[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.

[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.

[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.

[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.

[Current understanding of primary biliary cirrhosis].

AIM: To examine characteristics of the course of primary biliary cirrhosis (PBC). MATERIAL AND METHODS: The study of 150 PBC patients aged 26-82 years used clinical, biochemical, immunological and morphological methods. RESULTS: Antimitochondrial antibodies of type M2 (AMAM2) were detected in 85.4% patients with PBC. A positive correlation was found between clinicobiochemical activity of the disease and number of AMAM2. AMAM2-positive patients more frequently had extrahepatic manifestations, overlap syndrome, higher biochemical and immunological activity vs AMAM2-negative patients. CONCLUSION: The following variants of PBC course were identified: classic AMAM2-positive, AMAM2-negative, overlapping of PBC and autoimmune hepatitis. Concentration of AMAM2 has diagnostic and prognostic value in PBC.

[Anti-Helicobacter pylori antibodies in cases of stomach polyps].

UNLABELLED: The goal of the study was to study the content of anti-Helicobacter pylori antibodies (at-HP), their diagnostic and prognostic significance for stomach polyps. MATERIALS AND METHODS: The content of anti-Helicobacter antibodies (IgG-HP; IgA-HP; IgM + IgG + IgA-CagA-HP) was determined in the blood serum by way of immune-enzyme analysis of 46 patients with stomach polyps. Such test systems as EcoLab (Elektrostal) and Vector-Best (Novosibirsk) were used. RESULTS: Stomach polyps are accompanied by a regular increase of at-HP--serologic markers of helicobacteriosis content in the blood serum. The most significant increase in terms of percentage and absolute values is the IgG-HP concentration increase (88%, average titre 1: 1060, in the control group--1: 110) and summary (IgM + IgG + IgA) antibodies to CagA-HP (86%, average titre 1 : 180, in the control group 1 : 10), while the IgA-HP level is increased in 46%, average titre 1 : 660, in the control group 1 : 120). The IgG-HP content increase reflects the inflammatory process intensity, IgA-HP--atrophic process intensity, (IgM + IgG + IgA)-CagA-HP--1 intensity of proliferative processes of stomach polyps. CONCLUSION: The at-HP content increase is a diagnostic criterion for helicobacteriosis and reflects the intensity of infectious, inflammatory, atrophic and proliferative processes in cases of stomach polyps. A multiple long-lasting increase of the at-HP concentration may be one of the indications for administering an antihelicobacter stomach polyp therapy including administration before polypectomy.

[Cytokines and cytokine therapy in gastrointestinal diseases]. / Tsitokiny i tsitokinoterapiia pri zabolevaniiakh organov pishchevareniia.

AIM: To compare cytokine status in gastrointestinal diseases (GID) with reference to etiological factor, course, stage, therapy of the disease. MATERIAL AND METHODS: Enzyme immunoassay was used to examine cytokines in the peripheral blood, tissue homogenates of 560 GID patients. GID were represented by ulcer disease (UD), cholelithiasis, chronic hepatitis (CH), glutenic enteropathy (GE), Crohn's disease (CD), nonspecific ulcer colitis (NUC). RESULTS: In chronic recurrent GID (UD, cholelithiasis, GE) early exacerbation was characterized by elevated concentrations of IL-1 beta, IL-6, IL-8. Concentrations of IL-12, Inf alpha, g, TNF alpha reached maximum on the height of the disease. Intensification of regenerative processes raised concentrations of IL-4, IL-10. An overall level of serum cytokines averaged 190-780 pg/ml, reaching in some patients with active disease 1200-3000 pg/ml, in remission 30-110 pg/ml, in the control 40 pg/ml. In chronic progressive GID the levels of IL-1 beta, IL-2, IL-8, IL-6 reached 30-80 pg/ml, IL-12, Inf gamma, TNF alpha--150-370 pg/ml. A rise in cytokines concentrations in inflammatory viral, bacterial, autoimmune GID was higher than in cancer, alcoholism-related diseases, metabolic disturbances. Basic therapy in patients with chronic recurrent GID led to a significant fall in concentration of serum cytokines. Therapy with monoclonal antibodies to TNF alpha was associated with transitory pronounced favourable changes in peripheral blood cytokine status. CONCLUSION: GID provoke elevation of serum and tissue cytokines, impairment of cytokine balance in correlation with the etiological factor, variants of the course, stage of the disease, on-going therapy.

[Cytokines in primary biliary cirrhosis (diagnostic and prognostic value)]. / Tsitokiny pri pervichnom biliarnom tsirroze (diagnosticheskoe i prognosticheskoe znachenie).

