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Experimental and Clinical Gastroenterology

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No 7 (2017)

LEADING ARTICLE

4-50 2044
Abstract
Aim: to identify candidate biomarkers of ulcerative colitis and celiac disease by serum metabolomics analysis. Methods: 40 mild-to-moderate active left-sided UC patients, 43 CD patients in remission on a gluten-free diet and 42 healthy volunteers (HV) (125 patients in total) were enrolled in the study. Serum metabolomic assays were conducted using the GC-MS. Results: 28 out of 93 identified metabolites were of microbial origin. In serum of UC patients lactic acid, 2-hydroxybutyric acid (2-HBA), 3-hydroxyisobutyric acid (3-HIBA), 2-hydroxyisovaleric acid (2-HIVA), 3-hydroxycinnamic acid, succinic acid, benzoic acid and 4-hydroxyphenylacetic acid (4-HPAA) levels were significantly increased compared to HV. Serum levels of caproic acid, linoleic acid and eicosadienoic acid (EDA) in UC were significantly lower than in HV group. 2-HBA and 2-HIVA levels in UC patients were significantly increased as compared to CD patients. Serum levels of caproic acid, linoleic acid and glycolic acid in UC were significantly lower than in CD group. Serum of CD patients showed significant increases in stearic acid, 2-HIVA, succinic acid, fumaric acid and benzoic acid compared to HV. Serum arachidonic acid (AA) level in CD was significantly elevated compared to UC patients only. De novo lipogenesis index (DNL) (C16:0/C18:2n-6) was significantly elevated in UC patients compared to both HV and CD patients. The ELOVL6 elongase activity index (C18:0/C16:0) and the stearic acid/linoleic acid ratio (C18:0/C18:2n-6) in UC patients were significantly increased compared to HV. The ratio of AA to EDA (C20:4n-6/C20:2n-6) was increased in both UC and CD groups. Butyrate plus inulin significantly lowered serum levels of pro-inflammatory succinic acid (in both UC and CD patients) and 2-hydroxyisovaleric acid (in CD) and restored the lowered serum levels of linoleic acid and EDA in UC patients. Conclusions: Significant changes in serum levels of microbial and endogenous metabolites, reflecting some metabolic pathways disturbances (glycolysis, TCA cycle, fatty acid metabolism, ketone body metabolism, phenylalanine, tyrosine and tryptophan metabolism, microbial metabolism) are observed in both ulcerative colitis and celiac disease. ROC curve analysis showed that some of these metabolites of microbial or mixed origin, as well as a new metabolomic index (the ratio of arachidonic acid to eicosadienoic acid, C20:4n-6/C20:2n-6), reflecting the balance between pro-inflammatory and anti-inflammatory components of the omega-6 fatty acid pool, may be considered as candidate biomarkers of chronic intestinal inflammation. Reduction of pro-inflammatory microbial metabolites in serum indicates the ability of metabiotics (e. g. butyrate + inulin) to correct metabolic dysbiosis in both diseases.

