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The literature review gives an update on the frequency and risk factors of complications of colonic diverticular disease, the results of recent investigations, which suggest the success and safety of outpatient treatment for uncomplicated acute diverticulitis. It evaluates the efficacy of pharmacological agents from different groups in preventing complications of colonic diverticular disease.

Aim of this study was to estimate the markers of mineral turnover and BMD in young women with the central hypogonadism, to compare them with healthy young women and healthy postmenopausal women of middle/advanced age. Materials and methods. One hundred seventy women were included in the study: 73 patients with the central hypogonadism (isolated hypogonadism n=35, hypopituitarism n=38), age of 25 [21.2; 30.5] y.o., amenorrhea duration 5 [2.3; 10.1] years; 47 healthy women with regular menstrual cycles, age 24 [23.1; 28.0] y.o., and 50 healthy women with natural menopause, age 56 [53; 58] y.o., menopause duration 6.0 [2.1; 10.0] years. Groups did not differ by age. Results. In patients with central female hypogonadism concentrations of calcium and alkaline phosphatase were significantly higher than in healthy women of similar age, however did not differ from the parameters in postmenopausal women. T-scores

AIM: To define the value of adhesion molecules (sVCAM-1 integrin, P-selectin, E-selectin, and L-selectin) for the prediction and evaluation of the efficiency of treatment in patients with ulcerative colitis (UC) and Crohn's disease/MATERIAL AND METHODS: Twenty-six patients with UC and 14 patients with CD were examined. Of them, 16 patients took infliximab (INF) in a dose of 5 mg/kg of body weight according to the standard scheme; 14 patients received cultured mesenchymal stem stromal cells (MSSCs) in a quantity of 150·108 cells, and 10 had azathioprine (AZA) 2 mg/kg and glucocorticosteroids (GCS) 1 mg/kg of body weight. Enzyme immunoassay was used to determine the serum concentration of the adhesion molecules (L-selectin, E-selectin, P-selectin, and sVCAM-1 integrin) before and 2 months after treatment/RESULTS: The signs of bowel inflammatory disease activity and the elevated levels of adhesion molecules whose synthesis did not occur under normal conditions remained in the patients receiving GCS and AZA. INF treatment caused a decrease in P-selectin, E-selectin, and sVCAM-1 levels to 8.9±1.0, 5.5±1.7, and 9.5±4.4 ng/ml, respectively (p

AIM: To study biological (cell and anticytokine) therapy-induced changes in the levels of proinflammatory cytokines in patients with inflammatory bowel diseases (IBD)/MATERIAL AND METHODS: Forty-four patients with chronic continuous or chronic recurrent IBD were examined. According to the performed therapy, the patients were divided into 3 groups: 1) 16 patients who took infliximab; 2) 14 patients who received combination anti-inflammatory therapy with the cultured mesenchymal stromal cells (MSC) being administered; 3) 14 patients who had standard anti-inflammatory therapy with 5-aminosalycilic acid preparations and glucocorticosteroids. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and interleukins (IL)-2, -5, -8, -12, and -15 were determined in the patients' sera before and 2 months after therapy initiation/RESULTS: The elevation in the serum levels of the proinflammatory cytokines TNF-α, INF-γ, and IL-2, -5, -8, -12, and -15 indicates their implication in the pathogenesis of ulcerative colitis and Crohn's disease. Their levels may evaluate both the activity of an inflammatory process and the efficiency of the therapy. The higher level of these cytokines is accompanied by the enhanced activity of diseases, which may be used to diagnose their activity, to predict the course of IBD, and to perform adequate therapy. The decreased level of the proinflammatory cytokines is indicative of the efficiency of the therapy in patients with IBD/CONCLUSION: By reducing TNF-α levels, infliximab therapy results in a decrease in the concentrations of other proinflammatory cytokines (IL-1, -2, -5, -8), thus lowering the inflammatory activity of IBD. MSC transplantation also reduces the level of most proinflammatory cytokines, thus diminishing the intensity of immunopathological processes, which is shown by positive changes in the clinical picture of the disease.

