[Cytokine profile during experimental gastric and duodenal ulcers: the serotonin role].

We investigated the levels of proinflammatory and antiinflammatory cytokines in experimental gastric and duodenal ulcers. Precedence shown an increase of pro-inflammatory cytokine TNF-a level in the isolated simulation of gastric ulcers and duodenal ulcers and preferential increase in cytokine IL-4 level in a prior administration of serotonin. The development of chronic diseases of the gastrointestinal tract is largely mediated by immunological reactions and the activation of the serotonergic system. Diversion of functional activity of the immune system plays a big role in the pathogenesis of ulcer disease, particularly T-helper lymphocytes and cytokines produced by them. The formation of the ulcer was accompanied by massive apoptosis of epithelial cells, development of vascular reactions--a plethora of vessels, edema and development of fibrinoid necrosis and infiltration of the mucosa by neutrophils, plasma cells and proliferation of fibroblasts. These processes significantly induced and regulated by cytokines, particularly interleukin IL-1beta, TNF-alpha, IL-4, -6, -8, -12 [4-7]. The purpose of the study was to identify the role of serotonin in the development of immunological reactions during experimental gastric and duodenal ulcers.

[Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases].

AIM: to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID). SUBJECTS AND METHODS: Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion. RESULTS: A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only. CONCLUSION: The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].

UNLABELLED: The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC). MATERIALS AND METHODS: The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose. RESULTS: In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy. CONCLUSION: The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.

[Autoimmune reactions in diseases of the digestive system organs].

AIM: To examine content, diagnostic and prognostic role of autologous antibodies in gastrointestinal diseases (GID). MATERIAL AND METHODS: Enzyme immunoassay was used to measure content of autologous antibodies to N+/K+ ATPase (Aab) of gastric parietal cells, mitochondria, microsomes, tissue transglutaminase in blood serum of 196 patients with gastric, gallbladder, small and large intestinal diseases. Aab relations with heterologous antibodies were studied with kits provided by Bektor-Best (Novosibirsk), DRG-Diagnostics, Orgentec (Germany) and others. RESULTS: In GID high circulation of Aab to parietal cells (Ab-PC) was detected in 42% cases, mean content being 217 +/- 32.4 U/ml, 10 U/ml in the control. Maximal concentration (180 = 340 U/ml) occurred in hepatic cirrhosis, celiac disease, atrophic gastritis. In exacerbations of pancreatitis, colelithiasis and duodenal ulcer ab-PC concentration was 190-210 U/ml, in remission--6-12 U/ml. Minimal concentration (8-38 U/ml) was seen in polyps, gastric cancer, nonspecific ulcerative colitis. For primary biliary cirrhosis more typical was high A/ab concentration to mitochondria (in 83%; 200 U.ml), for autoimmune hepatitis--Aab to microsomes (in 81%; 170 U/ml), in celial disease--Aab to tissue transglutaminase (93%, 75 U/ml). High autoantibodies concentration in GID is accompanied with overcirculation of heteroantibodies to infectious-toxic agents confirming their role in development of autoimmune processes. CONCLUSION: GID are associated with high circulation of autologous antibodies--markers of systemic humoral autoimmune reactions differing in duration, severity, site of lesion, form, stage, disease duration. Maximal detection rate and concentration of serum autologous antibodies were observed in hepatic cirrhosis, active hepatitis, celiac disease, atrophic gastritis, exacerbations of cholelithiasis, ulcer, pancreatitis. Estimation of Aab concentration is essential for diagnosis, prognosis of autoimmune diseases, it reflects intensity and duration of autoimmune reactions in GID.

[Application of allogeneic mesenchymal stem cells in complex patients treatment with ulcerative colitis].

Systemic transplantation of mesenchymal stem cells (MSC) is known to promote reparative process in a number of tissue damage as well as mucous healing one. It provided the basis for our study which was aimed to the effect of systemic transplantation of allogenic MSC (intravenous transfusion) in complex therapy of patients with Ulcerative Colitis.

[Lymphoplasmocytic (IGG4-associated) cholecystitis developed in a case of prolonged gallbladder adenomyomatosis].

The article presented a rare clinical observation of 55 years old patient, long-suffering from gall bladder adenomiomatosis, for which the subsequent development was complicated by lymphocytoplasmocytic cholecystitis.

[Algorithm for diagnosis of small intestinal diseases].

