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More than a quarter of the world's population is infected with Mycobacterium tuberculosis . However, only about 10% of those infected develop active TB. This indicates a key role for innate immunity in limiting M. tuberculosis replication. Most often, bacteria can regulate the expression of host-specific molecules and weaken host immunity., Objective: To use a biological model, in order to determine significant molecular immunohistochemical markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of the M. tuberculosis Beijing genotype in lung tissue., Material and Methods: Lung samples of the C57BL/6 male mice were obtained during experimental infection with M. tuberculosis strains: the reference laboratory strain H37Rv, multidrug-resistant clinical strains 396 (highly lethal and hypervirulent «Buryat» genotype Beijing 14717-15) and 6691 (low-lethal and low-virulent "Omsk" genotype Beijing 1071-32) on days 14, 21, 60 and 120. They were studied by histological and immunohistochemical methods. The relative areas of expression of IL-6, IL-12A, iNOS, and TNF- α in the lung tissue of model animals were established., Results: A study of strain 396 showed that both disease progression and damage to lung tissue are associated with a highly reactive immune response and increased synthesis of iNOS and strain characteristics that block the production of TNF- α . On the contrary, for strain 6691 a low reactivity of the immune response was revealed, with statistically significantly lower values of the relative area of expression of NOS and TNF- α during all observation periods (days 14-120). All animals that survived to day 120 showed a similar morphological picture with differences in cytokine levels, indicating a nonlinear relationship between proinflammatory factors and the damage substratum., Conclusion: The progression of the disease and damage of lung tissue were associated with a highly reactive immune response and increased synthesis of iNOS, strain properties that block the TNF- α production. Thus, iNOS and TNF- α can act as molecular markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of M. tuberculosis in lung tissue.

Objective: To compare the epidemiological indicators of multiple sclerosis (MS) in Yaroslavl when comparing the 1999 and 2019 registers to study the pathomorphism of the disease in this territory., Material and Methods: During the work, the data of the 1999 and 2019 registers were used, including the age of the debut, the date of diagnosis, the form of the disease, clinical characteristics, the treatment received and its duration. In 1999, 257 patients living in the city of Yaroslavl (155 women and 102 men) were included in the MS registry with a reliable diagnosis of MS according to Poser's criteria with confirmation according to neuroimaging data. In 2019, 479 people living in the territory of Yaroslavl (342 women and 137 men) were included in the register with a diagnosis of MS based on the criteria of MacDonald 2005, 2010, 2017. As of 01.01.19, 970 patients (530 women and 440 men) were included in the patient register of the Yaroslavl region., Results and Conclusion: Clinical and epidemiological review of Yaroslavl MS Registry data in 1999 and 2019 showed significant changes in disease pattern. The prevalence rate increased from 42.6 to 78.5 cases per 100,000 people. The morbidity rate rose from 1.58 to 3.28 cases per 100,000 people. The reasons for the increase are improvement in the diagnostic quality, new diagnostic criteria and the true growth of prevalence and morbidity. The use of disease modifying drugs (DMDs) has extended «the time to EDSS 3,0» by 4 years, «the time to EDSS 6,0» by 5-8 years.

Aim: To evaluate an effect of mother's treatment with disease-modifying drugs (DMD) on the mental and physical development of the child in the first year of life., Material and Methods: Thirty pregnancies resulted in birth of live babies in patients with multiple sclerosis (MS) were studied. The diagnosis of MS was made to the mother before conception of the child. Seven mothers did not receive DMD at the moment of conception (controls), 13 mother were treated with interferon-beta (IFN) and 10 with glatiramer acetate. A structure interview, examination of the child with the assessment of common anthropometric indices, the WHO scale for achievement of six milestones, medical history and statistical analysis were used., Results and Conclusion: The data on the negative effect of MS on the growth and development of the fetus and the positive impact of treatment of the mother with DMD in the early stages of pregnancy on anthropometric indices and development of the child in the first year of life were confirmed. It has been concluded that DMD positively influence the disease course of the female patient and potentially improve the prognosis for her future offspring.

Experiments on 62 male albino outbred rats investigated the impact of 14-day use of the oral hepatotropic agents ademethionine and runihol in different doses in liver damage caused by a antituberculosis combination (HRZ). HRZ-induced liver damage was shown to be accompanied by the development of cytolysis and cholestasis. The test drugs in the doses under study had a mixed effect, by reducing the magnitude of biochemical manifestations of these syndromes. Both drugs favored the recovery of the structure of the liver and the reduction of the extent of carbohydrate, protein, and fat dystrophies of the organ. As in previous investigations, ademethionine was found to have enhanced activity of alterative processes in the liver.

