Molecular and cell biology have resulted in major advances in 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 analyses it is, on the one hand, possible to identify disease-related point mutations and single nucleotide polymorphisms in the context of genomewide association analyses (GWAS). On the other hand, using high throughput array and other technologies, it is 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 or risk and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient (‘personalized medicine’). All these aspects have greatly contributed to the recent advances in the diagnosis, treatment and prevention of human diseases.

Aim of review. To present up-to-date data on microbiome role in development of various esophageal diseases and options of probiotics application in esophageal diseases treatment. Summary. Gastro-intestinal microbiome is an invisible organ of our body integrating about 1014 microorganisms. Main bacteria types for the esophagus are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and TM7. The microbiome of the normal esophageal mucosa is represented by gram-positive bacteria like Firmicutes; microbiome in patients with Barret's esophagus and esophagitis is constituted mainly by gram-negative anaerobe bacteria: Bacteroidetes, Proteobacteria, Fusobacteria and Spirochaete; patients with eosinophilic esophagitis have Proteobacteria. Expression of tumor and inflammatory mediators (toll-like receptors, interleukins, nuclear factor κB, cyclooxygenase-2) can be determined by microbiome pattern. Conclusion. Results of original studies demonstrate microbiome changes of the esophagus at gastroesophageal reflux disease, Barret's esophagus, adenocarcinoma of the esophagus and eosinophilic esophagitis. Toll-like receptors, cytokines, nuclear factor κB, cyclooxygenase-2 can be potential mediators of inflammation and carcinogenesis which expression can be modified by microbiome spectrum. Probiotics can become the priority trend in treatment of diseases of the esophagus.

The aim of review. To assess protective mechanisms and efficacy of gaseous mediators based antiinflammatory therapy. Key points. Nowadays there are no reasonable and effective methods of prevention and treatment of NSAID-induced intestinal lesions. The discovery of powerful anti-inflammatory and cytoprotective effects of endogenous gaseous mediators (nitric oxide, hydrogen sulfide, carbon monoxide) led to development of new combined nonsteroidal anti-inflammatory drugs (NSAIDs), which in addition to cyclooxygenase inhibitor include gas-releasing molecules. One of such molecules is hydrogen sulfide (H2S) - the gaseous mediator that is produced under physiological conditions. H2S provides a powerful cytoprotective, antiinflammatory and antioxidant effects, optimizes the intestinal microbiota and improves gastroinesinal protection directly and through stimulation of other cytoprotectors, including prostaglandins, carbon monoxide and nitric oxide. Conclusion. Application of H2S-releasing NSAIDs provides powerful protection of the gastrointestinal tract, while maintaining and/or enhancing the antiinflammatory effect. H2S-releasing anti-inflammatory drugs show considerable promise as a safer option for treating chronic inflammatory diseases.

Aim of investigation. To study potential of «7×7» questionnaire to assess dynamics of patient’s state throughout treatment course at irritable bowel syndrome (IBS), functional dyspepsia (FD) and combination of these diseases. Material and methods. Original study included 50 patients (36 men and 16 women) aged 18 to 64 years with confirmed diagnoses of IBS, FD and their combination. Basic manifestations of above-mentioned diseases, presence and severity of symptoms initially (visit 1) and their development in 28 days after treatment onset (Visit 2) were estimated by Questionnaire «7×7». Correlation between the results of «7×7» Questionnaire and data of the General clinical impression scale (CGI-s; CGI-i) was evaluated. Results. According to the «7×7» questionnaire most of the patients estimated severity of their state as moderate disorder during the Visit 1. Statistically significant moderate correlation was revealed between the Questionnaire data and General clinical impression scale. During Visit 2, according to attending physician examination (General clinical impression scale), in 40% of patients symptoms have improved. At the same time during Visit 2 according to the «7×7» Questionnaire most of the patients (48%) estimated their state as borderline disorder. Statistically significant moderate correlation similar to that, obtained for Visit 1 was found between results of the Questionnaire and General clinical impression scale. Most of patients and doctors involved in the study highly appreciated convenience of Questionnaire utilization. Conclusions. Application of the «7×7» Questionnaire in clinical practice allows to estimate adequately severity of symptoms of FD and IBS and their dynamics along the treatment process. These results correlate well with results of the General impression scale (CGI-s; CGI-i). Most of the patients and physicians estimate convenience of «7×7» Questionnaire as good or excellent.