CLINICAL GASTROENTEROLOGY

51-53 280
Abstract
The aim was to study the spectrum of gastroenterological diseases in adolescents with morbid obesity. Materials and methods: The study 34adolescents with a BMI> 35, and 20 adolescents with a BMI of 25 to 34. EGD, US, Fibromax test, lipidogram, the level of blood glucose and insulin was studied. Results. When morbid obesity more often were diagnosed esophagitis (26 % and 11,3 %, p <0,05), hiatal hernia (6 % and 0 %, p <0,05), NAFLD (71 % and 42,5 %, p <0,001), chronic gastritis (59 % and 35 %, p <0,05) and duodenal ulcer (6 % and 0 %, p <0,05). The positive correlations between gastrointestinal diseases and BMI, hyperinsulinemia and dyslipidemia were found. Thus Gastroenterological incidence of teenage obesity increases with increasing BMI and progression of metabolic disorders
54-57 308
Abstract
The aim of this study was to investigate the motility of the stomach through the study of myoelectric activity in patients with the overlap syndrome of the gastroesophageal reflux disease and functional dyspepsia. Sixty-two patients with the overlap syndrome of the of gastroesophageal reflux disease and functional dyspepsia were examined. The control group consisted of 46 healthy volunteers. The diagnosis of the overlap syndrome of the of gastroesophageal reflux disease and functional dyspepsia was established on symptoms, data of esophagogastroduodenoscopy, 24-hour pH-meter or 24-hour impedance-pH-metry, Roman criteria III. Myoelectric activity of the stomach (MAS) was assessed by 24-hour electrogastrography (EGG) on an empty stomach and after taking a standard test breakfast (430 kcal, Nutri Drink). In preprandial and postprandial periods of detection of MAS, motility disorders were detected: a decrease in the dominant frequency of slow stomach waves, an increase in the coefficient of its instability. Chronotropic MAS dysfunction was characterized by a decrease in normogastric activity, an increase in bradygastric and tachigastric activities. Food intake led to a partial correction of MAS: an increase in normogastry and a decrease in bradygastria. The revealed disturbances are one of the mechanisms of the development of gastric motility disorders that cause the development of the overlap syndrome of the gastroesophageal reflux disease and functional dyspepsia.
58-64 241
Abstract
The purpose of the study is to examine the degree of influence of metabolic syndrome (MS) on the course of Barrett’s esophagus (SP) depending on gender characteristics and morphological patterns. Materials and methods. The study included 151 patients with Barrett’s esophagus (men 75 (49,6 %) and 76 women (50,3 %) aged 26 to 90 years). The patients were divided into two groups depending on the presence/ absence of metabolic syndrome. Flow analysis of PB was carried out taking into account gender characteristics and severity of morphological changes of the mucosa in segments of Barrett’s in two groups before and after treatment. Methods of research were endoscopy in various versions, data of morphological research of biopsy material, clinical and laboratory parameters. Results. The main peak of the presence of comorbid pathology, including PB and MS account for the age between 50-70 years, mainly in women in postmenopausal period. Before the start of the treatment the more pronounced morphological changes were revealed in the 2nd group of patients (PB+MS), but in the same group were obtained and better treatment results: epithelialization segment squamous epithelium occurred in 43,5 % and 48 % respectively. Conclusion. The presence of PB patients with comorbid pathology, particularly of the metabolic syndrome, contributes to more pronounced morphological changes in the mucosa of the esophagus. However, adequate therapy of concomitant pathology allows to achieve the best results. This fact confirms the claim that PB is a condition which can depend on many factors, including the presence of comorbid pathology. In this regard, the therapy “is not illness, but patient” can help to optimize the treatment of the most severe complications of gastroesophageal reflux disease, recognized as a disease of the XXI century
65-70 279
Abstract
Introduction: To date, among the somatic and gynecological diseases in women of childbearing age, habitual miscarriage (PNP) is considered as a multifactorial problem. The aetiology of PNP remains completely unknown, and the role of general somatic pathology in the development of PND is poorly understood. Chronic liver diseases, leading to a disruption of its detoxification function and metabolic disorders, are one of the causes of PNP in the first trimester of pregnancy. Study Aims. To study the state of the hepatopancreatobiliary system in patients with PNP Methods. The study involved 74 women, aged 20-44 years (mean age = 32.5 ± 1.13). Group I (n = 53) included women with PNP (main group), group II (n = 21) - women with normal pregnancy in the history (control group). All women underwent a clinical examination, a biochemical blood test, ultrasound of the abdominal cavity, echo cholystography. Results. In the 1 group, a significant increase in cytolysis and cholestasis, fasting glucose, insulin and HOMA-IR index, atherogenic lipoprotein fractions, atherogenicity index. According to the data of ultrasound in the main group, the change in liver size, hepatic structure by the type of steatosis, enlargement of the gallbladder and thickening of its walls, sediment in the gall bladder was detected more often. Evaluation of the motor-evacuation function of the gallbladder indicated a predominance in the main group of hypomotor dysfunction of the gallbladder. Conclusions. In patients with PNP, changes in hepatic, lipid and carbohydrate metabolism, hepatomegaly with signs of steatosis of the liver, changes in the state and content of the gallbladder with a violation of its function predominate, which confirms the opinion of the influence of the pathology of the hepatobiliary system on the development of PNP, both in isolation and in metabolic syndrome
71-81 284
Abstract
Objectives: The aim of our study was to evaluate bone mineralization and metabolism in children with Crohn’s Disease (CD) and ulcerative colitis (UC). Material and methods: 113 patients with inflammatory bowel disease (IBD) (2-17 years) and 40 healthy children were included in the present study. We assessed markers of IBD activity. Bone mineral density (BMD) of lumbar spine (DEXA), serum osteocalcin (OC), C-terminal telopeptides (CTT), parathyroid hormone (PTH), serum calcium, alkaline phosphatase and 25 (OH) vitamin D were measured. Results: BMD in patients with CD and UC were lower than in control group (Zscore -1,4 SD, -1,3 SD and 0,31 SD, p=0,00001, respectively). Differences in level of PTH (39,4 pg/ml, 41,7 pg/ml и 24,8 pg/ml, p=0,04), and CTT (1,09 pg/ml, 1,08 pg/ml, 0,84 ng/ml, p=0,03) between CD, UC and healthy patients respectively have been found. There were no differences in serum OC between groups. Positive correlation between BMD and albumin, OC concentration and linear growth have been detected. IBD activity and duration, cumulative steroid dose were negatively associated with BMD. Vitamin D deficiency was observed in 98 % and 94,1 % of children with CD and UC respectively. Conclusions: patients IBD have low bone mineral density with increased bone resorption due to systemic inflammation, steroids side effect, vitamin D and calcium deficiency.

