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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.

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.В обзоре представлены современные данные о клеточных и молекулярных механизмах воспалительных изменений слизистой оболочки пищевода при воздействии на нее различных типов рефлюктатов (желудочный, желчный или дуоденогастральный/смешанный). Авторами приведены данные о ключевых медиаторах воспаления при гастроэзофагеальной рефлюксной болезни (ГЭРБ) и их основных клеточных источниках, изменении иммунного профиля пациентов. Рассматриваются вопросы возможного влияния изменений клеточных и молекулярных компонентов формирования воспалительной реакции в пищеводе на особенности клинического течения ГЭРБ и развитие ее рефрактерных к терапии форм.

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.

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.

Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo. Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1-STAT3/6- SMAD3 macrophages have a pronounced anti-tumor effect in vitro, and in vivo, which was greater than anti-tumor effects of M1, M1-STAT 3/6, M1-SMAD3 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

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

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.

Predisposition to tumors is often determined by how effectively the genotype of an individual forms an immune defense. An important factor of such protection is macrophage NO. We assumed that the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. The content of NO in the tumor changed by ITU, inhibitor of iNOS, c-PTIO, traps and SNP, donor NO. Production of macrophage NO were evaluated by nitrites in the culture media. iNOS was assessed using the Western blot analysis. Phenotype of macrophages was assessed using cytometry for CD labels. Life span of mice C57BL/6N with Ehrlich tumor was 25% greater than that of the C57BL/6J. Reducing the content of NO in the tumor reduced life expectancy of high-resistance to tumor subline C57BL/6N at 23%. Increase of NO increased life expectancy of low-resistance subline C57BL/6J at 26%. Macrophages of C57BL/6N were 1.5 times higher contents of iNOS and NO production, as compared with macrophages of C57BL/6J. CD phenotype markers determined the macrophage phenotype C57BL/6N as M1 and C57BL/6J mice macrophage phenotype as M2. Thus, the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. C57BL/6J, unlike C57BL/6N does not synthesize NNT (nicotinamide nucleotide transhydrogenase) and have differences in the single nucleotide polymorphism (SNP). The important role of NO in the resistance to Carcinoma, NNT and SNP deserve attention in the development of new methods of antitumor therapy.

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