[Drug therapy's new options in the treatment of the severe irritable bowel syndrome].

BACKGROUND: Stress, individual characteristics of each patient, visceral hypersensitivity and intestinal motility have the key importance in the pathogenesis of irritable bowel syndrome (IBS). In recent years, there has been growing interest in the use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the complex therapy of IBS patients with somatoform disorders. AIM: To examine the effectiveness of the SNRIs antidepressant therapy in the treatment of patients with IBS and diarrhea (IBS-D) with extraintestinal manifestations. MATERIALS AND METHODS: 42 patients with severe IBS and diarrhea (IBS-D) were examined, among them 22 female with a median age of 32 years old (22; 38), and 20 male with a median age of 31 years old (25; 35). Treatment with duloxetine 60 mg/day was prescribed. The effectiveness of the therapy was assessed after eight weeks. The IBS clinical symptoms dynamics were assessed by the intensity of pain syndrome and bloating, which were determined using Visual Analogue Pain Scale (VAS), stool frequency and shape based on the Bristol stool scale; Visceral sensitivity threshold was assessed according to the Balloon dilatation test. There was studied the effect of the duloxetine on the extraintestinal manifestations of IBS. The psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale by psychiatrist, neurologist-vegetol. RESULTS: All patients showed positive dynamics after eight weeks duloxetine treatment: the decrease of pain syndrome from 9 (9; 10) to 2 (2; 3) points, bloating from 8 (8; 9) points to 2,5 (1; 3) points according to VAS, and defecation frequency from 10 (9; 12) to 2 (1; 2) times a day; the change of stool consistency from 6th (6; 7) to 3rd (3; 4) type. The visceral sensitivity threshold increased: the time of appearance of the first urge to defecate increased from 56 (34; 74) ml to 95 (80; 98) ml. Significantly decreased extraintestinal manifestations of IBS. In reassessing each patient's individual characteristics there were the decrease of the depression level according to the Beck scale from 26 (23; 32) to 11.5 (10; 13) points and personal personal anxiety level according to the Spielberger-Khanin scale from 42.5 (35; 53) to 22 (20; 24) points, as well as the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points. CONCLUSION: The severe course of IBS-D is mainly associated with the patients' individual characteristics and anxiety or anxiety-depressive syndromes. The positive impact of duloxetine therapy in severe IBS-D with extraintestinal manifestations is associated with the regulation of serotonergic and noradrenergic activity of the central.

[Visceral sensitivity in diagnostics and treatment of severe irritated bowel syndrome].

BACKGROUND: Irritable bowel syndrome (IBS) is a biopsychosocial model based on the malfunction of "brain-intestinal linking". AIM: To improve diagnostics of the severe IBS accompanied with somatoform disorders by using balloon dilatation test (BDT) and optimize the therapy by using antidepressants from the serotonin and noradrenaline reuptake inhibitor type. MATERIALS AND METHODS: 61 patients with severe IBS and diarrhea were examined, among them 29 female with a median age of 31 years old (24; 36), and 31 male with a median age of 31 (24; 36) years old. All patients were randomized into two groups, group 1 consisted of 30 patients (15 female, 15 male), group 2 consisted of 31 patients (15 female, 16 male). The symptoms of all patients were assessed using the Visual Analogue Pain Scale (VAS Pain), visceral sensitivity index (VIS) was assessed according to the J. Labus questionnaire (2007) and visceral sensitivity threshold was assessed according to the BDT, the psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale. Both group patients underwent a comparative effectiveness evaluation between the therapy based on the use of Trimebutine at a dose of 600 mg per day and the SNRI-Duloxetine therapy at a dose of 60 mg per day for 8 weeks. RESULTS: Patients from group with severe IBS and diarrhea who had undergone the antidepressant therapy showed the decrease of pain syndrome from 7 (5; 7) to 2.5 (2; 3) points according to VAS Pain; normalization of stool frequency from 7 (6; 9) to 2 (1; 2) times a day; normalization of stool consistency from 6 (6; 7) to 3 (3; 4) type; and decrease of VIS: first urge from 56 (34; 74) to 95 (80; 98) ml.; as well as the decrease of the depression level (Beck scale) from 26 (23; 32) to 11.5 (10; 13) points and anxiety according to Beck scale from 38 (31; 45) to 11 (10; 12), the decrease of personal anxiety level (Spielberger-Khanin scale) from 42.5 (35; 53) to 22 (20; 24) points, and the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points. During the trimebutine therapy in group 1, the clinical symptoms of IBS have persisted. According to the BDT, the visceral sensitivity (HF) threshold remained at a low level. And the indicators of anxiety and depression remained at a high level according to the psychometric scales. CONCLUSION: The insufficient effect of the trimebutine therapy can be explained by the somatoform disorders persistence in patients from group 1. Meanwhile SNRI-duloxetine therapy in group 2 showed a clinical remission of IBS: such as a reliable relief from pain and diarrheal syndrome, as well as an increase in the HF threshold. Thus, Duloxetine is a promising treatment for severe IBS with somatoform disorders. BDT can be used as an objective criterion to diagnose and evaluate the effectiveness of therapy in patients with IBS.

