[S-methylmethionin (vitamin U): experimental studies and clinical perspective].

Vitamin-like compound S-methyl-L-methionine (SMM, historically called vitamin U) is a metabolic agent, affects metabolic processes, which causes a wide variety of effects. The data of the studies demonstrating gastroprotective effect, hypolipidemic and antioxidant effect, participation in regulation of adipocyte function, homocysteine exchange are presented. SMM is involved in all methylation reactions in which another activated form of methionine, S-adenosylmethionine, normally participates. The results of the observed studies indicate a possible expansion of the clinical use of S-methylmethionine.

[Celiac disease detection rate in gastroenterological patients].

AIM: To determine celiac disease detection rate in patients with digestive disease. SUBJECTS AND METHODS: A total of 318 gastroenterological patients admitted to be treated at the Central Research Institute of Gastroenterology in September to October 2012 were examined. The patients' age was 18 to 74 years (mean 51.5±16.4 years). Immunoglobulin A (IgA) and immunoglobulin G (IgG) anti-gliadin antibodies (AGA), IgA anti-tissue transglutaminase (anti-tTG) antibodies and IgG anti-tTG antibodies were determined. When the antibodies were elevated, esophagogastroduodenoscopy with duodenal biopsy was performed. RESULTS: Forty-one of the 318 patients were found to have higher AGA (12.9%); out of them IgA AGA were in 17 (5.35%) patients and IgG AGA were also in 17 (5.35%). Elevated levels of both antibodies (IgA AGA and IgG AGA) were seen in 7 (2.2%) patients. Overall, the detection rate of increased AGA levels was 12.9%. The antibodies were more commonly higher in patients with liver diseases (21.8%) and in those with inflammatory bowel diseases (21.6%). Both IgA anti-tTG, IgG anti-tTG and IgA AGA, IgG AGA were detected in 6 (1.9%) of the 318 patients. The diagnosis of celiac disease was verified by duodenal histological examination in 3 (0.94%) of the 318 patients. CONCLUSION: The celiac disease detection rate in gastroenterological patients was 0.94%.

[Diagnostic value of serum markers of fibrosis in chronic liver diseases].

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 (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), platelets, tumor necrosis factor-alpha (TNF-alpha) in evaluating liver fibrosis. SUBJECTS AND METHODS: Sixty-seven patients with chronic diffuse liver diseases were examined. ALT, AST, gamma-GTP, and ALP were determined as indirect indicators of fibrosis. The levels of TIMP-1, HA, C-IV, and TNF-alpha 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 < or = 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-alpha 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.

[New possibilities for overcoming the secondary inefficiency of anti-cytokine therapy in patients with inflammatory bowel diseases].

A search for ways to overcome the secondary inefficiency of anti-cytokine therapy (ACT) with infliximab (IFX) in patients with inflammatory bowel diseases (IBD) remains relevant and determines the need for new approaches to solving this problem. The secondary inefficiency of ACT has been found to depend on the level of antibodies to IFX (anti-IFX Ab). The Department of Intestinal Pathology, Central Research Institute of Gastroenterology, is investigating the mechanisms for the occurrence of primary and secondary inefficiency of ACT, as well as ways to overcome them by cultured allogenic bone marrow mesenchymal stromal cells (MSC). In the framework of the searching investigation evaluating the efficiency and safety of MSC in patients with IBD, the investigators revealed that was a phenomenon of a decrease in anti-IFX Ab and came to the conclusion that the secondary inefficiency of ACT should be overcome in a patient with ulcerative colitis (UC). The elevated anti-IFX Ab levels were directly associated with the worsening clinical and endoscopic picture of UC and with the enhanced activity of an inflammatory process. The administration of cultures MSC contributed to lower anti-IFX Ab levels, overcome secondary inefficiency (an escape phenomenon) during ACT, and enhanced IFX sensitivity. The clinical observation indicated that MSC administration reduced anti-IFX concentrations and promoted UC remission during IFX therapy. Thus, MSC transplantation can be considered as a promising method for overcoming the secondary inefficiency of ACT, which aids in increasing the previously lost response to anti-inflammatory therapy.

[Antiproliferative activity of diclofenac at tumor cell cultures].

