[The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion].

AIM: To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP). MATERIALS AND METHODS: The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase - 504 (quartile 258, 708), sucrase - 43 (quartile 25, 58), lactase - 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks. RESULTS: In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase - up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases - up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase - up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue × min (quartile 10, 20, р<0.092). CONCLUSION: The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.

[Zonulin and I-FABP are markers of enterocyte damage in celiac disease].

AIM: To evaluate the level of serum I-FABP (Fatty-Acid-Binding Protein a protein that binds fatty acids) and fecal zonulin as markers of the permeability of the mucous membrane of the small intestine in celiac patients. MATERIALS AND METHODS: A total of 151 celiac patients (25 men and 126 women) were examined. The median age was 42 years. Group I included 58 patients with newly diagnosed celiac disease; in group 2 38 patients, knowingly or unknowingly violating the gluten-free diet; group 3 consisted of 55 patients strictly observing gluten-free diet. The control group consisted of 20 healthy volunteers: 4 men and 16 women. All patients underwent esophagogastroduodenoscopy by biopsy of the mucous membrane of the small intestine and assessment of duodenobioptates according to Marsh. In the blood serum, the level of antibodies to tissue transglutaminase IgA and IgG was determined by the enzyme-linked immunosorbent assay using kits manufactured by Orgentec Diagnostics GmbH (Germany), the concentration of I-FABP in blood serum was determined using Hycult Biotech kits (Netherlands). The content of zonulin in feces was investigated by enzyme-linked immunosorbent assay using kits from Immundiagnostik AG (Germany). Statistical analysis was performed using the Statistica 13.3 software (StatSoft Inc., USA). RESULTS: There was a significant increase in the level of antibodies to tissue transglutaminase IgA [120.0 (41.1200)] IU/ml and IgG [31.4 (5.578.9)] IU/ml in patients of group 1 compared with group 2 [IgA 9.1 (2.987.6)] and IgG [3.8 (2.219.7)] IU/ml and group 3 [IgA 1.6 (1.03.2)] and IgG [2.2 (1.152.53)] (p0.01). The level of I-FABP in blood serum in patients of group 1 averaged 2045 pg/ml, in patients in group 2 1406 pg/ml, in patients in group 3 1000 pg/ml. All patients showed a significant increase in the mean I-FABP values compared to controls (1, 2 and control p0.01, 3 and control p=0.016). In patients with Marsh grade III AC atrophy, the I-FABP level depended on the degree of damage to the mucosa and significantly differed from the control: March IIIA (median: 1310 pg/ml, interquartile range: 12121461 pg/ml), March IIIB (median: 2090 pg/ml, interquartile range: 18122322 pg/ml) as well as Marsh IIIC (median: 2058 pg/ml, interquartile range 18582678 pg/ml). The concentration of zonulin in feces in patients of group 1 averaged 111.6 pg/mg, in patients of group 2 90.5 pg/mg. In patients of group 3 50 IU/ml. The concentration of zonulin in feces increased as the degree of mucosa atrophy increased (r=0.585, p0.01). However, despite the fact that both of these markers may indicate impaired permeability, each of them indicates damage to a certain level of the intestinal barrier, which is not always associated with the degree of mucosa atrophy. CONCLUSION: Determination of serum I-FABP and fecal zonulin levels in celiac patients allows for the assessment of intestinal permeability and can serve as non-invasive markers for monitoring ongoing structural changes in the mucosa without the need for endoscopy.

[Enteropathy with impaired membrane digestion and the prospects for cytoprotective therapy].

The article describes enteropathy with impaired membrane digestion (EIMD) as a new nosological form. The main clinical manifestation of EIMD is the poor tolerance of food products, in particular carbohydrates and a decrease in the activity of membrane enzymes, in particular, carbohydrates, in the mucous membrane of the small intestine. The cause of the disease can be acute intestinal infections, viruses, drugs and other agents that damage the small intestine. The pathophysiology, clinical picture and diagnosis of EIMD are described. The basis of therapy is rebamipide, which has the ability to reduce the symptoms of carbohydrate intolerance and increase the activity of disaccharidases.

[Screening for celiac disease among patients of the gastroenterological profile].

AIM: To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection. MATERIALS AND METHODS: 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males 24.9%; 1019 females 75.1%). The average age was 40.415.4 (1886 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA). RESULTS: In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA in 54 (4.4%), and anti-TTG IgG in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron 33%, hypoproteinemia 12.6%, hypoalbuminemia 12%, hypokalemia 5.48%, hypocalcemia 21.9%. An increase in the level of AST 14.5%, ALT 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities. CONCLUSION: The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

[COVID-19 and the small intestine].

