Evaluation of the effectiveness of personalised therapy for the patients with irritable bowel syndrome.

Intestinal microbiota correction in the therapy of irritable bowel syndrome (IBS) is an important medical problem. We conducted a laboratory and pilot clinical trial to investigate the effect of autoprobiotic bacteria, indigenous bifidobacteria and enterococci isolated from faeces and grown on artificial media to use as personified food additives in IBS treatment. Convincing evidence of the clinical efficacy of autoprobiotic was demonstrated by the disappearance of dyspeptic symptoms. The microbiome of patients with IBS was compared to a group of healthy volunteers and changes in the microbiome after autoprobiotic use were detected by quantitative polymerase chain reaction and 16S rRNA metagenome analysis. The possibility of reducing opportunistic microorganisms in the treatment of IBS with autoprobiotics has been convincingly proven. The quantitative content of enterococci in the intestinal microbiota was higher in IBS patients than in healthy volunteers and increased after therapy. An increase in the relative abundance of genera Coprococcus, Blautia and a decrease in the relative abundance of Paraprevotella spp. were found at the end of therapy. A metabolome study which was performed by gas chromatography and mass spectrometry demonstrated an increase in the content of oxalic acid, a decrease of dodecanoate, lauric acid, and other metabolome components after taking autoprobiotics. Some of these parameters correlated with the relative abundances of Paraprevotella spp., Enterococcus spp., and Coprococcus spp. representative of the microbiome. Apparently, they reflected the peculiarities of metabolic compensation and changes in the microbiota. Therefore, the use of autoprobiotics for treatment of IBS may lead to a stable positive clinical effect, associated with compensatory changes in the intestinal microbiota, and accompanied by corresponding changes in metabolic processes in the organism.

[Biliary sludge: pathogenesis, etiology and drug therapy].

AIM: To evaluate the effectiveness of the use of ursodeoxycholic acid (UDCA) for the treatment of biliary sludge (BS) and to compare the therapeutic effectiveness of the German substance UDCA and generic drugs from other manufacturers. MATERIALS AND METHODS: The study involved 65 patients diagnosed with BS (K80.8). To assess the severity of BS, ultrasound of the gallbladder was performed before treatment, after 1, 3, 6 months during therapy, as well as an assessment of its contractility. All patients were randomized into 2 groups. Patients of the main group received UDCA Ursofalk (Germany) at a dose of 10 mg/kg for at least 6 months. Patients in the comparison group received UDCA (another manufacturer) at a dose of 10 mg/kg for at least 6 months. RESULTS: After 3 months of follow-up, the number of patients with dissolved sludge in the main group was 87.1%, while in the comparison group 50%. In 71% of patients, the normalization of the lean volume of the gallbladder was noted, and in the comparison group only in 47.1%. After 6 months of follow-up, complete resolution of BS in the main group was observed in 93.5% of cases, and in the comparison group in 73.6% of cases. CONCLUSION: As a result of the study, the high effectiveness of Ursofalk during oral litolysis in patients with stage I GI (BS) in the first 3 months of therapy, as well as the normalization of the contractile function of the gallbladder, were noted.

[Diet therapy for irritable bowel syndrome].

The review provides present information on the pathogenesis of irritable bowel syndrome (IBS), the relationship of endogenous and exogenous factors with the development of IBS-symptoms, questions of diet therapy are discussed, diets traditionally prescribed in IBS treatment and diets, such as FODMAP and gluten-free diet, which are the most promising and have a positive effect on the symptoms of IBS.

Complete Genome Sequences of the Probiotic Lactic Acid Bacteria Lactobacillus helveticus D75 and D76.

Lactobacillus helveticus D75 and D76 were isolated from the intestinal tract of a healthy child. Both strains possess symbiotic, probiotic, and antagonistic activities. We have sequenced and annotated the whole genomes of L. helveticus D75 and D76 and have conducted a preliminary genome comparative analysis.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

Low-molecular-weight components of the metabolome control the proliferative activity in cellular and bacterial cultures.

The effects of blood metabolites and model cell culture exometabolites found in the human and animal blood metabolomes have been assessed. Specifically, the influence of carboxylic acids that are structural analogues of amino acids and the drug Aktoflor-C have been studied. Methods of organotypic culturing of rat tissues and Escherichia coli bacterial culturing have been used. It has been found that all the tested compounds either stimulate or inhibit cell proliferation in tissue cultures and proliferation in bacterial cultures. The metabolites that are present in blood and interstitial fluids can exert regulation effects on the tissues of the body and intestinal microbiota.

