Репозиторий Университета

© 2020 Elsevier GmbH Lipopolysaccharides (LPSs) induce a wide spectrum of functional activities after interaction with blood cells. Effect of structure of toxic LPS from S- and Re-chemotypes of E. coli and/or non-toxic LPS of Rhodobacter capsulatus PG (R. caps.) on activation of neutrophils and monocytes of human whole blood were studied, particularly, expression of TLR4, CD14 and CD11b receptors, phagocytosis of BioParticles Alexa Fluor 488, synthesis of cytokines and chemokines. A leading role of CD11b receptor in phagocytic activity of neutrophils primed by LPS from various E. coli chemotypes was shown. The non-toxic LPS of R. caps. does not affect the efficiency of phagocytosis activity of the neutrophils. The LPS of R. caps. was shown to induce production of TRIF-dependent cytokine IFN-β in human whole blood leukocytes selectively, without activating MyD88-dependent pathway of pro-inflammatory cytokine synthesis, displaying properties of patrial agonist of TLR4. Structure and biological activity of LPS R. caps. allows considering it as a promising immunity stimulating pharmacological agent.

© 2020 Elsevier GmbH Lipopolysaccharides (LPSs) induce a wide spectrum of functional activities after interaction with blood cells. Effect of structure of toxic LPS from S- and Re-chemotypes of E. coli and/or non-toxic LPS of Rhodobacter capsulatus PG (R. caps.) on activation of neutrophils and monocytes of human whole blood were studied, particularly, expression of TLR4, CD14 and CD11b receptors, phagocytosis of BioParticles Alexa Fluor 488, synthesis of cytokines and chemokines. A leading role of CD11b receptor in phagocytic activity of neutrophils primed by LPS from various E. coli chemotypes was shown. The non-toxic LPS of R. caps. does not affect the efficiency of phagocytosis activity of the neutrophils. The LPS of R. caps. was shown to induce production of TRIF-dependent cytokine IFN-β in human whole blood leukocytes selectively, without activating MyD88-dependent pathway of pro-inflammatory cytokine synthesis, displaying properties of patrial agonist of TLR4. Structure and biological activity of LPS R. caps. allows considering it as a promising immunity stimulating pharmacological agent.

© 2019, Pleiades Publishing, Ltd. Preterm birth is not only medical, but also a social problem. The global goal of medicine is prevention of preterm labor and identification of risk factors leading to preterm birth. The objective of our study was to find the association between polymorphic markers in the cytokine IL-β, TNF-α, IL-1Ra, and IL-4 genes and development of preterm labor. The prospective study was conducted in 108 pregnant women with the risk of preterm birth. The main group consisted of 66 women whose pregnancy ended with preterm delivery despite the ongoing therapy. The comparison group included 42 women with the full-term delivery. The dominant T allele of the cytokine IL-1β gene polymorphism rs1143634 (3953C→T) was 7.6 times more common in women with preterm delivery vs. the comparison group (36.4 and 4.8%, respectively; RR, 1.802; 95% CI, 1.420–2.288; p < 0.05); its homozygous form was detected only in women with preterm delivery at the very early gestation age (less than 26 weeks). The dominant proinflammatory allele 2R of the IL-1 receptor antagonist gene (IL-1Ra) was 1.5 times more common in women with preterm delivery than in the comparison group (63.6 and 42.8%, respectively; RR, 1.400; 95% CI, 1.009–1.943; p < 0.05), which makes the 2R allele the risk factor for preterm birth. The 2R/2R and 2R/4R genotypes led to a very early and early preterm delivery, respectively. The combination of three or four proinflammatory genotypes was detected only in women with a very early preterm delivery, which confirms that the combination of several proinflammatory genotypes is an extremely unfavorable factor for the full-term pregnancy. Identification of genetic polymorphisms in the interleukin genes at the periconceptional stage will help to prevent the risk of preterm delivery, which will reduce the incidence of preterm births, as well as perinatal morbidity and mortality.

© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The review discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, markers for diagnosing and predicting the disease course.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. The lecture discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, and markers for diagnosing and predicting the disease course. In order to control the retention of the lecture material, the text includes case problems and multiple-choice tests.