It is known that for risk group's importance of early diagnostics and prevention of a cancer of a thick section of the intestines. The view was expressed that the use of nonsteroidal anti-inflammatory drugs prospectively. The article presents the data obtained after the determination of the effect on the domestic drug diclofenac on the ability of the lines of tumor cells of the human colon multiply this antiproliferativoe action on the dose of the drug. Used photometric method for determination antiproliferativoe action. In vitro determined the effect of the national drug diclofenac on the ability of the lines of tumor cells of the human colon multiply, and is set in a dose-dependent effect. It is established that under the action of NSAIDS metabolic activity of cells can both strengthen and weaken that depends on the line of tumor cells and the concentration of the drug.

[The specific features of pancreatic incretory dysfunction in chronic pancreatitis].

AIM: To reveal the specific features of pancreatogenic diabetes mellitus (DM) and to discuss the principles of its medical therapy. SUBJECTS AND METHODS: Sixty-six patients (55 men and 11 women) aged 30 to 65 years with chronic pancreatitis (CP) were examined. The disease was accompanied with pancreatic calcification and cyst formation in 22 and 13 patients, respectively; 5 patients were found to have a pseudotumorous form of CP and 10 had clinically and laboratorily verified DM. 14 resections and 11 drainages for complicated CP were performed. Its diagnosis was established on the basis of clinical, instrumental, and laboratory findings. Pancreatic exocrine function was evaluated from the results of the 13C-trioctanain breath test (BT) that is designed for its in vivo diagnosis. The level of C-peptide was studied by an enzyme immunoassay. RESULTS: The findings suggest that pancreatic exocrine function is diminished in CP patients both with and without complications as compared with the normal value in 44% (24.3 +/- 1.7 and 26.6 +/- 1.3%, respectively), as shown by BT. According to the results of BT, a substantial decrease in the total proportion of a released label was noted in patients with CP and pancreatic calcification, diabetes mellitus, after resection operations for complications of CP and there were also significant differences, as compared to a group of CP patients without complications. In these patient groups, the level of C-peptide fell to a larger extent than that in CP patients without complications and in patients with CP and DM it was decreased to 0.11 +/- 0.02 ng/ml, the normal level being 0.7-1.9 ng/ml. There was a direct correlation between C-peptide levels and BT results in the patients with CP after resection operations. Insulin antibodies were absent in all the examined patients with CP, which proves the specific type of DM in CP. These are detectable only in type 1 DM. Seven patients with CP and DM were found to have calcification, 5 underwent resection operations, 3 had calcification and underwent pancreatic resection operations. CONCLUSION: The development of DM may be predicted in CP patients with formation of pancreatic calcification and resections. In these patients, pancreatic exocrine dysfunction achieves a severe degree.

[Quality of life of patients with hyperendotoxemia after hemicolectomy].

UNLABELLED: The concept of "health" is defined by the World Health Organization (WHO) as a state of complete physical, mental and social well-being and not merely the absence of disease. Currently, one of the most widely used questionnaires of general type is the SF-36 Health Status Survey, proposed the Boston Institute for Health and created on the basis of other already existing tools for assessing QOL. Translated into Russian and testing methodology was conducted by the Institute of clinical and pharmacological studies (St. Petersburg). Any surgical intervention, in particular the removal of part of the colon can lead to a restriction of all aspects (physical, mental and social) of a normal human life. The goal of treatment of any disease should be considered as improving the quality of life of the patient on a background of positive clinical dynamics, assessing the quality of life indicators, which depend on many external and internal factors. AIM: to study the quality of life of patients after hemicolectomy, depending on the type of colon resection and the level of endotoxemia. RESULTS: Analysis of quality of life of patients after undergoing surgery--hemicolectomy carried out using questionnaire SF-36 indicates a decline in general condition and mental health in patients after left-sided hemicolectomy. The study showed a close pathogenetic relationship between endotoxemia and decreased quality of life of patients after hemicolectomy.

[Characteristics of the intestinal dysbiosis and endotoxemia after hemicolectomy].