AIM: To estimate the diagnostic value (DV) of direct markers of liver fibrosis, such as type IV collagen (C-IV), hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1) in combination with indirect markers of fibrosis, such as alanine aminotransferase (АLT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), platelets, tumor necrosis factor-α (TNF-α) in evaluating liver fibrosis/MATERIAL AND METHODS: Sixty-seven patients with chronic diffuse liver diseases were examined. ALT, AST, γ-GTP, and ALP were determined as indirect indicators of fibrosis. The levels of TIMP-1, HA, C-IV, and TNF-α were estimated by ELISA; the stage of fibrosis was determined by the results of indirect liver ultrasound fibroelastography (FE)/RESULTS: According to the results of FE, the patients were divided into 2 groups: 1) (n=25) F≤2 METAVIR and 2) (n=42) F3-F4. While estimating DV of severe fibrosis stages (F3-F4), the area under the ROC curve (AUC) increased for platelets, HA, and C-IV. DV of ALT, AST declined with the higher degree of fibrosis. The highest ratio of test specificity and sensitivity (TSp and TSen) and AUC were observed for AST and HA. ALT and platelets showed low TSen, and TNF-α and TIMP-1 had no TSp. For evaluation of fibrosis (F4), a HA increase of over 57.7 ng/ml had 92.6% TSen and 67.5% TSp; for a C-IV elevation of above 133.1mkg/l, TSen was 85.2%, TSp was 57.5%; for a TIMP-1 rise from 24.4 ng/ml, TSen was 74.1% and TSp was 62.5%. For the diagnosis of fibrosis (F4) with a HA rise of more than 57.7 ng/ml, DV of a positive test was 65.8 (48.65-80.4; 95% CI) and that of a negative test was 93.1 (76.8-99.2; 95% CI). Thus, the negative rather than positive test results are of great diagnostic value for evaluation of the degree of fibrosis/CONCLUSION: The results of the investigation convincingly suggest that examination of the serum markers of fibrosis allows one to estimate with a high probability its presence and severity in patients with hepatic cirrhosis. The so-called direct markers (substances reflecting the biochemistry and regulation of fibrogenesis) are undoubtedly of great diagnostic value.

Cytomegalovirus (CMV) is one of the common pathogens of opportunistic infections in patients with inflammatory bowel diseases. When the patients are treated with immunosuppressants that make them more susceptible to CMV, the course of ulcerative colitis (UC) becomes considerably worse. Antiviral therapy sometimes can reduce the risk of complications and the rate of colectomies. At the same time, antiviral therapy is not mandatory for all UC patients with CMV infection, as shown by the results of numerous investigations. One of the properties of mesenchymal stromal cells (MSC) is to suppress the body's immune reactions to allostimulation, rather than to infection invasion. In vivo and in vitro studies have demonstrated that MSCs have antiviral and antimicrobial activities. The described clinical case shows that clinical improvement occurred and a drastic activation of proliferative processes in the colonic mucosa was detected in the patient with UC after MSC transplantation. Administration of cultured MSCs also promoted the elimination of CMV without antiviral therapy and the overcoming of hormone dependence/resistance in the patient with UC.

Aim. To elaborate optimal cell culture administration regimens to enhance the efficiency of anti-inflammatory therapy for inflammatory bowel diseases. Subjects and methods. Three groups of patients with chronic continuous or chronic recurrent ulcerative colitis (UC) were formed according to the treatment option: 1) 15 patients with UC, in whom mesenchymal stromal cells (MSC) were thrice administered for a month at a one-week interval; 2) 20 patients with UC who received MSC once; 3) 20 patients with UC who had standard anti-inflammatory therapy with 5-aminosalycilic acid (5-ASA) preparations and glucocorticosteroids (GCS). The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index. UC histological specimens were scored using the Gebs scale. To ascertain the duration of remission, the authors used the Kaplan-Maier survival curve method and calculated relative risk (RR) and odds ratio with 95% confidence intervals.Results. Following 12 months, allogeneic bone marrow (BM) MSC transplantation performed thrice during a month caused the greatest reduction in the Rachmilewitz clinical activity index, Mayo endoscopic activity index, and Gebs pathohistological index in patients with UC as compared to those who had underwent one transplantation or received 5-ASA preparations and GCS (p

