Now it is conventional, that the syndrome of an angry intestine (SRK) is often meeting disease of organs of digestion. According to large-scale researches, to it suffers from 10 to 20 % of adults [35, 135, 139, 194, 219], thus women are ill (or men [66, 99, 145, 150, 173, 204] address to the doctor) more often, than.

Frequency SRK at children remains not found out, but, according to different sources, among children of school age and teenagers frequency SRK reaches from 2-4 % [110, 193] to 22 % [74]. The parity of number of girls and young men makes 2-4:1 [77, 128]. By results of our researches, SRK meets at children of age group of 11-17 years (81,8 %) is more often, the parity of girls and young men makes 1:1. Prevailing type SRK at children, according to our research, is diarejnyj (39,7 %), that frames certain difficulties in differential diagnostics with other diseases proceeding with diarejnym by a syndrome.

Last epidemiological researches testify to the important role of intestinal infections in development SRK [49, 50, 51, 214]. In the researches devoted to studying of functional disorders, it has been defined, that the postinfectious form makes, on the average, from 6 % to 17 % among all cases SRK and from 7 % to 33 % of patients as the answer to the nonspecific infections caused various, in basic, by the bacteriemic intestinal originators, suffer subsequently from disease symptoms [115, 158, 192, 213, 222]. According to our research, postinfectious SRK (PI SRK) it is established at 28 persons (23,1 %). At other patients the indicating on an intestinal infection prior to the beginning of symptoms was absent, that is, at the majority took place not postinfectious SRK (nepi SRK) - at 93 persons (76,9 %). In overwhelming majority of (64,7 %) the aetiology of a previous gastroenteritis had the virus nature, that contradicts literary data a little. Also by us it is established, that transferred Oka in the anamnesis does not play an essential role in development of certain type SRK, that, probably, specifies in a role
Other factors in formation of clinical variant SRK. Value of an infection, in our opinion, can have reflexion in more expressed changes of a microflora of an intestine at SRK. At children surveyed by us with PI SRK the tendency to more expressed changes, according to crops of a feces and to the hydrogen respiratory test is taped. Also at PI SRK the tendency to higher levels of proinflammatory cytokines, kalprotektina is noticed, to value of an inflammatory index, than at nepi SRK, that, possibly, specifies in more expressed immunologic and inflammatory shifts after the transferred infection.

SRK is biopsychosocial disease. It is known, that the regular mental strain promotes occurrence and advance SRK [127]. However remains not absolutely clear, whether is reason SRK the emotional distress. On our data, all children with SRK have psychoemotional disorders, a pathology of nervous system or the burdened neurologic anamnesis. It is known, that the stress activates sympathetic nervous system and strengthens sensitivity of receptors of a colon. Finally the vicious circle is formed, fastening, intensifying and persistirovanie symptoms can become its result. Standards of treatment SRK at adults provide carrying out of kognitivno-behavioural therapy [42], at children the question on its expediency remains opened.

However, in our opinion, for optimisation of treatment of patients SRK it is necessary to consider an accompanying psychoneurological pathology and to involve in teamwork of the neurologist, the psychologist and, at necessity, the psychiatrist.

Thus, by results of our research by the starting moment of development SRK at children in 63,7 % of cases the transferred emotional stress is, in 23,1 % - transferred Oka and in 13,2 % - the reasons remain unknown persons that coincides with results of other research works.

As a result of the research carried out by us clinical features SRK at children are specified. For all children with SRK, on our data, a leading symptom are abdominal pains. Primary localisation of pains
Depends on type SRK: at SRK with a diarrhoeia pains in the bottom departments of a stomach (47,9 %) dominate, at SRK with a constipation and the admixed type a pain has no accurate localisation (41,7 % and 50 % accordingly), at undifferentiated type - are localised more often in paraumbilical area (51,6 %). Pains usually happen aching and colicy character, to frequency not less than 2-3 times a week, arise both after food intake, and without communication with it, weaken after the defecation certificate, are stopped independently or after reception spazmolitikov. Besides abdominal pains, 97 % of children with SRK show complaints to feeling incomplete oporozhnenija an intestine and 52 % of children - on feeling raspiranija in a stomach. SRK at children it is always combined with others gastroenterologicheskimi diseases. The most frequent accompanying pathology at children with SRK is chronic gastroduodenit with motor disturbances, and also functional disorders biliarnoj systems, laktaznaja insufficiency, that, certainly, specifies in necessity comprehensively to survey children with SRK for optimisation of the therapeutic approach.

