The presence of infectious inflammatory process in a pregnant woman can lead to a disorder in the “mother – placenta – fetus” system.Aim of the study was to investigate the level of regulatory and pro-inflammatory molecules in pregnancy occurring against the background of chronic pyelonephritis without exacerbation.Material and methods. The concentration of IL-17A, monocytic chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and IgG autoantibodies to double-stranded DNA (AAT to nDNA) was determined in the blood serum of pregnant women with a gestation period of 36–40 weeks using ELISA.Results. It has been shown that in the third trimester of pregnancy occurring against the background of chronic pyelonephritis without exacerbation, compared with a normal pregnancy, the level of MHP-1 and IL-17A increases, the content of VEGF decreases, and the concentration of AAT to nDNA does not change significantly. An increase in the proinflammatory cytokine IL17A and a decrease in VEGF level can lead to intrauterine fetal growth retardation due to inhibition of amino acid transporters in the placenta.Conclusions. In pregnancy occurring against the background of chronic pyelonephritis without exacerbation, a change in the level of IL17A, MСP-1, VEGF can have a significant impact on the course of pregnancy.

Журнал для непрерывного медицинского образования врачей ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ Содержание цитокинов в сыворотке крови детей, перенесших мультисистемный воспалительный синдром, связанный с SARS-CoV-2 1 Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр фундаментальной и трансляционной медицины», 630117, г.Новосибирск, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный меди-

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ1 Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр фундаментальной и трансляционной медици-

The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Мaterials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June–August 2020, October–December 2020, June–August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann–Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 – August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave. Key words: adolescents, coronavirus infection, COVID-19, clinical manifestations, laboratory parameters

Острые респираторные вирусные инфекции (ОРВИ) играют значительную роль в формировании заболеваемости у детей.В то же время исследований, связанных с изучением этиологической структуры ОРВИ, недостаточно.Представлены результаты анализа структуры ОРВИ у детей с тяжелым и среднетяжелым течением заболевания, госпитализированных в детскую клиническую больницу г

Purpose: to study the clinical and laboratory efficacy of the platelet autoplasma use in the complex treatment of endogenous uveitis associated with systemic diseases accompanied by macular edema. Material and methods. The study included 46 people (72 eyes) with endogenous uveitis and macular edema. The diagnosis was made on the basis of the ophthalmological examination, including visometry, tonometry, biomicroscopy, ophthalmoscopy, perimetry, B-scan, optical coherence tomography of the macular zone, photoregistration of the anterior, posterior segment of the eye. The examination was carried out on the 1st and 10th day of treatment. The main group consisted of 22 people (36 eyes) who underwent anti-inflammatory therapy and the introduction of platelet plasma in the region of the pterygopalatine fossa. The control group consisted of 24 people (36 eyes) receiving only anti-inflammatory therapy (diprospan 0.5 paraequatorially №1, dexazone 4 mg intravenously №5, intravenous lasix 2.0 ml №5, electrophoresis with prednisolone № 7). All patients underwent the definition of IL-4, IL-6, IL-8, IL-17 in tear fluid before the study and on the 10th day. Results. The significant increase in the concentrations of pro-inflammatory cytokines (IL-17A and IL-8) and IL-4 and IL-6 involved in the development of autoimmune response and chronic inflammation was found in the patients with endogenous uveitis and macular edema. The use in the treatment of endogenous uveitis with macular edema of platelet autoplasma leads to more pronounced improvement of clinico-ophthalmological parameters (improvement in visual acuity, retinal photosensitivity, and retinal thickness reduction) relating to the comparison group. A decrease in the activity of the inflammatory process was noted in the main group after treatment, which is manifested by a significant decrease in the concentrations of IL-17A, IL-8, IL-4, IL-6, relating to the data obtained in the comparison group. The proposed scheme of complex treatment allows reducing the frequency of relapses of the pathological process.

Purpose: to study the clinical and laboratory efficacy of the platelet autoplasma use in the complex treatment of endogenous uveitis associated with systemic diseases accompanied by macular edema.Material and methods.The study included 46 people (72 eyes) with endogenous uveitis and macular edema.The diagnosis was made on the basis of the ophthalmological examination, including visometry, tonometry, biomicroscopy, ophthalmoscopy, perimetry, B-scan, optical coherence tomography of the macular zone, photoregistration of the anterior, posterior segment of the eye.The examination was carried out on the 1st and 10th day of treatment.The main group consisted of 22 people (36 eyes) who underwent anti-inflammatory therapy and the introduction of platelet plasma in the region of the pterygopalatine fossa.The control group consisted of 24 people (36 eyes) receiving only anti-inflammatory therapy (diprospan 0.5 paraequatorially №1, dexazone 4 mg intravenously №5, intravenous lasix 2.0 ml №5, electrophoresis with prednisolone № 7).All patients underwent the definition of IL-4, IL-6, IL-8, IL-17 in tear fluid before the study and on the 10th day.Results.The significant increase in the concentrations of pro-inflammatory cytokines (IL-17A and IL-8) and IL-4 and IL-6 involved in the development of autoimmune response and chronic inflammation was found in the patients with endogenous uveitis and macular edema.The use in the treatment of endogenous uveitis with macular edema of platelet autoplasma leads to more pronounced improvement of clinico-ophthalmological parameters (improvement in visual acuity, retinal photosensitivity, and retinal thickness reduction) relating to the comparison group.A decrease in the activity of the inflammatory process was noted in the main group after treatment, which is manifested by a significant decrease in the concentrations of IL-17A, IL-8, IL-4, IL-6, relating to the data obtained in the comparison group.The proposed scheme of complex treatment allows reducing the frequency of relapses of the pathological process.