Aim. The aim of the study was to determine causes of proton pump inhibitors (PPIs) inefficacy in some patients suffering from gastroesophageal reflux disease (GERD). Material and methods. In our study of 154 GERD patients, 50 received omeprazole, 51 - lansoprazole and 53 - pantoprazole in a standard daily dose. GERD symptoms (heartburn and regurgitation) were scored by Likert scale; the patients' quality of life (SF-36) and their mental status (SMALL) were examined. Upper gastrointestinal endoscopy, 24-h intraesophageal pH monitoring, esophageal manometry and pharmacokinetic study were performed. Results. The treatment with a standard dose of PPIs was ineffective in 21 (13.6%) patients. Causes of PPIs inefficacy in 4.5% patients were rapid PPI metabolism and in 9.1% - "driving gear" of symptoms formation related with psychic dysadaptation.

Aim. To develop criteria of early diagnosis of spontaneous bacterial peritonitis (SBP) in hepatic cirrhosis (HC). Material and methods. Clinical symptoms of SBP including systemic inflammatory reaction were analysed in 286 patients. The count of polymorphonuclear neutrophils (PNL) in ascitic liquid (AL), microbiological study of the blood and AL were made. Ultrasound investigation assessed acoustic homogeneity of AL. Blood serum (BS) and AL were tested for cytokines content: interleukine-1beta, TNF-alpha, interleukine-4, transforming growth factor beta, C-reactive protein. Gas chromatography - mass spectrometry (GC-MC) estimated quantity and quality of chemical components - markers of potential infectious agents of AL. Results. Three groups of patients were identified: group A (a classic SBP) consisted of 23 patients with clinical symptoms of SBP and PNL content > 0.25109/l; group B (control) consisted of 19 patients free of SBP symptoms and PNL content < 0.25109/l; group C (patients at risk) - 18 patients with SBP symptoms and PNL content < 0.25109/l. Cultural test of AL was negative in all the groups. Symptoms of SIR occurred equally often in groups A and C. CRP in AL was higher (23.8±4.3 g/l) in group A than in group B (p < 0.05). CRP concentration (8.6±2.1 g/l) was higher in group C than in group B (p < 0.05). Changes in cytokine composition were similar in groups A and C. The number of chemical bacterial markers was higher in groups A and C (p < 0.005). Conclusion. Patients of group C with SIR, elevated CRP, changed cytokine status, high content of chemical markers of AL infection by GC-MC are at high risk of SBP. Such patients need adequate and early antibacterial therapy.

Aim. To determine the role of immune response with production of auto- and heterologous antibodies (Ab) in development of the pathological process and in structural changes in colon mucosa (CM) in diverticulosis (Dv). Material and methods. Of 219 Dv patients, 39 were newly diagnosed with x-ray-detected signs of previous inflammation (group 1), 180 had earlier detected Dv which was confirmed and endoscopic examination detected inflammation (group 2). The comparison group consisted of 25 patients with irritable colon syndrome. The immune status was assessed by concentration of immunoglobulins (Ig), auto- and heterologous Ab. Antibodies to catalytic cytoplasmic antigens to proteinase-3, myeloperoxidase, bactericide protein BPI, tissue transglutaminase (tTG) and antiglycanic Ab were detected with solid-phase enzyme immunoassay. Results. IgA and IgG levels in group 2 were significantly higher than in group 1 and in the controls. Elevation of both IgA and IgG levels reflects activation of B-cell immunity. Group 2 patients had a higher level of Ab to endogenic peptides Saccharomyces cerevisiae (ASCA) of class IgG and IgA than group 1 and controls. The level of Ab to tissue molecules was elevated: antibodies to tTG IgG were detected in both groups - in group 2 twice more often than in group 1, while Ab to BPI - in 27% cases in group 1 and in 97% - in group 2. IgG Ab to antigens associated with phagocytic cells were detected in group 2, while Ab in group 1 were positive in single cases. Conclusion. Activation of immune response with a high concentration of IgA and IgG, Ab to tissue antigens (BPI, tTG) and IgGAb to catalytic antigens is characteristic of chronic course of Dv. Morphological changes in CM reflect different severity of inflammation-dystrophic process.

