Aim: to present the modern concept of physiological and pathophysiological impact of microbiome. Summary: Major advances in molecular and cell biology significantly improved our understanding of disease pathogenesis as well as in novel strategies for the diagnosis, therapy and prevention of human diseases. Based on modern molecular, genetic, epigenetic microbiologic and biochemical studies it is, on the one hand, possible to identify disease-related point mutations and single nucleotide polymorphisms within genome-wide association analyses (GWAS). On the other hand, high throughput array and other technologies made it possible to simultaneously analyze thousands of genes (DNA) or gene products (RNA and proteins), resulting in an individual gene or gene expression profile (‘signature’) or to characterize the individual microbiome and its pathogenetic potential. Such data increasingly allow to define the individual disease predisposition and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient (‘personalized medicine’). Conclusion: Studying of human microbiome along with GWAS contributed greatly to the recent advances in the diagnosis, treatment and prevention of human diseases.

Aim of review. To study and generalize in the single review the data on prebiotics and probiotics effect on microbiome, intestinal motility and enteric nervous system. Key points. Objective data indicate the ability of enteric bacteria to regulate electrophysiologic thresholds of enteric neurons and to produce a spectrum of neurotransmitters. These data presumes the presence of direct microbiota-induced responses of enteric nervous system as well as its development and intestinal glial cells hemostasis maintenance. No evidence of direct involvement of these neurotransmitters in regulation of proximal enteral neurons synaptic activity is obtained. However the fact of neurotransmitter production in close proximity to intestinal wall creates a basis for the further studies. Conclusion. Studying of probiotics and probiotics effect on enteric nervous system is of enormous interest. Accumulated data change the current concept on human microbiome and its potential, however further clinical trials required.

Aim of investigation. To estimate proportion of patients with Clostridium difficile-associated disease in the spectrum of patients of versatile hospital and reveal its risk factors. Material and methods. Retrospective analysis of 131 case records of the in-patients of Yekaterinburg City Hospital No. 40 for the year 2014 who developed diarrhea during antibacterial therapy was carried out. According to fecal filtrate test for Clostridium difficile (CD), patients were divided into two groups: 71 patients had positive test, 60 - negative. Results. Proportion of patients with C. difficile-associated disease in Yekaterinburg City Hospital No. 40 for the year 2014 was 0,14% of total in-patient number. Predictors of C. difficile-associated diarrhea risk were following: the age over 65 years (OR=3.43; 95%CI 1.06-11.08; р=0.0409), Charlson comorbidity index over 2 points (OR=2,92, 95%CI 1.33-6.44; р=0.0114), presence of anemia (OR=4,35, 95%CI 1.98-9.54; р=0.0003), admission to intensive care unit with staying for more than 1 day (OR=10.59; 95%CI 2.35-47.69; р=0.0002) and in surgical departments (OR=2.46; 95%CI 1.16-5.20; р=0.0276), surgical intervention (OR=3.06; 95%CI 1.33-7.04; р=0.0120), hospital stay for 5 days (OR=3.87; 95%CI 1.87-8.01; р=0.0004), chronic dialysis at chronic renal failure (OR=8.56; 95% of CI 1,05-69,69; р=0,0210), installation of an urethral catheter (OR=3,43; 95% of CI 1.06-11.08; р=0.0409), proton pump inhibitors (PPI) therapy for over 7 days (OR=7.76; 95% CI 1.69-35.53; р=0.0032), antibacterial therapy for over 5 days (OR=4.10; 95%CI 1.93-8.68; р=0.0003), more than one course} of antibacterial treatment (OR=5.31; 95% CI 1.12-25.03; р=0.0365), ceftriaxone therapy (OR=3.21; 95%CI 1.51-6.82; р=0.0036). Conclusions. Following risk factors for C. difficile-associated diarrhea were determined: age over 65 years, presence of several associated diseases (Charlson score >2), chronic renal failure that require hemodialysis, anemia, admission to intensive care unit and surgical departments, surgical treatment, PPI administration for over 7 days, more than one course of antibiotic treatment and duration of antibacterial therapy for more than 5 days, administration of 3rd generation cephalosporins.

Aim of review. To summarize the study of serotoninergic nerves stimulating the stomach and intestinal contractions. Key points. The authors established the fact that irritation of sympathetic trunk (ST) in in the chest cavity of dogs in most of the cases cause not inhibition, but rather stimulation of stomach contractions. The stimulatory effect is amplified at block of sympathetic nerve by Ornidum, and is eliminated by block of serotoninergic receptors of autonomic ganglia neurons by trimeperidine hydrochloride. It demonstrates that ST partially consists of serotoninergic nerves. Stimulatory effect for the stomach considerably exceeds brake action of sympathetic nerve. Comparative analysis of serotoninergic nerve functional properties versus sympathetic nerve was carried out. Serotoninergic nerve (as well as sympathetic) - is complex structure, that includes sympathetic trunks and their branches innervating internal organs. Conclusion. Block of serotoninergic nerve stimulation function by trimeperidine hydrochloride to our opinion may be the cause of postoperative constipation in patients who received trimeperidine hydrochloride.