© 2018, SPb RAACI. The aim of this prospective randomized clinical study was to investigate the role of preoperative carbohydrate admnistration in surgery-induced metabolic, immune and inflammatory reactions after thoracoabdominal operations. At the Surgical department I (B.V. Petrovsky National Research Center of Surgery), we investigated a modulatory role of carbohydrate preload upon surgical stress observed after major thoracoabdominal operations (thoracoscopic and open esophagectomy, retrosternal colonic esophagoplasty) followed by the enhanced recovery protocol. The study was performed in 2014-2017, it included 30 patients, divided into 2 groups. Group A patients (n = 16) received carbohydrates preload (12.5% maltodextrin solution per os or enterally). In patients with dysphagia, the 12.5% dextrose solution was used intravenously in equal volumes. Group B patients didn’t receive any additional preload with carbohydrates. The groups were age- and gender-matched, similar for disease and surgery types. Glucose and insulin levels (with HOMA insulin resistance index, HOMA-IR) were measured before surgery and on day +1, interleukin levels (IL-6, IL-10, IL-8) and index IL-8/IL-10 were assessed before surgery, and on days +1 and +5 after surgery. Cell-mediated immunity was investigated before surgery and on day +5. The stress-induced hyperglycemia (> 7.8 mmol/L) was detected more frequently in group B (50%), than in group A (6%), p = 0.012. Insulin resistance measured by HOMA-IR in group B was detected in 71% of patients and in 25% patients of group A only, p = 0.027. Individual analysis of immune response demonstrated that a trend for immune recovery was detected by the day +5 post-op in the group A. Postoperative levels of IL-6 and IL-10 were lower on day +1 and +5 in group A. Morbidity rates and the terms of hospitalization were similar in both groups. Local postsurgical infections in group A were developed in 6% of the patients vs 35.6% in group B (p = 0.072). In conclusion, a complex study of surgical stress, i.e., metabolic, immune and inflammatory reactions after esophageal surgery has shown that the carbohydrate preload decreased the incidence of postoperative insulin resistance and stress-induced hyperglycemia, being accompanied by lower release of proinflammatory cytokines and provides positive effects upon the patient’s immune system.

In a study of 537 patients with chronic generalized periodontitis and metabolic syndrome (MS) depending on age and gender, it was found that the increase of TNF-α and IL-6 in the content of periodontal pockets correlated with the severity of chronic generalized periodontitis and MS. For these cytokines, there was a clear gender relationship: women had higher levels in periodontal pocket content than men. For IL-1β and IL-4 cytokines, there is no coupling between the severity of the damage and the level of cytokines in the periodontal pocket. The developed model for calculating the risk of chronic generalized periodontitis depending on the level of TNF-α in the patient's periodontal pockets allows predicting and monitoring the dynamics of the disease.

© 2018 Media Sphera Publishing Group. All rights reserved. According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CÀNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative antiinflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

© 2018 Meditsina Publishers. All rights reserved. The spread of a latent tuberculosis infection - 2.3 billion people - is of emergency importance for the global task of mankind - to eliminate tuberculosis as a common disease by 2035. For children, due to the limited use of the radiological diagnosis methods, the main methods today are the immunological tests for the detection of tuberculous infection. The most common used method is the tuberculin skin test (Mantoux test) due to its lack of specificity has significant drawbacks, especially in countries using mass BCG vaccination. Relatively new methods using specific recombinant MTB proteins, both in vitro tests and in new skin tests, allow to determine tuberculosis infection in latent or active form much more specifically, however, they are somewhat less sensitive, in comparison with the Mantoux test, which requires development of these methods with the introduction of new additional specific antigens. It is obvious that crucial task is the development of new methods for distinguishing active and latent tuberculosis infection or being able to predict progression from latent to active TB diseases both in children and in adult population. The article shows new diagnostic techniques of blood cells and plasma samples based on the use of flow cytometry with the detection of antigen-specific T-cells producing interferongamma and tumor necrosis factor alpha, T-cells specific markers, as well as using combinations of the identification of various protein factors that have the prospect to determining active tuberculosis infection signs. However, these methods are still time-consuming and expensive. Currently, some new promising approaches based on the using of new genetically engineered products are being developed to determine specific antibodies in the blood serum. With the development of accelerated methods for the analysis of the expression of specific genes in blood cells, this direction also has the prospect of introducing into healthcare practice.

