Search

Chronic rhinosinusitis (CRS) is a disease caused by inflammation of the paranasal sinuses and its mucous membrane lasting for more than 4 weeks continuously. The aim of our study was to examine the main pathophysiological features of chronic IgE-mediated rhinosinusitis of bacterial etiology according to publications in the Russian Federation and in the world. A search was made through English- and Russian-language literature sources using the following databases: PubMed, MedLine, Web of Science, Russian Science Citation Index, Springer, Scopus, Scientific Research, Google Scholar, Crossref, eLibrary. The epidemiological features of CRS in the Russian Federation, bacterial pathogens and pathophysiological characteristics of CRS were analyzed. A 2-fold increase in the prevalence of CRS was registered over the past 20 years. Prevalence of the disease increases at longer age ranges. Chronic rhinosinusitis ranks first among all chronic diseases in the field of otorhinolaryngology. Allergic rhinitis, asthma, bronchiectasia, immunodeficiencies, cystic fibrosis, primary ciliary dyskinesia and autoimmune diseases are associated with CRS. The most common bacterial pathogens are S. aureus, Staphylococcus epidermidis and Propionibacterium acnes, Prevotella, Streptococcus and Veillonella, and some Gram-negative bacteria, e.g., Pseudomonas aeruginosa (P. aeruginosa), Proteus mirabilis and Klebsiella pneumoniae. Staphylococcus aureus (S. aureus) is involved in pathogenesis of nasal polyps. The colonizing bacteria may contribute to pathogenesis of CRS through the formation of biofilms. Alterations in the sino-nasal microbiome may also contribute to the development of CRS. An association of the CRS and CFTR gene mutations plays a significant role in the pathogenesis of chronic rhinosinusitis. An “immune barrier hypothesis” has been proposed as potential mechanism of CRS. Reduced expression of SPINK5, impaired STAT3 signaling, and T2R38 bitter taste receptor polymorphism have been identified in the pathogenesis of CRS. The T2R38 gene stimulates epithelial cells to produce nitrous oxide with a bactericidal effect, promotes mucociliary elimination of pathogens and prevention of upper respiratory tract infections, the polymorphism of this gene predisposes patients to gram-negative infectious diseases, and therefore is a risk factor for the development of CRS. In addition, antibody deficiency is the most common primary immunodeficiency associated with CRS.Hence, the pathogenesis of chronic IgE-mediated rhinosinusitis of bacterial etiology is associated with defects in innate immunity and mucociliary clearance, influence of the sinonasal microbiome, allergies, and genetic factors. A comprehensive assessment of these factors is necessary for the development of new preventive and therapeutic options for the correction of CRS.

When the body is infected with the bacterium Helicobacter pylori, a cytokine cascade is launched, which plays a key role in the progression of chronic inflammatory and destructive processes in the gastric mucosa. Thus, the secretion of a number of cytokines is stimulated, which in turn contribute to the attraction of immunocompetent cells and the development of inflammatory changes. However, hyperproduction of cytokines can lead to atrophic changes in the gastric mucosa and, as a result, degeneration into gastric cancer. Thus, the role of cytokines in precancerous conditions is ambiguous. On the one hand, they activate the immune response aimed at eliminating the pathogen. On the other hand, they themselves contribute to the progression of the disease.The complex clinical and laboratory study included patients: 60 with chronic gastritis (CG), 55 with chronic atrophic gastritis (CAG), 50 with gastric cancer (GC, stage I-II, morphological variant – adenocarcinoma) and 60 – control group. The diagnoses were verified according to international and Russian recommendations and confirmed by laboratory and instrumental studies. All patients were comparable in terms of gender and age characteristics (p > 0.05). All patients had specific IgG to H. pylori. The study was approved by the Local Ethics Committee of the FRC KSC SB RAS (protocol No. 11 dated November 11, 2013). All ethical requirements were observed, and the patients signed the informed consent form for participation. Patients and persons of the control group underwent a single blood sampling from the cubital vein upon admission to vacutainers with heparin.The levels of IL-2, IL-4, IL-8, TNFα, interferon-γ in the blood serum of patients and healthy individuals were determined using the enzyme immunoassay method using reagent kits manufactured by JSC “VectorBest”. Statistical data processing was carried out using the Statistica for Windows 8.0 application package.All patients with H. pylori-associated diseases (CG, CAG, GC) showed an increase in pro-inflammatory (IL-2, IL-8, IFNγ) with a significant increase in IL-8 in all patients and IFNγ in gastric cancer and antiinflammatory cytokine (IL-4) with a maximum value in gastric cancer. A combined Th1 and Th2 is found – a mediated immune response with a maximum violation of cytokine regulation in gastric cancer.

Stomach cancer is in the top ten in terms of prevalence and ranks 4th in terms of causes of death worldwide. The most common and most aggressive variant of gastric cancer is adenocarcinoma. The monocytic link of immunity provides the main line of the body's fight against malignant cells, while in patients with adenocarcinoma it is insufficiently studied. The purpose of the study was to evaluate the functional activity of monocytes in patients with gastric adenocarcinoma at different stages of the disease.Individuals (n = 164) were examined, among whom 85 were diagnosed with stage I-IV stomach adenocarcinoma. The study also involved 79 apparently healthy donors. The functional activity and oxygen-dependent phagocytosis of monocytes were assessed by the chemiluminescent method. Luminol was used as a chemiluminescence inducer. The respiratory burst was activated with opsonized zymosan.In patients with stomach adenocarcinoma, at rest (spontaneous chemiluminescence), an increase in the time the curve reached the maximum intensity of chemiluminescence (Tmax = 7957 s), the area under the chemiluminescence curve (Squr = 0.2 x 106), the activation index (1.89 c. u.) and a decrease in the maximum value of chemiluminescence intensity (Imax = 424 c. u.) relative to the control group (Tmax = 5533 s, Squr = 0.011 x 106, activation index = 0.88 c. u., Imax = 424 c. u., p < 0.05) were seen. When chemiluminescence is induced in patients with stomach adenocarcinoma, a statistically significant predominance of Squr is fixed (0.46 x 106, in the control group Squr = 0.031 x 106). Also, in the group of patients with stomach adenocarcinoma, monocytic phagocytosis was reduced by more than 2 times (29% vs 84% in the control group, p < 0.05). When analyzing the studied parameters, depending on the stage of the disease, it was found that the violation of the chemiluminescent reaction in patients with stomach adenocarcinoma is fixed already at an early stage. At the same time, in patients with stage IV stomach adenocarcinoma, the indicators of spontaneous and induced chemiluminescence are more than 2 times different from those in the control group and patients at stage I of the disease. The identified features indicate a decrease in the effectiveness of immune reactions of the monocytic link in stomach adenocarcinoma already in the early stages of the disease and can be used to detect early signs of immune disorders and optimize therapeutic approaches in this disease.

Conflicting data on the role of the metabolic syndrome (MS) in the development of hepatocellular carcinoma (HCC) require studies on the influence of molecular factors that are important in the development of HCC in MS, which was the goal of our review. Publications (scientific articles and reviews) over the past 10 years were studied and analyzed using the databases Web of Science, Scopus, PubMed, RSCI. The terms used for the search were “metabolic syndrome and non-alcoholic fatty liver disease”, “metabolic syndrome and non-alcoholic steatohepatitis”, “metabolic syndrome and hepatocellular carcinoma”. The total number of publications studied in all databases exceeded 570 units, while the review presents the most significant results at the present stage. Insulin resistance and obesity, through the development of a systemic chronic inflammatory state, lead to increased inflammation and fibrosis in the liver, which are prodromal signs of hepatocarcinogenesis, increase the production of insulin-like growth factor-1 and disrupt the regulation of the insulin-like growth factor pathway. People with HCC have been shown to overexpress IGF-2. IGF-binding proteins, due to the reduced bioavailability of free IGF-1 and IGF-2 in the circulation, are able to inhibit the growth of HCC. In MS, a pro-inflammatory state is detected, which is caused by the production of cytokines by adipocytes (IL-6, IL-8, IL-1β, tumor necrosis factor α (TNFα), VEGF and chemokine ligands 2 and 5), which recruit immune cells, promoting angiogenesis and enhancing chronic inflammation. Transcription factors (PPAR) are involved in hepatocarcinogenesis, the significance of different factors is not fully understood. Leptin has a positive prognostic value in HCC, improving overall survival, and visfatin has a negative effect on hepatocarcinogenesis. Activation of PAI-1 inhibits the progression of HCC through PPARγ stimulation. Adiponectin may be a prognostic marker in HCC, with a lower serum concentration positively correlated with worse prognosis.