Biological methods are widely used in the treatment of intestinal inflammation (II). The TNFalpha inhibitor infliximab can quickly correct recurrence, provide long-term remission and reduce hormone need in many patients with hormone-resistant and hormone-dependent forms of Crohn's disease (CD) and ulcerative colitis (UC). However, almost half of II patients fail anticytokine therapy. Some clinical trials of biological medicines were stopped because of toxicity and complications. One of promising approaches to II treatment is now transplantation of mesenchymal stromal cells (MSC). The trial with participation of 85 CD and UC patients demonstrates that intravenous injection of allogenic MSC significantly prolongs duration of remission, reduces recurrence risk and is indicated for patients with hormone-resistent, hormone-dependent forms of II. Cell therapy can be also used in combined treatment of other gastrointestinal diseases, hepatic cirrhosis, in particular. A clinical trial is initiated of efficacy of transplantation of bone marrow autologous cells CD133+ for stimulation of regeneration of the liver in its extensive resection and cirrhosis. The future of this method depends on the results of controlled, randomized clinical trials.

Aim. To assess prevalence of gastroesophageal reflux disease (GERD) in Russia in MEGRE trial in 6 cities of the Russian Federatiion (Kazan, Kemerovo, Krasnoyarsk, Ryazan, St-Petersburg, Saransk). Material and methods. Mayo Clinic questionnaire (USA) adapted for Russia was used to question 7812 people over 18 years of age from of random population sample. The symptoms (heartburn and regurgitation) were classified as frequent if they arose once a week and more often for the last 12 months, rare symptoms arose less often than once a week. The responders with frequent heartburn and/or regurgitation were regarded as persons with epidemiological quantitative criteria of GERD. Results. Heartburn occurred in 47.5% responders: frequent in 9%, rare in 38.5%. Regurgitation occurred in 42.9%: frequent in 7.6%, rare in 35.3%. GERD prevalence was 13.3% (city range 11.3-14.3%). Frequent GERD symptoms are associated with frequent gaseous eructation (24.3%), chronic cough (22.9%), chest pain (15.1%), dysphonia (11.4%.). To stop heartburn, 88% responders took antacids, 32% - blockers of histamine H2-receptors and only 23% - inhibitors of proton pump. Only 52.8% responders with frequent chest pain and 29.3% those with frequent hearburn visited a doctor. Conclusion. The population-based trial MEGRE conducted by international methodology in 6 cities of Russia demonstrated that GERD prevalence is 13.3%. Most of the patients pay little attention to the symptoms, do not seek medical advice and, therefore, receive no adequate treatment.

The paper reviews the literature on bronchopulmonary lesion, one of the least studied systemic manifestations associated with inflammatory bowel diseases (IBD). Knowledge of the entire diversity of extraintestinal manifestations of IBD, including respiratory diseases, allows clinicians to optimize their diagnosis and treatment as the asymptomatic course of the latter may lead to the development of severe respiratory complications. The detection of bronchopulmonary pathology in its early period or during current therapy contributes to the objective assessment of the pattern of the disease, to the correction of treatment and improvement of disease prognosis.

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)108 cells 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 comparison 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.

