[Frequency and risk factors for thromboembolic complications in patients with inflammatory bowel diseases].

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic immune inflammation of the mucous membrane and/or the thickness of the intestinal wall, and are also accompanied by disorders of the blood clotting system and the development of a hypercoagulation state. AIM: To identify the frequency of thromboembolic complications (TEC) in IBD patients and to determine the influence of acquired and inherited hypercoagulation factors that contribute to the development of TEС. MATERIALS AND METHODS: The clinical status of 1,238 IBD patients who were treated in 2019 was evaluated. Of these, 748 patients with ulcerative colitis (UC) and 490 patients with Crohn's disease (CD). Among UC patients, there were 369 (49.3%) men and 379 (50.7%) women. In 10.1% of patients with UC, there were clinically significant feasibility studies. There were 227 (46.3%) men and 263 (53.7%) women among patients with CD; 7.3% of patients with CD had clinically significant feasibility studies. RESULTS: In general 112 (9.0%) of 1,238 IBD patients had clinically significant feasibility studies. Among patients with UC (n=748), 76 (10.2%) showed clinically significant feasibility studies. Among patients with CD (n=490), 36 (7.3%) had a feasibility study. Of 112 IBD patients with clinically significant TEC, 45 (40.2%) had genetic polymorphisms that increase affinity for fibrinogen, increase platelet aggregation, and contribute to a decrease in the activity of folate cycle enzymes, including methylenetetrahydrofolate reductase, which may be manifested by a moderate increase in homocysteine levels. Of the 45 IBD patients with clinically significant TEC due to inherited factors, 30 (66.6%) patients had UC, 15 (33.7%) patients had CD (hazard ratio 1.038, 95% confidence interval 0.7461.444; 2=0.049; p=0.83921); 67 (59.8%) patients with IBD who had clinically significant TEC did not have genetic polymorphisms leading to hypercoagulation. CONCLUSION: Based on the analysis, we can conclude that such risk factors for the development of TEC as the status of a smoker, long bed rest, taking hormonal contraceptives, varicose veins of the lower extremities, high activity of the disease, glucocorticoids therapy, the extent of intestinal damage in patients with IBD, genetic factors, should be taken into account by gastroenterologists in the treatment of patients with UC and CD. The hereditary factor of hypercoagulation equally affects the development of TEC, both in patients with UC and CD.

[Loss of response and frequency of adverse events in patients with ulcerative colitis and Crohn's disease when switching from the original infliximab to its biosimilars].

AIM: To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohn's disease (CD), treated with original medicine infliximab (IFX) "Remicaide" and its biosimilars. MATERIALS AND METHODS: We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar. RESULTS: Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar ­ 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p>0.05). CONCLUSION: Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events.

[Elaboration of immune stimulating lipid-saponin subunit antigen carrier based on glycolipid monogalactosyldiacylglycerol from sea macrophytes and triterpene glycosides from Cucumaria japonica].

The ability of some triterpene glycosides of holothurians: holotoxin A1 from Apostichopus japonicus and a mixture of monosulphated triterpene glycosides from Cucumaria japonica called cucumarioside (CD) to form supramolecular complexes with cholesterol (Chol) and monogalactosyldiacylglycerol (MGDG) or phosphatidylcholine (PC) was studied. A transmission electron microscopy method was used to observe supramolecular lipid-saponin complexes formed by holotoxin A1 and CD with cholesterol in the presence of membrane lipids. The observed supramolecular complexes are tubular nanoparticles with a length of 100-300 nm, an external diameter of 10-16 nm and an internal diameter of 2-6 nm. The formation of tubular nanoparticles was more effective in the presence of MGDG than with PC. Nanoparticles forming in the presence of MGDG are shaped as a tubule, have a constant diameter and a strongly pronounced internal channel. In contrast, PC has no such properties; this lipid is unable to fully integrate in tubular nanoparticles. Based on electron-microscopy data the range of weight ratio of MGDG-Chol-CD was determined as a 1-10:2:3 that provided most effective formation of tubular nanoparticles. Different methods of incorporation of model antigens in complex MGDG-Chol-CD were studied. Influenza haemagglutinin and neuraminidase from commercial vaccine "Influvac" and pore forming protein YompF from Yersinia pseudotuberculosis were used as model antigens. From 54 to 72% of protein of "Influvac" vaccine and 88-92% of YompF were incorporated in supramolecular complexes depending on the method of incorporation. The loss of functional activity of haemagglutinin of vaccine "Influvac" was the result of applying ultrasonic disintegration for incorporation of this protein in complex MGDG-Chol-CD. YompF incorporation in MGDG-Chol-CD complex led to the increased diameter of tubular particles, in the same time incorporation of vaccine "Influvac" antigens produced the "cap" formation at the end of tubules. The possibility of a described supramolecular complex MGDG-Chol-CD to be a carrier for subunit bacterial and viral antigens is shown.