Purpose: to study the activity of the local inflammatory process in patients with complicated cataracts with pseudoexfoliation syndrome before and after phacoemulsification with the primary posterior capsulorhexis. 54 patients (54 eyes) aged 50 to 92 years (76 ± 7.43) appealed for surgical treatment of complicated cataracts with pseudoexfoliation syndrome were examined. The concentration of IL-6, IL-10, MMP-9, TGF-β1 was determined in the tear fluid of patients before and on the 5th day of the postoperative period. It was established that the activity of local inflammatory process (high concentrations of IL-6 and MMP-9) is determined in patients with complicated cataracts with pseudoexfoliation syndrome. The identified increase in TGF-1 concentrations is a significant factor in the formation of the pseudoexfoliation material. It has been established that the use of a modified surgical technique in patients with pseudoexfoliation syndrome does not lead to activation of the local inflammation process

The purpose of the study was to examine the characteristics of the content of cytokines in the peritoneal fluid in women of reproductive age with infertility against the background of chronic inflammatory diseases of the pelvic organs in the stage of clinical remission.Material and methods. A study was conducted of 50 patients aged 23-36 years with a verified diagnosis of infertility of tubal peritoneal genesis against a background of chronic inflammatory diseases of the reproductive sphere in the stage of clinical remission. As a control group, 15 practically healthy women aged 25-37 years were examined. Concentration of cytokines TNF-a, IL-4, IL-6, IL-10, IFN-y, MCP-1 in the peritoneal fluid was measured by enzyme-linked immunosorbent assay.Results and discussion. In the main group of patients with tubal-peritoneal infertility, the activity of local inflammatory reactions is tested in the period of clinical remission of a chronic inflammatory process. This is confirmed by a significantly higher level of TNF-a, IL-4, IL-6, IFN-y, MCP-1 in the peritoneal fluid compared to the control group. The studied biologically active substances play a significant role in the development of the immune response, as well as fibroplastic processes. The results can be regarded as the latent development of the immune response in reactions to constant antigenic stimulation from the focus of chronic inflammation, which is a significant factor in the development of adhesions in the formation of infertility, and requires the inclusion of immunotropic therapy methods in treatment.

Purpose. To study the content of the transforming growth factorbeta 2 (TGF-β2), vascular endothelial growth factor (VEGF), pigment epithelium factor (PEDF) and several cytokines in the vitreous body in patients with proliferative diabetic retinopathy (PDR), to evaluate an activity of proliferative and immune-inflammatory process.Material and methods. Vitreous samples of patients with proliferative diabetic retinopathy and retinal detachment traction were examined as well as patients with traction retinal detachment without the PDR (control). Concentration of TGF- β 2, VEGF, PEDF MCP-1, interleukin 4, 6, 8, 10, 17A was determined by the ELISA method.Results. A reliable increase in the concentrations of pro-inflammatory cytokines IL-17A, IL-8, IL-6, MCP-1, anti-inflammatory cytokine IL-4, transforming growth factor-beta 2, vascular endothelial growth factor, factor of pigment epithelium and monocyte chematacticprotein-1 was detected in the vitreous of PDR patients.Conclusions. The findings indicate the existence of cytokine regulation violations in the PDR pathogenesis. It was noted that the activity of local inflammatory and proliferative processes was determined in the PDR pathogenesis. The revealed correlative relationships indicate interdependence of these processes. The detected reliable increase of monocyte chemotactic protein-1 in the vitreous of PDR patients, allows to make an assumption about its participation in the mechanisms of vascular proliferation.

ABSTRACT Purpose. To measure concentrations of transforming growth factor-β1 (TGF-β1), matrix-metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in the lacrima of cataract patients with pseudoexfoliation syndrome (PEX). Material and methods. Determination of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima was performed by the immune-enzyme analysis method in 71 cataract patients (71 eyes) with pseudoexfoliation syndrome (PEX) aged from 50 to 92 years (76±0.91). Results. It was found a significant increase of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima of patients with PEX. Conclusions. Increase of IL-6 and MMP-9 level may play an important role in the PEX pathogenesis. These cytokines are involved in the development of «subclinical» inflammatory process and activate the processes of destruction and proliferation. TGF-β1 has significant proliferative and anti-inflammatory activity. Increase of TGF-β1 level activates the processes of fibrosis and may be one of the pathogenetic factors in the formation of pseudoexfoliation material.