[The role of a combined probiotic in the treatment of lactase deficiency].

AIM: To study the effectiveness of the combined probiotic Bifiform and the enzyme lactase in the treatment of secondary lactase deficiency (SLD). MATERIALS AND METHODS: We examined 79 patients with SLD, isolated from the group of patients with post-infectious irritable bowel syndrome (IBS) with a predominance of diarrhea. The age of patients reached 273.5 years, women predominated by gender 62%. Diagnosis of SLD was carried out in biopsies of the small intestine mucosa using a color rapid test. To diagnose small intestinal bacterial overgrowth (SIBO) all patients underwent lactulose breath test (LBT) during 2 hours by gas analyzer. All patients with lactase deficiency (LD) were divided into 2 groups: group 1 included 54/79 patients who received the combined probiotic Bifiform (1 capsule per day), group 2 was treated with the enzyme lactase [1 capsule (3450 ME) 3 times a day]. The effectiveness of therapy was evaluated by the dynamics of clinical symptoms, indicators of LBT and the detection of hypolactasia in biopsies of the small intestine mucosa twice, before and 2 weeks after treatment. RESULTS: In the group of patients with LD, as a result of 14-day therapy with the combined probiotic Bifiform, 85.2% showed positive clinical dynamics, the values of SIBO in the small intestine decreased from 5814 to 219 ppm, p0.05, and the activity of the lactase enzyme was completely restored. In 14.8% of patients, LD was preserved against the background of persistent SIBO. In the second group of 25 patients, 84% of patients did not achieve a positive dynamics of the disease as a result of taking the lactase enzyme, and hypolactasia and changes in the lumen microflora of the small intestine were preserved after repeated examination of small intestine biopsies. Recovery of the activity of the lactase enzyme was observed in a small percentage of patients, which was 16%. CONCLUSION: In 85.2% of patients, as a result of therapy with the combined probiotic Bifiform, the activity of the lactase enzyme was restored, due to the suppression of bacterial contamination in the lumen of the small intestine. Replacement therapy with the enzyme lactase only led to remission of LN in 14.2%, while in the majority 85.8% hypolactasia and SIBO remained. Pathogenetic therapy of LN in the adult population includes the appointment of a combined probiotic Bifiform 1 capsule 3 times a day, a course of at least 14 days. As a symptomatic therapy for LN, replacement therapy with the enzyme lactase can be prescribed.

[The role of visceral hypersensitivity in the pathogenesis of irritable bowel syndrome].

This research includes visceral sensitivity and its mechanisms involved in the development of irritable bowel syndrome. Visceral hypersensitivity occupies the key place. The research has the description of etiological factors that form visceral hypersensitivity and also visceral sensitivity instrumental research methods, based on the use of the balloon dilation. The research also has the schemes of drug therapy for irritable bowel syndrome meanwhile the special attention is paid to the possible use of the sorbed probiotics and psychopharmacological drugs.

[Multidisciplinary treatment of the patient with a severe irritable bowel syndrome].