UNLABELLED: The normal intestinal microflora important for maintaining the optimum level of metabolic processes in the human body, the immune system, as well as to create a high colonization resistance against the pathogenic microbes. With aging, changes microbiocaenosis intestine, resulting in an increase in the total number of microbes in the gut and profound changes in the functional properties of microorganisms. Under physiological conditions, the main reservoir of endotoxin in the human body is the intestine. Endotoxins, penetrating through the intestinal mucosa, arrive first at the local (intestinal), and then through the portal system in the liver, are able to initiate it various lesions, including fatty degeneration of the parenchyma. OBJECTIVE: Based on clinical and laboratory studies to determine changes in gut microbiota and the level of endotoxemia in elderly patients in the remote period after undergoing surgery--hemicolectomy. RESULTS OF THE STUDY: Metabolic activity of microflora in the colon according to the concentrations of short chain fatty acids in the feces of elderly patients in distant periods after hemicolectomy revealed in various degrees of violation of the microbiota of the colon. Violation of gut microbiota leads to endotoxaemia, which has a toxic effect on liver function, level of endotoxin and protein that binds to endotoxin was significantly higher in patients who underwent left-sided hemicolectomy.

[The frequency of anemia among patients of gastroenterological hospital].

The article analyzes the prevalence of anemia among 18 800 patients treated at the CSRI of Gastroenterology in 2-year observation. Set the frequency of anemia, which was 8.63%, clarified the influence of gender and age on the frequency of anemia. Characteristics of anemia severity, morphological changes of erythrocytes. Highlights the major disease entities: cirrhosis, PBC, IBD, celiac disease tumors in the organs of the gastrointestinal tract, threatening the development of anemia.

[Risk of development of clinical and pathogenetic features of anemia on the background of basic therapy of inflammatory bowel disease].

Anemia in IBD is the result of a combination of iron deficiency and anemia of chronic disease. Therapy of IBD is relief of inflammation, but the drugs usage may cause the development hemolytic anemia and myelodysplastic syndrome. We studied the effect of basic therapy on the incidence of anemia and assess the impact of modern biological therapies on the main markers of AHZ. A total of 153 patients with ulcerative colitis (UC) and 53 patients with Crohn's disease (CD), which at the time of the study received basic anti-inflammatory therapy for at least 1 year. All patients underwent blood tests, iron metabolism parameters were determined by the level of erythropoietin and G-gepsidina C reactive protein. Modern biological therapy increases the effectiveness of the treatment of anemia in patients with IBD. The use of Remicade gives a quick positive response, which is due to the decrease of gepsidin negative influence on iron metabolism and unlocking the synthesis of erythropoietin. The use of MSCs does not inhibit the synthesis of erythropoietin, and is likely to stimulate erythropoiesis at the erythroblast precursors.

[Clinical and diagnostic significance of gepsidin level in the regulation of iron metabolism in patients with inflammatory bowel disease].

UNLABELLED: Gepsidin is an iron regulatory protein that inhibits ferroportin, limiting the transport of iron into the cell of the small intestine villi and blocking the exit of iron from macrophages, that often leads to disruption of iron homeostasis, iron deficiency and the development of anemia. The Aim was to study the levels of gepsidin in patients with IBD and determine its prognostic significance for the development of anemia. We examined 80 patients with IBD, 45 (56%) men and 35 (44%) women with the average age of 39,0 +/- 15,8 years. In 40 patients with anemia and 40 patients with IBD without anemia syndrome, studies were conducted in the status of iron metabolism, the level of gepsidin, TNF, C-reactive protein. CONCLUSION: IBD with systemic inflammatory response leads to increased levels gepsidina and increases the risk of anemia in IBD. Determination of gepsidin in IBD patients enables identify patients at risk for anemia and to clarify the effectiveness of the basic treatment of the disease.

[Syndrome of iron overload and its impact on the clinical course and risk of complications in patients with liver cirrhosis].

The paper presents the results of a study of iron metabolism in 185 patients with cirrhosis of different etiologies. The frequency of iron deficiency in 28.6% of patients and the syndrome of iron overload - 18.9%. The gender and etiology of cirrhosis role in the frequency of occurrence of the syndrome of iron overload and iron deficiency. The iron metabolism disorders in relationship with the frequency of complicated cirrhosis, the severity of liver cirrhosis, according to Child-Pugh's grade of severity of liver disease, the severity of cytolytic syndrome.

[Pharmacokinetics of iron medication and efficacy of therapy with oral iron supplementation].