Non-alcoholic fatty liver disease currently affects more than 30% of the population. Recent studies highlight the role of genetic polymorphisms in genes associated with fat catabolism and anabolism in the manifestation of this condition and its progression. The work analyzes foreign publications on the molecular and biochemical aspects of these polymorphisms, as well as works studying their effect on the state of the liver and markers of its pathology over the past 10 years. Thus, polymorphisms of the PNPLA3, MBOAT7, and TM6SF2, affecting the functionality of the proteins they express, lead to a change in the metabolism of fatty acids in the liver, which in turn leads to the development of NAFLD and its progression. Despite the fact that the contribution of the rs738409 polymorphism of the PNPLA3 gene is well described both in foreign and Russian articles, polymorphisms of the MBOAT7 and TM6SF2 genes and their effect on NAFLD, as well as the molecular biochemical mechanisms underlying it, have been studied much worse in foreign studies and are little mentioned in Russian ones. In addition, the issue of the severity of the influence of the above polymorphisms on populations of different ethnic and age groups requires additional research. This work attempts to systematize the available data on these issues.

Obesity and metabolic syndrome are one of the major public health problems in the 21st century due to their prevalence. Nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, arterial hypertension, chronic inflammation and anemia are non-communicable diseases accompanying obesity. With obesity, there is a violation of iron metabolism, iron deficiency, which further contributes to the development of metabolic disorders. Iron is the second most abundant metal on Earth, and its bioavailability is reduced due to the formation of insoluble oxides, while iron deficiency is the most common nutritional disorder. Iron metabolism in the body is associated with the formation of reactive oxygen species involved in lipid peroxidation processes. Iron metabolism in the human body is regulated at all levels; dysregulation of any stage of metabolism can lead to iron deficiency and the development of anemia associated with obesity. This review article summarizes data on molecular and cellular abnormalities in iron metabolism in obesity and metabolic syndrome. The aim of our study was to study, according to the literature, pathophysiological disorders in iron metabolism in the development of obesity and metabolic syndrome. In the future, more research is required to study iron metabolism in obesity with the aim of their preventive and therapeutic effects. The role of oxidative stress in impaired iron metabolism in obesity has not been fully studied, while iron deficiency enhances lipid peroxidation processes in antioxidant deficiency. Under these conditions, oxidative stress can damage cells and destroy red blood cells. The question arises whether the restoration of iron homeostasis in obesity can improve metabolic, inflammatory disorders and reduce the manifestation of oxidative stress, becoming a new innovative approach to the treatment of concomitant metabolic diseases associated with obesity.

Obstructive jaundice caused by cholangiocarcinoma takes a special place among malignant disorders and surgical pathology in Russia. Involvement of nonspecific immunity and the role of neutrophils in carcinogenesis are ambiguously evaluated. The aim of this study was to study functional activity of peripheral blood neutrophilic granulocytes and their phenotype in obstructive jaundice caused by cholangiocarcinoma. The study included 56 patients with obstructive jaundice associated with cholangiocarcinoma at the T2- 3N0- 1M0 stage (clinical stages II-III), and 90 apparently healthy volunteers of similar age group. Neutrophilic granulocytes were isolated from peripheral blood by means of double-density Ficoll-Urografin gradient.Venous blood was collected in patients into vacutainers with heparin upon admission to the hospital, before the surgery was performed. Spontaneous cytokine production (IL-8, IFNá) was determined by enzyme-linked immunosorbent assay using Vector-Best diagnostic kits. To assess phagocytic activity of neutrophilic granulocytes, the phagocytic index (according to Hamburger), number of phagocytes (according to Wright) and the index of completed phagocytosis (according to Rudik, 2006) were calculated. Immunophenotyping of neutrophilic granulocytes was carried out using an FC500 flow cytometer (Beckman Coulter, USA) with monoclonal antibodies to CD11b+, CD16+, CD95+. The results were statistically analyzed using the Statistica v.12.0 software (StatSoft Inc., USA). To assess intergroup differences, the nonparametric Kruskal-Wallis tests (for three or more comparison groups) and Mann-Whitney tests (for pairwise comparison) were used. Comparison of groups for a qualitative binary trait was carried out using the two-sided Fisher’s exact test. Data are presented as Median (25 quartile-75 quartile).The study of the functional activity of peripheral blood neutrophiles in obstructive jaundice patients caused by cholangiocarcinoma revealed an increase in their relative and absolute number, increased phagocytic index and decreased phagocytic number of neutrophilic granulocytes, increased expression of CD11b+, CD16+, CD95+ immunological markers. The changes in neutrophil secretory activity were characterized by a decrease in cytokine production (IL-2, IFNá). An increase in functional activity of neutrophilic granulocytes, along with a decrease in their cytokine production suggests that, in obstructive jaundice observed in cholangiocarcinoma at clinical stage T2-3N0-1M0, an equilibrium stage is revealed between the cells of immune system and malignant tumor.

Background. The problem of gastric cancer remains unresolved throughout the world, while chronic atrophic gastritis (CAG) increases the likelihood of its development by 15 times. In the Russian Federation, the incidence of gastric cancer (GC) is among the highest, with it prevailing among males. One of the leading mechanisms in molecular pathology of membranes is lipid peroxidation (LPO). The severity of oxidative membrane damage depends on concomitant diseases, contributing to emergence and progression of pathological processes and development of cancer. Currently, the problem of LPO is unsolved in biological systems.The aim of this study was to investigate the state of LPO and antioxidant defense system in CAG and GC. Materials and methods. The parameters were studied in 45 patients with CAG and 50 patients with GC. The control group included 50 practically healthy volunteers without gastrointestinal complaints, who did not have changes in the gastric mucosa according to the fibroesophagogastroduodenoscopy (FEGDS) findings.Results. In patients with CAG, an increase in malondialdehyde, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase was found in the blood plasma compared with the control group. In patients with CAG, lipid peroxidation was activated, and the malondialdehyde level increased by 3.5 times relative to normal values. At the same time, the body fought against oxidative stress by increasing the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase. All patients with GC showed pronounced oxidative stress in the blood plasma in the form of a 45-fold increase in malondialdehyde. The activity of the main antioxidant enzyme superoxide dismutase was reduced in GC. Catalase was activated, which indicated pronounced oxidative stress, significant damage to blood vessels, and massive cell death. Glutathione-related enzymes (glutathione S-transferase and glutathione peroxidase) and the antioxidant protein ceruloplasmin were activated, which also indicated significant oxidative stress and severe intoxication in patients with GC.Conclusion. Depending on the stage and type of cancer, an in-depth study of lipid peroxidation and factors of the antioxidant defense system can be used to correct therapy and prevent cancer and can serve as markers of progression and prognosis in gastric cancer.