[Clinical variants post hemicolectomy syndrome].

UNLABELLED: Hemicolectomy (hemicolectomia) - the surgical removal of about half of colon, left or right half of the colon. The reasons, which can lead to surgery hemicolectomy are tumors of the colon, colon polyps, complicated diverticular disease, inflammatory bowel disease (Crohn's disease or ulcerative colitis). Intestine dysbiosis develops as a result of effects on the multiple risk factors (surgery, antibiotic therapy, reduced immune status, presence of inflammatory processes, stress, etc.) in patients with various diseases of the gastrointestinal tract. The aim of our work was to study peculiarities of clinical manifestations in patients after hemicolectomy depending on the location of colon resection. RESULTS: We examined 365 patients who underwent surgery hemicolectomy. There were women and men the ages of 30 to 85 years, of which 151 patients after right-sided hemicolectomy and 214 patients after left-sided hemicolectomy. Right- sided post hemicolectomic syndrome clinically manifests itself as pain syndrome in parumbilpical area in 62.9% of patients, flatulence (68.9%), constipation (7.9%), diarrhea (3.9%), apetite decrease (16.5%) patients. Left- sided post hemicolectomic syndrome manifests asa pain in the right upper quadrant in 64.0% of patients with symptoms of bloating (81.8%), constipation (64.1%), diarrhea (31.3%) and appetite decrease (32.2%). Right- sided post hemicolectomic syndrome prognostically is more favorable than the left-sided post hemicolectomic syndrome.

[Role of intestinal microbiocenosis and endotoxemia in the development of accompanying diseases and functional status of liver in patients after hemicolectomy].

UNLABELLED: The state of dynamic equilibrium between the host micro-organisms, it settled, and the environment called "eubiosis" in which human health is at an optimum level. The development of the gastrointestinal tract requiring surgical intervention was determined not only by the degree of pathological process activity, endotoxemia level dysbiotic bowel disturbances, but also disturbances in the patient's immune system. The aim of our study was to examine the influence of gut microbiota and endotoxemia on the development of comorbidity and functional status of the liver in patients after hemicolectomy. Were studied a total of 365 patients after undergoing surgery hemicolectomy (right-and left-handed). RESULTS: violations in microbiocenosis intestine, which is most frequently observed in patients after left-sided hemicolectomy, leads to the development of endotoxemia, its toxic effects on the liver, were realized in the development of liver steatosis and steatohepatitis. Thus, the left-sided hemicolectomy increases the risk of steatohepatitis in the late period, which may affect the core functions of the liver and the development of other metabolic disorders. Hyperendotoxemia that was developed in patients as a result of violations of microbiota after left-sided hemicolectomy, increases the risk of developing diseases pancreat-duodenal zone and cardiovascular changes. Certainly, the pathogenesis of these diseases was not determined by left-sided hemicolectomy, but her conduct contributed to the development and progression of these diseases.

[Protein that binds fatty acids (I-FABP)--a new perspective evidence for injury of the small intestine].

The article presents literature data on the diagnostic value of the new indicator of the epithelial damage of the small intestine--I-FABP (protein binding fatty acids) and the results of our investigation of this indicator in 63 patients with functional bowel disease, and 20--the control group presented patients with erosive gastritis. Also presented diagnostic value of this indicator and defined the boundaries of normal values for this indicator.

[Quality of life of patients with hyperendotoxemia after hemicolectomy].

UNLABELLED: The concept of "health" is defined by the World Health Organization (WHO) as a state of complete physical, mental and social well-being and not merely the absence of disease. Currently, one of the most widely used questionnaires of general type is the SF-36 Health Status Survey, proposed the Boston Institute for Health and created on the basis of other already existing tools for assessing QOL. Translated into Russian and testing methodology was conducted by the Institute of clinical and pharmacological studies (St. Petersburg). Any surgical intervention, in particular the removal of part of the colon can lead to a restriction of all aspects (physical, mental and social) of a normal human life. The goal of treatment of any disease should be considered as improving the quality of life of the patient on a background of positive clinical dynamics, assessing the quality of life indicators, which depend on many external and internal factors. AIM: to study the quality of life of patients after hemicolectomy, depending on the type of colon resection and the level of endotoxemia. RESULTS: Analysis of quality of life of patients after undergoing surgery--hemicolectomy carried out using questionnaire SF-36 indicates a decline in general condition and mental health in patients after left-sided hemicolectomy. The study showed a close pathogenetic relationship between endotoxemia and decreased quality of life of patients after hemicolectomy.