© 2018, SPb RAACI. The aim of the study was to determine efficiency of Glutoxim, aimed for correction of immune disorders. The drug was administered to the patients with chronic cerebral ischemia (CCI, Stage I and II) complicated by arterial hypertension. Increased contents of pro-And anti-inflammatory cytokines, IFNγ, IL- 2, G-CSF, and activation of the complement system have been revealed for these conditions, at both functional stages of the disease. The patients with stage II CCI showed elevated markers of oxygen-dependent activity in polymorphonuclear leukocytes (increased levels of spontaneous and stimulated nitroblue tetrazolium (NBT) reduction tests, phagocytic capacity and stimulation index of neutrophils). Stage I of chronic cerebral ischemia was characterized by normal values of NBT reduction tests and functional reserve of neutrophils, along with decreased stimulation index of neutrophils. Among 26 parameters of immune status, 73.1% and 80.8% of indices proved to be changed, respectively, in the patients with stage I and II CCI. 66.7% of immune indices appeared similar in magnitude and direction of changes, whereas the resting 33% are identical in orientation. Usage of Cereton and Actovegin in treatment of the stage I CCI caused normalization of 5.3% immune parameters, with partial normalization of 26.3% tests, and 68.4% of the indexes remaining unchanged or increased posttreatment. Inclusion of Glutoxim into the combined pharmacotherapy proved to be more effective since it totally normalized 52.6% of the indexes, along with partial normalization of 21.1%, while 26.3% of the indicators were not affected by the therapy. Administration of Cereton and Actovegin at the second stage of chronic brain ischemia was followed by partial normalization for 47,6% of the tests, while leaving unchanged or increased 52.4% of the indicators. Glutoxim Use fully normalize 19.0% and partially normalizes 57.1% of immune parameters.

© 2018, Media Sphera Publishing Group. All rights reserved. Objective. To study the association between proinflammatory cytokine genes and depression. Material and methods. IL-1B С-511T and TNF-a G-308A gene polymorphisms were studied in patients diagnosed with depression and age and sex-matched healthy controls. Results and conclusion. The IL-1B С-511T and TNF-a G-308A polymorphisms were associated with depression; CC genotype (р=0,001, OR=1.9 CI 1,3—2,7) and GG genotype (р=0,001, OR=3,0 CI 1,8—4,9) were the risk factors. The results suggest that immune factors may play a role in the development of depression. The authors highlight the role of clinical polymorphism of depression that makes it difficult to form homogenous groups of patients and to select phenotypes for biological studies.

© 2018 Ima-Press Publishing House. All rights reserved. Atherosclerosis is now considered as chronic inflammatory vascular disease connected to «pathological» activation of innate and adaptive immunity, characterized by lipid deposition, leukocyte infiltration and proliferation of vascular smooth muscle cells. Subclinical (low grade) inflammation plays fundamental role at all stages of atherosclerotic process progression and determines cardiovascular catastrophes development and mortality. Proinflammatory cytokines including interleukin (IL) 1, IL6, tumor necrosis factor α (TNFα), IL17, IL18, IL27, IL33, IL37 tightly interacting within cytokine network occupy an important place among numerous mediators participating in immunopathogenesis of atherosclerosis and rheumatoid arthritis. IL1β playing an important role in the development of many acute and chronic immunoinflammatory diseases attracts particular attention. IL1β significance in the development of atherosclerosis is determined by many mechanisms including procoagulant activity, enhancement of monocytes and leucocytes adhesion to vascular endothelium, vascular smooth muscle cells growth and others. Fundamental role of inflammation in the development of atherosclerosis is well proved in investigations of anti-atherosclerotic effect of canakinumab. Randomized placebo-controlled trial CANTOS (Canakinumab ANti-inflammatory Thrombosis Otcomes Study) assessing efficacy of canakinumab as new tool for secondary prophylaxis cardiovascular complications in general population of patients with severe atherosclerotic vascular damage. CANTOS results in combination with accumulated in rheumatology data on cardiovascular effects of anti-inflammatory drugs are of great importance for personification of approach to secondary prophylaxis of caused by atherosclerosis cardiovascular complications. They also contribute to the development of inflammatory theory of atherosclerosis pathogenesis in the whole.