Aim of investigation. To study antisecretory activity of the first dose of esomeprazole (20 or 40 mg) (Emanera®, «KRKA», Slovenia) by long-term intragastric pH monitoring. Material and methods. Long-term intragastric pH monitoring was carried out in 20 patients with acidrelated diseases by «Gastroskan-24» device («IstokSistema», Fryazino, Russia). In the first 24 hours patients received no antisecretory agents, in the morning of the next day - they received esomeprazole 20 or 40 mg orally 30 min. prior to the breakfast. Median pH, both time with various pH values and area under pH distribution curve, percent of this time with values from 1,0 to 10,0 per day before and after esomeprazole administration were estimated. The respective scores were compared, using Wilcoxon criterion. Differences were considered to be significant at р<0,05. Results. At intake of esomeprazole in a dose of 20 mg higher antisecretory effect in comparison to several earlier investigated omeprazole generics by all studied parameters was found. Intake of 40 mg of esomeprazole was followed by more significant and long-lasting acid suppression, i. e. the dose-dependent antisecretory response was received. The dispersion of individual values was minimal. Conclusions. Esomeprazole generic drug Emanera® in a dose of 40 mg complies requirements to the degree of secretion suppression and predictability required for eradication treatment, treatment of severe gastroesophageal reflux disease (GERD), GERD with extraesophageal manifestations, Barret's esophagus and gastro-intestinal bleeding (after iv treatment stage) and can be considered as a drug of choice in these states. According to its antisecretory activity Emanera 20 mg has advantages over omeprazole generics that allows to recommend it for application at functional dyspepsia, non-erosive reflux disease, mild GERD, for GERD maintenance therapy, and also for the treatment and prophylaxis of NSAID-associated gastropathies.

Aim of review. To acquaint general practitioners with a rarely diagnosed disease - the hereditary deficiency of lysosomal acid lipase (DLAL) which can develop under the «mask» non-alcoholic fatty liver disease (NAFLD). Summary. There are two forms of DLAL clinical manifestations: as fulminant lethal Wolman disease and slowly progressing cholesterol ethers storage disease (CESD). This overview is devoted to more clinically relevant form of DLAL, significant for physicians and gastroenterologists - CESD which is often mistaken for NAFLD, however these diseases have different etiology, pathogenesis, pathomorphology and clinical course. Criteria of the clinical and pathomorphological differential diagnosis of DLAL and NAFLD are presented in the review, modern methods DLAL diagnosis confirmation and treatment perspectives are presented. Conclusion. Early detection of DLAL patients and adequate treatment can prevent development of the liver cirrhosis associated to this disease, as well as cardio-vascular complications.