AIM: To study concentrations of serum pro- and anti-inflammatory cytokines (CK), CK correlations with clinicobiochemical activity, diagnostic and prognostic implications in primary biliary cirrhosis (PBC). MATERIAL AND METHODS: Enzyme immunoassay has been used to study content of IL-1 beta, IL-4, IL-6, IL-8, TNF-alpha, INF-gamma in peripheral blood of 96 women aged 26 to 82 years (mean age 56.2 +/- 12.6 years) with PBC (kits "Protein Contour", "Cytokine", St-Petersburg). The control group consisted of 20 healthy women matched by age. RESULTS: PBC is associated with changes in serum CK content correlating with the disease activity and stage. Elevated levels of proinflammatory IL-6, TNF-alpha, INF-gamma and anti-inflammatory IL-4. CONCLUSION: Definition of the cytokine spectrum in PBC has made a prognostic significance as it allows judging about the disease activity, stage and prognosis.

[Therapeutic effect of gastrozolum in stomach ulcers]. / Terapevticheskii éffekt gastrozola pri iazvennoi bolezni.

Gastrozolum is the proprietary name of a drug made in Saint Petersburg. Its international nonproprietary name is Omeprazole. The absorption rate is not related to food. Its pharmacotherapeutic action becomes apparent as an inhibitor of the proton pump leading to the inhibition of H+/K(+)-ATPase of the secretory membrane of parietal cells of the stomach mucous membrane and blocking of the concluding stage of hydrochloric acid secretion. The entire action leads to the decrease of the level of basal and induced secretion regardless of the nature of stimulus. As a result of this, symptoms of stomach ulcer decrease, and gastroduodenal ulcers heal faster. Penetrating into the stomach mucous membrane cells, the drug also has a cytoprotective action. The maximum blood concentration (0.6-1.5 mg/l) is found 2-3 hours after a single intake of 40 mg of the drug. It was determined that after the intake of 20 mg of Gastrozolum its action lasts for 24 hours and provides for the inhibition of both night and day secretion. The ricochet syndrome does not take place when the treatment is over. It was proved that Gastrozolum has a bactericidal action on Helicobacter pylori due to the sharp increase of stomach pH, which contributes to the realization of the effect of used components of the anti-helicobacter therapy. The experiment failed to establish any teratogenic or poisonous action on the embryos. The dosage form is a capsule containing 20 mg of Omeprazole in the form of pellets.

[Interleukins in chronic diseases of digestive organs]. / Interleikiny pri khronicheskikh zabolevaniiakh organov pishchevareniia.

AIM: To characterize quantitatively and functionally interleukines (IL) in chronic gastrointestinal diseases (CGD) depending on the affected organ, etiology, activity and stage of the disease. MATERIAL AND METHODS: Levels of IL-1 beta, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), gamma interferon (Inf-gamma) in peripheral blood of 300 patients with chronic hepatitis, gastroduodenal ulcer, cholelithiasis, glutenic enteropathy and other CGD were measured by enzyme immunoassay. RESULTS: CGD are accompanied by cytokine imbalance the severity of which depended on the etiological factor (virus, alcohol, etc.), the disease activity, stage and kind of IL. A maximal IL rise was seen in exacerbations of ulcer, cholelithiasis, chronic viral, autoimmune diseases. At early disease stages higher were the levels of Inf-gamma, IL-1 beta, IL-8, IL-6; at late stages--of TNF-alpha, IL-4. In patients with highly and moderately active CGD content of IL reached 250-750 pg/ml that is 3-5 times higher than in inactive CGD. In alcohol-induced CGD and metabolic disturbances IL level was under 150 pg/ml. CONCLUSION: Assessment of the cytokine spectrum in CGD holds prognostic importance as this spectrum allows conclusion on the disease activity, its progression.

[Primary biliary cirrhosis: 12-year experience in observation]. / Pervichnyi biliarnyi tsirroz: 12-letnii opyt nabliudeniia.

AIM: To ascertain initial signs of primary biliary cirrhosis (PBC), criteria of its early diagnosis, variants of the course, clinical picture and life quality of PBC patients. MATERIAL AND METHODS: 128 PBC patients were examined in the Central Research Institute of Gastroenterology from 1991 to 2002. Quality of life was assessed by SF-36 questionnaire adapted for patients with chronic cholestatic diseases of the liver. RESULTS: The patients complained of skin puritus (80%), jaundice (66%), fatigue (68.8%), weight loss (24.6%). The disease manifested with skin pruritus in 75.8%, jaundice--in 12.5% patients. Decompensated hepatic cirrhosis (Child-Pugh C) at first hospitalisation was diagnosed in 11.7% cases. The earliest and most significant biochemical markers of PBS were high activity of gammaglutamil-transpeptidase (GGTP) and alkaline phosphatase (AP). IgM level was high in 70.5% cases. Antimitochondrial antibodies were detected in 83.6% examinees. Overlapping with autoimmune hepatitis was seen in 9.4%. One-third of the patients had systemic symptoms. Quality of life deteriorated. CONCLUSION: PBC may be long asymptomatic. The absence of skin pruritus is not a sure sign of the disease absence. To detect PBC early, young and middle-aged women with unexplained weakness or skin pruritus should undergo a comprehensive examination including measurements of GGTP, AP, AMA, IgM, morphological investigation of liver tissue. PBC patients had low quality of life. This should be accounted for when treating patients, in determination of their working ability and for early referral for liver transplantation.