[TROPHOLOGY ASPECTS OF NOOCPHEROGENESIS. On the 90th anniversary of A M Ugolev].

This paper presents an analytical review of A. Ugolev's scientific heritage (the theory of adequate nutrition, all-purpose functional blocks, the unity of natural and artificial technologies, the discovery of membrane digestion, new doctrine--trophology) to explain trophological aspects of noospherogenesis. The authors have presented their specific views for the development of these ideas; the theory of therapeutic infections, the holistic theory of nutrition, the endoecological deficiency syndrome, the activation of all-purpose functional blocks, evasion receptors, new principles of treatment with the effects on microbiota, combining the essence of the diseases and their treatment.

[THE INFLUENCE OF ANAESTHESIA ON PERIOPERATIVE VALUES OF AMINOTERMINAL FRAGMENT OF THE BRAIN NATRIURETIC PEPTIDE PRECUSSOR IN PATIENT WITH POSTINFARCTION CARDIOSCLEROSIS UNDERGOING NONCARDIAC SURGERY].

BACKGROUND: The importance of postoperative values of cardiac damage biomarkers studying (such as troponine and NTproBNP) is stressed by recommendations of the European Society of Cardiology and the European Society of Anaesthesiologists (2014). AIM OF THE STUDY: the effects of general and spinal anaesthesia on perioperative dynamics of NTproBNP in patients with postinfarction cardiosclerosis in the surgical treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: 67 men aged 60 to 75 years were included in a prospective, randomized study. Patients were undergone elective open surgery for prostatic hyperplasia. All patients had a history of myocardial infarction. Depending on the type of anaesthesia the patients were divided into 2 groups: The first group (35) was operated under spinal anaesthesia (SA). The second group (32) was operated under general anaesthesia (GA). The volume infusion was 2700 ± 250 ml in the first group and 1600 ± 250 ml in the second group during perioperative period. Determining the level of NTproBNP in the venous blood plasma realized four times: 1 hour before surgery, at once at the end of surgery, 12 and 24 hour after surgery. RESULTS: The first group patients was registered an increase the values of NTproBNP in plasma 2 times from 628.6 ± 107.4 pg/mol to 1204.1 ± 141.9 pg/mol 12 hour after the operation (P < 0.01). After 24 hours the level of NTproBNP in blood plasma of the first group patients was reduced by 28%, but, however, exceeding the values in the second group is more than 1.7 times (P < 0.05). CONCLUSION: The extra volume of the infusion during the spinal anaesthesia in the early postoperative period after the elimination of the sympathetic blockade to leads volume overload in patients with accompanying cardiac pathology.

NUTRITIONAL FACTORS OF ANEMIA IN ULCERATIVE COLITIS PATIENTS.

The study aim was to assess the relationship between nutritional markers decrease and hemoglobin level in ulcerative colitis (UC) patients. METHODS: The cross-sectional retrospective analysis was performed. Data from medical records of 103 ulcerative colitis patients was included to analysis. Demographic characteristics, disease behavior, gut involvement extension, hemoglobin and total serum protein levels were collected. Body mass index (BMi) and fat-free mass index mass were collected retrospec- tively from bloimpedance analysis data. A multiple linear regression analysis was performed to study the relationship be- tween nutrition status parameters and hemoglobin level adjusted for demographic and diseaseTassociated characteristics. RESULTS: Prevalence of anemia in the sample was 37.9%. In adjusted multiple linear regression model total serum protein level and fat-free mass index were directly associated with the hemoglobin level: standardized ß 0.369 (p = 0.010) and standardized ß = 0.509 (p <0.001) respectively. CONCLUSIONS: We assume undernutrition is one of causative agents of anemia in UC patients. It is likely the anemia treat- ment in UC patient with undernutrition must be performed with nutritional support.

IDENTIFICATION OF BACTERIOCIN GENES IN PROBIOTIC STRAINS OF LACTIC ACID BACTERIA LACTOBACLLUS ACIDOPHILUS D-75 AND LACTOBACILLUS ACIDOPHILUS D-76.