The patient E., aged 39, was described with a severe form of the irritable bowel syndrome that developed after the stress. In addition to the clinical manifestations of IBS, the patient got the somatoform disorders, which manifested itself with a large number of extraintestinal symptoms and led to a disability. According to the recommendations of the Rome Criteria IV 2016, the main medicines for the treatment of biopsychosocial model of IBS are antidepressants. The remission of the disease with a complete recovery of the patients disability was achieved by duloxetine, an antidepressant from the group of serotonin and noradrenaline reuptake inhibitors.

[Efficacy of adalimumab for Crohn's disease in real clinical practice]. / Effektivnost' adalimumaba pri bolezni Krona v real'noi klinicheskoi praktike.

AIM: To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. SUBJECTS AND METHODS: All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. RESULTS: A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. CONCLUSION: The findings demonstrate the efficacy and safety of ADA used in clinical practice.

[Long-term infliximab therapy for ulcerative colitis in real clinical practice]. / Dlitel'naya terapiya yazvennogo kolita infliksimabom v real'noi klinicheskoi praktike.

AIM: to retrospectively evaluate the efficiency of long-term infliximab (INF) therapy in patients with refractory ulcerative colitis (UC). SUBJECTS AND METHODS: The investigation enrolled 48 patients with refractory UC who had taken IFL in 2008 to 2014. Steroid-dependent or steroid-refractory UC was established in 40 (83.3%) patients; 8 (16.7%) were noted to be refractory to therapy with azathioprine or 6-mercaptopurine. Cytomegalovirus DNA was identified in the biopsy specimens of the large intestinal mucosa (LIM) from 7 patients. One patient received antiviral therapy. Induction therapy with IFL was in its administration in a dose of 5 mg/kg at 0, 2, and 6 weeks, then maintenance therapy was continued every 8 weeks. RESULTS: After an IFL induction cycle, 3 (6.3%) patients were unresponsive to therapy and were excluded from the investigation. At present, 25 (55.5%) of the 45 patients who have responded to the therapy continue to take IFL 5 mg/kg every 8 weeks and are in clinical remission; 4 (8.8%) patients receive intensified IFL therapy. Initially 23 patients received combined therapy with IFL + an immunosuppressive drug; 22 had IFL monotherapy. Escape from the effect of the performed therapy was observed in 5 (11.1%) patients, which required its intensification. The intensified therapy resulted in sustained remission in 4 (8.8%) patients; colectomy was carried out in one (2.2%) case. Secondary loss of response to IFL, its intolerance, development of severe infectious complications, which did not allow for further maintenance therapy with IFL, were seen in 11 (24.4%) patients; 5 (11.1%) stopped the therapy because they had been excluded from the additional drug subsidy list. Maintenance therapy with IFL proved successful during 64 months in 29 (64.4%) of the 45 patients and during 64 months if its intensity, when the occasion required, was enhanced. CONCLUSION: The long-term use of IFL in UC confirmed its high efficacy in achieving clinical response, in inducing a clinical remission and its capacity to heal LIM, and in sustaining remission.

[Irritable bowel syndrome in the light of Rome consensus III (2006): 10 years later].

Irritable bowel syndrome (IBS) is the most common diagnosis in gastroenterology. Over 10 years after Rome consensus III (2006), there has been much new information on the pathogenesis of IBS and its therapy options. The paper analyzes basic investigations that have contributed to the theory of this disease and to a better quality of life in patients.

[Small intestinal bacterial overgrowth as a cause of lactase deficiency].

AIM: To establish the rate of lactase deficiency (LD) in patients with post-infectious irritable bowel syndrome (PI-IBS), to define a role of enteric bacteria in the pathogenesis of hypolactasia, and to evaluate the efficiency of probiotic therapy. SUBJECTS AND METHODS: Examinations were made in 386 patients with PI-IBS, including 112 (79.4%) women; mean age 33.9 ± 9.1 years; disease duration 2.6 ± 1.4 years. Rapid tests of small intestinal mucosa (SIM) biopsy specimens obtained from the duodenal retrobulbar segment were used to diagnose LD. Bacterial growth was estimated by a hydrogen breath test using a H2 MICRO gas analyzer. RESULTS: The patients with PI-IBS were revealed to have moderate and severe LD in 25.6 and 10.9%, respectively. All the patients with LD were detected to have small intestinal (SI) bacterial overgrowth (BOG). An inverse correlation was found between LD and the degree of SI BOG (r = -0.53; p < 0.001). 73.7% of the patients with moderate LD showed a positive effect of probiotic therapy as regression of clinical symptoms of LD, a decrease of hydrogen levels in expired air from 72.4 ± 25.1 to 16.41 ± 3.2 ppm (p < 0.05), an increase of lactate activity in the SIM biopsy specimens and an improvement of quality of life from 2.69 ± 0.53 to 5.53 ± 0.64 scores according to the GCI scale. No improvement occurred in 73.8% of the patients with severe LD. CONCLUSION: LD was identified in 36.5% of the patients with PI-IBS. There was an inverse correlation between the degree of LD and SI BOG. The good therapeutic effect of probiotics in LD suggests that the symbiotic gut microflora positively affects the activity of lactase in the human SIM. No therapeutic effect of probiotics in patients with severe LN serves as the basis for a search for more active probiotic therapy.