The SARS-CoV-2 virus enters the body through the angiotensin-converting enzyme 2 (ACE-2), which is the entry point of the virus into the cell. The most dense fabric of ACE-2 is the lungs. The small intestine also contains large amounts of ACE-2 in the enterocyte membrane and is often involved in this process. Intestinal symptoms can appear at different stages of the disease. The review describes the mechanisms of interaction of SARS-CoV-2 with enterocytes, the fecal-oral route of infection, diagnosis and treatment of COVID-19 with intestinal symptoms.

[Chronic intestinal pseudoobstruction: difficulties in diagnosis and treatment. Case report].

The article presents a clinical case of a 23-year-old patient with an extremely severe congenital form of chronic intestinal pseudoobstruction coupled with a neuromyopathy,colon malrotation, malabsorption, bacterial overgrowth syndrome, cholelithiasis and gastrostasis, which excluded bowel transplantation. Long-term treatment in the intensive care unit with combined, mainly parenteral nutrition for 6 months, using antibiotics, prokinetics, intestinal decompression allowed to achieve partial stabilization of the patients condition and transfer to home treatment with the continuation of adequate complex therapy.

[Celiac crisis in patients with celiac disease. Case report].

Celiac crisis (CC) is a rare life-threatening course of celiac disease, observed mainly in children. In adults, CK can be the first manifestation of the disease and, very rarely, a relapse that occurs in patients who do not follow the gluten-free diet (AGD). Triggers can be stress, surgery, childbirth, etc. A clinical observation of CC developed in a 49-year-old patient with previously established latent celiac disease with subtotal villous atrophy, stage Marsh III C is presented. The patient did not comply with AHD. After severe angina, she developed anorexia, diarrhea, emaciation, coagulopathy, bilateral pulmonary embolism, infarction pneumonia, and enterogenic sepsis. As a result of intensive therapy with prednisolone, Fraxiparine, antibiotics, fresh frozen plasma and strict adherence to hypertension, remission of the disease was achieved.

[Chronic intestinal pseudo-obstruction].

Chronic intestinal pseudo-obstruction a rare violation of the motor skills of the gastrointestinal complex, similar to mechanical obstruction, but without a mechanical obstacle. The development of chronic intestinal pseudo-obstruction is caused by a disturbance on the part of the smooth muscles and the nervous system of the gastrointestinal system. Common symptoms include constipation, abdominal pain, nausea, vomiting, bloating. Violation of peristalsis leads to food stagnation in the hinges of the small intestine, their dilation, the development of bacterial insemination syndrome. Eating disorders, bacterial contamination syndrome (CDDs) lead to impaired suction syndrome, cahexia. Treatment is aimed at providing adequate nutrition, the use of drugs that activate motor skills, suppress the growth of microbes in the small intestine, the implementation of intestinal decompression. Surgical treatment: resection of the affected segment of the gut. In the refractory course of the disease intestinal transplantation.

Rebamipide increases the disaccharidases activity in patients with enteropathy with impaired membrane digestion. Pilot study.

AIM: To evaluate the effectiveness of enteroprotector Rebamipide in the treatment of enteropathy with impaired membrane digestion (EIMD). MATERIALS AND METHODS: We examined 102 patients aged 18 to 50 years (41 men and 61 women) with clinical signs of irritable bowel syndrome (n=65), functional diarrhea (n=33), and functional constipation (n=4) according to Rome IV criteria (2016). The activities of glucoamylase (GA), maltase, sucrase and lactase were determined by Dahlquist-Trinder method in duodenal biopsies obtained during esophagogastroduodenoscopy. The control group consisted of 20 healthy people aged 23-47. They showed following average enzyme activity: lactase - 42±13 ng glucose on 1 mg of tissue per minute, GA - 509±176, maltase - 1735±446, sucrase - 136±35 ng glucose on 1 mg of tissue per minute. These numbers were taken as the norm. RESULTS: The activity of the disaccharidases was reduced in 89.2% out of 102 patients, and they were diagnosed with EIMD. Thirteen patients with EIMD were recommended to maintain the FODMAP diet and take enteroprotector Rebamipide 100 mg 3 times a day for 12 weeks. After 3 months 11 patients reported decreased or no flatulence, abdominal pain, stool disorder; 2 patients reported no change. The activity of GA increased to an average of 149±82 (by 78%, p=0.016), maltase - to 864±472 (by 131%, p=0.0019), sucrase - 63±35 (by 95%, p=0.0041) and lactase - 10±8 ng glucose on 1 mg of tissue per minute. The activity of lactase did not change. CONCLUSION: We discovered a previously unknown phenomenon of the disaccharidases activity increase in duodenal mucosa and improved carbohydrates tolerance in the patients with EIMD taking Rebamipide in the dose 300 mg/day for 12 weeks.