The aim of our study was to evaluate the clinical-anamnestic, serological, immunological and biochemical tests used for early diagnostics of gastric cancer associated with Helicobacter pylori infection in the adult population of the Krasnoyarsk Territory. Materials and methods. The control group consisted of 104 apparently healthy blood donors, the comparison group – 97 patients with chronic atrophic gastritis as well as a group of patients with early gastric cancer comprising 98 subjects. Assessment of monocyte and neutrophil spontaneous and induced chemiluminescence (CL) was carried out on a 36-channel biochemiluminometer BLM-3607. Phagocytosis was measured by using a Beckman Coulter FC 500 flow cytometer. A Varian Cary Eclipse spectrofluorometer was used to study lipid peroxidation and factors of the antioxidant defense system. Results and discussion. While studying the phagocytic arm of immunity, it was found that all patients with early gastric cancer were reported to have parameters of the maximum intensity for neutrophil spontaneous CL from 17 831 c.u. and lower, whereas induced CL reached at least 30 000 c.u. Phagocytic activity of neutrophilic granulocytes in patients with early gastric cancer was 36% or less. While studying the indicators of monocytes, it was found that spontaneous and induced CL decreased from 454 c.u. and 1186 c.u., respectively, in the patients with early gastric cancer. Monocytic activity in early gastric cancer was 34% or less. In the study of lipid peroxidation, an antioxidant defense in patients with chronic atrophic gastritis and gastric cancer had increased malondialdehyde (MDA) level. Patients with gastric cancer had decreased activity of the enzyme catalase (CAT), whereas subjects with chronic atrophic gastritis had reduced glutathione peroxidase (GPO) level. In contrast, patients with early gastric cancer were featured with increased GPO activity. We have proposed coefficients for assessing the factors of the antioxydant defence system in patients: the ratio for superoxide dismutase to catalase activity (SOD/CAT) as well as the ratio for superoxide dismutase to glutathione peroxidase activity (SOD/GPO). Conclusion. During the study, threshold values of parameters were obtained for assigning groups at high risk of developing early gastric cancer, which can be used for screening in adult population.

Aim. A study of the overlap syndrome of uninvestigated dyspepsia and heartburn at an industrial hub city of Eastern Siberia.Materials and methods. A total of 1,382 subjects (684 men and 698 women, mean age 40.6 years) were randomly selected and examined for the central district of Krasnoyarsk. The clinical check-up and interviewing results were registered with a standard questionnaire. Heartburn was diagnosed as per the Montreal Consensus. Since no endoscopic patient examination had been performed, dyspepsia was assumed uninvestigated. Dyspepsia was diagnosed as per the Rome IV criteria. The study conduction complied with ethical standards. Each participant signed an informed examination consent, in accordance to the regulations by the World Medical Association’s Declaration of Helsinki. The survey data were analysed with common statistical methods.Results. Heartburn, uninvestigated dyspepsia and their overlap syndrome had prevalence of 12.4, 21.1 and 5% in study population, respectively. Uninvestigated dyspepsia was registered in 40.4% patients with and 18.4% — without heartburn (p < 0.001). The risk factors of overlap syndrome were age >40 years (p = 0.002), obesity (p = 0.002), nonsteroidal anti-inflammatory drug and/or aspirin intake (p = 0.004) and tobacco smoking (p = 0.007). Among total patients with the heartburn/uninvestigated dyspepsia overlap syndrome, only 33.3% systemically had proton pump inhibitors, and only 17.4% had a prokinetic therapy.Conclusion. The heartburn/uninvestigated dyspepsia overlap syndrome is an actual issue in the Krasnoyarsk population. Attention is warranted to this problem to optimise treatment and prevention measures.

Aim. To study the content of cytokines in the blood serum of patients with obstructive jaundice of gallstone origin before and after surgical treatment, depending on the development of postoperative complications.Materials and methods. The treatment group consisted of 70 patients with the diagnosis of obstructive jaundice of gallstone origin, verified following a comprehensive clinical and instrumental examination. In 54 patients, the postoperative period was uncomplicated, and in 16 patients, various infectious complications in the postoperative period were revealed. The control group consisted of 125 healthy volunteers. The concentration of six cytokines (interleukin (IL)-2, IL-4, IL-18, IL-10, tumor necrosis factor alpha (TNFα), and interferon gamma (INF γ)) was determined using reagent kits manufactured by Vector-Best LLC (Novosibirsk, Russian Federation) by enzyme-linked immunosorbent assay on the Thermo Scientific analyzer (BioMerieux, France).Results. We identified significantly high concentrations of proinflammatory cytokines in the blood serum of patients with obstructive jaundice of gallstone origin upon admission, compared with the data obtained in the study of blood serum in the control group and in patients with obstructive jaundice after surgery. In the postoperative period in patients with obstructive jaundice without complications, the proinflammatory cytokines are significantly reduced and IL-4 is increased, whereas with the development of infectious complications, the level of proinflammatory cytokines is significantly elevated.Conclusion. In the pathogenesis of obstructive jaundice, a local inflammatory process plays an essential role. This is confirmed by statistically significant changes in the studied cytokines. The established increase in the concentration of IL-4, which has anti-inflammatory activity, indicates its importance in the mechanisms underlying the absence of infectious complications in the postoperative period of obstructive jaundice of gallstone origin. The revealed increase in the levels of IL-18, TNFα, and INFγ in the blood serum of patients suggests their role in the pathogenesis of infectious complications in the postoperative period of obstructive jaundice of gallstone origin.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in highly developed countries. The risk of developing NAFLD and associated complications varies greatly among people of different nationalities and is determined by environmental and genetic factors. Genome-wide studies have revealed strong and reproducible associations between gene variations such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1, and NAFLD. In this article, we consider the influence of genes and environmental factors on the pathophysiological features of NAFLD. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants, will inevitably improve the understanding of the pathogenesis of NAFLD, and will allow the development of a technology for personalized risk in assessing the disease in a patient. The aim of our study was to study the genetic predictors of NAFLD based on literature data with the interpretation of the studies. There is now strong evidence that specific variants of genetic risk have a large effect on NAFLD, and their effect is comparable to that of major metabolic risk factors such as obesity and type 2 diabetes. The increased risk extends to the onset and progression of the entire spectrum of NAFLD manifestations, including overall mortality due to liver disease. Currently, individual genetic variants do not allow the creation of a personalized risk profile; therefore, the most expedient approach today is the development of polygenic risk assessments. The number of genetic loci associated with the prevalence and outcome of NAFLD remains limited. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants and will inevitably improve the understanding of the pathogenesis of NAFLD and will allow the development of a technology for personalized risk in the assessment of the disease.

Aim. A study of monocyte chemiluminescent activity at variant stages of gastric cancer.Materials and methods. The study enrolled 90 gastric cancer patients and 70 healthy donors. Spontaneous and induced chemiluminescence in monocytes was assessed for 90 min with a “BLM 3607” 36-channel chemiluminescence analyser (Russia). Opsonized zymosan-induced chemiluminescence enhancement was measured as a ratio of the areas under the induced vs. spontaneous chemiluminescence curves, the activation index. Statistical significance was estimated with the Mann—Whitney criterion (p < 0.05).Results. The maximal spontaneous monocyte chemiluminescence intensity significantly decreased in stage IV gastric cancer patients compared to the control cohort (p = 0.035). Time to maximum in spontaneous chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.043). The areas under a curve in spontaneous and induced monocyte chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.037). The activation index was higher in all gastric cancer cases compared to control (p = 0.001).Conclusion. All patients with gastric adenocarcinoma, irrespective of the stage, revealed changes in the monocyte chemiluminescence activity, i.e. a longer time to maximum in spontaneous chemiluminescence and larger area under the curve of spontaneous and induced chemiluminescence, the activation index. Maximal monocyte spontaneous chemiluminescence intensity diminished in stage IV gastric cancer compared to the control cohort. Immune activity reflected in monocyte chemiluminescence correlates with the stage of gastric adenocarcinoma.