SURGICAL GASTROENTEROLOGY

82-88 219
Abstract
Aims: Obesity is one of the most pressing problems of modern medicine, being not only an independent cause of increasing disability and mortality, but also the basis for the development of the metabolic syndrome with its many manifestations and type 2 diabetes. Meanwhile, attempts to reduce weight with low-caloric diets, pharmacotherapy and lifestyle changes have limited effectiveness and rarely give a lasting result. Minimally invasive methods, such as intragastric baloon, are effective only in some patients, and large surgical interventions are highly effective in most obese patients, but require lifelong limitations and medical supervision. Thus, in order to create an effective algorithm for choosing the treatment of the metabolic syndrome, it is required to identify the predictors of the response to each of the indicated treatment methods, which is the goal of this work. Materials and methods: Study and analysis of literature on studies of foreign authors. Results: as predictors of weight loss during the intragastric balloon treatment can be considered female gender, lower levels of initial BMI, no compulsive overeating (“binge eating”); for large surgical interventions - BMI, C-peptide level and duration of type 2 diabetes. Conclusions: Summarizing the results of numerous studies, the predictors with good evidence base in reducing body weight of patients with diabetes include BMI, and gender. Well studied factors of glycemia compensation during treatment are the preservation function of beta cells, which effectively confirms the level of C-peptide and concomitant glucose-lowering therapy. The age characteristics, the level orexigenic and anorectic hormones, psycho-social characteristics of patients, the initial compensation level of glycemia require further study.