The authors evaluated reparative osteogenesis after incorporation of roncoleukin into combination therapy for experimental drug-resistant tuberculous osteitis. Roncoleukin (12.5 pg/kg, 5 injections, once every 3 days) was used during antituberculosis therapy before and after combined plasty (autobone + OsteoSet-T) in repairing surgical defects. When used in the postoperative period of combined osteoplasty, roncoleukin was shown to contribute to a reduction in the spread of specific inflammatory foci in bone tissue, cessation of an alternative necrotic component, an increase in the rate of osteogenesis with newly formed bone trabeculae, and activation of hematopoietic processes in the bone marrow. In parallel with intensified bone reparative processes, there was immunomodifier-induced stimulation of the absorption and digestion of peritoneal macrophages suppressed in experimental tuberculous osteitis.

Experiments on male albino outbred rats investigated the hepatoprotective activity of remaxol and ademethionine in liver damage caused by reserve-series antituberculosis drugs. The test drugs had a mixed action, by reducing the degree of cytolytic and cholestatic syndromes. Remaxol and ademethionine assist in diminishing the degree of liver structural and functional impairments occurring with reserve-series antituberculosis drugs, by restoring the girder structure of lobes and decreasing the magnitude of dystrophic changes to stimulate reparative processes. Histological examination of liver tissue sections from rats receiving ademethionine revealed the enhanced activity of alterative processes in the liver.

Experiments on 160 male albino outbred rats investigated the hepatoprotective activity of S-adenosyl-L-methionine (SAM) and runihol in liver damage caused by subtoxic doses of reserve-series antituberculous drugs (ATD) (PASA, cycloserine, prothionamide) and their combination. It was established that a combination of ATDs had the maximum hepatotoxic activity, cycloserine had the least. There was evidence that SAM versus runihol had a more pronounced ability to correct ATD-induced evolving cytolysis syndrome. Histological study indicated that SAM and runihol also showed a marked hepatoprotective effect. When added to PASA, prothionamide, or a combination of ATDs, both drugs promoted recovery of the hepatic architectonics and a reduction in the prevalence of albuminous dystrophy. The use of SAM additionally led to activation of alterative processes in the hepatic parenchyma.

To provide effective primary and secondary stroke prevention, the epidemiological stroke rates were investigated in the open population of a large Transbaykal town by the register method. During one year, 989 cases have been examined in the population aged above 25 years. The age-standardized stroke incidence rate (per 100 000 persons) was 300 in women and 329 in men. The age-standardized stroke morbidity (per 100 000 persons) was 390 in women and 409 in men. Stroke mortality was 77 in women and 81 in men per 100 000 (p = 0.01). The stroke mortality in men was higher than in women. Stroke case fatality was 20% in men and 16% in women. The prevalence and significance of the main cardiovascular risk factors were revealed among patients by case-control study. Hypertension, psychological and social risk factors were the most significant in Chita's population of stroke patients.

The aim of the study is to analyze frequency and character of blood lipids abnormalities in patients after ischemic stroke (IS). Blood lipids were studied in 54 patients who survived ischemic stroke at 38-70 years. Atherogenic dyslipidemia was found in 49 (90.7%) patients, 37% had a selective low level of HDL cholesterol (< 37 mg/dl). Patients with dyslipidemia, IV type, (27.8%) showed a high level of triglycerides (413 +/- 72mg/dl) and patients with IIa or IIb types--LDLP cholesterol (223 +/- 12.5 mg/dl). A complete analysis of blood lipids allows detecting atherogenic dislipedimia in the majority of patients who survived ischemic stroke (90.7%), which can be treated with statins or fibrates. An adequate therapy of such patients may significantly improve prognosis for those who survived ischemic stroke and, in some cases, prevent its development.

Macrophagal-phagocyting immunity was studied in 59 children with cicatricial acquired stenosis of the larynx and cervical trachea aged 1 year 9 months to 14 years 8 months. It was found that children with acquired cicatricial stenosis had a sharp depression of all functions of the cells of the macrophagal-phagocyting system (chemotaxis, absorptive, digestive, oxidation-reduction) as well as reduction of their number. This is, on the one hand, a defense reaction of the organism to continuous antigenic stimulation; on the other hand, this marks feasibility of progressive immunocomplex and/or autoimmune processes. The most prominent alterations were seen in patients with concurrent affection of the CNS.