Celiac disease associated with ulcerative colitis.

The article provides clinical observation of a patient who was diagnosed with celiac disease when he was 52 years (Marsh stage IIIB). Following gluten-free diet (GFD) clinical remission and restoration of small intestinal mucosa (SIM) structure occurred, however in 6 years ulcerative colitis developed and an impairment of SIM morphological structure was identified (Marsh stage IIIA). Ulcerative colitis and celiac disease remission is supported by GFD, anti-cytokine therapy (adalimumab) in combination with mesalazine.

The role of small intestine in pathogenesis of common variable immune deficiency.

AbstractThe article presents the results of examination of 32 patients with common variable immune deficiency (barn) with involvement in the patho- logical process of the digestive system. The features of the clinical picture, the content of immunoglobulins in the blood serum, morphological structure of the mucosa and small intestine as well as treatment. Special attention is paid to the small intestine in the pathogenesis of the barn.

Reproductive disorders, osteoporosis and secondary hyperparathyroidism with celiac disease.

A clinical observation of a patient with celiac disease, aged 23, with severe form of osteoporosis, accompanied by atraumatic fractures bones, lameness, late onset of menstruation and pathology of pregnancy is described. It is emphasized that only a timely diagnosis celiac disease and timely prescribed treatment make it possible to avoid severe complications.

[Disaccharidase deficiency and functional bowel diseases]. / Disakharidaznaia nedostatochnost' i funktsional'nye zabolevaniia kishechnika.

AIM: To elucidate the role of intestinal carbohydrases (glucoamylase, maltase, sucrose, and lactase) in the etiology and pathogenesis of functional bowel diseases (FBD). SUBJECTS AND METHODS: 74 patients (36 men and 38 women) aged 18 to 50 years with FBD were examined. According to Rome IV criteria (2016), there was diarrhea-predominant irritable bowel syndrome (IBS) in 21 patients, functional diarrhea (FD) in 33, constipation-predominant IBS in 6, functional constipation (FC) in 4, and mixed IBS in 10. The activity of carbohydrases in the small intestine mucosa (SIM) was investigated by the Dahlquist method modified by Trinder in the duodenal biopsy specimens obtained during esophagogastroduodenoscopy. RESULTS: Lactase deficiency was identified in 87.8% of the patients; maltase deficiency in 48.6%; sucrose deficiency in 51.3%; and glucoamylase deficiency in 85.1%. The activity of all the investigated enzymes was reduced in 23 (31.1%) patients with FBD; deficiency of 1-3 carbohydrases was found in 47 (63.5%). Normal enzymatic activity was established in 4 (5.4%) patients. CONCLUSION: In the majority of patients with FBD, the intestinal symptoms are caused by the decreased activity of SIM carbohydrases. Therefore, disaccharidase deficiency associated with an established damaging agent (nonsteroidal anti-inflammatory drugs, antibiotics, acute intestinal infections, etc.) should be considered to be a more precise diagnosis.

[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.

[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%.

[Seronegative celiac disease: A case report].

The paper describes a rare case of celiac disease in the absence of serum anti-tissue transglutaminase (anti-tTG) antibodies. A 51-year-old patient has been suffering from diarrheas for 20 years. He has lost 15 kg gradually; weakness progressed; muscle cramps, leg edemas, and signs of dynamic pseudoobstruction appeared. Morphological examination revealed small intestinal mucosal (SIM) villous atrophy (Marsh IIIC stage). IgA anti-tTG and IgG anti-tTG antibodies were 0.086 and 0.178, respectively. The patient was prescribed a gluten-free diet, water electrolyte solutions to correct metabolic disturbances, and prednisolone. During a control examination after 6 months, the patient had no complaints and gained 22 kg, and the SIM villus height was increased. The specific feature of the case is specific negative serological tests for celiac disease.

[Safety of mesenchymal stromal cell therapy for inflammatory bowel diseases: results of a 5-year follow-up].

AIM: To compare the safety of therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) who have received combination anti-inflammatory therapy using bone marrow mesenchymal stromal cells (MSC) and standard therapy with 5-aminosalicylic acid, glucocorticosteroids, and immunosuppressive agents. SUBJECTS AND METHODS: Unfavorable consequences were analyzed in 103 patients (56 with UC and 47 with CD) with inflammatory bowel disease (IBD) after MSC administration. The findings were compared with data obtained in 208 patients with UC and CD on standard anti-inflammatory therapy. All the patients were similar in demographic parameters, the duration of disease, the extent of intestinal injury, the nature of a course, the type and degree of disease. The analyzed groups did not include patients who had received therapy with anti-TNF-α drugs. The safety of therapy was evaluated from the presence of complications occurring during the follow-up. RESULTS: By analyzing the unfavorable consequences in 103 patients with IBD and comparing them with treatment results in 208 patients with UC and CD on standard anti-inflammatory therapy, the authors revealed no differences in the development of acute posttransfusion reactions, infectious complications, exacerbations of chronic inflammatory diseases, severe infectious complications, malignant transformation, and fatal cases in patients with UC and CD, except for those with transient fever. CONCLUSION: The results of this study demonstrate that the innovative method of cell therapy is clinically safe.