AIM: to detect the bacteriocin genes of probiotic strains Lactobacillus acidophilus 0-75 and Lactobacillus acidophilus D-76 (components of Vitaflor dietary supplement). MATERIALS AND METHODS: The antagonistic activity of L. acidophilus D-75 and L. acidophilus D-76 strains was estimated by the deferred antagonism method. The identification of bacteriocin genes was performed by PCR using helveticin J gene primers. Amplified fragments were sequenced using ABI PRISM' 310 Genetic Analyzer and were analyzed using NCBI/BLASTX. RESULTS: The test bacteria exhibit pronounced antagonistic activity (AA) against Escherichia coli 075 and Salmonella Enteritidis 209. In the presence of Actoflor-S (metabiotic dietary supplement) the antagonistic activity of tested probiotic strains was 2-2.5-fold increased indicating its inducible nature. The identical sequences of 537 bp homologous to gene fragment of helveticin of L helveticus DPC457l (hv_1632 gene) were detected in DNA of both strains. Sequencing of these fragments showed difference in three nucleotides.compared to the reference DNA of DPC4571 strain (A instead of G at position 46, C instead of T at position .249 and A instead of T at position 537), but all these replacements do not lead to changes in the amino acid sequence of a bacteriocin. For L acidophilus D-76 another bacteriocin gene fragment of 283 bp was identified (in addition to 537 bp fragment). The latter had 95% homology with the helveticin J gene of L helveticus R0052 (R0052_09025 . gene). In NCBI/BLASTX database the sequences homologous to the helveticin gene of L. helveticus DPC4571 were found in 11 microorganisms related to L. acidophilus, L. amylovorus, L. crispaus, L gallinarum, L. helveticus and L. kitasatonis. CONCLUSION: Thus, our study shows that there are at least two bacteriocins in L. acidophilus D-76 and one bacteriocin in L. acidophilus D-75. However, the true potential of these probiotic bacteriocins for human health has yet to be releized.

METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS.

Existing methods of clustering of gut microbiota (enterotypes, clusters, gradients), as well as the term 'phylogenetic core' do not reflect its functional activity. The authors propose to describe the key microbiora using term 'phylometabolic core of intestinal microbioca which more accurately reflects the functional importance of metabolically active microbiota. Phylometabolic core includes functional groups of microorganisms that perform similar metabolic functions: butyrate-producing bacteria, propionate-producing bacteria, acetate-produc- ing bacteria (acerogens), hydrogenosrophic microorganisms (reductive acetogens, sulfate-reducing bacteria, methanogens), lactate-producing and lactate-utilizing bacteria, bacteria involved in bile acids metabolism, bacteria that metabolize proteins and amino acids, vitamin-producing microorganisms, oxalate-degrading bacteria and others. The hypothesis that disturbance of microbial metabolism is the root of many human diseases is discussed. The microbial dysmexabo- lism leads to the metabolic dysbiosis (a particular form of dysbiosis) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary, fetal or exhaled air). Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiora composition that called taxonomic dysbiosis. Since in the metabolic dysbiosis metabolic pathways can be switched only, it means the need for completely different approaches to its assessment using metabolomics (metabolic fingerprinting, metabolic profiling, meta-metabolomics). Metabolites concentrations in colon (feces, biopsy samples), blood (serum, plasma), urine or exhaled air, as well as metabolic profiles of examined substrates can serve as biomarkers. The main clinical variants of metabolic dysbiosis are due to the disturbances in microbial synthesis of short-chain fatty acids (primarily butyrate and propionate) and due to increasing bacterial production of hydrogen sulfide, ammonia and secondary bile acids (particularly deoxycholic acid). These kinds of metabolic dysbiosis can eventually lead to inflammatory bowel disease (IBD) or colorectal cancer (CRC). The metabolic dysbiosis due to bacterial choline dysmetabolism followed by overproduction of trimethylamine (TMA), arherogenic precursor of trimethylamine N-oxide (TMAO), is associated with atherogenesis and increased risk of cardiovascular disease. Dysmetabolism of aromatic amino acids leads to changes in the microbial production of phenylalanine and tyrosine derivatives (phenyl carboxylic acid, p-cresol) and tryptophan indole derivatives (indole carboxylic acid, indole) and contributes to pathogenesis in lBS. IBD, CRC, chronic liver and kidney diseases, cardiovascular diseases, autism and schizophrenia. Metabiotics, a new class of therapeutic agents, e.g. based on microbial metabolites, can correct metabolic dysbiosis, prevent diet- and microbiota-relared diseases and increase the effectiveness of treatment.

FUNCTIONAL FOODS ARE CRITICAL COMPONENTS OF TREATMENT OF METABOLIC DISORDERS IN CELIAC DISEASE.