© 2018 Ima-Press Publishing House. All rights reserved. The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- A nd anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1â (IL-1â), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: Nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.

© 2018, Dynasty Publishing House. All rights reserved. We analysed the association between levels of various cytokines and specificities of the clinical course and severity of toxic syndrome in pregnant women with influenza А(H1N1)pdm09, complicated by pneumonia. Cytokines reduce the sensitivity of the warm receptors and increase that of the cold receptors, which is regarded by patients as episodes of chills. According to correlation analysis data, IL-6 has the largest direct correlation with the persistence of fever, whereas interrelations between other cytokines and persistence of higher temperature proved to be less significant. It is noteworthy that elevated IL-6 levels lead to impairment of sleep architecture, which contributes to increased and persistent weakness, drowsiness. As has been shown, persistence of cough is to a significant degree determined by correlations between the levels of such cytokines, as TNF-α, IL-4 and IL-8. We assessed correlations between individual signs of systemic inflammatory response syndrome (SIRS) and cytokine levels. In diagnosing SIRS according to procalcitonin levels in viral-bacterial pneumonia 3 significant correlations were found (association with IL-8 – 0.72, TNF-α – 0.76 and IL-6 – 0.66). In pregnant women with pneumonia, generalised inflammatory process and a subsequent development of SIRS lower levels of the anti-inflammatory cytokine IL-4 have been found. A quantitative correlational approach to assessment of cytokine interrelationships has been proposed, permitting to differentiate between uncomplicated and complicated forms of influenza.

© 2018 Dynasty Publishing House. All rights reserved. The objective: To study M-CSF levels in venous blood and CSF1R gene polymorphism in women with tuboperitoneal infertility, who enter an IVF programme, and to assess their prognostic role. Patients and methods: The examination included 120 women, who were divided into two groups: 40 women with effective IVF (group I) and 80 women with ineffective IVF (group II). M-CSF serum levels were determined by ELISA method, the polymorphic marker rs386693509 of the c-fms gene UTR-3 region was examined by PCR method with subsequent Sanger sequencing. Results: Based on OR calculation, prognostically significant concentrations of M-CSF and c-fms genotype were found for diagnosing the development of pregnancy (95% CI = [1.934-11.116], p = 0.0021; 95% CI = [5.92-37.73], p = 0.0001, respectively). In women with effective IVF, weak correlation was found between M-CSF and the number of oocytes recovered by transvaginal puncture (TVP) (r = 0.3321, p = 0.0363). conclusion. The results of this work confirm a significant role of M-CSF in realisation of female reproductive function. The study has shown that serum M-CSF concentrations and polymorphism of its c-fms gene receptor have a predictive significance for pregnancy due to IVF procedure at the preconceptive stage. The obtained data contribute to our knowledge of the contribution of cytokines and gene polymorphisms to the development of an IVF pregnancy.

