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Aim of the study. To investigate the esophageal dysmotility, changes in the esophageal mucosa and the immune response depending on the type of refluxate in gastroesophageal reflux disease (GERD) patients.Material and methods. 68 patients with GERD were recruited: 28 (14 men; mean age, 45.74 ± 2.23 years) nonerosive reflux disease (NERD), 22 (15 men; mean age, 45.0 ± 3.24 years) erosive reflux disease (EE), 18 (13 men; mean age, 47.22 ± 2.95) Barrett’s Esophagus (BE). GERD patients underwent esophageal high-resolution manometry (HRM) with a 22-channel water-perfused catheter and Solar GI system (Medical Measurements Systems, Enschede, the Netherlands), 24-hour impedance and pH monitoring using the Ohmega Ambulatory Impedance pH Recorder (Medical Measurements Systems). We analyzed receptor characteristics of monocyte-derived macrophages in all groups of patients.Results. On HRM examination, we showed that DCI (distal contractile integral) in NERD patients was higher than in EE (p = 0.088) and BE (p = 0.076), also LES RP (lower esophageal sphincter resting pressure) in NERD patients was higher than in EE (p = 0.039) and BE (p = 0.012). The analysis of reflux characteristics showed that the total reflux time with pH < 4 for BE patients was longer than that for NERD and EE patients. An analysis of receptor characteristics of monocyte-derived macrophages showed the prevalence of CD25 and CD80 expression in all groups of patients.Conclusion. An analysis of the phenotype of macrophages derived from blood monocytes of GERD patients revealed a prevalence of М1 macrophages that was typical for the Th1 type of immune response. The degree of esophageal dysmotility was correlated with GERD severity and type.

Aim. To analyze level of circulating biomarkers of plasma vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) during 3-month therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24, AO Vertex, Russia), as well as to evaluate the antihypertensive efficacy of a fixed-dose combination of ramipril/indapamide (Konsilar-D24, JSC “Vertex”, Russia) in hypertensive (HTN) patients with type 2 diabetes (T2D).Material and methods. This prospective open-label study included 44 patients (aged 35 to 60 years) of both sexes with essential grade 1-2 HTN and concomitant compensated T2D, who did not reach the target blood pressure (BP) level using single or dual antihypertensive therapy, as well as patients who did not take antihypertensives. All patients included in the study initially underwent a set of standard clinical, laboratory and functional examinations in accordance with the clinical guidelines for the management of patients with HTN and T2D, as well as an assessment of the level of C-reactive protein, VEGF and TNF-α. Patients were monitored and treated with Konsilar-D24 for 3 months.Results. In 93,2% of patients, individual target BP values were achieved during the first 2-4 weeks of therapy with a fixed combination of ramipril/indapamide (Konsilar-D24). In the subsequent 3-month follow-up, the average daily BP level in all patients ranged from 129/79 mm Hg to 110/70 mm Hg. Three-month Konsilar-D24 therapy showed a decrease in microalbuminuria: the median values of microalbuminuria decreased by 2 times, and the decrease in the maximum recorded values reached 40% of the baseline. Decrease in mean TNF-α values after 3-month therapy with Konsilar-D24 was 33% of the baseline values, while the maximum recorded values during the specified period decreased by 17%. Decrease in median VEGF values after 3-month Konsilar-D24 therapy was 28%, while the maximum value decreased by 7%, the minimum — by 8%.Conclusion. Konsilar-D24 improves the prognosis in hypertensive patients not only by reducing BP to target values, but also by reducing the level of VEGF and TNF-α biomarkers that determine the progression of endothelial dysfunction, diabetic retinopathy, and microalbuminuria.

Aim of investigation. To characterize the systemic immune response at patients various forms of gastroesophageal reflux disease (GERD).Material and methods. Overall 45 patients with GERD and 10 healthy volunteers were included in prospective study. All patients underwent following investigation: taking complaints and past history, detection of GERD risk factors; esophagogastroduodenoscopy and 24-hour рН-impedance recording. Levels of 7 cytokines were determined by flow cytofluorometry: two antiinflammatory: IL-4 and IL-10, three proinflammatory: IL-8, IFN-γ and TNF-α and two cytokines which can demonstrate both anti-inflammatory and proinflammatory activity in relation to conditions (bivalent) — IL-2 and IL-6.Results. Patients with erosive and/or ulcerative esophagitis in comparison to patients with non-erosive reflux disease (NERD), Barret's esophagus and healthy patients had increased expression of proinflammatory cytokines. In patients with Barret's esophagus in comparison to others GERD patients and healthy volunteers hyperproduction of anti-inflammatory cytokines was revealed. TNF-α and IL-8 levels correlated to total number of acidic refluxes and exposition of acidic bolus, while IL-4 and IL-10 level — with total number of weakly alkaline refluxes and exposition of weakly alkaline bolus. High level of IL-8 was associated with increased frequency of relapses of erosive esophagitis within 2 years, despite of carried out therapy.Conclusions. Relation of cytokine levels to the form of GERD was revealed. At erosive and/or ulcerative esophagitis in comparison to NERD and Barret's esophagus production of proinflammatory cytokines IL-8, the IFN-γ and TNF-α prevails, that indicates development of Th1-mediated immune response. At Barret's esophagus expression of anti-inflammatory cytokines IL-4 and IL-10 is increased, that indicates on development of Th2-immune response.