Aim. To discover relations between allergic diseases and H.pylori infection in patients with gastroduodenal diseases. Material and methods. The study was made of 113 patients (age 22-65, 34 males and 79 females) with chronic gastritis and duodenal ulcer. Of them, 60 patients (group 1) had concomitant allergy (urticaria, bronchial asthma, atopic dermatitis, food allergy, pollinosis), while 53 patients (group 2) had no allergy. H.pylori infection was diagnosed with the respiratory and rapid urease test, histological and cytological tests. Enzyme immunoassay determined total antibodies (AB) to H.pylori in IgG, IgA, IgM classes; IgA-AB in the kits Vector Best (Russia), IgG-AB to H.pylori in the kits of ECOLab (Russia) and total IgE in the kits IgE-EIA (Stavropol). Results. In group 1 total AB to H.pylori were positive in 48 (80%), IgG-AB and IgA-AB to H.pylori in 38(63.3%) and 43 (71.6%) patients, respectively. In elevated concentration of AgG-AB to H.pylori 46 (76.6%) patients had elevated total IgE (mean 364 IU.l). In group 2 total AB to H.pylori were detected in 45 (85.0%) patients, IgG-AB and IgA-AB to H.pylori in 47 (88.6%) and 32 (60. 3%), respectively. Among patients with high level of IgG-AB to H.pylori in the serum high total IgE was only in 35.8% patients. Mean IgE was 250 IU/l. Conclusion. Patients with gastroduodenal diseases associated with H.pylori and allergy and not associated had similar level of total AB to H.pylori, while higher total IgE and specific IgE-AT to H.pylori occurred in the former. Thus, H. pylori infection is associated with allergic (atopic) immune response.

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-ip, IL-6, IL-8. Concentrations of IL-12, Infa,g, TNFa reached maximum on the height of the disease. Intensification of regenerative processes raised concentrations of IL4, 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-10, IL-2, IL-8, IL-6 reached 30-80 pg/ml, IL-12, Infy, TNFa 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 TNFa 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.

Aim. To study prevalence of the principal symptoms of gastroesophageal reflux disease (GERD) in Moscow. Material and methods. A total of 1065 respondents aged 15-85 years (a random representative sample of population of one of the typical Moscow districts) participated in a questionnaire survey using the international questionnaire for detection of GERD incidence. Results. Epigastric burning (EB) occurs in 39.6% examinees. GERD prevalence is 14.2%. Subjects with EB have the following symptoms of GERD: regurgitation (66.3%), epigastric pain (discomfort) (53.0%), nausea (43.6%), vomiting (23.2%), dysphagia (20.6%), chest pain (18.0%), odinophagia (5.5%), singultus (4.6%). There is a direct correlation between incidence rate of EB, height, body mass index, number of alcohol excesses and smoked sigarettes. Conclusion. EB occurs in both young and aged men and women with similar frequency. Significant differences were detected only in the age group 45-59 years in which EB is more frequent in women. All the symptoms excluding cough and singultus were seen in women significantly more frequently. With age, these differences disappeared but noncardial pain in the chest that was less frequent in the elderly. Muscovites with GERD symptoms are older (61.26 ± 13.47 years) than those without such symptoms (58.44 ± 16.28, p < 0.0001).

Background. Ferritin is an important integral and diagnostic marker of liver diseases. In 1/3 of patients with nonalcoholic fatty liver disease (NAFLD), manifestations of hyperferritinemia are revealed. Increased ferritin level indicates the severity of the disease course and affects the prognosis.Objective: to determine the prevalence and character of hyperferritinemia manifestations in NAFLD patients and to evaluate the effectiveness of its correction with human placenta hydrolysate.Material and methods. We examined 158 patients aged from 20 to 63 years (92 men and 66 women). There were no significant differences in age between men and women. The control group consisted of 20 practically healthy individuals. Molecular mechanisms of peptide components of human placenta hydrolysate (Laennec®) impact on pathophysiological processes of serum ferritin disorders, iron metabolism indicators, and inflammation manifestations were analyzed.Results. Nineteen peptides potentially important for regulation of iron homeostasis were identified in Laennec® composition. These peptides contribute to the elimination of iron metabolism disorders by regulating the levels of hepcidin (the main hormone of iron homeostasis), reducing ferritin synthesis, as well as exhibiting anti-inflammatory, and immunomodulatory effects. The efficacy of the drug monotherapy in patients with hyperferritinemia was shown.Conclusion. Laennec® was found to be one of the medicines contributing to the reduction of hyperferritinemia manifestations, iron metabolism disorders, and systemic inflammatory process in NAFLD.