[Characteristics of the intestinal dysbiosis and endotoxemia after hemicolectomy].

UNLABELLED: The normal intestinal microflora important for maintaining the optimum level of metabolic processes in the human body, the immune system, as well as to create a high colonization resistance against the pathogenic microbes. With aging, changes microbiocaenosis intestine, resulting in an increase in the total number of microbes in the gut and profound changes in the functional properties of microorganisms. Under physiological conditions, the main reservoir of endotoxin in the human body is the intestine. Endotoxins, penetrating through the intestinal mucosa, arrive first at the local (intestinal), and then through the portal system in the liver, are able to initiate it various lesions, including fatty degeneration of the parenchyma. OBJECTIVE: Based on clinical and laboratory studies to determine changes in gut microbiota and the level of endotoxemia in elderly patients in the remote period after undergoing surgery--hemicolectomy. RESULTS OF THE STUDY: Metabolic activity of microflora in the colon according to the concentrations of short chain fatty acids in the feces of elderly patients in distant periods after hemicolectomy revealed in various degrees of violation of the microbiota of the colon. Violation of gut microbiota leads to endotoxaemia, which has a toxic effect on liver function, level of endotoxin and protein that binds to endotoxin was significantly higher in patients who underwent left-sided hemicolectomy.

[Pharmacoeconomic analysis of treatment of certain diseases of the digestive system].

The article provides data of the pharmacoeconomic analysis (cost/effectiveness) of treatment of peptic ulcer, ulcerative colitis, Crohn's disease, gastroesophageal reflux disease, biliary sludge and cholelithiasis. It was shown that the most appropriate treatment scheme is one that characterized by lower costs per unit of effectiveness. Analysis of cost/effectiveness can give an economic assessment of clinical efficacy, compare alternative treatments and help to choose the method by which the efficiency increases faster than the level of costs.

[Immunostimulatory characteristics of a novel carrier on the basis of cucumarioside A2-2 and monogalactosyldiacylgycerol].

A novel antigen carrier has been formulated on the basis of a cucumarioside-A2-2 triterpene glycoside (CD) complex with cholesterol and monogalactosyldiacylglycerol from Ahnfeltia tobuchiensis (MGDG(At)) and Ulva fenestrate (MGDG(Uf)). Morphological and immunostimulative characteristics of the carrier were studied. Electron microscopy experiments demonstrated the formation of homogeneous tubular structures in a mixture of CD, cholesterol, and MGDG in molar ratio of 1:2:3. In animals immunized by the carrier bearing pore forming protein monomer of pseudotuberculosis agent CD and MGDG synergically affected synthesis of specific antibodies, interleukin-2, and gamma-interferon and delayed hypersensitivity reaction when compared to Freund's complete adjuvant or to immunostimulatory complexes between Quillaja saponaria saponins and phosphatidylcholine from egg yolk. The immunostimulatory effect depends upon the composition of polyunsaturated fatty acids of MGDG. The new tubular adjuvant carrier is a competitive adjuvant, as it includes CD obtained from far-eastern sea cucumber commercial species Cucumaria japonica, and MGDG from seaweed.

[Elaboration of new adjuvant lipid-saponin complex and its use at experimental immunization by bacterial antigen].

Results of experiments on modification of immunostimulating complexes (ISCOM's) matrix by the replacement of the phospholipid for the glycolipid (monogalactosyldiacylglycerol) from sea macrophytes, and saponin QuillA to triterpene glycoside of cucumarioside A2-2 from Cucumaria japonica are shown. The resultant complexes include the morphological structures of two types: ISCOM-like structures with the characteristic morphology and sizes and also the tubular structures with diameter of approximately 40 nm and length of 150-400 nm. We have named these structures as TI-complexes. These TI-complexes exhibit considerably lower toxicity than ISCOM. They may include an amphiphilic protein antigen and provide immunoadjuvant effect during experimental vaccination. Under conditions of experimental immunization of mice by a weak immunogen--(subunit membrane pore protein from Y. pseudotuberculosis), TI-complexes with antigen provided stronger humoral immune response to antigen than the complexes of porin with classical ISCOM, liposomes and Freund's adjuvant. Thus, it's shown the prospect of the use of TI-complexes as a new type of adjuvant carriers for antigens.