EXPERIMENTAL GASTROENTEROLOGY

89-96 421
Abstract
Faster recovery of the microbiota and evacuatorial functions of the colon was observed after the introduction of autoprobiotics (indigenous strains of Enterococcus faecium) and probiotic (E. faecium L-3), groups A and P, respectively, for the correction of intestinal antibiotic-associated dysbiosis (AAD) in Wistar rats. First control group of animals (C 1) received phosphate buffer (p. b.) after the introduction of antimicrobial agents. Second control group (С2) take water and p. b. The weight of the cecum was greater in rats from group C 1, than in group C 2 and in animals from groups A and P. The amplitude of spontaneous contractions of rats colon segment (studied by device for work with isolated organs) of rats from group C 1 was less than that from other animals, but completely recovered only in group P. Direct effect of butyric acid on the colon segment led to the changes similar for the effect of E. faecium L-3 in vivo. The more rapid recovery of motility in the group of P, correlated with the increased amount of Faecalibacterium sp. (which produce butyrate) content in the composition of the intestinal microbiota.
97-100 233
Abstract
Purpose of the study. To study the effect of prolonged exposure to low-frequency acoustic fluctuations on the morphofunctional state of the liver. Materials and methods. The experiments were performed on 48 white male rats. Three experimental groups of animals were subjected to a daily one-hour noise impact in the low-frequency range with a sound pressure level of 110 dB according to the schedule: 5 days a week with two-day breaks for 1, 3 and 6 weeks. Three control groups were kept in silence. In the blood plasma, aminotransferase, gamma glutamyltranspptedase, alkaline phosphatase, total bilirubin, total protein were studied. Morphological study of liver preparations stained with hematoxylin and eosin was performed under light microscopy. Results. It was found that prolonged exposure to low-frequency acoustic fluctuations was accompanied by cytolytic syndrome and an increase in total blood lipids, without disturbing the protein-synthetic, pigmentary function of the liver. The activity of aminotransferases in animal experimental groups was 20-21 % (p≤0.5) higher than the control ones after the first week of exposure to low-frequency acoustic fluctuations. An increase in the duration of the action of LFN did not lead to an increase in the cytolytic syndrome: after a 6-week exposure, the level of alanineaminotransferase and aspartateaminotransferase was higher than the control ones by 27 % and 25 % (p≤0.5). There was also an isolated increase in alkaline phosphatase after the third week of exposure to low-frequency acoustic fluctuations with a relative increase to 23 % (p≤0.5). Morphological changes in the liver were nonspecific in nature and were represented by focal necrotic changes and a violation of intrahepatic hemodynamics with an extension of the sinusoidal channel and increased venous plethora. Conclusion. The performed studies indicate a non-specific effect of low-frequency acoustic fluctuations on the morphofunctional state of the liver. In this experimental model, reproducing the mode of professional activity, the liver state was characterized by the predominant development of cytolytic syndrome and compensatory morphological shifts, which do not lead to severe violations of liver functions. On the basis of this, it can be assumed that changes in the liver in persons who have been exposed to low-frequency acoustic fluctuations for a long time in professional activity will be subclinical.
101-106 205
Abstract
By the JEM-100S electron microscope, reactive changes in the plasma cells of the mucous membranes digestive organs (antrum stomach, duodenum, colon and ampulla of the rectum) were studied 30 patients with various pathologies (gastroduodenitis, irritable bowel syndrome, Crohn’s disease). At the ultrastructural level, the number of plasma cells in the colon of 6 patients with irritable bowel syndrome was counted and in 3 patients without signs of pathology in all parts of the colon (control). As a result of the study, the following are shown for the first time: ultrastructural changes in plasmacyttes during their functional activity associated with the production of immunoglobulins (antibodies) in response to the effect of antigens; Two ways to separation immunoglobulin complexes from plasma cells; The structure of immunoglobulin complexes freely located in the loose connective tissue of the proper mucous plate. All the patients examined had an increase in the content of active plasmacyttes. The reliable data on an increase in the amount of plasmacytes in the colon mucosa with irritable bowel syndrome have been obta ined.

LECTION

107-114 355
Abstract
The review of the modern researches about a role of Helicobacter pylori (as one of the most famous and widespread bacterial agents) in pathogenesis of a metabolic syndrome is presented in article. However results of scientific works are sometimes contradictory that dictates need of make new further researches for specification of features of influence of Helicobacter pylori in formation of different components of a metabolic syndrome.
115-120 470
Abstract
The literature review argued that probiotic therapy can increase the effectiveness of standard schemes for management of patients with IBS. Personalized therapy autoprobiotics proved its benefits before treatment of industrial strains. Questions autoprobiotics therapy require further study (the use of other strains of autoprobiotics, the possibility of autoprobiotics of cocktails, expanding the range of nosological forms).
121-125 397
Abstract
The continuous study of the role of genetic factors, intestinal microbiota, and immune system in the pathogenesis of inflammatory bowel diseases is due to the ongoing increase of incidences of ulcerative colitis and Crohn’s disease, unknown etiology, and insufficiently studied pathogenesis of these diseases, as well as insufficient efficiency of existing treatment methods. The role of genetic factors determining predisposition to autoimmune reactions leading to chronic inflammation as well as association of genetic factors and particular composition of intestinal microbiota in pathogenesis of inflammatory bowel diseases are discussed recently. Changes of intestinal microbiome are considered to be one of the triggers of autoimmune inflammation. Violation of recognition of bacterial molecular markers by dendritic cells, leading to activation of Th1, Th2 and Th17 lymphocytes adaptive subpopulations is considered to be the key defect predisposing to inflammatory bowel diseases development. Probably it is the peculiarities of the composition of the intestinal microbiota that can be the cause of chronic autoimmune inflammation induction in inflammatory bowel diseases.
126-134 336
Abstract
Patients with metabolic syndrome are in a risk group of trombotic complications of various localisation. Firstly it concerns cardiovascular system thus antiplatelet drugs are widely used in order to prevent that. Another frequent problem is locomotor system diseases and chronic pain of other localisation, which compel patients to take NSADs, but taking both antiplatelet agents and NSAID greatly increase risk of emerging the ulcers and gastrointestinal bleeding. To prevent and cure such problems the proton pomp inhibitors (PPI) have worked well, but some of them, in their turn, may reduce the effect of antiplatelet drugs. Despite many researches the final decision on safety of the combination of antiplatelet drugs (tienopiridins?) and PPI hasn’t taken yet.

