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INTRODUCTION

Theme urgency

Anaemia widespread among patients with chronic arthritises. According to various researches prevalence of an anaemia at patients with a pseudorheumatism makes from 33,3 to 59,1 % [185].

At children with juvenilnym a pseudorheumatism (JURA) prevalence of an anaemia varies from 18,9 % at oligoartikuljarnoj to form JURA, to 80,5 % at system form JURA [136,169].

The anaemia is one of independent factors of an invalidism at patients with chronic arthritises. Possibly, reduction anemizatsii owing to effective therapy of a basic disease can play an independent role in improvement of a physical condition of the patient [19]. Besides, the anaemia at chronic arthritises associates with more poor quality of a life, both at children, and at adults [63,244]. It is known, that if arthritis treatment effectively concerning an anaemia, most likely, dynamics from a lesion of joints will be positive [185].

The anaemia, assotsiirovannaja with a pseudorheumatism (a rhematoid anaemia), is caused by effects of proinflammatory cytokines and is a typical example of the anaemia developing at chronic illnesses (AHB) [149]. The basic mechanism of development AHB is a disturbance of a homeostasis of iron with the raised consumption and iron accumulation in cells of reticuloendothelial system under action gepsidina which expression raises owing to hyperproduction ИЛ-6, that, in turn, leads to a redirection of iron from circulation in storehouses, with the subsequent restriction of availability of iron for erythroidal cells-precursors and, as consequence, to an iron deficiency erythrogenesis [43,245].

Now gepsidin it is considered a key system regulator of a metabolism of iron in a human body. Gepsidin inhibits an absorption
Gland in a gastroenteric tract and its representation by the macrophages utilising old erythrocytes [73,71,94,213]. Also it has been shown, that synthesis gepsidina occurs and in the tubular apparatus of kidneys, and in other cells, tissues and organs, including adipotsity and brain cells that can speak about the important role gepsidina in autocrine and parakrinnom the control of an exchange of iron at local level [73,221,162,255]. Gepsidin operates, modulating export of cellular iron to plasma and an extracellular liquid, means ferroportina. Ferroportin is simultaneously both a receptor gepsidina, and unique known the exporter of cellular iron [99,129,220].

The inflammation plays the leading part in synthesis regulation gepsidina, leading to rising of its production. The expression gepsidina is induced lipopolisaharidami and interlejkinom-6, and inhibited FNO [12,107]. ИЛ-6 is the basic inductor gepsidina and operates through STAT3-dependent transkriptsionnyj the mechanism [89,92,95,106,213,239]. Production ИЛ-6 significantly raises at development of an arthritis and correlates as with a disease degree of activity, and development of an anaemia [17,233].

Thus, ИЛ-6 is the basic things in common in pathogenesis AHB and JURA, that proves to be true high efficiency of therapy by inhibitors ИЛ-6, both concerning an arthritis, and concerning an anaemia [50,54,108,127].

Recently the great value is given to potentially high diagnostic value serumal gepsidina and possibilities of its use as a target for therapy, including at patients with a pseudorheumatism and an anaemia [48,70,72,91,202].

System research "gepsidin-interlejkin-6" as factor of management of an anaemia current at chronic arthritises at children, it is represented timely and actual for today.

Research objective

Estimation of a role of a link "gepsidin-interlejkin-6" in management of an anaemia current at chronic arthritises at children, and working out of references to destination antitsitokinovoj biological therapy at children with an anaemia in structure of chronic arthritises.

Research problems

1. To define prevalence of an anaemia and degree of its gravity in group of patients with various forms of a clinical current juvenilnogo a chronic arthritis.

2. To study level communication gepsidina in plasma with clinical and laboratory characteristics of a current of an anaemia, a lesion of joints and an iron metabolism at juvenilnom a chronic arthritis.

3. To investigate concentration of soluble receptors of a transferrin, as prognostic marker of a current of an anaemia at patients with juvenilnym a chronic arthritis.

4. To establish possibility of use of concentration gepsidina in plasma for early diagnostics of an anaemia in syndrome structure makrofagalnoj activation at children with a chronic arthritis.

5. To carry out the comparative analysis of efficiency of traditional and biological therapy juvenilnogo the chronic arthritis complicated by an anaemia, and also to develop references for early appointment antitsitokinovoj therapies at children with a serious anaemia in structure of a chronic arthritis.

Scientific novelty of research

1. For the first time communication of value of concentration gepsidina in a blood plasma and clinico-laboratory indicators of an anaemia is described at chronic arthritises at children.