[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.

[Clinical efficacy of functional nutrition in patients with gastrointestinal disorders].

AIM: To identify micronutrient deficiencies in patients with functional bowel diseases (FBD) and to reveal their correction with functional foods and probiotics. SUBJECTS AND METHODS: The health status was evaluated in 90 patients aged 18 to 67 years with FBD. All the patients were randomized into 3 groups according to the treatment regimen. Group 1 took Amaltea goat's milk 200 ml/day during basic therapy; Group 2 received multispecies and multistrain RioFlora Balance probiotics in addition to the above components; Group 3 (a control group) had traditional basic dietary therapy. All the groups continued their treatment for 14 days. RESULTS: The performed examinations have demonstrated that diet-based treatment fortified with goat's milk and multispecies probiotics makes it possible to more promptly achieve remission and to level off clinical manifestations than in the control group. The patients using multispecies probiotics versus the control group showed a reduction in fat-soluble vitamin deficiencies and a considerable improvement in quality of life. CONCLUSION: FBD lacks a specific clinical picture and may be masked as lactase deficiency, which commonly leads to noticeable limitations in patients' diet and favors the development of vitamin deficiency. Of particular concern is the development of vitamin D deficiency in young patients, which may result in the early development of osteoporosis in the future. To specify the composition of enzymes in the patients gives grounds to refuse restricted diets, and the dietary addition of functional foods (goat's milk fortified with vitamins and minerals), particularly in combination with multistrain probiotics, produces a pronounced clinical effect and eliminates fat-soluble vitamin deficiencies.

[Value of adhesion molecules for evaluating the efficiency of therapy for ulcerative colitis and Crohn's disease].

AIM: To define the value of adhesion molecules (sVCAM-1 integrin, P-selectin, E-selectin, and L-selectin) for the prediction and evaluation of the efficiency of treatment in patients with ulcerative colitis (UC) and Crohn's disease. SUBJECTS AND METHODS: Twenty-six patients with UC and 14 patients with CD were examined. Of them, 16 patients took infliximab (INF) in a dose of 5 mg/kg of body weight according to the standard scheme; 14 patients received cultured mesenchymal stem stromal cells (MSSCs) in a quantity of 150 x 10(8) cells, and 10 had azathioprine (AZA) 2 mg/kg and glucocorticosteroids (GCS) 1 mg/kg of body weight. Enzyme immunoassay was used to determine the serum concentration of the adhesion molecules (L-selectin, E-selectin, P-selectin, and sVCAM-1 integrin) before and 2 months after treatment. RESULTS: The signs of bowel inflammatory disease activity and the elevated levels of adhesion molecules whose synthesis did not occur under normal conditions remained in the patients receiving GCS and AZA. INF treatment caused a decrease in P-selectin, E-selectin, and sVCAM-1 levels to 8.9 +/- 1.0, 5.5 +/- 1.7, and 9.5 +/- 4.4 ng/ml, respectively (p < 0.001). Incorporation of MSSCs was followed by a reduction of the concentrations of P-selectin and E-selectin to 6.9 +/- 1.1 and 5.7 +/- 1.3 ng/ml, respectively (p < 0.001). The level of integrin (cVCAM-1) fell to 12.2 +/- 2.2 ng/ml (p > 0.1); that of L-selectin did not drop after MSSC administration and INF induction therapy. CONCLUSION: P-selectin, E-selectin, L-selectin, and sVCAM-1 integrin are current inflammatory markers and may be used to evaluate the efficiency of standard and biological therapies for inflammatory bowel diseases and to predict disease course.