The analysis of clinical and anamnestic data carried out by us has allowed to tap the most significant risk factors of development SRK at children and teenagers: the transferred stressful situations, the long and repeated antibioticotherapia, the transferred intestinal infections, regular disturbances of a diet and a diet. As at overwhelming majority of patients these factors were combined, it is necessary to assume, what exactly set of risk factors can have the greatest value in development SRK in children and teenagers.

The majority of authors regard visceral hypersensitivity as biological marker SRK [5, 38, 101, 109, 138]. At all children surveyed by us volume-threshold sensitivity of a rectum which, on the average, has been raised has made 102,04,11 (a median 100,0) ml. The maximum hypersensitivity was observed at SRK with a diarrhoeia and SRK with a constipation (102,4411,06 and 102,3112,48 ml accordingly); a little bit more low - at undifferentiated type (108,59,19 ml); minimum - at admixed type SRK (113,33120,0 ml). Depending on communication with a transferred infection,
Larger rising OPCH is noted at nepi SRK, than at PI SRK (101,0535,87 and 111,8813,98 ml accordingly). Thus, the data obtained by us confirm opinion of other authors that visceral hypersensitivity can be surveyed as obligatory diagnostic criterion SRK at children.

One of problems of our research was to define degree of expression of inflammatory changes in SOTK at SRK. The research of 121 children carried out by us, which on clinical data corresponded to criteria SRK offered by the International consensus on functional diseases (the Roman criteria III), has shown, that at overwhelming majority (97,5 %) from them are available weak chronic inflammation SOTK that has been confirmed by histological data, that is, the microscopical distal colitis took place. Thus endoscopic signs of a distal colitis have been taped only at 66,9 %, that is, at endoscopic research at patients with SRK almost in half of cases it is not revealed any changes. Our opinion coincides with opinion of other authors, that in diagnostics of weak inflammatory changes SOTK the endoscopy does not differ sufficient accuracy, for convincing judgement histological research bioptatov, taken of a colon [2, 7, 8, 20, 43, 54] is necessary. Recently in the literature discussions concerning a recognition of that fact are conducted, that differences between "functional" and "organic" changes are washed extremely away [53, 128]. We support opinion that the minimum signs of an inflammation at functional disorders are admissible if they do not explain all complex of clinico-laboratory changes.

The data obtained by us about rising of level fecal kalprotektina (FK) became indirect acknowledgement of presence of inflammatory changes in an intestine at SRK also. Despite opinion of many authors that concentration FK can serve as authentic criterion in differential diagnostics of functional and inflammatory diseases of a colon [67,
106], our data have coincided with other works [178]. It has been established, that at a significant amount of patients with SRK raised level FK that assumes some degree of an inflammation takes place. Level FK at patients SRK in our research has been raised slightly (among all children with SRK the average level kalprotektina has made 83,5118,22 (a median 33,0) feces mg/g), many times more low, than at inflammatory diseases of an intestine, but nevertheless exceeded almost in 2 times the top border of norm (50 mg/g), that testifies about low, but present activity of a chronic inflammation.