© Izdatel'stvo Meditsina. All rights reserved.  Introduction. Single-walled carbon nanotubes (SWCNTs) can create risks to human health when they enter the body by oral route when used in packaging materials, as promising agrochemicals and pesticides. The aim of the study. Evaluation of the subacute oral toxicity of SWCNT in rats. Material and methods. In the 92-days of the experiment, the SWCNTs were administered to rats along with drinking water at doses of 0 (control); 0.01; 0.1; 1.0 and 10 mg/kg body weight (BW) in the groups 1-5, respectively. Hematological indices of blood, apoptosis of hepatocytes, levels of pro- and anti-inflammatory cytokines in blood plasma and their production by cells of the spleen ex vivo, the content of the main and transient components of the intestinal microbiocenosis in the cecum were studied. There were determined hematological blood counts, hepatocyte apoptosis, levels of pro- and anti-inflammatory cytokines in blood plasma and their production by spleen cells ex vivo, content in the cecum of the main and transient components of the intestinal microbiocenosis. Results. At the SWCNT dose of 0.01 mg/kg BW there was a decrease in the number of neutrophils and basophils, an increase in the number of lymphocytes, and a decrease in the number and volume of platelets. At a dose of 0.1 mg/ kg bw there was noted a decrease in the number of cells in the early stage of apoptosis and the total number of cells in apoptosis, as well as a significant decrease in the levels of cytokines IL-10, IL-2, IL-4, IL-13, chemokine MIP-3a, TGF-β isoform 1; at a dose of 1.0 mg/kg IL-12p70, and TGF-β isoforms 1 and 3. TGF- β 2 level was significantly elevated in group 5. The suppressive effect was noted for SWCNTs on the mold flora in intestinal contents at all doses of nanomaterial used, whereas the number of yeasts increased at 1 mg/kg BW. The immunization of rats with ovalbumin had a clear modulating effect on the immunotropic effects of SWCNTs administered at a dose of 0.1 mg/kg BW in a 28-days experiment. Discussion. The mechanisms of the observed changes development are likely to be associated with both systemic anti-inflammatory effects and with a decrease in the effect of SWCNT on the permeability of the intestinal barrier to protein antigens and microbial toxins. Conclusion. SWCNTs exhibit a number of effects in relation to the studied indices that do not demonstrate a monotonic dependence on the dose of nanomaterial, which, apparently, is related to the processes of aggregation of the SWCNT.

© 2018, SPb RAACI. Periodontal disease, including gum disease, gingivitis, periodontitis and periodontal disease is frequently associated with progressive loss of bone and soft periodontal tissues. Recent studies suggest effectiveness of platelet-derived growth factor, fibroblast growth factor and other growth factors, which may stimulate regeneration of connective and bone tissue. A number of cytokines and growth factors participate in regulation of angiogenesis, but vascular endothelial growth factor (VEGF) is the most powerful agent, acting directly on the vascular endothelium. VEGF detected in saliva and endothelial cells of periodontium. VEGF plays a dominant role both in periodontal health maintenance as well as in chronic inflammatory periodontal disease. The aim of this work was to develop implementation of VEGF in periodontology, and a search for laboratory markers of therapeutic efficiency in periodontitis. We observed 19 patients aged 53-79 years with I-II grade periodontitis. In frames of periodontal therapy, the patients used a drug "Rebon. Gel for Gum" ("GF group", Russia). The drug represents a composition of bioresorbable carbohydrates on the basis of carboxymethylcellulose, forming the cellular basis for similar extraclean matrix. It contains different sodium, potassium, phosphorus, chlorine salts in order to balance the tissue pH, and a complex of glycated recombinant polypeptides identical to cytokines and human growth factors. ELISA method was used in the biological samples for detection of VEGF, human isoform A-165 ("SCI store" Ltd., Russia), and IFNγ (JSC "Vector Best", Russia). All our patients noted a decrease in pain after the treatment, as well as a significant acceleration of healing processes in oral cavity. Observation of the oral cavity state showed good dynamics and acceleration of bone tissue regeneration. After the treatment course, the level of IFNγ increased from 14.48 to 27.45 pg/ml. The difference before and after treatment values was significant (p = 0.022), despite a sufficient range of measured values. VEGF in gingival fluid showed a large scatter of values, from 26 to 279 pg/ml before treatment, and 16 to 198 pg/ml after treatment. Generally, a tendency for VEGF decrease was observed after treatment. To diagnose the current state of the periodontium, an importance of analyses of the gingival sulcus fluid is actual. The developed diagnostic approaches based on measuring the IFNγ, VEGF levels in screening and monitoring regimens help to provide a more effective treatment. Introduction of a complex preparation with growth factors and peptidoglycan-recognizing protein seems to accelerate epithelialization and regeneration of connective and bone tissue.