[Combination biological therapy for fistular Crohn's disease: clinical demonstration].

Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD.

Cell therapy of refractory Crohn's disease.

We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy.

[Prospects for nutritional support of patients with ulcerative colitis].

The article presents the data on the assessment of the degree of severity of ulcerative colitis and the selection of nutritional support with the account of the violations of the nutrition status with ulcerative colitis.

[The role of small bowel microflora in the development of secondary lactase deficiency and the possibilities of its treatment with probiotics].

AIM: To estimate the incidence of secondary lactase deficiency (SLD) in patients with postinfectious irritable bowel syndrome (PIBS) and the value of the small bowel microflora in its development and to elaborate treatment options for SLD. SUBJECTS AND METHODS: One hundred and thirty-eight patients with PIBS, including 112 (81.2%) women and 26 (18.8%) men, were examined. The patients' mean age was 33.9 +/- 9.1 years. The duration of the disease was 2.6 +/- 1.4 years. Lactase deficiency (LD) was diagnosed using the color scale to test biopsy specimens from the duodenal retrobulbar region. The bacterial overgrowth syndrome (BOS) was identified by a 2-hour lactulose (20 ml) hydrogen breath test. Sixty patients with moderate SLD were randomized to 2 groups: 1) 41 patients received basic therapy (mesim forte as one tablet t.i.d., no-spa, 40 mg, t.i.d.) and combined probiotic bifiform (Ferrosan) containing Bifidobacterium longum 107, Enterococcus faecium 107 as one capsule t.i.d. for 14 days. Group 2 patients (n = 19) had basic therapy in combination with placebo. RESULTS: SLD was detected in 59.4% of the patients with PIBS, including 43.5 and 15.9% with moderate and severe forms, respectively. In all cases, SLD was accompanied by BOS in the small bowel lumen, as confirmed by the results of a hydrogen breath test [101 +/- 37 ppm (a normal value of < 20 ppm)]. After a 14-day course of therapy with the combined probiotic bifiform, restoration of eubiosis in the small bowel lumen was achieved in 70.8% of the patients, as shown by the lesser degree of BOS (86.9 +/- 40.9 and 17.4 +/- 6.6 ppm before and after treatment, respectively; p < 0.01) and by normalization of the lactase test (p < 0.01). In the comparative placebo group, 68.4% showed no clear positive changes, SLD and BOS remained. CONCLUSION: The changes in the small bowel intraluminal microflora, which developed after prior intestinal infection, played a great role in the development of SLD. Bifiform belongs to the currently available probiotics and may be recommended to correct SLD in patients with PIBS resulting from the impaired microbiota of the small bowel and to prevent BOS.

[Gluten-sensitive celiac disease associated with recurrent aphthous stomatitis and schizophrenia].

The paper describes a clinical case of celiac disease with grade 3 malabsorption, which is associated with recurrent aphthous stomatitis and schizophrenia. On readmission after 8 months of strict adherence to his gluten-free diet, the patient was observed to be in clinical remission and to have normalized laboratory indices and immunological tests. The signs of recurrent stomatitis disappeared. However, the symptoms of the mental disease remained.

[New possibilities for overcoming the secondary inefficiency of anti-cytokine therapy in patients with inflammatory bowel diseases].