One of the essential tasks of sustainable forest management is to maintain native biodiversity. Primary forest research is one of the ways to understand what this biodiversity is. Matherials and methods. The primary, as confirmed by their land-use history and structural peculiarities, mesic dark-conifer forests remain in Visim and Pechora–Ilych nature biosphere reserves (boreal and sub-boreal zones respectively, the Ural Mountains, Russian Federation). We compared the primary forests and post fire 100-year small-leaved deciduous forests by diversity of vascular flora and soil invertebrate macrofauna. Results and discussion. The diversity of some functional groups of species (low boreal herbs, earthworms) in post fire forests is lower than in primary forests, the research shows. These species largely depend on deadwood and other tree-related microhabitats common in the primary forests but not so in the 100-year post fire forests. Repeated fires at intervals of several decades, as is the case with the use of prescribed fires in forest management, will be expected to reduce the biodiversity quality of these specialist species. Additionally, we revealed that post fire forest flora is more synanthropic in the woodland of a small area (Visim reserve) than in the intact forest landscape (Pechora–Ilych reserve). It demonstrates that, within extensive woodlands, native forests are more resilient to sporadic stand-replacing disturbances than small woodlands. Conclusion. Strict conservation of intact forest landscapes is necessary as they serve as large buffer areas around the remaining primary forests to maintain native biodiversity.

Chronic atrophic gastritis and gastric cancer represent distinct steps of one pathogenic process. The risk of developing cancer of the stomach is directly proportional to the degree of atrophic changes simultaneously detected in antral segment and in the body of the stomach. The role of immune system in transformation of precancerous diseases into cancer is beyond doubt. During development of the malignant disease, the changes in lipid peroxidation systems – antioxidant defense become significant and contribute to the progression of the tumor and the development of metastases. A simultaneous study of lipid peroxidation and antioxidant defense indices along with phagocytic activity will allow us to evaluate relative contribution of these processes to development of chronic atrophic gastritis and gastric cancer. Purpose of the present study was to assess correlations between the lipid peroxidation indices, i.e. antioxidant protection, and chemiluminescent activity of neutrophilic granulocytes and monocytes in chronic atrophic gastritis and gastric cancer. Forty patients with chronic gastritis, 22 patients with chronic atrophic gastritis and 40 patients with gastric cancer were examined. The control group consisted of 50 practically healthy age-matched volunteers. Evaluation of spontaneous and induced production of reactive oxygen species by neutrophils and monocytes was carried out by chemiluminescent analysis. The parameters of lipid peroxidation/ antioxidant protection were determined by spectrophotometric methods. Statistical data processing was carried out using the Statistica v. 8.0 program (StatSoft Inc., USA). The normal distribution of indices was tested using the Kolmogorov–Smirnov method (adjusted by Lillefors). Quantitative indicators, given the normal distribution, were described using the median (Me) and interquartile scatter (Q0.25-Q0.75). To study statistical significance of differences between quantitative characteristics, the Mann–Whitney test was used. To study strength of relationships of these indicators, the Pearson rank correlation coefficient (r) was calculated. The critical significance level (p) when testing statistical hypotheses was taken equal to 0.05. Correlation analysis showed that the weight of positive correlations increases in patients with chronic atrophic gastritis, and it decreases in patients with gastric cancer, the strength of the correlation dependence and new relationships appear between chemiluminescent activity of neutrophils and monocytes in a spontaneous and induced state, and the amounts of malonic dialdehyde, enzyme activities of superoxide dismutase and catalase. In chronic atrophic gastritis and gastric cancer we have established the features of correlation patterns between lipid peroxidation/antioxidant protection indices, and activity of neutrophils and monocytes.

Helicobacter pylori is the most widespread human pathogen, with prevalence reaching up to 20—40% and 80— 90% of adult infection in developed and developing countries, respectively. Many authors consider this infection as a major factor in the development of gastric cancer. In case of H. pylori infection, free homogeneous oxidation is augmented, that elevates the blood amount of POL products. Hyperproduction of reactive oxygen species stimulates free radical POL, accompanied by membrane destruction, damage to proteins, lipids, and DNA. Thus, the destruction of the intracellular and cell outer membranes occurs resulting in cell death. In diseases associated with H. pylori infection, there is a dysregulation of the lipid peroxidation system — antioxidant defense contributing to inconsistency in the regeneration phases triggering disease progression. The aim of our work was to study indicators of POL (diene conjugates, malonic dialdehyde) and antioxidant protection (AOP) (superoxide dismutase enzymes, catalase) in chronic gastritis and chronic atrophic gastritis associated with H. pylori infection. In patients with CG associated with H. pylori as well as CAG and CAG associated with H. pylori they were featured with increased amount of primary (↑DC) and end TBA-active products of lipid peroxidation (↑MDA), whereas activity of superoxide dismutase was decreased, additionally highlighted with reduced catalase activity (↑CAT) in CAG and CAG associated with H. pylori. H. pylori just triggers the mechanisms of ROS generation in host cells. The energy of redox reactions is used by the microorganism to carry out its physiological functions and serves as a factor in its own pathogenicity, the ROS generated in such reactions can have a damaging effect on the structure of gastric mucosa. In addition, examining H. pylori genome has shown that it bears the genes encoding oxidative metabolism enzymes, such as SOD, catalase, nitroreductase, flavodoxin oxidoreductase. Long-term persistence of H. pylori in the gastric mucosa paralleled with its increased biomass accounts for it being the main source of ROS production able to augment lipid peroxidation and cause damage to the membrane structures and DNA of gastric epithelium cells.

At present, the level of Helicobacter pylori infection is determined by geographic area, gender and age of the examined individuals, and can reach up to 95% of the total population. Environmental adaptation of H. pylori is exhibited in its ability to adhere to the gastric mucosal epithelium and modulated expression of its own virulent factors. Current concepts implicate that H. pylori can survive inside epithelial cells, evading host immune response. Cytokines are produced by immune cells and act to regulate its major stages. A cytokine cascade launched after Helicobacter pylori infection triggers immune reactions, progression of chronic inflammatory and destructive processes in the gastric mucosa. The role of cytokines in precancerous diseases of the stomach is ambiguous because, on the one hand, they activate immune response aimed at eliminating the pathogen, whereas on the other hand, they do contribute to the disease progression. The aim of our study was to examine profile of some cytokines and features of cytokine regulation in H. pylori-infected middle-aged males with chronic gastritis (CG) as well as chronic atrophic gastritis (CAG). In patients with CG with H. pylori, CAG and CAG with H. pylori, an increase in the cytokine IL-2 was observed that might contribute to augmented damaging effect of cytotoxic lymphocytes, as well as implementation of antitumor effect. CAG with H. pylori was featured with IL-8 hyperproduction, which resulted in increased absolute numbers of band neutrophils in peripheral blood and their decreased phagocytic activity evidencing about altered host defense mechanisms. There was increased amount of IFNy involved in recognition of malignantly transformed cells and upregulated expression of the major histocompatibility complex molecules on antigen-presenting cells. In patients with CG with H. pylori and CAG with H. pylori, production of IL-4 was increased, which might serve as a contributing factor to the chronicity of H. pylori-associated diseases. Overproduction of type 1 and type 2 cytokines indicates about activated Th1 and Th2 type immune reactions in H. pylori-associat-ed CG. A potent pro-inflammatory cytokine cascade triggers inflammatory changes in gastric mucosa with developing neutrophil infiltration and lymphocyte activation. Damage and death of epithelial cells upon inflammation form erosive and ulcerative defects, or changes manifested as gastric mucosal atrophy, metaplasia and neoplasia. The data obtained may be used as additional diagnostic criteria in early diagnostics of precancerous stomach diseases.