The pharmacokinetics of iron oral medication in was studied in patients with liver cirhorosis. In patients with hepatocellular insufficiency and high level of gepsidin found a decrease of the iron absorption constant, which led to a change in pharmacokinetic parameters. Tests on the absorption of iron have been conducted in 25 patients with liver cirrhosis, 36% of them showed a decrease of iron absorption, which led to the decrease in the efficiency of subsequent iron therapy. Found that elevated levels of gepsidin that lead to violation of iron metabolism and absorption and reduce the effectiveness of the treatment of iron deficiency.

[Oncogenesis humoral mechanisms regulation and NSAIDs ability in prevention of tumors].

The article observes modern data in mechanisms and pathways of carcinogenesis and tumor progression and the role of oncogenes, cytokines, growth factors in this process. The protective effects of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for colorectal cancers in experimental and clinical studies are also demonstrated in this review.

[Peculiarities of diabetes mellitus course in chronic pancreatitis].

In order to identify features of the course pancreatic diabetes and discussion of the principles of conservative therapy were examined 66 patients with CP in age of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed with formation of calcification of pancreas, 13 - pancreatic cysts, and 5 revealed pseudo tumor form of CP, 10 patients had clinical and laboratory evidence of diabetes. Concerning CP complicated course were performed 14 resection and 11 draining operations on the pancreas. Based on clinical, instrumental and laboratory data was made the diagnosis of CP. Exocrine pancreatic function was assessed on the results of the breath test, using 13C-trioktanaine, which is applied for exocrine pancreatic function in vivo test. The content of C-peptide was investigated by enzyme-linked immunosorbent assay (ELISA). The data indicate pancreatic exocrine function decrease in patients with CP with complications and without complications in compare with the norm of 44% (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test. Significant decrease of the cumulative output tags based on the test data of patients with CP and pancreatic calcification, diabetes mellitus, after resection surgery with CP complications, and there were significant differences in compare with a group of patients with CP without complications (p = 0.5). The level of C-peptide in these groups of patients decreased significantly in compare with a group of patients with CP without complications, and patients with CP and Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie below the minimum values of norm. Obtained a direct correlation between the level of C-peptide and indicators breath test in patients after resection HP (r = 0,84, p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were negative, which proves the specific type of Diabetes at HP. Antibodies to insulin can be detected only at diabetes type 1. In 7 patients with CP and CD detected calcification, 5 patients performed resection surgery, 3 patients had calcification and conducted the pancreas resection. Thus, we can conclude that in patients with CP and formation of pancreas calcification, pancreas resections may predict the development of diabetes.

[Bone mineral density in patients with gluten-sensitivity celiac disease].

AIM: to determine the frequency of development of osteopenia/ostoporosis (OP) vitamin D deficiency, some population risk factors, and the effects of alpha-calcidol and calcitriol on bone mineral density (BMD) in patients with gluten-sensitivity celiac disease (GSCD). SUBJECTS AND METHODS: Densitometry of the lumbar vertebra and femoral neck (FN) was carried out in 47 patients with GSCD. Their sera were tested for 25OHD3, 1,25(OH)2D3, total alkaline phosphatase, calcium, phosphorus, parathyroid hormone (PTH), type 1 collagen type C-telopeptides (CrossLaps) and tumor necrosis factor-a (TNF-alpha), as well as urinary creatinine and calcium. RESULTS: The T score below -1 was found in 37 (78.7%) of the patients. BMD reduced to the level of osteopenia in 51.1% of the patients; OP was detected in 27.7%. Lower BMD was noted in 19 (95%) of the 20 menopausal women and in 15 (68.2%) of the 22 females with preserved menstrual function (p = 0.047). The mean value of 250 HD3 was 47.8 +/- 5.0 in patients with OP patients and 85.6 +/- 7.1 ng/l in those with normal BMD (p < 0.001). The latter had no decreased level of vitamin D, suggesting its deficiency, but 11 (30%) osteopenic patients were found to have vitamin D deficiency (25OHD3 < 30 ng/l). Impaired calcitriol synthesis (69.9 +/- 24.0 ng/l) was observed only in patients with OP; the level of calcitriol was 85.6 +/- 31.2 ng/ml in those with normal BMD. Decreased BMD was accompanied by elevated PTH levels in 25 (67%) patients with GSCD. There were increases in the bone resorption marker CrossLaps and in the level of TNF-alpha in 28 (76%) and 8 (22%) osteopenic patients, respectively. A more significant BMD reduction was seen in the presence of antibodies to gliadin and tissue transglutaminase. A significant correlation was found between the titer of immunoglobulin A antibodies to gliadin and TNF-alpha (rho = -0.57; p = 0.035), CrossLaps (rho = -0.58; p = 0.035), Tscores in the vertebral column and FN (rho = -0.62; p = 0.030) and (rho = -0 37; p = 0.06), respectively. CONCLUSION: The risk for OP in patients with GSCD is affected by menopause and the clinical features of the disease: secondary hyperparathyroidism due to impaired calcium and vitamin D absorption, by the activity of immunological inflammation and the compliance with a gluten-free diet. The immunological activity of inflammation is closely related to the activation of bone resorption and enhances a BMT reduction in patients with celiac disease. The use of vitamin D preparations (alpha-calcidol and calcitriol) in combination with calcium salts lowers BMD in patients with celiac disease just within the first 6 months.