A search for ways to overcome the secondary inefficiency of anti-cytokine therapy (ACT) with infliximab (IFX) in patients with inflammatory bowel diseases (IBD) remains relevant and determines the need for new approaches to solving this problem. The secondary inefficiency of ACT has been found to depend on the level of antibodies to IFX (anti-IFX Ab). The Department of Intestinal Pathology, Central Research Institute of Gastroenterology, is investigating the mechanisms for the occurrence of primary and secondary inefficiency of ACT, as well as ways to overcome them by cultured allogenic bone marrow mesenchymal stromal cells (MSC). In the framework of the searching investigation evaluating the efficiency and safety of MSC in patients with IBD, the investigators revealed that was a phenomenon of a decrease in anti-IFX Ab and came to the conclusion that the secondary inefficiency of ACT should be overcome in a patient with ulcerative colitis (UC). The elevated anti-IFX Ab levels were directly associated with the worsening clinical and endoscopic picture of UC and with the enhanced activity of an inflammatory process. The administration of cultures MSC contributed to lower anti-IFX Ab levels, overcome secondary inefficiency (an escape phenomenon) during ACT, and enhanced IFX sensitivity. The clinical observation indicated that MSC administration reduced anti-IFX concentrations and promoted UC remission during IFX therapy. Thus, MSC transplantation can be considered as a promising method for overcoming the secondary inefficiency of ACT, which aids in increasing the previously lost response to anti-inflammatory therapy.

[Immune response to biological therapy of inflammatory bowel diseases].

AIM: To study biological (cell and anticytokine) therapy-induced changes in the levels of proinflammatory cytokines in patients with inflammatory bowel diseases (IBD). SUBJECTS AND METHODS: Forty-four patients with chronic continuous or chronic recurrent IBD were examined. According to the performed therapy, the patients were divided into 3 groups: 1) 16 patients who took infliximab; 2) 14 patients who received combination anti-inflammatory therapy with the cultured mesenchymal stromal cells (MSC) being administered; 3) 14 patients who had standard anti-inflammatory therapy with 5-aminosalycilic acid preparations and glucocorticosteroids. The concentrations of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma), and interleukins (IL)-2, -5, -8, -12, and -15 were determined in the patients' sera before and 2 months after therapy initiation. RESULTS: The elevation in the serum levels of the proinflammatory cytokines TNF-alpha, INF-gamma, and IL-2, -5, -8, -12, and -15 indicates their implication in the pathogenesis of ulcerative colitis and Crohn's disease. Their levels may evaluate both the activity of an inflammatory process and the efficiency of the therapy. The higher level of these cytokines is accompanied by the enhanced activity of diseases, which may be used to diagnose their activity, to predict the course of IBD, and to perform adequate therapy. The decreased level of the proinflammatory cytokines is indicative of the efficiency of the therapy in patients with IBD. CONCLUSION: By reducing TNF-alpha levels, infliximab therapy results in a decrease in the concentrations of other proinflammatory cytokines (IL-1, -2, -5, -8), thus lowering the inflammatory activity of IBD. MSC transplantation also reduces the level of most proinflammatory cytokines, thus diminishing the intensity of immunopathological processes, which is shown by positive changes in the clinical picture of the disease.

[Optimization of cell therapy in patients with inflammatory bowel diseases].

AIM: To elaborate optimal cell culture administration regimens to enhance the efficiency of anti-inflammatory therapy for inflammatory bowel diseases. SUBJECTS AND METHODS: Three groups of patients with chronic continuous or chronic recurrent ulcerative colitis (UC) were formed according to the treatment option: 1) 15 patients with UC, in whom mesenchymal stromal cells (MSC) were thrice administered for a month at a one-week interval; 2) 20 patients with UC who received MSC once; 3) 20 patients with UC who had standard anti-inflammatory therapy with 5-aminosalycilic acid (5-ASA) preparations and glucocorticosteroids (GCS). The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index. UC histological specimens were scored using the Gebs scale. To ascertain the duration of remission, the authors used the Kaplan-Maier survival curve method and calculated relative risk (RR) and odds ratio with 95% confidence intervals. RESULTS: Following 12 months, allogeneic bone marrow (BM) MSC transplantation performed thrice during a month caused the greatest reduction in the Rachmilewitz clinical activity index, Mayo endoscopic activity index, and Gebs pathohistological index in patients with UC as compared to those who had underwent one transplantation or received 5-ASA preparations and GCS (p < 0.05). The duration of remission also depended on the chosen therapy option for UC and the frequency of cell culture administration: the longer duration was recorded in patients who were infused thrice with allogeneic BM MSC. CONCLUSION: In the patients who had undergone one MSC administration, the risk of recurrent UC was higher than in those who had received MSC thrice during a month (a 2-year follow-up) and comparable with the RR of recurrent UC in the patient receiving only 5-ASA preparations, GCS, and/or immunosuppressants.