Purpose. To measure concentrations of transforming growth factor-β1 (TGF-β1), matrix-metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in the lacrima of cataract patients with pseudoexfoliation syndrome (PEX). Material and methods. Determination of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima was performed by the immune-enzyme analysis method in 71 cataract patients (71 eyes) with pseudoexfoliation syndrome (PEX) aged from 50 to 92 years (76±0.91). Results. It was found a significant increase of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima of patients with PEX. Conclusions. Increase of IL-6 and MMP-9 level may play an important role in the PEX pathogenesis. These cytokines are involved in the development of «subclinical» inflammatory process and activate the processes of destruction and proliferation. TGF-β1 has significant proliferative and anti-inflammatory activity. Increase of TGF-β1 level activates the processes of fibrosis and may be one of the pathogenetic factors in the formation of pseudoexfoliation material.

Abstract. Patients with exacerbation of chronic herpesvirus infection were subjected to immunocorrection therapy. In the course of treatment, time-dependent correlations were found between the changes in production of IFNγ, IL-1β and IL-6, and initial level of IFNγ. The patients with high initial concentrations of IFNγ did also exhibit above-normal initial IL-1Β and IL-6 values, as compared to appropriate parameters for a sub-group with low IFNγ levels. In the course of immunocorrection with Echinacea, all the patients showed increase in IFNγ levels. However, due to initially low IFNγ values, its increase was more pronounced than in persons with high background levels of IFNγ. Dynamics of IL-1Β decrease and changes in IL-6 concentrations were more expressed in cases of higher initial levels of these cytokines. The alterations revealed for IFNγ, IL-1Β and IL-6 levels confirm that immunocorrection with Echinacea causes reduced intensity of inflammation and activation of antiviral immune response. (Med. Immunol., 2008, vol. 10, N 2-3, pp 283-290).

Abstract. In present work, we studied some interrelations between tobacco smoking and the processes of immune system stimulation in healthy blood donors. In our opinion, this issue is especially important for the big industrial center, with rather strong antigenic exposure of the organism. The levels of circulating immune complexes (CIC) were used as a marker index which reflects specific antigen-antibody interactions during inflammation. According to the results obtained, the majority of persons who have high CIC levels were tobacco smokers (53.76%). Moreover, the percentage of persons with high CIC content, like as the mean values of this index is increased proportionally to the duration of smoking. A mixture of tobacco smoke components seems to exert direct toxic effect upon various compartments of the immune system and causes local irritation of bronchial tree, thus producing local and systemic inflammatory reaction. It is, possibly, an additional factor which determines activation of immune system, with a background of adverse antropogenic exposures typical to industrial centers. The data obtained allow us to affirm a toxic action of tobacco smoke upon the organism of smokers, with development of inflammatory reactions that are displayed as increased CIC levels at preclinical stage.

The analysis of inflammatory reaction to the implantation of artificial irido-lenticular diaphragm (ILD) in preand postoperative period in patients with congenital and posttraumatic aniridia was performed basing on the content of cytokines IL-1β and IL-4 in tears, as well as on the assessment of the permeability degree of the blood-aqueous barrier according to the findings of Laser Flare Cell Meter (LFCM). A significant increase of IL-1β concentration (more than 5.5 times) and IL-4 concentration (3.2 times more) in the early postoperative period was revealed, a return to normative values of IL-1β in a month after the operation and maintenance of elevated concentrations of IL-4 in the course of the year were also established. The permeability of the blood-aqueous barrier according to the findings of LFCM remains impaired for 6-12 months after the surgery.

Study activity the local immunoinflammatory process in patients with autoimmune uveitis. We examined 60 patients with autoimmune uveitis (study group) not receiving basic treatment system autoimmune disease and 20 control patients. In the lacrimal fluid of patients before treatment, by enzyme immunoassay, was conducted determination of IL17A, IL8, IL6, IL4. Found that in the pathogenesis of uveitis associated with systemic autoimmune diseases, an important role is the development of local immunoinflammatory process, which is manifested in a significant increase in tear fluid of surveyed patients, concentrations of proinflammatory cy tokines IL17A, IL8, that accompanied by increased concentrations of IL4, IL6, which play a significant role in the development of autoimmune response and chronic inflammatory processes in their relationship, which was confirmed data correlation analysis

To study the features of immunobiochemical disorders in the pathogenesis of late gestosis of pregnancy, we studied 80 women in the third trimester of pregnancy. 60 women were diagnosed with late gestosis, and 20 pregnant women with physiological course of pregnancy. In women with late gestosis we revealed high concentrations of proinflammatory cytokines IL-1ƒ, IL-6, IL-8, acute phase proteins lactoferrin and the ratio of proinflammatory / antiinflammatory interleukins. Also we revealed the high level of markers of cell destruction autoantibodies to antigen native DNA and markers of endothelial dysfunction vascular endothelial adhesion molecule 1. Thus in the pathogenesis of late pregnancy gestosis significant role is played by integrated development of the destructive inflammatory process and endothelial dysfunction.