REVIEW

135-140 300
Abstract
The development of civilization and technological progress (especially among the inhabitants of developed countries), led to the formation of a special way of life, including a physical activity reduction, usual social stresses, a change in the nutrition (an increase in the proportion of carbohydrates and fats), the total using of antibacterial drugs. The frequent combination of hypertension, lipid metabolism, diabetes mellitus and obesity in patients led to the introduction by G. Reaven by the term “syndrome X”, or “metabolic syndrome” in 1988. Experts of the World Health Organization named this syndrome “pandemic of modern times”. This disease also has a tendency to rejuvenate the population of risk. According to epidemiological studies, the prevalence of the metabolic syndrome among the population varies from 10 to 84 %, depending on the age, sex, nationality and the diagnostic criteria used. The metabolic syndrome has a clinical importance due to the high cardiovascular patients’ risk. The article considers the main pathophysiological and clinical components of the metabolic syndrome, presents the features of the biological models used to study this disease, and the results of experimental studies conducted in recent years that prove the essential role of the state of the intestinal microbiota in the development of the metabolic syndrome.
141-145 223
Abstract
Prevalence of metabolic syndrome (MS) continues to grow currently but the syndrome causes and pathogenesis are unclear. It is legitimate to study this syndrome in terms of psychosomatic medicine. It is required to give attention to risk factors such as addictive behavior (alcohol abuse, smoking, disturbed eating behavior) and disorder of affective spectrum (depressive manifestations) which have potentiative effects in MS formation to generate vicious circle.
146-150 275
Abstract
According to the World Health Organization (WHO) every fourth inhabitant of our planet already has excess body weight or suffers from obesity. According to forecasts of epidemiologists it is supposed that by 2025 40 % of men and 50 % of women will already suffer from obesity. Obesity is regarding clinicians of the whole world as conducting from potentially removable reasons of mortality. As a rule, the metabolic syndrome clinically debuts at people of the most active age in the social plan (35-40 years). In these conditions personal disorders are aggravated comorbid metabolic: depression of physical activity is combined with the progressing changes of the psychological status of patients. Prevalence indicators the comorbid of depressions vary over a wide range from 14,4 to 41,3 %, and gravity of depressive implications correlates with many symptoms of a metabolic syndrome. The combination of metabolic pathology is also disturbing depressive disorder closes peculiar “vicious circle”. The article considers ethiopathogenetic interrelations of metabolic syndrome with depressive disorders and the urgency of pharmacotherapy with antidepressants in the complex treatment of patients with metabolic syndrome.
151-154 851
Abstract
The modern data on epidemiology, etiological factors of functional constipation development are presented in the review. The role of metabolic disorders in chronic constipation development, and also importance of intestinal microbiota in intestine motility disorders appearance at patients with a metabolic syndrome are analyzed.

DISCUSSION

155-160 285
Abstract
Based on the analysis of the literature, long-term research of the author and the staff of the department of 993 patients with gastroesophageal reflux disease, chronic esophagitis, chronic gastritis, peptic ulcer disease, disorders of biliary system, hernia hiatal developed and proposed for discussion the classification of chronic esophagitis with consideration of the etiology and pathogenesis, morphological and clinical features of the disease.