Background. Acute hemorrhage remains the leading cause of death on the operating room in emergency surgery. However, the correlation of the central hemodynamics, oxygen balance and homeostasis in such victims during emergency surgical treatment with the outcomes of surgical treatment has not yet been evaluated.Material and methods. We examined 100 patients with acute massive blood loss, who had emergency surgery. We determined heart rate, arterial pressure by direct and indirect methods, central venous pressure, oxygen saturation of blood, cardiac index, systemic vascular resistance, gas and acid-base contents of arterial and venous blood, oxygen consumption, oxygen delivery, oxygen extraction ratio according to generally accepted formulas. Two groups of patients were formed of 50 people, depending on the oxygen balance (Group 1 - subcompensation, Group 2 - decompensation).Results. At the time of admission to the operating room and after the surgery, the indicators of systemic hemodynamics in patients of both groups did not differ statistically significantly. In the Group 2, at the time of admission to the operating room, there were statistically significantly higher VO2 (195 (158, 256) ml/(min-m2) and 112.5 (86; 145.3) ml/(min-m2)), ERO2 (50 (45.1, 60) % and 25.1 (19.6, 33.2) %) and low SvO2 (54.4 (48.5, 67.5) % and 75.1 (67,8; 83) %) (p

Solving the problems of sustainable existence of the biota in Northern Eurasia requires a detailed analysis of the interactions between human and nature at the initial stage of the development of this territory. Paleoreconstructions of the structural and functional organization of the biota in the analyzed territory at different stages of its development constitute the necessary basis for solving the problems of preserving and restoring natural laws, which are absolutely necessary for a deep understanding of natural mechanisms, as the main condition for the survival of mankind. The initial stage of interaction between human and nature called “appropriating economy” was marked by the destruction of complementary systems – the basis of the sustainable existence of nature as a whole. The main reason is the almost complete destruction of the giant phytophagous mammoth complex. The next period of interaction between human and nature is “the stage of the productive economy”, in which slash-and-burn agriculture became the main method of agricultural development of forest areas in Northern Eurasia. This type of Nature management caused a decrease in the productivity of forest ecosystems, associated with the loss of nutrients after the burning of the stand, with the loss of soil biota and a decrease in soil fertility. Thus, the pre-anthropogenic biota is replaced by modern fragments of anthropogenically transformed areas. Currently, when the still preserved species and their groups cannot be maintained by nature itself, we need to develop and implement large-scale measures to restore the biota and its climate-regulating functions as soon as possible.

This commentary is devoted to the article by V. G. Gorshkov and A. M. Makaryeva (2020), in which the division of biota in forest ecosystems is considered using the concepts of both "immotile life" and "locomotive life". The article presents well-known arguments to prove the erroneousness of using such concepts, because motion is a fundamental property of living creatures and is realised at all levels of living system organisation. Representatives of all the kingdoms are widely distributed in space at different stages of the life cycle. In opposite the view by Gorshkov and Makarieva (2020), which the large herbivorous are destroyers of terrestrial ecosystems emphasizes, in the current commentary is considered the importance of mammals in forests, for the circulation of matter and energy flow in forest ecosystems to maintain biodiversity and the efficiency of trophic systems.

Most woodlands of the Northern Eurasia are represented by bilberry-green moss spruce-fir forests. At the same time, a tall herb type of spruce-fir forests that occupies a much smaller area was identified and described. The objective of this work is to evaluate and compare the species richness and productivity of the ground vegetation of tall herb spruce-fir (unique) and bilberry-green moss spruce-fir (typical) forests of the Northern Urals. Based on previous studies, two forest types were selected in the foothill part of the Pechora-Ilych nature reserve with tall herb and bilberry-green moss ground vegetation, where total mapping, determination of microsite area and geobotanical descriptions had been carried out previously. Material for determination of the aboveground and below-ground phytomass and chemical composition of plant species was collected in 2017–2018. The concentrations of C and N in plant samples were measured on the elemental analyzer, and Mg, Al, P, S, Cl, K, Ca, Fe, and Zn content was found using the method of measuring mass fraction of the element in powder samples by X-ray fluorescence analysis. It was found out that the total phytomass of vascular plants in the ground vegetation of tall herb forests is 5 times higher than that of bilberry-green moss forests. The phytomass of mosses, on the contrary, is 4.4 times lower in tall herb forests in comparison with bilberry-green moss forests. Examination of ecological-coenotic groups of plants in terms of the content of chemical elements taking phytomass in consideration shows that the greatest contribution to the accumulation of macro- and microelements in the tall herb spruce-fir forest is made by the plants from tall herbs, boreal dwarf shrubs and boreal small herbs groups; in the bilberry-green moss spruce-fir forest, the main role is played by mosses and boreal dwarf shrubs. To assess the content of biogenic elements in the ground vegetation a differentiated approach was suggested, which included accounting for above-ground and below-ground phytomass by ecological-coenotic groups of plants within different types of microsites.

Colorectal cancer is one of the most common malignant diseases in Russia worldwide making up 5-6% of all human malignant tumors. Neutrophilic granulocytes are actively involved in development of antitumor response. A key role in tumor regression is assigned to active forms of oxygen produced by neutrophils. In connection with these pre-requisites, our goal was to study functional characteristics of spontaneous and induced chemiluminescent activity of neutrophil granulocytes in patients with rectal cancer before starting pathogenetic therapy and in subsequent dynamics. The paper presents some laboratory results, i.e., functional indices of neutrophilic granulocytes’ activity in 36 patients with rectal cancer being at different stages of oncological process. The control group consisted of 112 practically healthy volunteers, comparable in sex and age to the group of patients under study. To perform the study venous blood was taken from patients to vacuum test tubes with lithium heparin in the morning time before surgical treatment, and on day 7 after the surgical intervention. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes in a 36-channel “CL 3606” chemiluminescence analyzer (Russia). The following characteristics were determined: time of the curve transition to maximal chemiluminescence intensity (Tmax), maximal value of chemiluminescence intensity (Imax), integral area under the chemiluminescence curve (S). Luminol was used as the chemiluminescence enhancer. Opsonized zymosan was used to induce the respiratory explosion. Chemiluminescence amplification induced by opsonized zymosan was evaluated by the ratio of induced-tospontaneous chemiluminescence (Sind/spont) designated as an activation index.Analysis of chemiluminescence activity in neutrophilic granulocytes showed a significant increase in spontaneous chemiluminescence activity at the stages III and IV of the disease. The production of active oxygen forms induced in neutrophilic granulocytes by opsonized zymosan increased in all the study groups, relative to control parameters. The area under the curves of spontaneous and induced chemiluminescence in patients with colorectal cancer at all stages of the oncological process is less, as compared to the control group, which, despite high indices of maximal chemiluminescence activity, may indicate insufficient total production of reactive oxygen species. The time-to-peak values of the chemiluminescence curves in patients with rectal cancer at all stages of the disease did not show statistically significant differences from the control group.

The state of the Earth's living cover raises serious concern about its ability to successfully exist and fully implement its ecosystem functions in modern conditions. Hence the need to revise our relationship with the Nature on the basis of modern scientific achievements reflected in the concept of complementarity which is mutual favour of living beings during their lives and after death. Data analysis has shown that complementary relations on the territory of Northern Eurasia were most developed during the Miocene – Pliocene period, which resulted in a huge biodiversity, the highest productivity, as well as the maximum implementation of climateregulating functions of the Biota. Mass destruction of the giant herbivores of the mammoth fauna who organized complementary systems had global consequences, i.e. changes in the temperature regime, reduction of feed resources, decreased soil fertility, changes in the size and boundaries of ranges of animals, plants, fungi and representatives of other kingdoms as well as the replacement of complementary systems of giant herbivores and grasses by systems dominated by trees which made these landscapes unsuitable for remaining the herbivores. Further transformations of the Biota of Northern Eurasia were determined by human activity.