AIM: To review diagnostic approaches in chronic diseases of the small intestine. MATERIAL AND METHODS: A total of 1096 patients with chronic diseases of the small intestine were admitted to the clinic of the Central Research Institute of Gastroenterological Diseases in 1987-2006. RESULTS: Most of the patients (90.5%) had celiac disease, hypolactasia and other types of disaccharidase deficiency, yersiniosis ileitis, Krohn's disease, postresection syndrome of a short small intestine, mesenterial ischemia and endocrine enteropathy. Rare diseases (general variable hypogammaglobulinemia, lymphoma, Wipple's disease and diverticulosis of the small intestine) were diagnosed in 5.8% cases. Primary amyloidosis of the small intestine, eosinophilic gastroenteritis, arteriomesenterial obstruction, primary intestinal pseudoobstruction, hypogammaglobulinemic spru, primary intestinal lymphangiectasia, tuberculosis, total polyposis, Peutz-Eggers and Cronkhite-Canada syndromes, collagenic sprue, erosive-ulcerative jejunoileitis, adenocarcinoma and heavy alpha-chain disease were detected in 3.7% examinees. These diseases were encountered in one to 5 cases for the latest 20 years. CONCLUSION: Clinical diagnosis of small intestinal diseases is based on the syndromes of chronic diarrhea, defective absorption, enteral protein loss, small intestinal obstruction and intestinal hemorrhage. Differential diagnosis of the nosological entities employs x-ray, endoscopic, histological, immunological and other methods. Most of the small intestinal diseases including rare can be diagnosed in any gastroentorological department.

[The role of neuromediators and cytokines in pathogenesis of chronic pancreatitis of alcohol etiology].

AIM: To determine the role of acetylcholine (AC), serotonine (5-HT) and cytokines in progression and complications of chronic alcohol pancreatitis (CAP). MATERIAL AND METHODS: 50 CAP patients were examined in the exacerbation, remission and complications of CAP (48 males, 2 females) aged 30-50 years. Control group consisted of 15 healthy subjects. IL-1beta, IL-6, IL-8, IFN-gamma, TNF-alpha, IL-4 were studied with enzyme immunoassay, 5-HT--with Ch. Sadovanquivad method, AC and activity of cholinesterase (CE) in the blood--by the method of Sh. Hestrin. Pancreatic tissue fibrosis was assessed according to computer tomography findings. RESULTS: Patients with CAP in exacerbation had significant rise of proinflammatory, anti-inflammatory cytokines, AC and 5-HT. In a complicated course of CAP there is a pronounced rise in TNFalpha in normal level of IL-4. CAP patients with destructive changes in the pancreas showed significant rise in the level of AC and 5-HT and lowering of cytokines. CE activity in complicated course of CAP is low this indicating protein-synthetic insufficiency in CAP patients. CONCLUSION: In CAP the action of 5-HT and AC aims at maintenance of secretory activity of the pancreas. In inflammation participation of neuromediators decreases. Stimulation of pancreatic secretory activity switched to autonomic regulation which is prognostically unfavourable.

[Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

[Diagnostic and prognostic value of humoral immune status indices for alimentary system diseases].

The paper describes the results of studying the immune status of 1,960 patients with stomach, pancreas, liver, gall bladder, small and large intestine disorders, who were treated in the Central Research Institute of Gastroenterology. The results of the study demonstrate that alimentary system diseases are concomitant with changes in the functional activity of the immune system and development of the systemic immune response aimed at the neutralization and elimination of pathogenic agents. Impaired regulatory and efferent lymphocyte capacities, increased synthesis of cytokines, immunoglobulins, heterologous (anti-viral, anti-bacterial or antigliadin), autologous (to parietal cells, microsome mitochondria, tissue transglutaminase) antibodies, formation of immune complexes, autoimmune reactions and secondary immunodeficiency are specific immune mechanisms of the pathological process development, its synchronization and progression in patients with alimentary system diseases. Changes in the immunological status indices are expressed in varying degree depending on the organ involved, etiological factor, clinical course and stage of the disease, as well as treatment used. The immunological status indices have maximal values in cases of chronic hepatitis, hepatic cirrhosis, peptic or duodenal ulcer, cholelithiasis, chronic pancreatitis, gluten-sensitive enteropathy and minimal values in cases of chronic gastritis, gastroesophageal disease, steatohepatitis and irritable bowel syndrome. These data are sufficient for developing an algorithm of immune diagnostics for a number of alimentary system diseases. The study of immune status indices is of great diagnostic and prognostic value as it defines the etiological factor, intensity of inflammatory, infectious and autoimmune processes as well as disease stage and activity, its forecast and the efficacy of treatment of alimentary system diseases.

[Antibodies to Helicobacter pylori in gastric diseases].

AIM: To study the count of antibodies to Helicobacter pylori (ABHP), their role in diagnosis and prognosis in gastric diseases (GD). MATERIAL AND METHODS: Enzyme immunoassay (kits from EcoLab and Vektor-Best, Russia) was used to measure serum levels of ABHP (IgG, IgA, IgM+IgG+IgA) in 46 GD patients. RESULTS: It is shown that GD are characterized by a regular rise of serum ABHP which are serological markers of Helicobacter pylori infection. Percentage and absolute value of IgG-HP were the highest (78%, mean titer 1:604 vs control 1:110) as well as (IgM+IgG+IgA) antibodies to CagA-HP (approximately 82%, mean titer 1:160 vs. control 1:10); the level of IgA-HP was elevated by 39%, mean titer 1:442, control 1:120. Elevated levels of IgG-HP reflect intensity of inflammatory processes, IgA-HP--atrophic processes, IgM+IgG+IgA)-CagA-HP--proliferative processes in GD. CONCLUSION: High concentrations of ABHP are a diagnostic criterion of HP infection, reflect intensity of infectious, inflammatory, atrophic and proliferative processes in GD. Long-term persistence of elevated ABHP concentrations is one of the indications for application of antichelicobacter therapy in GD associated with HP while ABHP fall is an additional criterion of efficacy of the treatment.