Aim of investigation. Considering prognostic value and dynamic nature of liver fibrosis in chronic cholestatic diseases: primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), severity assessment by liver biopsy and/or noninvasive methods should be obligatory component of the investigation plan during patient follow-up to estimate treatment response. The aim of the present study was to evaluate diagnostic value of noninvasive tests based on indirect liver fibrosis serological markers for the estimation of fibrosis severity in PBC and PSC. Materials and methods. Original study was based on retrospective evaluation of 95 patients with PBC and 27 patients with PSC. According to routine laboratory test data and abdominal ultrasound, indexes of AST to ALT ratio (AAR); AST to platelet count ratio (APRI); platelet count to the spleen diameter ratio - PLT/ SPD and Fibrosis-4 score index (FIB-4) were calculated. All patients underwent liver biopsy with fibrosis stage assessment in biopsy specimen (METAVIR scale). Diagnostic value of estimated indexes was evaluated and compared by ROC-analysis with ROC-curve plotting and calculation of the area under the ROC-curve (AUROC). Results. In PBC group (median age Me [interquartile range] was 54 years [49-62]) 50,5% (n=48) of patients had significant liver fibrosis (F≥2) and 21,1% (n=20) - liver cirrhosis (F4). In PSC group (Me=40 [28-50] years) 63% of patients (n=17) had severe fibrosis (F≥2) and 33,4% (n=9) - and liver cirrhosis (F4) respectively. PLT/SPD index provided the highest AUROC values at significant fibrosis (F≥2), severe fibrosis (F≥3) and liver cirrhosis (F4) in PBC group (0,763 [95% CI 0,664- 0,861], 0,764 [0,662-0,866], and 0,805 [0,694-0,915], respectively). However in PSC group, highest AUROC was found for FIB-4 index (0,844 [0,682-1,000], 0,845 [0,698-0,993], and 0,785 [0,594-0,975], respectively). Conclusion. Application of FIB-4 index in PSC allows to reveal significant liver fibrosis stage (F≥2) with high accuracy (80,7%). Efficacy of other indexes (AAR, APRI, and PLT/SPD) in these patients, as well as AAR, APRI, FIB-4, and PLT/SPD indexes in PBC, should be characterized as quite low that makes their clinical application inexpedient.

Aim of review. To present literature data of the treatment of incomplete rectal fistulas with application of biological substances. Summary. Treatment of rectal fistulas remains burning issue in coloproctology due to unsatisfactory results of surgery resulting in high relapse rate, usually regardless of applied surgical method and high risk of severe complications as anal sphincter incompetence. This is why development of sparing methods of rectal fistula treatment that will allow to decrease intraoperative trauma of the anal sphincter at minimal risk of disease recurrence and, therefore, to prevent development of sphincter incompetence is important. Application of biological materials in rectal fistulas treatment result in reduction of the wound size, accelerates reparative processes and decreases degree of traumatization. Minimization of surgical impact on the anal sphincter allows repetitive application of biological materials up to the achievement of positive effect. Conclusion. Application of biological materials at sphincter-preserving technique provides decreased risk of development of postoperative anal sphincter incompetence.

Aim of review. To present modern data on the possible mechanisms of development of side effects of the proton pump inhibitors (PPI). Summary. Proton pump inhibitors is the class of pharmaceuticals that block N+/K+-ATPase of gastric parietal cells. In this regard they are widely applied in acid-related diseases of upper gastro-intestinal tract. Short term intake of PPI is well tolerated by patients and can rarely cause side effects. The risk of development of iron deficiency, vitamin B12, magnesium is discussed. The interrelation between PPI intake and osteoporosis development is of special interest. Cases of the PPIassociated acute interstitial nephritis are presented. The risk of intestinal infections development, C. difficileassociated disease, and spontaneous bacterial peritonitis in liver cirrhosis patients are still under discussion. Conclusion. The majority of side effects develops in elderly patients have and concomitant diseases. Thus, PPIs can be considered only as supplementary risk factor, and before onset of the long-term treatment all pro et contra consideration should be evaluated.

Aim of review. To discuss results of application of the Russian drug dalargin in the treatment of gastroenterological diseases. Summary. Dalargin is the first synthetic opioid peptide agent created on the basis of endogenous leucineenkephaline. Pharmacological effects of dalargin are caused by opioid receptors. The pilot studies showed protective properties for ulceration and antisecretory effect. In therapeutic practice it is applied for treatment of peptic ulcer of the stomach and duodenum, acute and chronic pancreatitis and pancreatic necrosis. Article presents results of use of hexapeptide, algorithm and guideline on its application are analyzed, possible mechanisms of action are discussed. The therapeutic effect of dalargin at various gastro-intestinal diseases is determined by its bioregulator properties maintaining body homeostasis up to standard. Conclusion. Dalargin has demonstrated high therapeutic efficacy and safety for almost 30 years of application in practical gastroenterology and significantly expanded facilities of gastroenterologists in treatment of digestive diseases.