[Fecal excretion of short-chain fatty acids as a marker of the severity of ulcerative colitis].

AIM: to determine the fecal excretion of short-chain fatty acids (SCFA) in patients with active ulcerative colitis (UC) depending on the duration, activity, and severity of the disease. SUBJECTS AND METHODS: The study enrolled 53 patients, including 9 patients with proctosigmoiditis, 18 with left-sided colitis, and 26 with total colonic lesion. The total levels of metabolites, the concentrations of acetic, propionic, and butyric acids in the feces were measured by gas liquid chromatography. RESULTS: Comparison of the excretion of bacterial metabolites with the clinical activity index (CAI) and the endoscopic activity index (EAI) revealed that the level of bacterial metabolites increased with an EAI of 21-30 scores and a CAI of 9-12 scores and then drastically decreased with excess of these values (a group of patients with total colonic lesion). With an EAI of less than 20 scores, the total level of metabolites was 8.91 +/- 1.027 mg/g. It rose steeply up to 17.12 +/- 1.55 mg/g in the activity range of 21 to 30 scores, but dropped up 5.291 +/- 0.916 mg/g when the EIA was more than 31 scores. The more severity of UC by the CAI resulted in a reduction in the total level of the metabolites from 12.84 +/- 2.039 to 5.114 +/- 1.186 mg/g. CONCLUSION: SCFA deficiency caused by impaired synthesis occurs only in severe total UC. In patients with UC, fecal SCFA excretion increases with the longer duration of an inflammatory process and with its higher activity.

[Effect of enzyme supportive therapy of the Ermital' on a quality of life of patients with chronic pancreatitis].

The purpose of the study was to evaluate the quality of life in patients with chronic pancreatitis with the presence of complications treated conservatively and surgical treatment. With the help of a questionnaire MOS SF-36 were asked 80 patients with CP, of whom 15 patients were after the operation, the PDR, 10 patients underwent draining operations, 15 patients had a history of pancreatic necrosis, in 20 patients with CP were characterized by complications (cyst calcification, kalkulez, pseudotumoral form of HP, diabetes) and surgical interventions were not performed in 20 CPs proceeded without complications. Were obtained significant differences on all scales of the questionnaire with the control group all CP patients. Assessment of coping with pain in long-terms after various operations was revealed significantly better results and got rid of persistent pain in patients with a complicated course, who underwent surgery. 23 CP patients with a complicated course, as enzyme replacement therapy received in ermital dose of 20,000 IU lipase 3-4 times a day for 3 weeks. The assessment of quality of life before and after therapy with ermital. The intensity of pain significant changes in the groups received. On the other hand the improvement in general health, physical and social functioning.

[Efficiency of famotidin in prophylaxis of NSAIDs-induced gastropathy: result of multicenter research ZASLON-1 (protection of gastric mucosa from non-steroidal anti-inflammatory drugs].

This article presents results of the first Russian randomized study of NSAID-gastropaty prevention at patients receiving NSAIDS. Results of clinical and endoscopic monitoring of two groups of patients: 1st - 108 patients with AA or RA treated with diclofenac and famotidin and 2nd--116 patients with AA or RA receiving diclofenac treatment only. It was shown that combined use of diclofenac and famotidin reduces to 2.6 times frequency and significantly reduces severity of painful dyspepsia symptoms and antipain manifestations reduces more than twice frequency of erosive-ulcerous lesions of gastric mucosa and duodenum.