Mechanical jaundice (MJ) of malignant genesis is a clinical syndrome caused by obturation of bile ducts due to malignant tumor growth. It is characterized by specific pigmentation of skin, mucous membranes and sclerae due to increased accumulation of bilirubin in blood serum and other fluids and tissues of the organism. Various immune disorders are detected in patients with mechanical jaundice. Immune reactivity in mechanical jaundice is affected by toxic, infectious, or tumor factors. In connection with these findings, the aim of our study was to measure levels of some pro-inflammatory (IL-2, IL-18, TNFα, IFNγ) and antiinflammatory (IL-4 IL-10) cytokines in patients with malignant disease, depending on serum bilirubin levels. The study included 50 patients with MJ by malignant origin. A control group consisted of 125 practically healthy volunteers comparable with the study group by sex and age. Blood serum cytokine contents in patients and controls was determined by enzyme immunoassay using reagent kits produced by ZAO Vector-Best. Statistical evaluation of data was carried out by means of Statistica for Windows 8.0 and Microsoft Excel software. The levels of IL-2, TNFα, IFNγ and IL-18 were increased before surgery in the patients with mechanical jaundice of malignant genesis, while IL-4 and IL-10 values were reduced in comparison with healthy controls. Altered cytokine regulation in the MJ group manifests as increase in proinflammatory and immunostimulatory cytokine levels, along with decrease in anti-inflammatory cytokine amounts. Predominant feature of immune response may be regarded as prevalence of Th1-immune response when taking into account cytokine levels in blood serum of patients with MJ of malignant genesis. The features of cytokine regulation of patients with malignant MJ depend on the bilirubin content in blood serum. These changes were most frequent in patients with bilirubin level exceeding 60 μmol/L. In general, the quantitative indices of cytokines exhibited unidirectional changes in the groups of MJ patients with different bilirubin levels, except of IL-10. This parameter showed almost 6-fold increase in MJ patients with bilirubin level < 60 μmol/L against control group, and approximately 40 times with respect to the remaining 2 groups. This biological effect may occur due to malignant etiology of the MJ.

Hysterectomy is an extensive surgical intervention, which is accompanied by heavy post surgical pain syndrome. Despite mainstreaming of the combined anaesthesis concept, which implies the simultaneous prescription of several analgesics with different mechanisms of action, frequently the quality of postoperative anesthesia continues to be unacceptable. Another option of the problem solution is to introduce the additional regional anesthesia practices, in particular the nerve block anesthesia in the transversus abdominis plane. This study allowed concluding that the block anesthesia of transversus abdominis plane block before hysterectomy does not result in significant reduction of postsurgical pain syndrome and morphine consumption during the first day after surgery, while significantly increases time of the first demand for morphine and helps reducing the dermic hyperalgesia area postoperatively.

Chronic gastritis is the most common disease of gastro-intestinal tract. Precancerous potential is among most important epidemiological features of chronic gastritis. Immune system plays a distinct role in transformation from precancerous state to malignancy. In this context, the aim of our work was a study of spontaneous and induced chemiluminescence activity of neutrophilic granulocytes in patients with chronic superficial gastritis, chronic atrophic gastritis and gastric cancer. The work presents results of comprehensive laboratory examination of patients with chronic gastritis (CG) (a total of 85 persons. 25 patients with chronic atrophic gastritis (CAG), and 50 patients with gastric cancer (GC) at the age of 19 to 70 years were enrolled. Control group included 115 healthy donors without gastrointestinal complaints at the age of 19 to 67 years. The study was performed with venous blood samples taken from cubital vein into Vacutainer tubes with sodium heparin (5 U/mL) prior to starting any pathogenic treatment. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes at a 36-channel “CL 3606” chemiluminescence analyzer (Russia). In our study, patients with gastric cancer showed clear unidirectional changes in chemiluminescent activity of neutrophilic granulocytes (NG). When measuring spontaneous and induced NG chemiluminescence, we diagnosed a decreased phagocytic activity characterized by prolonged time-to-peak and area under the curve for spontaneous and induced CL, thus presuming longer activation time required in cases of reduced phagocytic function. The NG activity in patients with chronic gastritis is not impaired, but, similar changes of time-to-peak and area under were detected. Chemiluminescent activity of NG is increased in the group of CAG patients, and, considering similar changes in activation time and area under the curve, NG also produce greater amount of reactive oxygen species. Thus, for all H.pylori-associated diseases, the blood NG take longer time to activate, whereas their functional activity is not disturbed in CG, enhanced in CAG patients, and reduced in gastric cancer.

The reconstruction of the verbal pre-anthropogenic Northern Eurasia forest cover has been proposed on the basis of paleontology and historical ecology data analysis. It was used as a basis for evaluating the ability of the reserves in the studied area to act as reference objects capable of performing the ecosystem living soil cover functions. The analysis indicated immense anthropogenic transformation of the Biota in this territory and the requirement for urgent measures to restore the full-fledged Biota of the reserves at the state and global levels. A list of necessary activities for the initial phase of Biota recovery in the modern protected areas has been proposed.

Mechanical jaundice (MJ) is a severe pathological condition, caused by obstruction of the bile ducts, requiring immediate surgical intervention. Etiologically, MJ can be of benign (60-80% of the cases,) or malignant origin. MJ progression depends on the underlying pathology, and, moreover, on bilirubin levels. Focal inflammation in affected area represents a significant mechanism of the MJ progression. Neutrophilic granulocytes, are primarily involved into the immune response, i.e., pathogen elimination. Hence, the MJ progression may depend on their functional activity. In this context, the aim of our study was to investigate chemiluminescent activity of neutrophil granulocytes in progression of MJ, depending on the bilirubin levels and origin of the jaundice. All the MJ patients showed altered chemiluminescent activity of granulocytes. Both spontaneous and induced chemiluminescence (CL) intensity was decreased in the patients with gallstoneassociated MJ. Meanwhile, the CL intensity did not change in MJ caused by benign tumors (BTP). An increased activation index reflected higher induced activity of phagocytes. In patients with MJ of malignant origin, the largest number of changes was found, i.e., an increase in the induced luminescence intensity and higher activation indexes were revealed. The MJ progression depends on blood bilirubin levels. All the patients with gallstone-related MJ exhibited a decrease in spontaneous and induced CL activity of the neutrophils. In cases of BTP-caused MJ, the indexes of spontaneous and induced CL decreased at the bilirubin levels of 60 to 200 mmol/L, with increased activation index suggesting elevated induced activity over its spontaneous levels. In patients with MJ and bilirubin levels >200 mmol/L, distinct unidirectional changes in the granulocyte activation were observed, with increased spontaneous and induced CL intensity. In patients with MJ caused by malignancies with bilirubin levels 200 mmol/L, an increased spontaneous and induced activity of granulocytes was registered in these cases, probably, due to development of multi-organ failure and toxic effects of bilirubin. The granulocytes seem to exhibit their maximal activity, until exhaustion of their functional limits.