Abstract. Macrophages are among key players of inflammatory events, acquiring either pro-inflammatory M1, or anti-inflammatory M2 phenotype, dependent on their microenvironment. Some endogenous macrophagereprogramming factors (MRFs), e.g., TGF-β (an M2-inducing agent), are found in blood serum. This work confirms a hypothesis on in vitro M1-to-M2 phenotype reprogramming of cultured macrophages, by means of decrease or increase in serum concentration. Noteworthy, the macrophages from C57BL/6 и BALB/c mice strains did not differ with their reprogramming capacity. In general, our results allow of extending present knowledge about a role of environmental factors in regulation of macrophage activities.

Stratification of cardiovascular risk using the SCORE method in presumably healthy working age males with fat metabolism disorder

Metabolism of NO, an endogenous vasodilatator, and lipid peroxidation intensity were analyzed in young subjects with normal blood pressure (BP) (

Aim. A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro - or anti-inflammatory phenotype of the cells when exposed to reluctate. Materials and methods. Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). Results. The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate.

The review presents modern data on the cellular and molecular mechanisms of inflammatory changes of esophageal mucosa exposed to different types of reluctate (gastric, biliary or duodenal/mixed). The authors describe data on key mediators of inflammation in gastroesophageal reflux disease (GERD) and their major cellular sources, changes of the immune profile of patients. Discusses the possible impact of changes in the cellular and molecular components in the development of the inflammatory response in the esophagus on the clinical features of GERD and its therapy-refractory forms.

Aim. To test the hypothesis that an impaired pulmonary immune response in asthma, gastroesophageal reflux disease (GERD) and their concurrence of these diseases is largely determined by disordered alveolar macrophage (AM) reprogramming and to assess the pulmonary immune response and an AM phenotype in patients with asthma, GERD and their concurrence. Subjects and methods. The levels of proinflammatory M1 cytokines, such as IL-1β, IL-8, IL-12p70, IFN-γ, TNF-α, and TNF-β, anti-inflammatory М2 cytokines, such as IL-4, IL-5, and IL-10, and bivalent М1/М2 cytokines, such as IL-2 and IL-6, were determined in bronchoalveolar lavage fluid (BALF) and AM culture medium. Results. Serious deformations in the pulmonary immune response were first detected in patients with mixed pathology towards to an anti-inflammatory M2 phenotype. The change in the pulmonary immune response phenotype in GERD towards M1 and in comorbidity towards M2 was coincident with that of the AM phenotype. In asthma, the change in the pulmonary immune response phenotype occurred towards to M2 and that in the intrinsic AM phenotype did towards M1. This phenotype is likely to form a proinflammatory component and to cause an asthma exacerbation. Conclusion. Analysis of the spectrum of cytokines in BALF and produced by macrophages in asthma, GERD and their concurrence validated the hypothesis that impaired pulmonary immune responses in these diseases are associated with disordered AM reprogramming. The findings also suggest that therapy for the inflammatory component in these diseases should be performed by taking into account the specificity of the cytokine structure of an immune response and the phenotypic heterogeneity of immune cells.

Combination of bronchial asthma (BA) with gastroesophageal reflux disease (GRD) is now most prevalent among combined pathology of the respiratory and gastrointestinal tracts. Interaction of these diseases is stated basing on clinical picture and pathogenetic aspects of BA development in the presence of GRD and GRD in the presence of BA. Development of combined affection of gastrointestinal and respiratory tracts occurs in secondary immunodeficiency. Main lines of the paradigm of macrophage phenotypes M1/M2 and mechanisms of alternative development of the immune response Th1/Th2 in combination of GRD with BA are presented. Investigation of macrophage functional activity and Th1/ Th2 balance gives ground for development of the method of macrophage phenotype reprogramming which is a promising approach to effective treatment of combined pathology of the respiratory tract and upper gastrointestinal tract including cases resistant to pharmacological treatment.