[Significance of a method for determination of deamidated gliadin peptide in the diagnosis of celiac disease].

AIM: To define the value of a new enzyme immunoassay in determining the level of anti-deamidated gliadin peptide (DGP) antibodies (Abs) in the diagnosis of celiac disease. SUBJECTS AND METHODS: One hundred and twenty-four patients treated at the Department of Intestinal Pathology, Central Research Institute of Gastroenterology, were examined. Enzyme-linked immunosorbent assay (ELISA) was employed to determine Abs to tissue transglutaminase (tTG) and DGP of the IgA and IgG classes in the sera of all the patients. The diagnosis of celiac disease was verified by the histological examination of small bowel mucosa biopsy specimens. RESULTS: The examinees were divided into 3 groups: 1) 27 patients first diagnosed with celiac disease; 2) 40 patients keeping a gluten-free diet (GFD); 3) 57 patients with other gastrointestinal diseases (a comparison group). In the patients first diagnosed with celiac disease, the detection rate of elevated titers of anti-tTG and anti-DGP Abs in the IgA class was equal and constituted 92.5%; that in the IgG class was 96.2 and 55.5%, respectively. The comparison group showed an increase in the DGP levels in the IgA and IgG classes in 4 (7%) patients and a rise in tTG concentrations in the IgA and IgG classes was seen in only 2 (3.5%) patients. CONCLUSION: In the patents first diagnosed with celiac disease, the detection rate of elevated levels of anti-DGP Abs in the IgA and IgG classes is 92.5 and 96.2%, respectively, and significantly indifferent from that of IgA and IgG anti-tTG Abs. The patients keeping GFD displayed a reduction in anti-DGP Abs. The high detection rate of IgA anti-DGP Abs in the patients first diagnosed with celiac disease allows this method to be recommended for immunological diagnosis of this disease in adults.

[Reproductive disorders in women with celiac disease. Effect of the etiotropic therapy].

UNLABELLED: Violation of reproductive function in patients with celiac disease can manifest as delayed puberty, infertility, amenorrhea, premature menopause, spontaneous abortion, low birth weight. The aim of the study was to establish the frequency and nature of reproductive function violation in patients with CD in the Russian Federation. MATERIALS AND METHODS: The study included 132 women (average age 38,5 +/- 1,17 years) with CD observed in CSRIG in the period from 2000 to 2010. Comparison group consisted 105 women (average age 38,7 +/- 1,6 years) with predominantly functional bowel disorders (irritable bowel syndrome, functional constipation, functional bloating, inert colon). Were took into account information regarding obstetric history, physical and laboratory signs of malabsorption syndrome (MS) study of antibodies to alpha-gliadin immunoglobulin (IG) A class (AGA) and tissue transglutaminase (AtTG). RESULTS: The average age of onset of menses was 14,3 +/- 1,4 years, and in the control group - 13,0 +/- 1,3 years (p > 0.05), half of patients with C (43.9%) had menstruation begun at age 15 years and older, while 7.6% of the women--aged 17 and older. In the comparison group menses beginning after 15 years was only at 13.3% of women. In 61.3% of patients with CD was irregular menstrual cycle while in the comparison group such violations were noted in 13.3% (p < 0.001). Prolonged periods of amenorrhea we observed in women with newly diagnosed GC 3 times more likely than the comparison group: 43.9% and 11.4% respectively (p < 0.01). They also had nearly 3 times more likely to occur spontaneous miscarriage: at 46.9% and 14.3% respectively (p < 0.01). The frequency of dead children birth was about the same: 2.3% and 1.9% respectively (p > 0.05). The frequency of reproductive disorders increased with the growth of the severity of MS. In 43% of women after 6-8 months of strict adherence to a gluten-free diet (GFD) had disappeared amenorrhea and there were regular menses. Three women of childbearing age, strictly abided the GFD and had a history of repeated spontaneous abortion during the year managed to get pregnant and give birth to healthy full-term baby. CONCLUSIONS: Reproductive disorders in women with celiac disease are significantly more likely than at women with functional bowel disease. One of the reasons of reproductive disorders in patients with CD can be malabsorption of necessary nutrients in the small intestine. The presence of reproductive disorders should be considered as a risk factor for celiac disease, so these women should be screened for celiac disease.