AIM: To evaluate the effectiveness of Native-complex functional food to correct nutritional disorders and to normalize gastrointestinal motor activity in celiac disease (CD). METHODS: 20 CD patients with constipation and metabolic disorders were included in the study (age 31.8?9.5 years, male to female ratio 1:5.3). The diagnosis of CD was confirmed by clinical and anamnestic data, endoscopy, histopathology of duodenal biopsy specimens, HLA-DQ2 and HLA-DQS typing. All patients received Native-complex Fucus jelly (Kelp jelly) within 2 months. RESULTS: At the beginning of the study45% of patients had stools corresponding to the Bristol Stool Form ScaleType 1,40% of patients had Type 2 stools and 15% of patient had Type 3 stools. 15 patients (75%) showed a decrease in fat mass and 13 patients (65%) showed a decrease in fat-free mass indicated by bloimpedance measurement. All patients had low values of total bacterial counts and increased abundance of pathobionts including fungi and viruses in fecal microbiota. Supple- mentary nutrition significantly improved symptoms, intestinal circadian rhythms and stool consistency in CD patients. At the end of the study 70% of patients had daily bowel movements, 30% of patients had stools every other day. The average stool frequency was 5,95 ? 1,80 per week. 80% of patients had Type 4 or Type 5 stools,20% of patients had Type 3 stools according to the Bristol Scale. Supplementary nutrition significantly improved gut microbiota profile. CONCLUSION: Long-term gluten-free diet in celiac disease leads to a decrease in dietary fiber and polysaccharides consumption and promotes intestinal dysbiosis. Functional foods improve symptoms; stool consistency and gut microbiota profile in adult celiac patients on gluten-free diet.

EFFECT OF CARBOXYLIC ACIDS OF GUT MICROBIAL ORIGIN ON HOST CELL PROLIFERATION IN ORGANOTYPIC TISSUE CULTURES.

Intestinal microbiota produces many carboxylic acids, especially short chain fatty acids (SCFA) as a result of carbohydrates, fats and proteins fermentation and which are intermediates in the interaction of the microbiota and the host. SCFA (formate, acetate, propionate, butyrate) are formed by the anaerobic carbohydrates fermentation and branched-chain fatty acids (BCFA), such as isobutyric and isovaleric acids, are derived from amino acids valine and leucine. Phenylcarboxylic acids (PCA), such as phenylacetic acid (PAA), phenyipropionic acid (PPA), phenyllactic acid (PLA) and some other acids, are metabolites of amino acids phenylalanine and tyrosine involved in host adaptation and regulation. ma unique experiment, the authors first examined effect of the carboxylic acids on host cell proliferation in organotypic tissue cultures (rat spleen explants). The study showed that almost all biogenic aliphatic carboxylic acids have a positive effect on cell proliferation in rat spleen tissue. This fundamentally distinguishes them from amino acids, many of which have an inhibitory effect at the same concentrations. These findings suggest that SCFA, including hydrox~ and oxo derivatives, can act as positive regulators of host immune tissues. Some SCFA (for example, butyric acid), stimulate proliferation of normal host cells (immune tissue, intestinal epithelium), but inhibit growth and induce apoptosis in colorectal cancer cells ('butyrate paradox'). Unlike SCFA, phenylcarboxylic acids have a negative effect on host immune tissues explants and induce apoptosis. These data confirm the potential contribution of phenylcarboxylic acids in the pathogenesis of chronic disorders associated with impaired immune response, including autoimmune diseases. The authors suggest that PCA may serve as early metabolic markers of sepsis, immune-related diseases and chronic inflammation, such as inflammatory bowel disease (iBD), colorectal cancer, chronic kidney disease and liver, secondary imrnunodeficiency. It can be assumed that carboxylic acids are evolutionary precursors of amino acids that have a wide variety of functions and able to modulate not only proliferation but also apoptosis. The results agree well with the data obtained in the study of Actoflor-C (microbial metabolites complex) and can be used to study mechanisms of action of probiotic strains and metabiotics (e.g. butyrate and propionate-containing formulations), as well as for the development of innovative medicines.

[Use of analgesia and sedation in dental implantology in patients with concomitant hypertension].

Dental implants surgery in patients with hypertension increases the risk of vascular complications. The aim of the study was to examine the effect of analgesia and sedation on blood pressure and postoperative pain in dental implantology. In 76 patients with hypertension implant surgery was performed under local anesthesia only (40 patients) or under local anesthesia with propofol sedation and pre-emptive analgesia with ketorolac (36 patients). Intraoperative systolic blood pressure in the second group was 20% less than in the first group while the intensity of pain in the postoperative period in the second group was three times less than in the first one. Propofol sedation in dental implantology provides hemodynamic stability in patients with concomitant hypertension and preemptive analgesia with ketorolac allows minimizing postoperative pain.