Old-growth spruce and spruce-fir forests can be extremely variable in the composition and diversity of their ground layer of vegetation, sometimes with over 10 times difference in diversity between various forests. What is the reason for such a big difference? Here we propose a hypothesis that the ground layer of vegetation is most strongly affected by fire history of boreal forest ecosystems. We estimated composition, structure and diversity of vascular plant and bryophyte species in seven forest types in old-growth forests dominated by either Picea obovate or Picea obovate together with Abies sibirica, which were located in the plains of the Komi Republic. All the study areas were either at elevated or hilly plains with good and moderate drainage, or in valleys of small rivers and streams, away from wets and bogs. We analyzed Landolt’s species ecological values, coverage of vegetation layers and deadwoods at different stages of decay, bedrock parameters, and soil charcoals in order to explain differences in the plant species composition and diversity. We showed that there are weak but statistically significant correlations between the coverage of deadwoods at different decay stages and vascular species composition and a positive correlation between the total deadwood coverage and bryophyte species diversity. Among the studied forests, those that are dominated by boreal and nitrophilous tall herbs (located in watersheds and in river valleys respectively), have no fire scars on stems of Pinus spp. and almost no charcoal in the soil and demonstrate the highest species diversity. We estimated that these forests have not experienced fires for over 400 years. In contrast, the diversity of vascular plants in the forests dominated by green mosses, dwarf shrubs, small boreal herbs and large ferns was low; we evaluated that the last time when these forests suffered intense multiple fires was at least 150 years ago.

From the prospective of ecosystem ecology, the huge role of the concept "complementarity" in perceiving the mechanisms of sustainable existence of the natural (pre-anthropogenic) biota is substantiated. A comparison of structural and functional organization between the paleobiota of Northern Eurasia and its fragments, survived until the present day, the modern biota, was performed in the main types of conservation areas. The incompleteness of the modern biota in natural reservations and its main cause are shown: direct or indirect destruction of key species that determined the possibility of the existence of large groups of subordinate species is described. It has been found out that as the anthropogenic exploration of Northern Eurasia intensifies, the ability of the biota’s fragments ("debris") to support ecosystem functions of the biosphere decreases. It is concluded that a fundamentally new direction in the protection of nature is to be developed: "Pleistocene Rewilding" formed on a world-wide basis as a result of the awareness of the need for active restoration of the biosphere functions of the Earth's ground cover.

The aim of present work was to study some activation features of neutrophilic granulocytes from peripheral blood of the patients with G type of multiple myeloma (MM), as depending on clinical stage of the disorder. In this study, a number of parameters were evaluated, as follows: time dynamics of the up-to-maximum luminescence increase; maximal luminescence levels, areas under the curves (AUC) for the dynamic luminescence registration. Zymosan was used as chemiluminescence inducer, and luminol, as enhancer of the “respiratory burst”. The chemiluminescence enhancement was assessed as a ratio of AUC values corresponding to induced-to-spontaneous chemiluminescence being denoted as an ‘activation index’. The onset and progression of MM in humans was accompanied by disturbance of neutrophil functions. MM patients at stage II and III exhibited a significant increase of spontaneous ROS production relative to controls. The inducible ROS production by neutrophils was also increased in all groups, as compared with spontaneous production and and control parameters, thus arguing for a distinct role of neutrophils, as potentially cytotoxic effectors against tumor cells, along with their basic function of nonspecific antimicrobial protection.

Cytokines are wide-range modifiers of biological reactions. Cytokine regulation provides proliferation, differentiation, cell function, cell-cell and inter-systemic interaction, direction and nature of immune response to invasion of infectious and non-infectious pathogens. There are several distinct groups of cytokines: pro-inflammatory, anti-inflammatory factors, regulators of cellular and humoral immunity etc. A distinct role of cytokines is not excluded for infectious complications accompanying multiple myeloma (MM). Cytokine regulatory effects on immune defense in the organism as a whole, and a balance between proand anti-inflammatory cytokines in blood of MM patients depend on the stage of multiple myeloma progression and possibility of infectious complications. Therefore, the aim of our study was to evaluate proand anti-inflammatory cytokines and cytokine regulation in patients with MM G-immunochemical option. Our study involved 101 patients with MM (IgG-variant), their age ranging between 40 and 76 years. The diagnosis was verified by clinical and laboratory examinations. The G-variant of MM was verified by immunofixation and electrophoresis. The definite diagnosis and disease staging was confirmed by a combination of diagnostic criteria. Heparinized blood samples were taken from the cubital vein in the morning (8 to 9 hours), in fasting state upon admission, prior to the starting a pathogenetic therapy. Dynamic monitoring of patients was carried out over the period of their staying in hospital. All patients were staged according to Durie and Salmon (1975) (stages II, III). At each stage, we discerned two sub-groups: A, without renal disease, B, with renal impairment. The control group consisted of 125 healthy volunteers matched for age and sex with the main group. IL-2, IL-4, IL-8, TNFα, and IFNγ levels in sera of the patients and healthy individuals were determined by enzyme immunoassay kits (JSC “Vector-Best”,Novosibirsk). In the myeloma patients, we have revealed an imbalance between pro-inflammatory (IL-2, IL-8, TNFα, IFNγ), and antiinflammatory cytokines (IL-4), with a predominance of pro-inflammatory factors. This finding does not exclude their potential pathogenetic role in growth and stimulation of tumor progression, and occurrence of infectious complications at any stage of the disease. The disturbances in cytokine regulation in MM patients may manifest as a deviation of cellular immune response by Th-1 way. As seen from our data, TNFα, IL-2 and IL-4 are the most significant cytokines for MM progression.

The article deals with scientific and geographical features of the study of natural and cultural heritage in the mainstream of development of education for sustainable development. The analysis of researches of scientists-geographers in the field of heritage study allowed to conclude that the key geoecological aspects of heritage associated with the idea of heritage as a unique cultural and environmental phenomenon, reflecting the idea of co-creation and the balanced development of man and nature. Natural heritage is revealed on the basis of specially protected natural areas and cultural heritage - based cultural landscape. Presents ideas important use in the study of natural and cultural heritage in school geographic education. A special place is given to the school of geography of Russia and geoecological studies that create the preconditions for cognitive, value, activity-based heritage study. The content of these courses provides the motivation of pupils to study natural and cultural heritage, promotes awareness of the involvement of pupils in their conservation in line with the ideas of sustainable development.

The article discusses the scientific and geographical features of the study of natural and cultural heritage in line with the cultural-ecological approach and the implementation of the ideas of culture of nature management. The analysis of researches of scientists-geographers in the field of heritage study allowed to conclude that the key geo-ecological aspects of heritage associated with the notion of heritage as a unique cultural and environmental phenomenon, reflecting the idea of co-creation of man and nature, the idea of a cultural nature. The stages explore the natural and cultural heritage in the geographical science. It is established that the study of natural heritage based on scientific studies geo-ecology, and cultural heritage is studied in the framework of the scientific field of "cultural geography". It is revealed that the conservation of natural and cultural heritage closely linked to the idea of rational nature management, implementation of rules and regulations cultural resources management. These ideas define the main methodological and methodological aspects of the study of natural and cultural heritage in the school of geography of Russia, and also implement the most important educational function of the school of geography in the formation of a responsible citizen and patriot of his country. These ideas are important to use when studying natural and cultural heritage in the school of geography of Russia.

The article covers the methodology of study of natural and cultural heritage in the school of geo-ecological education aimed at the development of geographical and ecological culture of pupils by means of geographical education for sustainable development.

Abstract. We examined metabolic status of blood lymphocytes in forty-four patients with chronic myeloid leukemia (CML), and in fifty-seven patients with chronic lymphoid leukemia (CLL). The most pronounced changes of enzyme activities are found in blood lymphocytes of CML and CLL patients during terminal stage of the disease. All the patients with chronic leukemia at both stages showed a decreased intensity of metabolic processes in blood lymphocytes. In addition, CML patients at both clinical stages exhibited a decrease in antioxidant cell protection. The more pronounced biochemical disturbances in CML patients at progression stage concerned carbohydrate metabolism, whereas the changes at terminal stage of disease affected both carbohydrate and fat metabolism. The most marked biochemical alterations in CLL at progression stage are registered for carbohydrate and protein metabolism, and carbohydrate, fat and protein metabolism at terminal stage of disease. The revealed changes showed indicate to more severe clinical course in the patients with CML. These changes and differences depict some aspects of immune pathogenesis in development and progression of CML and CLL.