Humoral immunity was studied in 63 children with acquired laryngotracheal stenosis 1 year 9 months to 14 years 8 months of age. The study discovered humoral immunity dysfunction which was most pronounced in patients who developed scary stenosis after critical care for acute stenotic laryngotracheobronchitis. It was found that if a child has allergy (atopy) in conduction of critical care requiring long-term nasotracheal intubation, he/she is at risk to develop scary stenosis.

T-cell immunity was studied in 59 children (39 boys-66.1% and 20 girls-33.9%) with acquired stenosis of the larynx and cervical trachea at the age of 1 year 9 months to 14 years 8 months. Compromised T-cell immunity was revealed in the examinees, especially in those who had acute infectious-inflammatory diseases or CNS damage before critical care responsible for development of the stenosis. These changes in T-cell immunity should be considered as a factor of risk to develop immune and autoimmune diseases.

The examination for Chlamydial infection was carried out in 49 children aged from 1 year 10 months to 15 years (mean age 9 years 6 months +/- 3 years 8 months) with laryngotracheal cicatricial stenosis (CS) provoked by long nasotracheal intubation. Antibodies to C. pneumoniae in diagnostically significant titers were detected in 13 of 49 children (26.5%), to C. trachomatis--in 1 patient who had both infections. All the infected patients except the latter carried tracheal canules or were decanulated. Age of the patients with Chlamydial infection at the time of examination and development of CS was significantly older than of non-infected children. No significant difference was found between these patients by duration of the intubation and of the disease. Consideration of the fact that 12 of 13 children with C. pneumoniae infection carried tracheocanules suggests that the infection may be secondary.

Based on WHO MONICA methods and diagnostic criteria, it is shown that first-ever stroke incidence and mortality in Siberia (a total number of residents included in the analysis varied from 450,000 to about 800,000) that are among the highest in the world. In Novosibirsk, for the period from 1982 through 1991 there was a trend towards decreasing stroke incidence and mortality rates, but for the period from 1992 through 1997 there was a trend towards increasing there rates in both men and women. Age-standardized (US white population was used as a standard) stroke incidence rates increased from west to east and from south to north across Siberia, with a corresponding increase in the proportion of hemorrhagic strokes. In 1987-1988, age-adjusted stroke incidence rate in Novosibirsk was 212 per 100,000 residents per year, in Krasnoyarsk--325, in Tynda--329, in Anadyr--348. Stroke-case fatality rates ranged from 28% in Tynda to 41% in Anadyr. A multivariate regression analysis revealed that hypertension, left ventricular hypertrophy, ischemic heart disease. mitral valve disease, current cigarette smoking, excessing body mass index, winter season, and low ambient temperature are all significant and independent risk factors for the occurrence of ischemic stroke in Novosibirsk. A significant association between stroke occurrence and air pressure/geomagnetic activity change was found. Possible reasons for such unfavorable trends in stroke incidence in Siberia are discussed, and an optimal approach for improving organization of cerebrovascular disease care is suggested.

Pathomorphosis of the disease has been studied on the basis of clinical and autopsy observations in the last three decades. The importance of staphylococcus, enterococcus, and gram-negative bacteria has been shown to increase among the causative agents of septic endocarditis; frequently the infectious agents have been observed to alternate in the course of the disease. Many manifestations of endocarditis were established to be associated with the circulating immune complexes containing bacterial antigens. In the last decade, primary septic endocarditis comprised about half of the observations. The proportion of isolated endocarditis and destructive changes of aortal valves increased. Myocarditis has become more frequent and in more than half of the cases it is associated with glomerulonephritis. In contrast, peripheral manifestations of endocarditis have considerably lost their diagnostic value. Among thromboembolic complications, venous thromboembolus of the pulmonary artery, and pulmonary infarction became more prevalent.

The international histological classification of bones has been issued by the World Health Organization in 1972. The article discusses merits of the classification, its importance in unification of the nomenclature on bone tumours, in studies of their nature and histogenesis, etc. At the same time some drawbacks of the classification are noted: lack of accuracy with respect to the nomenclature and grouping of the so-called giant-cell tumours of bones, with respect to the group of tumours of the "bone marrow", the group of mesenchymomas, etc. The author makes his critical notes on the basis of the experience gained by his co-workers and by himself.

The analysis of the literature data and the author's own findings justifies the conclusion that a single mechanical trauma may be of importance in the development of tumours of various genesis, as well as in the development and localization of metastastatic foci.