[Long-term dental interventions in mentally retarded children under general anesthesia with sevoflurane].

Dental procedures in mentally retarded children is challenging for both dentist and for anesthesiologist. The aim of the study was to evaluate the efficacy and safety of dental care procedures under general anesthesia with sevoflurane by means of laryngeal mask in mentally retarded children. The randomized controlled study included 65 mentally retarded children with ASA 2-3 who underwent dental treatment. All patients had multiple caries. The children were divided into two groups. The first group included 35 children with normal body weigh while the second one - 30 obese children. All patients received a rapid induction with sevoflurane with the subsequent installation of the laryngeal mask. In the second group the signs of hypoventilation recorded an average of 10 ± 4 minutes after induction of anesthesia, which was manifested in increasing Pсо2greater than 50 mm Hg. In the first group, the signs of hypoventilation marked an average of 18 ± 3.5 minutes from the start of induction of anesthesia. All patients were transferred to the artificial lung ventilation through the LMA. By dental treatment under general anesthesia with sevoflurane and laryngeal mask all mentally retarded children had respiratory depression with increased levels of carbon dioxide greater than 50 mmHg, but obese children developed these signs of hypoventilation twice as fast. Conducting long dental treatment in mentally retarded children require artificial lung ventilation.

[NEW TECHNIQUE OF SPINAL ANESTHESIA WITH EPIDURAL VOLUME EXTENSION FOR CAESAREN SECTION IN PREGNANT WOMEN WITH CONCOMITANT CARDIAC PATHOLOGY].

BACKGROUND: Spinal anesthesia with the epidural volume extension provides the possibility of using small doses of local anesthetics and the low frequency of hypotension. However, the dose of the local anesthetic and the volume of normal saline for administration into the epidural space, remain unclear. OBJECTIVE: To study the influence of new techniques of spinal anesthesia with the epidural volume extension at the level of sensory block and hemodynamic in pregnant with concomitant cardiac pathology during cesarean section. METHODS: In an observational study were included 24 pregnant women with cardiac pathology. Women were divided into 3 groups, depending on the value of intra-abdominal pressure (lAP). Expansion of the epidural space was performed before spinal anesthesia. For spinal anesthesia we used heavy bupivacaine 0.5% (5.5 ± 0.1 mg). The volume of saline for administration into the epidural space depends on the level of lAP RESULTS: The average upper level of sensory block did not difer significantly in groups and amounted Th 2.1 ± 0.5, 95% C.I. 1.6-4.0 (p = 0.001). The only one woman in group 3 (4.1%) developed hypotension. The maximum level of motor block (Bromage score) among the groups was similar and amounted to 1.5 ± 0.2, 95% C.I. 1.0-2.0 (p < 0.001). CONCLUSIONS: The new technique of spinal anesthesia with the epidural extension provides qualitative analgesia and stable hemodynamics in pregnant women with concomitant cardiac pathology

[FEATURES OF FUNCTIONAL DISORDERS GASTRODUODENOBILIARY SYSTEM IN PATIENTS WITH CELIAC DISEASE].

The disturbances in synchronous functioning of gastroduodenal and biliary system and in their consequent interaction underlies functional disorders of the digestive tract. Motor and evacuation functioning of the gastrointestinal tract depends on the bile flow to the duodenum, which influences on digestive processes. Functional disorders of the biliary tract, contributing disturbances of the gastrointestinal motor activity, cause gastrointestinal symptoms. The cause of biliary dysfunctions often are gallbladder anomalies, which are accompanied by disturbances in drainage system of bile flow, development of the pathological refluxes, inflammation and formation of the biliary sludge. The progression of the biliary system deflux dysfunction leads to motor and evacuation dysfunction of the gut. According to the numerous data, gall bladder anomalies, which underlies functional disorders in bile deflux, are common in patients with coeliac disease. The results, obtained in the conducted research, revealed hypertonic hyperkinetic motor disorders of the upper part of the gastrointestinal tract and inflammation changes of the gastroduodenal zone in patients with coeliac disease with fixed bend in the gallbladder neck, necking and different deformation of the gallbladder, which are the visceral signs of undifferentiated connective tissue dysplasia. Disorders in every component of the digestive tract upper part motor activity lead to the corresponding clinical manifestations.