case rate at teenage age.

the Hypokinesia simultaneously with increase of a psychological strain (because of restriction of the general motor performance and monotonous muscular work in the conditions of modern educational process and a life of teenagers) is powerful stressornym the agent and a pathogenetic risk factor of development first of all cardiovascular and cerebrovascular disorders. Sharp unitary restriction of a motor performance, let alone repeated, its chronic restriction, leads to serious long behavioural changes. The long chronic hypokinesia in a combination to the big streams of the processed information promotes development of an information pathology vegetonejrotsirkuljatornyh dystonias and other neurotic disorders. Intensity of the immunologic status is combined with maintenance depression in lymphocytes of the oxidised forms piridinovyh nucleotides, redox potential I / 7/(a marker dezadapatatsionnyh processes in power supply system) and NADF/NADF/(a marker of a plastic exchange), correlation disturbance between redox potential NADF/NADF/and maintenance IgE. Thus the maintenance of a free serotonin raises, and adrenaline decreases that conducts to sharp depression of relations [adrenaline] / [serotonin] and
[Noradrenalinum] / [adrenaline]. It is established, that degree of depression / [serotonin] correlates relations [adrenaline] with frequency of occurrence of attacks of a bronchial asthma at night. For the first time it is shown, that at a bronchial asthma teenagers have a coordination weakening between metabolic system of lymphocytes and functional activity immunnokompetentnyh cells. On the basis of the found out depression of activity of a number mitohondrialnyh oksidreduktaz at persons with the persistent form of a bronchial asthma and at chastobolejushchih ORZ teenagers it is possible to assume disturbance of anaerobic processes of lymphocytes, stimulation of oxidising reactions. The taped disturbances of a metabolism of lymphocytes define depression of their function that leads to development of a secondary immunodeficiency and disease synchronisation.

Practical references.

to Survey complex influence stressornogo the agent or sochetannoe influence various stressornyh agents on an organism of teenagers on system of power maintenance, a condition sismpato-adrenal, dofaminergicheskoj and serotoninergicheskoj and immune systems as uniform system, disturbance in which one link essentially raises risk of formation of a vicious circle of metabolic and neurocirculatory disturbances.

to Use the taped various correlations of level and an exchange nejromediatorov for early diagnostics of disturbances deep nejrohimicheskih processes at teenagers under the influence of various stressornyh agents and workings out of their rational therapy.

to Spend an estimation of a condition of system of power maintenance, redoks - potential, the maintenance of cytochrome with, aktivnostej OVER - N-oksidaz for early revealing of risks-factors of development immunodefitsitnyh conditions.

At a bronchial asthma as a marker of development of deep difficultly reversible changes to consider rising of the maintenance of endothelin-1 at simultaneous depression of the maintenance of adrenaline and a redox potential of system of power maintenance.

to Use approved in work vysokoinformativnyj and the readily available test of an estimation of toxicity of action of serious metals on oppression of oxidation NADH quality of test system early diagnostikinarushenija endoekologii an organism of the teenager.

work Approbation. Work was approved on joint faculty meeting of pediatrics and teenage medicine of the Tbilisi state medical university and the Republican research centre of medical biophysics and introduction of new biomedical technologies of N.V.Karsanova.

the Dissertation is recommended to public protection.

the Basic results of work were reported and discussed on X-XI the All-Russia National congress the Person and the Medicine, Moscow, 2003, 2004; Third International Conference of Children's Health and Environment, London, 2004; III Russian congress on patofiziologii with the international participation Dizreguljatsionnaja a pathology of organs and systems, Moscow, 2004; International Symposium Biological Motility, Pushino-on Oke, 2004; the World congress of allergists and immunologists, Moscow, 2004, Tbilisi, 2004; medicine Pressing questions, Kobulety, 2004; the All-Russia congress Modern problems of pediatrics and clinical diagnostics in pediatrics, Moscow, 2004

On dissertation materials 18 works are published.

Structure and dissertation volume. Dissertational work consists of introduction, the heads devoted to the review of the literature, to the description of methods of research, a statement of results and their discussion, conclusions and the list of the literature including 328 sources.

Work is stated on 254 pages of the typewritten text and illustrated by 36 drawings and 22 tables.


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Scientific source INGA MAMUCHISHVILI. INTERRELATION STRESS-INDUCED of DISTURBANCES In nejrogumoralnoj to SYSTEM And SYSTEM of POWER SUPPLY At TEENAGERS. The DISSERTATION on competition of a scientific degree of the doctor of medical sciences. Tbilisi - 2006. 2006

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  2. Introduction