[Hepatoprotective properties of balm Herbamarin and hydrolysates from marine invertebrates in toxic hepatitis and ethanol intoxication].

Protective properties of a syrup balm "Herbamarin" and food hydrolysates of scallop, octopus and crab were investigated using experimental toxic hepatitis and ethanol intoxication. Preventive administration of the balm and hydrolysates to animals subjected to an intoxications by 40% alcohol and CCl4 normalized clinical-diagnostic parameters of liver and blood plasma of experimental animals.

[Physicochemical and immune properties of glycoglycerolipids from Laminaria japonica within immunostimulating complexes (ISCOMs)]. / Fiziko-khimicheskie i immunologicheskie svoistva glikoglitserolipidov iz Laminaria japonica v sostave immunostimuliruiushchikh kompleksov (ISCOM).

Certain physicochemical properties of glycoglycerolipids from marine alga Laminaria japonica (monogalactosyl diacylglycerol, digalactosyl diacylglycerol, and sulfoquinovosyl diacylglycerol) and their ability to be incorporated into immunostimulating complexes (ISCOMs) used for presentation of microbial and tumor antigens in vesicular form were comparatively described. These glycolipids proved to considerably differ by fatty acid composition, degree of unsaturation, and phase transition temperature. Possible production of modified ISCOMs through incorporation of these glycolipids into the vesicle instead of the glycolipid component was demonstrated. Preliminary data demonstrated no significant increase in immune response to Yersinia pseudotuberculosis porin within the modified (with monogalactosyl diacylglycerol) and classical (with phosphatidylcholine) ISCOMs as compared to individual porin.

[Celecoxib and Tramadol as an alternative osteoarthrosis therapy in patients with NSAID gastropathy]. / Tselikoksib i tramadol kak al'ternativnaiia terapiia osteoartroza u bol'nykh s NPVP-gastropatiei.

OBJECTIVE: To determine whether it is possible to continue the anti-inflammatory NSAID therapy of osteoarthrosis patients with the NSAID-induced duodenal ulcer. The results of the treatment of 38 patients with osteoarthrosis of II-III degrees in which the NSAID treatment was complicated with duodenal ulcers were analyzed. The treatment of 20 osteoarthrosis patients was carried out with the help of Celecoxib while 18 patients were on Tramadol as an analgesic therapy against a standard antiulcer therapy. The efficacy of osteoarthrosis treatment was assessed based on the pain syndrome dynamics by the VAS and functional Lequin test; the efficacy of duodenal ulcer treatment was assessed on the basis of clinical signs dynamics under EGD (esophagogastroduodenoscopy). A clinical remission (the endoscopy confirmed the healing of the ulcerous affection) was achieved in 19 Celecoxib patients with duodenal ulcer and osteoarthrosis, and 18 Tramadol patients with osteoarthrosis and duodenal ulcer against a standard antiulcer therapy. Celecoxib can serve as a drug of choice for continuing the anti-inflammatory and analgesic therapy in patients with osteoarthrosis and NSAID gastropathy.

[Effects of Gerbamarin T balms on functions of the cardiovascular and hepatobiliary systems]. / Vliianie bal'zamov "Gerbamarin" T na funktsional'noe sostoianie serdechno-sosudistoi i gepato-biliarnoi sistem.

The effects two balms of "Herbamarin" T series on some parameters of cardiovascular and hepatobiliary systems were studied in mice either kept on the cholesterol diet or treated with CCl4. The results allow to recommend these balms as additional components to the therapy of various cardiovascular and hepatic diseases.

[Efficacy of gastrosidine (famotidine) in the treatment of gastroesophageal reflux at the reflux esophagitis stage]. / Effektivnost' gastrosidina (famotidina) v terapii gastroézofagal'noi refliuksnoi bolezni v stadii refliuks-ézofagita.

There is a disclosure of the results of the therapy of gastroesophageal reflux disease at the stage of reflux esophagitis with gastrosidin (famotidine), 40 mg twice a day during 4-8 weeks. The dosage of gastrosidin (famotidine) was reduced to 40 mg a day only if side effects appeared: diarrhea (4) and urticaria (3). After four weeks of treatment, endoscopic symptoms of esophagitis disappeared in 17 patients out of 28 (60.7%), and a positive dynamics was recorded in 11 patients. After eight weeks of treatment, the disappearance of endoscopic symptoms of esophagitis was recorded in 7 patients out of 8 (including the healing of the peptic esophagus ulcer in one patient). Three patients (who were feeling good) refused to undergo a control endoscopic examination.