[Hepatic lesion in patients with hepatocerebral dystrophy].

AIM: To study hepatic affection in hepatocerebral dystrophy (HCD) regarding clinical course and duration of the disease. MATERIAL AND METHODS: The records on 63 HCD patients were studied retrospectively as to early clinical symptoms, onset dynamics, biochemical tests for hepatic function, morphological changes of the liver, immune and cytokine status, markers of hepatotropic viruses. RESULTS: Six variants of HCD course were identified: hepatic (24 patients), endocrine (17 patients), neurological (12 patients), psychoemotional (5 patients), hemolytic (3 patients), renal (1 patient). Early hepatitis and hepatic cirrhosis progress were characteristic for the hepatic variant. The other variants were characterized by hepatic fibrosis, lipofuscinosis, fat dystrophy of the liver. Markers of viral hepatitides B, C, G, TT were detected primarily in patients with a hepatic variant of HCD. A moderate rise of aminotransferases, immunoglobulins, cytokines level indicate weak inflammation in hepatic tissue. Disorders in proteins synthesis, hepatic detoxication function reflect changes in the microsomal system and endoplasmic network. CONCLUSION: Hepatic lesions in HCD are different. Clinical, biochemical, morphological activity and immune status affections were most severe in patients with hepatic and endocrine variants of HCD, being the least severe in neurological, psychoemotional and hemolytic variants. Hepatotropic viruses in some patients deteriorate hepatic lesion caused by copper imbalance.

[A cytokine status in chronic alcoholic and biliary pancreatitis].

AIM: To determine characteristics of a cytokine status in chronic pancreatitis (CP) depending on etiological factor, stage of the disease, complications, therapy. Material and methods. 72 patients had chronic alcoholic pancreatitis (CAP), 38 patients--chronic biliary pancreatitis (CBP). Control group consisted of 20 healthy subjects. RESULTS: At early stages and height of CAP exacerbation, concentrations of IL-1beta, IL-6, IL-8, TNF-gamma and TNFalpha were elevated (951.1 +/- 104.2 pg/ml; 172.8 +/- 24.3 pg/ml; 432.6 +/- 68.5 pg/ml; 823.3 +/- 97.5 pg/ml; 158.7 +/- 19.6 pg/ml, respectively). Regenerative processes in CP were accompanied with IL-4 elevation to 614.9 +/- 64.6 pg/ml. In CAP without complications and with them the levels of cytokines differed significantly. The level of TGF-beta1 stimulating development of fibrosis was in CAP patients 627.8 +/- 92.2 pg/ml, in CAP patients with complications--796.8 +/- 102.5, in the controls--40.2 +/- 4.6 pg/ml (p < 0.05). In early stages of CBP exacerbation, IL-1beta rose to 527.2 +/- 62.7 pg/ml, IL-6--to 80.9 +/- 11.4 pg/ml, IL-8--to 290.4 +/- 46.8 pg/ml, INF-gamma to 853.3 +/- 91.6 pg/ml; TNF-alpha--to 79.7 +/- 8.3 pg/ml, TGF-beta1--534.1 +/- 78.4 pg/ml. With attenuation of acute syndromes and development ofregeneration, levels of IL-4 went up (226.7 +/- 32.4 pg/ml). CONCLUSION: CP is accompanied by increase in cytokine contents depending on the etiological factor, variants of course, stage, presence of complications.

[HCV infection in the elderly].

AIM: To investigate prevalence, clinical picture and course of hepatitis C virus (HCV) infection in elderly patients. MATERIAL AND METHODS: A total of 1045 patients aged 60- 74 years with chronic diseases of the liver (CDL) were examined for hepatitis. RESULTS: HCV monoinfection was detected in 210 (20.1%) patients. Alcohol-viral etiology of HCV was revealed in 22% cases. HCV RNA was identified in 117 (76%) out of 154 elderly patients. All the HCV infected patients had 1b genotype, high viremia. Pain and asthenic syndromes were main clinical manifestations of HCV infection. Most often the activity of HCV infection in the elderly patients was low (88.6%), progression was slow (94.7%). The latter was registered in 22.8% patients. HCV infection in the elderly entails higher inflammation activity and incidence of HCV RNA. CONCLUSION: Complex examination of elderly patients for early detection of HCV, early diagnosis and treatment slows down progression of CDL, reduces the rate of development of severe complications and lethality.