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It is revealed that Roncoleukin (12.5 mg/kg, intraperitoneally, 5 injections a day), Betaleukin (0.1 mg/kg, intraperitoneally, 1 time in 3 days (5 weeks)), Bestim (0.1 mg/kg, intraperitoneally, 10 injections), cycloferon (3.6 mg/kg, intraperitoneally, 3 times a week for 6 weeks), Glutoxim (40 mg/kg subcutaneously (4 weeks)and the preparation of succinic acid remaxol (at a dose of 25 mg/kg intraperitoneally, daily 14 introduction), when you enter them in a comprehensive drug therapy pilot MDR tuberculosis in mice produce a positive effect on the regression of inflammation in the lung tissue, stimulate local immunity of the lungs, activate and digestive absorption capacity of peritoneal macrophages an average of 1.4 and 1.9, p0.05, inhibited the tuberculosis infection and chemotherapy.

The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection. Runihol has no impact on the effectiveness of chemotherapy in the absence of a stimulating influence on the phagocytic function of the peritoneal macrophages.

The paper sets forth the stages of design and introduction of the new Russian tuberculosis (TB) drug perchlozon registered in the Russian Federation in 2012. Based on the results of Phases I-III clinical trials, the authors evaluate the efficacy and safety of the agent and consider the adverse effects of its treatment for respiratory TB. The use of perchlozon as a component of combination therapy versus standard chemotherapy regimens significantly reduces abacillation time in pulmonary TB caused by its drug-resistant pathogen. In terms of the higher prevalence of TB induced by its pathogen resistant to many drugs (with multiple and broad-spectrum drug resistance), perchlozon is an essential drug that has antituberculous activity mainly against multidrug-resistant Mycobacterium tuberculosis strains and gives patients with the severest and epidemiologically poor form of TB the chance to recover.Изложены этапы разработки и внедрения нового отечественного противотуберкулезного препарата перхлозон, зарегистрированного в Российской Федерации в 2012 г. С учетом результатов клинических исследований I-III фазы оценены эффективность и безопасность препарата, рассмотрены нежелательные эффекты лечения туберкулеза (ТБ) органов дыхания. Перхлозон в составе комплексной терапии по сравнению со стандартными схемами химиотерапии достоверно сокращает сроки абациллирования при ТБ легких, вызванного устойчивым к лекарственным препаратам возбудителем. В условиях роста распространенности ТБ, вызванного возбудителем, устойчивым ко многим лекарственным препаратам ('с множественной и широкой лекарственной устойчивостью'), перхлозон является необходимым препаратом, который обладает выраженной противотуберкулезной активностью, прежде всего в отношении штаммов микобактерий, устойчивых к лекарственным препаратам, и дает шанс на выздоровление пациентам с наиболее тяжелой и эпидемиологически неблагоприятной формой ТБ.

The results of an experimental study of the efficiency of cycloferon included in a complex chemotherapy of generalized drug-resistant mycobacterium tuberculosis (MBT) are presented. It is established that cycloferon (3.6 mg/kg) produces a significant therapeutic effect, which is manifested by an increase in the lung clearance from MBT, a decrease in the spread of specific inflammation in the lungs, and the disappearance of MBT-induced alterations. In addition, activation of the signs of tension in the local immunity of lung tissues is observed as manifested by changes in the cellular composition of granulomas and more frequent detection of large lymphocytic and macrophage infiltration. The administration of cycloferon significantly increases the absorptive and digestive activity of phagocytosis by peritoneal macrophages, which has been inhibited during the development of experimental MBT infection.

Efficacy of remaxol in complex chemotherapy of generalized drug resistant tuberculosis was studied on mice. Mycobacterium tuberculosis 5419 SPBNIIF isolated from a patient with freshey diagnosticated pulmonary tuberculosis resistant to isoniazid (10 mcg/ml), rifampicin (40 mcg/ml), streptomycin (10 mcg/ml) and ethionamide (30 mcg/ml) was used in the experiments. The main polychemotherapy included 4 antituberculosis drugs in the highest therapeutic doses: isoniazid, amikacin, ethambutol and tavanic, the treatment course was 8 weeks. Remaxol was administered in a dose of 25 ml/kg intraperitoneally 5 times a week (14 injections). Significant activating effect of remaxol on the tension of the lung tissue local immunity was revealed by changes in the granuloma cell composition (from mainly epitheliod to mainly lymphoid) and by more frequent large lymphohistiocytic infiltrates. The use of remaxol also greatly increased the absorptive and digestive activity of the peritoneal macrophages phagocytosis, inhibited in the process of the experimental tuberculosis development.

