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Pathogenetic mechanisms stressornyh reactions at a bronchial asthma atopicheskogo a genesis.

In a development and advance pathogenesis atopicheskoj forms BA the great value has a condition of endothelial system [Hay D.W.P., Henry P.J., Goldie R.G., 1996]. The known factors inducing disbalans between vasopressor and vazodilatirujushchimi by components of endothelial system are a hypoxia [Elton T.S., et al., 1992; Li H., et al., 1994], proinflammatory cytokines [Kanse S.M., et al., 1991] and stress [Harrison V.J., et al., 1998].

The vasopressor peptide, endotelin-1 is produced by an epithelial layer of bronchuses and alveolar macrophages [Yanagisawa M., et al., 1988; Redington A.E., et al., 1992] also possesses bronhokonstriktivnymi
properties at linkage with specific endotelinovymi receptors And and In [Li H., et al, 1994]. Expression -1 epithelial cells of bronchuses at BA increases [Vittori E. et al, 1992] also can stimulate sputum secretion, an edema, mitogenez smooth muscles and geperreaktivnost bronchuses [Hay D.W.P., 1996, Trakada G., et al, 2000]. It is shown, that degree of rising of maintenance -1 in plasma is interfaced to gravity of symptoms BA [Chen W.Y., Wang I-Y., 1995]. Ability endotelina-1 to raise level of mediators of an inflammation, interlejkina-1 and interlejkina-8 underlies its proinflammatory effect [Mullol J., et al, 1996].

the Mechanism starting endothelial dysfunction at vospalitelnoallergicheskih diseases, activation svobodnoradikalnyh reactions [Vittori E is., et al, 1992; Freeman B.A., et al, 1982], basically AFK [Freeman B.A., et al, 1982]. The hypothesis expresses, that super-regulation of system of an endothelium in the conditions of a hyperoxia of lungs is a consequence of rising of level AFK and failure of compensatory mechanisms of system of antioxidatic protection [Freeman B.A., et al, 1982], with the subsequent activation perekisnogo oxidations of lipids, liberation reactive gidroperoksidaz lipids and 8-izoprostana [Roberts L.J., Morrow J.D., 1997]. However in which image, AFK or products of their interactions conduct to direct stimulation of emission endotelina-1 in lungs remains to unknown persons [Saugstad O.D., 2000]. In this connection studying of a condition of reserve possibilities of adaptic systems of lymphocytes at teenagers with the persistent form atopicheskoj BA was the purpose of the present work.

the Maintenance of endothelin-1, a vasopressor peptide of endotheliocytes at atopicheskoj to a bronchial asthma easy and moderately severe raises on 81 % and is interfaced to rising of activity NaDn-oksidazy on 76,4 % (tab. 18).

the Associativity of hyperformation of endothelin-1 and activity rising NADN - oksidazy which sites in endotheliocytes are located in immediate proximity from the formation centres peroksinitrila can to break indirectly transport NO in a cell. Strong linkage NADFN in the active centre of a catalase, is necessary for enzyme transition in the active form (hydroperoxide neutralisation) [Hekirman S., Galiano S., Gaetani G.F., 1987]. In this connection, it is possible to assume, that rising of activity NaDfN-oksidazy can konkurentno reduce to (limit) activity of a catalase.

the Problem studying of molecular mechanisms of regulation of metabolic adaptation of patholologically changed bronho-pulmonary system remains the important direction
modern experimental and clinical medicine, pediatrics. Especially it is important in modern conditions when the quantity of children and teenagers with atopicheskimi diseases and atopicheskoj form BA in particular is considerably enlarged.

It has great value on the one hand for revealing enzimaticheskih breakages (enzymopathies) and an establishment of character of disturbances of the metabolic block and the endothelial dysfunction, developing at atopicheskoj to form BA.

Table 18. The maintenance endotelina-1, superoksidnogo aniona, peroxides of hydrogen, adrenaline and adrenohroma, activity of a catalase, superoksiddisumutazy and NADN - oksidazy at teenagers sick atopicheskoj the form of a bronchial asthma.

the Indicator Groups
control the Basic
lgE, ME/L 51,2 yo 5,0 45632 ***
Endothelin-1, pg/ml 1,460,05 2, 640, 15 **
Rate of generation About 2 - , mkmol/mines 36,11,4 66, 13, 6 ***
N 2 About 2 - , mkmol/l of mines 0,10 0,04 0,560,13 **
NaDn-oksidaza, nmol/mg of fiber of mines 10614 18721 **
SOD, usl. Ed/ml 213 375 *
the Catalase, nmol H 2 O 2 - / ml of mines 4,00,6 6, 70, 9 **
Adrenohrom, pmol/ml 2,1 yo 0,3 6,60,2 ***
Adrenaline, nmol/ml 1,75 yo 0,20 1,23 yo

0,23 *

Adrenaline/adrenohrom 83031 18735 ***

the Note: * - reliability of differences of averages in the control and basic groups, one sign - r < 0,05, two - < 0,01, three - < 0,001.