According to literary data, definition tsitokinovogo the status at SRK has the important prognostic value as level pro-and antiinflammatory cytokines correlates with expression of leading clinical symptoms SRK [63, 98]. In the literature there are data about disbalanse in system of cytokines at SRK for adults: depression of secretion of antiinflammatory cytokines (IL-10), augmentation of production of proinflammatory cytokines (IL - І in, IL-6, IL-8 and FNO), in comparison with healthy faces [33, 48, 63, 134, 154, 156, 196, 213]. The works devoted to definition tsitokinovogo of the status at SRK at children, to us has not met. In our research we have established, that approximately at half of children with SRK (45 %) have been raised level of proinflammatory cytokine IL-8 which has averaged 214104,4 pg/ml (norm less than 50 pg/ml), that corresponds to data of previous researches of adults with SRK. As to the information concerning level of proinflammatory cytokine IfN-yv SOTK by us it is not found the works studying its level neither at adults, nor at children. By us for the first time it has been established, that level of a proinflammatory cytokine IFN - y in SOTK is raised at overwhelming majority (90 %) children with SRK. It has made, on the average, 83,526,7 pg/ml (norm less than 50 pg/ml). Level of proinflammatory cytokines correlated with expression of an abdominal syndrome and degree of a deviation of visceral hypersensitivity from age norm. Rising of level of proinflammatory cytokines (IL-8, IFN-y), found out in SOTK the majority of the surveyed patients, along with the histological
Data and level FK, also confirms presence of a chronic inflammation in SOTK, independent of type and aetiology SRK. However absence of accurate correlation between expression of activity of an inflammation on morphological data and level of proinflammatory cytokines, specifies in some differences of the immunologic mechanisms underlying a chronic inflammation and more difficult mechanism, participating in formation SRK as a whole more likely.

Morphological and histological signs of an inflammation correlate with each other, but character of endoscopic changes (catarral or is catarral-follicular) has no essential histological differences. Level kalprotektina and proinflammatory cytokines is raised at patients SRK, irrespective of its type, including at endoscopically not changed SOTK. It, along with histological data, confirms possibility of existence of weak, endoscopically negative, microscopical colitis at SRK and specifies in higher informativnost definitions of indicators as markers of a chronic inflammation in SOTK.

Results of our research according to microbiological changes at SRK coincide with literary data [18, 67, 92, 131]: patients SRK have the changed structure of an intestinal microflora. By results of our work, at any SRK, irrespective of type and communication with the transferred infection, in 100 % of cases depression of level of an obligate intestinal microflora with presence at 54,5 % of cases UPF that coincides with results of other research works [24, 131] takes place. According to the hydrogen respiratory test with a load a lactulose, at 85,1 % of children with SRK us has been diagnosed SIBR, that almost completely coincides with data randomizirovannogo researches M. Pimentel from co-workers., according to which at 84 % of adult patients with SRK is present SIBR [191].

According to literary data, having developed for any of several reasons, SIBR initiates the inflammatory answer in a mucosa of a small bowel which, in turn, strengthens clinical implications of the intestinal
Dysfunctions; regarding cases SIBR is the reason of development of a microscopical inflammation of a small bowel [52, 211, 151]. In our research it is established, that presence UPF authentically influences level kalprotektina in a feces, that indirectly confirms its role in development of a chronic inflammation. 93,4 % of children with SRK had the clostridiums which quantity correlated with level of proinflammatory cytokines in SOTK, especially with IL-8. Level laktobaktery negatively influenced condition SOTK (at their appreciable depression in an intestine there were catarrh signs); between level laktobaktery and level IL-8 in SOTK there was an inverse relationship.

Thus, our data confirm, that changes intestinal mikrobioty are accompanied by immune disturbances in SOTK. Being based on results of our research, we part a hypothesis, that the intestinal microflora exists in constant interaction with an epithelium and immune system of an intestine, it posesses a role of a stimulator of immune system, both structurally, and is functional. Under the influence of microbic stimulus there is an activation of membranous and cellular receptors, the differentiation of Th-lymphocytes is regulated, there is a development of cytokines and secretory IgA, permeability of an epithelium decreases, the protective barrier of an intestine [9, 29, 60, 61, 203] becomes stronger. Changes of an intestinal microflora morfologicheski are shown by weak signs of an inflammation in an intestine mucosa. Inflammation and motility communication is carried out at level of interaction of immune and nervous systems of an intestine: Enteral neurones can answer as inflammatory stimulus, and immediately to be activated bacteriemic and virus components therefore the intestine motility is broken. In the course of an inflammation permeability of an intestinal barrier that promotes a sensibilization is enlarged also; the inflammation is reflected in functionality of an intestinal epithelium, strengthening digestion disturbances that aggravates semiology. As a result
"Vicious circle" and the dominant centre of a boring in TSNS which is fixed in the form of a hyperalgesia and allodinii [11, 29, 60] is formed.