Abstract. We examined immunological state in 100 patients with acute non-lymphoblastic leukemia (ANLL, M4), and in 73 cases of acute lymphoblastic leukemia (ALL, common variant). The most expressed disturbances of immune status in ANLL patients were revealed during relapses, and in patients with ALL they were detected in the state of clinical remission. In cases of ANLL, T cell immunodeficiency did develop in crisis and remission, whereas combined T- and B-cell immunodeficiency occurs during relapse of ANLL. T cell immunodeficiency was found to develop at all stages of ALL. These changes and differences may characterize specific immunopathogenetic aspects of development and progression of ANLL and acute ALL.

Abstract. We studied immunological state and activity of enzymes in blood lymphocytes from the patients at different stages of acute lymphoblastic leukemia. We have revealed that immune state in all the patients was characterized by decreased contents of T-lymphocytes. Upon first attack of the disease, they showed a decrease in CD4+cells, as well as increased concentration of IgM and IgG. During remission, we have found the lowest values of all the parameters under study. In relapsing patients, high content of NK-cells, and imbalance between the main Ig classes were noted. When studying metabolism of lymphocyte, it was revealed that, in first attack and relapse phase, both intensity of anaerobic glucose oxidation, and levels of macromolecular synthetic reactions were decreased. In remission, all these processes did recover to normal range. At all stages of disease, glutathione reductase activity was found to be decreased in blood lymphocytes. (Med. Immunol., vol. 10, N 6, pp 543-550).

Аbstract. The purpose of study was to evaluate some characteristics of immune state in the patients with acute non-differentiated leukemia (ANLL) and acute lymphoblastic leukemia (ALL), and to detect interrelations between the features of immune state and their dependencies on disease stage and quantities of blast cells, using a neuronet modeling approach. A decrease in immune system reactivity was revealed in acute leukemia patients. At any ALL stage, a T-cell immunodeficiency is registered. A decrease of T lymphocyte amounts and reduction of CD4+:CD8+ ratio are associated with occurrence of ALL relapse. Increased contents of NK cells are a feature of ALL recurrence. T cell deficiency emerges during ANLL relapse and remission. Meanwhile, a combined immunodeficiency develops upon relapse of the disease, affecting both T and B systems of immune response. Exhaustion of NK cell contents is a characteristic feature of ANLL, thus potentially promoting progression and relapse of the disease. By means of a neuronet predictor, a significance of information for certain immune state parameters was assessed, by determining amounts of blast cells in bone marrow. It was found that a specific histogram of informativity is revealed for each group of the patients. A computer-based experiment was performed which proves the specificity of interrelations between the immune state indices in a neuroprediction model for ALL and ANLL. (Med. Immunol., 2011, vol. 13, N 1, pp 49-54)

Abstract. Supervision over 70 patients with acute no lymphoblastic leukemia and 65 patients with acute lymphoblastic leukemia, admitted in hematological department of Regional clinical hospital of № 1 of Krasnoyarsk city were made. It was established, that at a combination of G6PDG activity in blood lymphocytes in limits from 10,02 to 32,74 mkU and NADPMDG in limits from 8,29 to 15,37 mkU the development of infectious complications in patients with acute leukemia after chemotherapy is predicted.

Abstract. In this study, we have identified functional features of immune system cells in patients with acute lymphoblastic leukemia (ALL), depending on clinical stage of the disease. At all stages of the disease, the patients developed T-cell immunodeficiency. A decrease in T lymphocyte scores and diminished CD4/CD8 ratio was associated with development of primary ALL attack. An increase in NK-cells was typical to ALL relapse. In general, ALL cell populations were characterized by a significant reduction of intracellular metabolic processes in lymphocytes. Chemiluminescent activity of neutrophil granulocytes changed in ALL patients with disease progression, being intensified at the stage of primary attack, followed be decreased activity during complete clinical remission and relapse, probably, due to depletion of internal reserves. The study confirmed that significant changes in ALL are associated with functional and metabolic state of lymphocytes and neutrophils upon progression of the disease, which is probably responsible both for development of complications, but it also may influence relapse risks and determine worse prognosis in general.

Background. One of the pressing aims of today’s natural resource management is its re-orientation to preserving and restoring ecological functions of ecosystems, among which the function of biodiversity maintenance plays an indicator role. The majority of today’s forests have not retained their natural appearance as the result of long-standing human impact. In this connection, refugia studies are becoming particularly interesting, as they give us an insight into the natural appearance of forests. Materials and methods. Studies were performed in dark conifer forests of the Pechora–Ilych reserve, in the lower reaches of the Bol’shaya Porozhnyaya River in 2013 yr. Vegetation data sampling was done at 50 temporary square plots of a fixed size (100 m2) randomly placed within a forest type. A list of plant species with species abundance was made for each forest layer. The overstorey (or tree canopy layer) was denoted by the Latin letter A. The understorey layer (indicated by the letter B) included tree undergrowth and tall shrubs. Ground vegetation was subdivided into the layers C and D. Layer C (field layer) comprised the herbaceous species (herbs, grasses, sedges) and dwarf shrubs together with low shrubs, tree and shrub seedlings. The height of the field layer was defined by the maximal height of the herbaceous species, ferns, and dwarf shrubs; the height varied from several cm to more than 200 cm in the ‘tall-herb’ forest types. Layer D (bottom layer) included cryptogamic species (bryophytes and lichens). Species abundance in the each layer was usually assessed using the Braun-Blanquet cover scale (Braun-Blanquet 1928). The nomenclature used follows Cherepanov’s (1995) for vascular plants, and Ignatov & Afonina’s (1992). Results. The present article contains descriptions of unique tall-herb boreal forests of European Russia preserved in certain refugia which did not experience prolonged anthropogenic impact or any other catastrophes. Comparative research into species and ecological diversity of typical (anthropogenically transformed) and unique (tall-herb) boreal forests has been conducted. On the basis of the collected field data, a map of the diffuse area for tall-herb boreal forests has been compiled and a set of species characteristic for these forests has been determined. The obtained data fundamentally change our notions of potential vegetation in boreal forests. Conclusions. Considerable species- and ecological diversity of tall-herb forest flora fundamentally changes our notion of the appearance of European boreal forests and determines their unique role in maintaining the highest possible level of biodiversity. The presence of tall-herb forests in various parts of eastern European taiga together with Eurasian habitats of most tall-herb species lead us to a suggestion that it is exactly this type of forests that represented the prehistoric boreal forests. In this connection, further research into still preserved fragments of tall-herb forests within the boundaries of northern Eurasia acquires huge significance. This research will help put forward systems of forest management aimed at restoring potential biodiversity of boreal forests in general.

A study of the peculiarities of clinical manifestations and immunity in patients with chronic myeloid leukemia, depending on the stage of disease was made. In patients at admission were more prevalen t shortness of breath, palpitations, lymphadenopathy, hepatomegaly, splenomegaly, hemorrhagic manifestations. Patients diagnosed at any stage had immune disturbances, with the greatest change — in the terminal stage. In patients in an expanded and in the terminal stages T-cell immunodeficiency developed. The peculiarity of the terminal stage was the reduction of NK-cells and B-lymphocytes.

According to the anamnesis data 38% of multiple sclerosis patient population had neuritis retrobulbaris as the first clinical symptom. The examination of visual evoked potentials detected that 88% of patients who had suffered from neuritis retrobulbaris earlier, and 19% of those, who had not, had changes revealing possible subclinical demyelinization of a visual nerve.

The influence of different beta-blockers (anaprilin, atenolol, nebilet) on the level of 11-oxycorticosteroids in rats with experimental chronic heart failure.