At teenagers with atopicheskoj form BA development of oxidising stress becomes perceptible. Despite rising of activity of the basic enzymes of antioxidatic protection - SOD and catalases, in a blood plasma the maintenance as superoksidnogo aniona (rate of generation is enlarged by 83 %), and hydrogen peroxides (raises on 460 %) raises. It specifies in an incompetence and development of the latent insufficiency of system of antioxidatic protection. Rising of maintenance O2 - is the major factor
risk of development and advance bronholegochnoj dysplasias, dysregulations of factors of growth of lungs, including fibroproliferativnye changes [Wedgwood S., Dettman R.W., Black S.M., 2001]. As a result, adrenaline/adrenohrom towards cardiotoxic adrenohroma [Rona G raises maintenances adrenohroma, a product autookislenija adrenaline in the conditions of excess superoksidnogo aniona and shift of a parity., 1985] (tab. 18).

it is possible, that activation SOD inadequate to hyperformation AFK grows out of accumulation of the bonds co-operating with ions of metals in the active centre of enzyme or influencing their degree vosstanovlennosti, and also a consequence of interaction of the active centre of it enzima with hydroperoxides of nonsaturated fat acids [Jankov R.P., et al., 2000], acting in a role of precursors dienovyh konjugatov. Rising of maintenance MDA testifies To it also, is formed not only as a result of degradation dienovyh konjugatov fat acids, but also in the course of formation of Prostaglandinums | dalmers G.W., et al, 1997].

a Fig. 32. Interrelation between maintenance change endotelina-1 and adrenaline/adrenohrom (between the maintenance endotelina-1 and superoksidnogo aniona () practically healthy teenagers (a light small square) and teenagers with a bronchial asthma atopicheskogo a genesis (a black small square).


a Fig. 33.


Timely revealing of teenagers stressornyh the reactions threatened on formation of a chronic pathology, considering complex influence of hereditary predisposition and the external factors promoting its realisation, is the extremely actual medical and social problem. However in practice the doctor has no possibility to consider in aggregate variety of factors - biological, ethnic, socially-hygienic (including a dwelling microenvironment, character of a food), social and economic (including a share of expenses of a society on public health services in a total product and availability of medical aid), ecological), - affecting developing organism of the teenager. At the same time, the state of health of the teenager is in many respects defined by cumulative interaction of various factors changing in time. In particular it concerns the diseases characterised by advance of pathological process, that finally raises risk of an invalidism. Proceeding from stated, it is represented expedient to speak about the continuum of transitive conditions defining health and illnesses of the developing organism and depending on set of risk factors, about absence of accurate borders between norm and a pathology or, in mathematical sense, about continuous function. Depending on in what interval there is a value of function, concepts are formed: norm, functional deviations, borderline cases, a chronic pathology. Practical realisation of this approach is shown at use of is discrete-continuous algorithms of recognition of norm and a pathology, an estimation of degree of risk and the forecast of development of disease [to B.A.Kobrinsky, D.I.Buhny, 1986]. The continuous function characterising a condition of an organism, was defined by us methods regressionnogo the analysis, and specification of borders between norm and a pathology, between different risk levels (digitization of conditions) - with the help bajesovskogo a method. The above-stated allows, by analogy to the concept of a continuum of genesial losses [A.M.Lilienfeld, E.Parkhurst, 1951; K.B.Nelson, 1968] to formulate a hypothesis of a continuum of transitive states of health of a developing organism: norm - functional deviations - borderline cases - chronic diseases - an invalidism which, in case of forward development of this process, conduct to health loss. Possibility of their change in foetus and child development is defined by interaction of the risk factors influencing in ante - intra - and postnatalnom the periods of a life of children. This hypothesis allows to explain change of one condition by another under the influence of risk factors and to prove necessity of the dynamic forecast of risk of formation
chronic multifactorial and, to a lesser degree, monogene (with varying age of the beginning) diseases.

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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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