Aim of investigation. To present to the new data on initial digestive potential of the full-term and premature newborns according to the level of digestive enzymes in serum of the puerperant woman and her child, stomach content of latter and amniotic waters. Material and methods. Material was received from 76 puerpera and their newborns at the full-term and premature pregnancies. Content of hydrolases: amylase, lipase, pepsinogens-I and II was assessed in blood serum of umbilical cord, venous blood of the mother, amniotic fluid and newborn stomach content. Enzymes were detected by Roche diagnostic kit, pepsinogens - Abbott immunoassay test. Results. Fetal development of different enzyme systems digestive potential develops in different terms, and is significantly lower in the newborn, then in the mother, in premature children it is lower, than in those born often normal gestation term. Pepsinogen II concentration is higher than that of pepsinogen I both in stomach content and amniotic fluid. Conclusions. Newborn digestive potential at the end of gestation is determined by his/her digestive glands and can be characterized by hydrolases activity in amniotic fluid, umbilical cord blood and stomach content. This potential acts as is gastroenterological criterion for breast-feeding readiness.

Aim of review. To present the key points of medical approach for treatment of edema syndrome (ascites, hydrothorax, dependent edema) at liver cirrhosis (LC). Key points. Most commonly LC is diagnosed at decompensated stage when portal hypertension becomes the leading syndrome. Generalized edema is the most common manifestation of portal hypertension which is associated with significant decrease in life quality, high risk of spontaneous bacterial complications, hepatorenal syndrome and poor prognosis. Diuretics play important role in the treatment of edema and prevention of relapses. The doctor should be aware of diuretic-related complications spectrum (hemodynamic, electrolytic, acid-base metabolism disorders) that will provide timely diagnostics and elimination and consequently, increase in treatment efficacy. Conclusion. Therapeutic approach for edema syndrome at LC should be based on series of fundamental steps: edema pathophysiology understanding; comprehensive investigation of patients; assessment of edema severity and presence of complications; awareness of pharmacological features of diuretic drugs, their interaction and side effects; albumin or plasma substitutes administration, use of vasoconstrictors, transjugular intrahepatic portosystemic shunting and liver transplantation when required.

Aim of investigation. To study the urinary infection rate in patients with liver cirrhosis (LC) and indications for liver transplantation with assessment of etiologic spectrum and features of the progression of liver disease at development of this complication. Material and methods. The study included patients with liver cirrhosis Child Pugh class B and C with indications for liver transplantation, who were hospitalized at Sverdlovsk Regional hepatological center for liver disease decompensation in 2015 (n=137). Results. Of all enrolled patients 28,5% had urinary infectious complications. In those with more severe liver decompensation (Child-Pugh class C), the rate of patients with urinary tract infection was higher (66,7%). The most commen signs included leukocyturia and bacteriuria. Esсheriсhia сoli и Klebsiella pneumoniae were the most common infectious agents in liver cirrhosis patients. Frequency of urinary tract infections was higher in those with severe liver cirrhosis complications (in past history as well) such as hepatic encephalopathy, ascites, spontaneous bacterial peritonitis. Conclusion. High frequency of infections at decompensated liver cirrhosis require thorough examination of these patients using all available diagnostic methods. Early diagnostics and treatment of urinary tract infections is of paramount importance for patients, listed for liver transplantation, for it can help to keep the patient in waiting list and improve the operation outcomes.

Aim. To estimate efficacy and safety of direct antiviral drugs for hepatitis C treatment in donor lung recipients. Key points. The first cases in Russian literature and one of the first-ever cases of hepatitis C treatment by direct antiviral agents in lung transplant recipients are presented. Combined therapy by asunaprevir and daclatasvir for 24 weeks resulted in sustained virologic response. No significant adverse effects on drug to drug interactions, except for mild and controllable alteration of tacrolimus blood level, were noted. Conclusion. Daclatasvir and asunaprevir combination is effective and safe treatment mode for hepatitis C in donor lung recipients