2. For the first time the expediency of use of value of concentration gepsidina in a blood plasma for the forecast of a current of an anaemia is shown at chronic arthritises at children.

3. For the first time the expediency of early transition from traditional therapy to therapy with use of blockers the TNF-ALPHA and ИЛ-6 in cases of a serious anaemia is shown at chronic arthritises at children.

4. For the first time it is shown, that level gepsidina blood plasmas can be used for early differential diagnostics of an anaemia and a syndrome makrofagalnoj activation.

The practical importance

1. Concentration definition gepsidina in a blood plasma gives the chance more exact differential diagnostics of an aetiology of the anaemia accompanying chronic arthritises.

2. Earlier transition to therapy with use of blockers the TNF-ALPHA and ИЛ-6 in cases of a serious anaemia in structure of chronic arthritises at children allows to carry out the system control over a current of an arthritis and leads to fast normalisation of level of haemoglobin and improvement of quality of a life of patients.

The substantive provisions which are taken out on protection

1. Without use of genno-engineering therapy at children suffering ravmatoidnym by an arthritis, the anaemia develops in 64 % of cases in the first 5 years from the arthritis beginning. The serious anaemia is registered in 4,8 % of cases, basically, at children with the system form of an arthritis.

2. Concentration gepsidina in plasma can from 96 % probability be predicted on a complex of the laboratory indicators including levels of a ferritin and soluble receptors of a transferrin in plasma, quantity of leucocytes in blood, the general zhelezosvjazyvajushchuju ability of Serum and a hematocrit. The average haemoglobin content in an erythrocyte is more sensitive controlled gepsidinom the factor in comparison with the general level of haemoglobin.

3. Presence in structure juvenilnogo a pseudorheumatism of a serious anaemia and a moderately severe anaemia the TNF-ALPHA and ИЛ-6 does tselesoobrazymn early transition to therapy of an arthritis with use of blockers.

4. The high probability of development of a serious anaemia becomes perceptible at levels gepsidina less than 70 ng/ml and a ferritin more than 180 mkg/l that is caused by high risk of development of a syndrome makrofagalnoj activation, and also, at levels gepsidina more than 220 ng/ml and a ferritin less than 140 mkg/l, that, most likely, is caused by a combination of an anaemia of an inflammation to deficiency of iron.

Work approbation

Dissertation substantive provisions are reported and discussed on VII International workshop Kastelli (Oulu, Finland, 2010г.), XI severoyozapadnoj scientifically-practical conference on rheumatology (S-peterburg, Russia, 2011), the All-Russia youth scientifically-practical conference Adaptation of the person in the north (Arkhangelsk, 2012), the Workshop of children's rheumatologists (PRSYM) (Orlando, the USA, 2014).

Concrete participation of the author in reception of scientific results

The author had been carried out the analysis of literary data devoted to a role of system "gepsidin-interlejkin-6" in management by a current of an anaemia at chronic arthritises at children. The research objective is formulated, problems are defined, optimum methods of research for carrying out of scientific work are chosen. The research plan has been developed. The author spent a clinical estimation of dynamics of an articulate syndrome and datas of laboratory against carried out treatment according to the research plan. During training at Howard's university the competitor has mastered a method tandemnoj mass spectrometry for definition gepsidina plasmas. During work as the competitor the electron base has been developed for storage and statistical processing of the received data for the subsequent analysis. The author was 100 % of the statistical are spent
Processings of a material and on the basis of the received results and their analysis have been formulated conclusions and practical references.

Volume and dissertation structure

The dissertation is stated on 117 pages of the typewritten text and consists of introduction, the review of the literature, heads with a statement of a general characteristic of the patients, used methods of research, own results of research, the conclusion, conclusions, the list of reductions and the literature list. The dissertation contains 5 domestic and 251 foreign sources of the literature, is illustrated by 20 tables and 15 drawings.

Publications

On dissertation materials 16 printing works, 5 of which - publications in the leading reviewed scientific magazines recommended for the publication of the basic results of dissertational researches, from them 2 scientific articles, 2 publications in a foreign press are published. 9 articles and theses of reports in other editions, 1 from which in a foreign press.

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Scientific source EGOROV Andrey Sergeevich. THE GEPSIDIN-INTERLEUKIN-6 SYSTEM AS A FACTOR FOR MANAGING THE COURSE OF ANEMIA IN CHRONIC ARTHRITIS IN CHILDREN DISSERTATION for the degree of candidate of medical sciences. St. Petersburg - 2016. 2016

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