Thus, in pathogenesis SRK play a role many factors complementary and aggravating actions each other. Interaction disturbance between TSNS and enteral nervous system, vegetative disorders, the disturbances of neuroendocrinal humoral regulation leading to disorders of an intestinal motility, disturbance of a threshold of sensitivity of visceral receptors of an intestine, change of an intestinal biocenosis in aggregate also frame a vicious circle causing duration and firmness of functional disturbances and clinical symptoms.

The understanding of the pathogenetic mechanisms which are taking part in formation of symptom-complex SRK, leads to a logical conclusion about the possible therapeutic approach not only by means of the preparations influencing a motility of an intestine, but also correcting it mikrobiotu. Therefore we in the research have compared some medical approaches: monotherapy by a preparation influencing on opioidnye receptors GASTROINTESTINAL TRACT (trimebutin), monotherapy various probiotikami and the combined therapy including probiotik and trimebutin, or probiotik and prebiotik. Research of results of treatment was opened randomizirovannym platsebo - supervised. In control group there were patients SRK receiving platsebo.

The choice probiotikov in our research was not casual. Concerning positive action the big demonstrative base is saved up for a microbiocenosis and a motility of intestine Lactobacillus reuteri, a part preparation Rela Lajf [60, 69, 88, 205]. Medical effect Lactobacillus reuteri is caused by a combination of antiinflammatory action, influence on sensitivity and perception of a pain, and also on regulation of the impellent answer. It allows L. reuteriсоучаствовать in correction of such key factors of a pathogenesis, as disbioz, an inflammation, a hyperalgesia, allodinija, motility disturbances [31, 88, 102, 205]. Earlier carried out researches have shown, that
Treatment by strains L. rhamnosus GR-1 and L. reuteri RC-14 can promote augmentation of the intestinal immune answer that reduces quantity patogenov in an intestine of the owner [91].

According to literary data, application L. reuteriможет to be potential mishenevoj therapy, effective production for inhibition IL-12 and TNF-a (and IL-6), and thus to induce antiinflammatory IL-10. It gives the chance the alternative therapeutic approach for indemnification of proinflammatory medium of cytokines of an intestine, resetting T Іі 1/Т Іі 2/Т Іі 3-stimulirujup іих abilities of an intestine, proceeding from structure of an intestinal microflora and prescribing probioticheskuju therapy [114].

As another probiotika Enterolum, predstavljaoshchy by itself nonpathogenic yeast funguses Saccharomyces boulardii, received of tropical plants has been chosen. Trophic immunomoduliruoshchee Enterolum action is caused it sposobnosto to synthesise Polyaminums (a spermine, a spermidine), which, in svoo turn, stimuliruot activity of digestive enzymes of a small bowel and stimuliruot synthesis IgA and components of other immunoglobulins in a mucosa of an intestine [9]. It also renders positive influence on a condition of local immunity of an intestine by stimulation of a phagocytosis, action intensifying komplementnoj systems, suppression of secretion of antiinflammatory cytokine IL-8, is noted expressed podavljaoshchy effect of a preparation on UPF [56, 6 І].

By us has been estimated complex probiotik Lineks, containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium.Входящие in its structure Bifidobacterium infantisобладаот antiinflammatory aktivnosto, inherent to the majority to the strain bifidobaktery: podavljaot development IL-12 [73, 182], strengthen production IL-10 and IL-1 [73, 131, 155]. Other component simbiontnoj florae, Lactobacillus acidophilus as it has been shown in experiment on animals, influences on kannabinoidnye and opioidnye intestine receptors. This influence so powerful, that corresponds to the dose of Morphinum peer 1 mg/kg [168].