Aim of publication. To present recent RGA evidencebased medicine centered guidelines on diagnosis, rational pharmacotherapy and management of irritable bowel syndrome (IBS). Summary. IBS - is a functional bowel disorder is manifested by recurrent abdominal pain that develops at least once per week and characterized by at least two of the following signs: it is related to bowel movements, associated to the change in stool frequency and/ or shape. These symptoms should be present in the patient for the last 3 months at overall duration of observation for six months or more. Similar to other functional gastrointestinal disorders, the diagnosis of IBS can be established at compliance of symptoms to Rome IV criteria and the absence of organic gastrointestinal diseases that could cause patient’s symptoms. Due to complexity of differential diagnostics, IBS should be considered as diagnosis by exclusion that require following investigations: clinical and biochemical blood tests; IgA or IgG anti-tissue transglutaminase antibodies; thyroid hormone levels; fecal occult blood test; glucose or lactulose hydrogen breath test for bacterial overgrowth syndrome; stool test for coliform bacteria, stool test for Clostridium difficile toxins A and B; fecal calprotectin level; abdominal ultrasound; upper and lower endoscopies, at indications - with biopsies. IBS treatment requires diet and lifestyle modifications, intake of pharmacological agents and psychotherapy. Antispasmodic medications (e.g.: hyoscine butylbromide, pinaverium bromide, mebeverine) are recommended for abdominal pain relief. For diarrhea-predominant IBS such medications as loperamide hydrochloride, dioctaedric smectite, non-absorbable antibiotic rifaximin and probiotics may be prescribed. For treatment of IBS with constipation use of bulking agents (psyllium), osmotic laxatives (macrogol 4000, lactulose), laxatives stimulating intestinal motility (bisacodyl) may be applied. Enterokinetic agent prucalopride may be prescribed at inefficacy of laxatives. Peripheral opioid agonists (trimebutine maleate) normalizing intestinal motor activity via action on different subtypes of peripheral opioid receptors, combined plant-derived medication STW 5 are applied as well. Conclusion. Implementation of clinical guidelines can determine timely diagnosis and treatment of various IBS types. The IBS is characterized by scalloping course with relapse periods that are provoked by psychoemotional stress and remissions. The risk of organic bowel diseases IBS patients is not higher, than in total population.

Aim of review. To present the modern concept on etiology and pathogenesis of food intolerance, to analyze the modern strategy of diagnosis and treatment of carbohydrate intolerance. Key points. Patients, who presented with abdominal pain, diarrhea, flatulence at the absence of organic diseases should be investigated to exclude intolerance of nutritional components, first of all - carbohydrates. If food intolerance was confirmed, high performance treatment methods should be applied including dietary modification with elimination of intolerable food products, addition of specific enzyme preparations to the treatment mode. Conclusion. Carbohydrate intolerance results in abdominal pain, flatulence and diarrhea in generally healthy population and patients with functional gastrointestinal diseases. Early detection of integrated agentт and its elimination from the ration will provide significant decrease in symptom severity.

Aim of review. To discuss the recent updates in classification of constipation of functional origin (both as separate entity, and within the pattern of constipationpredominant irritable bowel syndrome), the concepts on pathogenesis and recommended treatment approaches. Key points. In 2016 multinational consensus statement on functional gastrointestinal disorders (so-called Rome IV criteria) was presented. In the section devoted to the bowel diseases the new entity - opioid-induced constipation was defined; besides that diagnostic (mostly - the time-based criteria) of irritable bowel syndrome and functional constipation were modified. In new Rome consensus different types of functional bowel diseases were considered as specific forms of certain continuum. The origin of functional bowel diseases is still presented in the context of biopsychosocial model; that develop due to impact of constitutive factors, in particular features of serotoninergic and adrenergic regulation, dietary habit, bile acid metabolism etc. In the recent years the role of intestinal microbiota changes was studied intensively. The treatment approach for functional constipation underwent no significant changes. First of all it is required to attempt to modify dietary habits and lifestyle, including consumption of fermented milk products; at the second stage food fibers are prescribed, at inefficiency of these measures - relatively safe laxatives, and if necessary - drugs to relieve pain. Administration of probiotics and prebiotics is the promising trend in the functional bowel disease treatment, being pathogenically justified and. Promising results are received at administration of specific strains of bifidobacteria and lactobacilli, in particular the combined probiotic «Florasan D» that includes Bifidobacterium bifidum, B.longum, B. infantis, Lactobacillus rhamnosus. Largescale studies proving efficacy of B. lactis DN-173 010 strain (the commercial name «ActiRegularis») at constipation and functional flatulence are received, the drug is included to the spectrum of functional nutritional products for daily intake.

Aim of investigation. To evaluate the results of surgical treatment of obstructed defecation syndrome caused by rectocele due to posterior vaginal wall prolapse by original reconstruction method of perineal muscles. Material and methods. Original method of sphincter plication and levatorplasty was approved at surgical treatment of obstructed defecation syndrome due to pelvic floor muscles incompetence in 134 patients. Results. Defecation function in studied group of patients was evaluated by Wexner constipation score. Prior to the surgery the average score was 23.5±4.1, after operation - 12.4±2.2, in 1 month after operation it decreased to 5.8±1.9, difference in score in comparison to preoperative level was statistically significant (р<0.05) and prove efficacy of surgical treatment. The functional result was also generally estimated as good, satisfactory or unsatisfactory. The good and satisfactory functional result was obtained in 127 (94.7±1.9%) patients. The analysis of questionnaire for estimation of character and severity of colonic motor and evacuatory function disorders in remote period demonstrated significant improvement in all patients. In terms of 6-24 months rectocele recurrence was diagnosed in 7 women i.e. 5.22±1.9% of all patients or 8.4±3.0% of those who consented to undergo examination in late postoperative period. Conclusions. The original method of sphincter plication and levatorplasty at pelvic floor muscles incompetence provides good results for rectocele and accompanying obstructed defecation syndrome treatment.