It is as for now evident that in-depth researches of the genotype of a patient are needed to enhance the efficiency of therapeutic measures. The purpose of the present study was to enhance the efficiency of complex antituberculous therapy, by genetically identifying the allelic polymorphism of the HLA-DRB1* gene in a person who had ill with tuberculosis. The material of the study was the results of a followup and treatment of 100 patients with pulmonary tuberculosis. The subject of a special study was the molecular typing of the HLA genes of the DRB1* locus by polymerase chain reaction (PCR-SSP). The findings suggest that an individual approach to choosing treatment regimens (chemotherapy and pathogenetic therapy) for patients with pulmonary tuberculosis, by taking into account the HLA-DRB1* genotype enables one to enhance the efficiency of treatment in the major clinical and X-ray parameters.

In vitro experiments showed that islacet produced an inhibitory effect on the growth of laboratory drug-sensitive Mycobacterium strains when used at a concentration of 25 microg/ml. A considerable reduction in death rates and a significant decrease in the mass index and in the indices of pulmonary lesion and bacterial isolation from splenic homogenates were observed on the model of generalized tuberculosis in mice and rabbits given islacet. In parallel with the higher efficiency of therapy using islacet, there was ConA- and PPD- stimulated proliferation of splenocytes and their production of interleukin-2 drastically inhibited in mice that had long received multidrug therapy (HRZ and HRE). Islacet was found to enhance the functional activity of phagocytes and that inhibited during the development of infection and under the influence of long-term (more than 1 month) etiotropic therapy: the generation of superoxide by murine peritoneal macrophages and rabbit neutrophils, as well as by the absorptive and digestive function of peritoneal macrophages.

The use of roncoleukin in the combined therapy in patients with pulmonary tuberculosis caused by drug-resistant Mycobacterium tuberculosis (MBT) led to better immunological parameters and therapeutic efficiency: by month 3 of therapy, there was abacillation (69.2% versus 33.3% in the control) (p0.05), decay cavities closed by months 6 to 7 (59.0% versus 23.1%). The immunotropic effect of betaleukin on chemotherapy promoted accelerated involution of a specific process with the least pronounced residual changes in the lung tissue; by the end of an inpatient stage of therapy, the proportion of patients with minor residual changes (Type I and Type II) was 72.5% in the experimental group versus 36.8% in the control one (p0.05).

Studies dealing with the design of new antituberculous agents based on goal-oriented synthesis have provided the agent Perchlosone which is similar to isoniazid and rifampicin, produces in tuberculostatic activity against sensitive laboratory cultured mycobacteria, produces an inhibitory action on polyresistant clinical strains. Experiments on animals (mice, rabbits) with experimental tuberculosis have established that Perchlosone and isoniazid have equal therapeutical properties, and the former shows a synergist interaction with rifampicin, has neither mutagenic activity nor negative effects on immunity and the surfactant system of the lung.

The paper presents the Institute's activities in qualification rating of its staff from January 1994 to September 1998. It analyzes theses prepared and defended by the Institute's researchers and competitors. The activities of the dissertation council are briefly characterized.

A plasmapheresis (PA) model was developed to be used in chronic rabbit experiments. Test results obtained in 96 generalized tuberculosis animals demonstrated a more benign tuberculosis process in animals subjected to plasmapheresis, which was confirmed by parameters of the coefficients of mass and indices of animals' organ affecting, findings of the cation-lysosomal test and peptide molecules content in the peripheral blood. Rabbit studies involving registration of bromsulphalein half-life, hepatic blood flow and relative parenchymatous clearing showed that the isoniazide and rifampicin action significantly decreased under the PA influence. Studies in a hospital accommodating 90 patients with different renal tuberculosis forms and poor tuberculostatic tolerance showed that PA promoted restoration of tolerance to specific preparations and renal function improvement. PA was found to be practicable and safe method which relieves side effects of antituberculous preparations and contributes to tuberculosis treatment efficiency.