CLINICAL PHARMACOLOGY

161-166 351
Abstract
The article presents modern principles of diagnostics and treatment of candidiasis of the upper digestive tract (oropharynx and esophagus) described the clinical picture and complications of this disease. Metabolic syndrome, occurring with disorders of carbohydrate metabolism - a typical risk factor for candidiasis. Standard for diagnosis is the detection of filamentous forms (pseudomycelium) of micromycetes of the genus Candida a morphological study of biomaterials mucous membrane. Culture of biopsy specimens with identification of the species of the pathogen becomes mandatory for maintaining tolerance to standard treatment or recurrent candidiasis. The drug of choice when treating candidiasis is fluconazole, however, in some cases, necessary alternative antimycotic drugs. Feature of the treatment of candidiasis in patients with the metabolic syndrome is an increased risk of drug damage to the cookies, especially against the background of steatosis and steatohepatitis, which is characteristic for this category of patients.
167-183 546
Abstract
The purpose of review: to determine clinical and pharmacological approaches to the choice of gastroparesis therapy. Basic provisions. Prokinetics are medicines that accelerate the movement of content along the digestive tract, affecting dopamine, serotonin, acetylcholine, motilin, cholecystokinin and other receptors. Fixed combination of the proton pump inhibitor and prokinetic proved effective in the therapy of stomach functional disorders. In clinical study on the efficacy and safety of the combination of omeprazole and domperidone sustained release in patients with gastroesophageal reflux disease of mild or moderate severity, according to NNT criteria, it was shown that the drug containing 20 mg omeprazole and 30 mg of domperidone sustained release is very good preparation for the full cupping reflux symptoms (NNT = 2.5), and a good drug for the elimination of esophagitis (NNT = 3,7). It is also shown that this combination is well tolerated (very good and good tolerability at 100 %) and is safe (the frequency of adverse mild degree reactions of 6.7 %, 95 % CI = 0,8-22,1). Conclusion. The use of a combination of omeprazole and domperidone sustained release in gastroparesis is pathogenetically justified. The clinical efficacy and safety of a formulation containing a fixed combination of 20 mg of omeprazole and 30 mg of domperidone sustained release in the treatment of gastroparesis are high.

CLINICAL CASE

184-191 488
Abstract
Inflammatory bowel diseases (IBD) are an actual problem of reproductive medicine, and the care of women in childbearing age suffering from IBD has a high medical and social significance. The main peak of incidence of IBD falls on the age of 20-40 years, when childbirth is planned. Questions that need to be addressed and discussed in patients with IBD: is it possible for the normal course of pregnancy with IBD, how does the IBD affect pregnancy, what medications are contraindicated and others. The article presents and discusses theoretical aspects and practical issues related to pregnancy management, IBD therapy in the period of preparation to pregnancy, during pregnancy, in the postpartum period, the effectiveness and safety of pharmacotherapy in patients of this category is discussed.
192-199 273
Abstract
In article we presented dynamic analysis of liver function and structure in children with Wilson’s disease based on the author’s system for determination the degree of liver function and structure disorder that was created on the basis of the International Classification of Functioning using the statistical analysis of the digital expression of a set of changes in indices reflecting major violations of liver function and structures and severity of portal hypertension. We found that that the first examination in children with Wilson’s disease in 96,6 % of cases showed a decrease in the liver function by 25,0-95,0 % corresponding to a moderate and severe degree of impairment, whereas after 6 and 12 months of treatment, similar changes registered significantly less often - in 87,5 %, and 86,6 % of patients, respectively. Moderate and severe disruption of liver structure and severity of portal hypertension according to the offered system at the first hospitalization was noted at 77,8 % of children with cirrhosis in the outcome of Wilson’s disease, after 6 months of therapy in 50,0 % of patients, and after 12 months - only in 36,0 % of children. The ROC analysis of the proposed scoring system established its moderate significance in determining indications for liver transplantation in terms of the extent of liver function impairment and high significance in determining the extent of liver structure disorder and the severity of portal hypertension in children with Wilson’s disease. Thus, the proposed scoring systems for assessing the degree of impairment of the function and structure of the liver can be an objective criterion for assessing the severity of liver damage, controlling its changes in dynamics, assessing the effectiveness of the therapy and indications for liver transplantation. The proposed method can be used to create of “the patient’s model” with Wilson’s disease, followed by the development of standards and protocols for the provision of medical care, and also used in the medical and social expertise of children to determine the degree of disruption of the structure and function of the liver when determining the category of “disabled child”.


ISSN 1682-8658 (Print)