The research of efficiency of different therapeutic approaches carried out by us has shown, that, in comparison with platsebo, authentic clinical improvement was observed in all medical groups. The greatest effect on cupping of symptoms SRK at children (a pain, an abdominal distention, chair disturbance) has been reached in group of the combined therapy (trimebutin + probiotik). The greatest positive effect on features of the certificate of a defecation at children with SRK it was possible to reach as a result of a course of the combined therapy and monotherapy by Enterolum.

In comparison with platsebo, authentic depression of level kalprotektina was observed in all groups of treatment. The greatest difference of level kalprotektina before treatment has been reached by appointment of the combined therapy (trimebutin + probiotik), and also monotherapies probiotikami (Enterolum and Rela Lajf).

According to the hydrogen respiratory test, probioticheskaja and the combined therapy have appeared authentically more effectively platsebo and trimebutina in elimination SIBR. Against the combined therapy пробиотиком+тримебутином improvements managed to be reached at 81,8 % of patients, against monotherapy probiotikami - at 76,9 %, probiotikom in a combination with prebiotikom - at 77,8 %.

Disbiotichesky disturbances, according to feces crops, have been in full or in part eliminated as a result of appointment probiotikov, both at monotherapy, and in a combination with trimebutinom or prebiotikom.

The best result in correction of visceral hypersensitivity of a rectum it was possible to reach after a course of the combined therapy (trimebutin + probiotik) and monotherapies trimebutinom (48,62,8 % and 36,71,7 % accordingly). In group probiotikov the best result is received after course of treatment by Enterolum (27,12,5 %), in comparison with course of treatment Rela Lajf and Lineksom (11,22,5 % and 5,61,4 % accordingly). After course of treatment by a combination prebiotika with probiotikom OPCH has improved on 20,91,2 %, that above similar indicators in monotherapy groups probiotikami. In group
platsebo indicator OPCH has not changed. Thus, as a result of appointment of the combined therapy (trimebutin + probiotik) it was possible to approach indicators OPCH to age norm as much as possible. In comparison with group platsebo, authentic results on depression OPCH have been received after monotherapy trimebutinom and monotherapies by Enterolum.

As it has been presented in table 50 (chapter 6), unlike group platsebo, in all other groups of treatment will reach good effect of therapy.

The results of efficiency received by us probiotikov, both concerning depression of visceral hypersensitivity, and concerning cupping inflammatory and disbioticheskih changes, confirm participation of a microflora in formation of the "vicious circle" inherent SRK. Rupture of this vicious circle and semiology improvement probably both through motility correction, and through correction of a microbiocenosis and elimination SIBR, as us it has been shown. Spent by us opened randomizirovannoe platsebo-supervised studying of efficiency of various schemes of therapy SRK at children has shown, that authentic improvement of all indicators, clinical and laboratory, is reached after a course of the combined therapy trimebutinom and probiotikom and monoteripii probiotikom Enterolum. Trimebutin it has appeared more effectively in depression of visceral hypersensitivity, probiotiki - in correction disbioticheskih disturbances, elimination SIBR and depression of level of an inflammation. Among probiotikov the greatest efficiency has shown Enterolum, a little smaller Rela Lajf and Lineks. The combination pre - and probioticheskoj therapies had advantages in correction of a microbiocenosis of an intestine.

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Scientific source TIPIKINA Maria Jurevna. ESTIMATION of the ROLE of INFLAMMATORY And MICROBIOLOGICAL CHANGES AT the SYNDROME of the ANGRY INTESTINE At CHILDREN. The dissertation on competition of a scientific degree of the candidate of medical sciences. St.-Petersburg - 2014. 2014

Other medical related information Chapter 7 DISCUSSION of RESULTS of RESEARCH:

  3. Chapter 4 Discussion of the received results
  9. the Table of contents
  10. Chapter 5 Discussion of the received results
  17. the Chapter VI. DISCUSSION of the RECEIVED DATA