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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.

This review is focused on recent advances in development of new vaccines for the prevention of tuberculosis. The main reasons for lack of BCG vaccine efficacy in different populations and geographic regions are presented. Design of new vaccines based on live modified strains of Mycobacterium bovis BCG, attenuated strains of Mycobacterium tuberculosis, recombinant proteins and viral vectors is considered in the specific examples. The usage of the heterologous "prime-boost" vaccination strategy against tuberculosis is discussed.

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.

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.

At present, the conception of the use, efficacy and safety of hepatotropic agents in treatment of drug-induced liver injury, in particular due to antituberculosis drugs is not yet final, which is conditioned by extremely rare clinical trials on the subject adequate to the up-to-date principles of the conclusive medicine. The review presents data on the hepatotoxic effect of antituberculosis drugs, analysis and systematization of the data on the use of hepatotropic agents in liver injury induced by antituberculosis drugs, the principles and characteristics of their clinical use. The mechanism of action of remaxol, a new original hepatotropic agent and the indications of its use are discussed. The experimental findings on the remaxol ability to decrease the antituberculosis drug-induced liver injury through lowering the carbohydrate, albuminous and fatty degeneration and activating the organ reduction are presented. The clinical trials are evident of the most efficient action of remaxol on the signs of toxemia, as well as cytolysis and cholestasis, which along with its antiasthenic and antidepressant action allows to use remaxol as an universal hepatotropic agent in the treatment of diverse drug-induced liver injuries in both the therapeutic and prophylactic schemes.

DST was ascertained to have a high sensitivity in virtually all patients with tuberculosis and a positive reaction was first noted in the infected. With stabilization and regression, the response to DST was much less pronounced than that in clinical and primary infection (that to the Mantoux test being more evident). DST showed its use as a marker of active tuberculosis not only in its local forms, but also in latent tuberculous infection. This makes it possible to apply DST when preventive treatment is performed. The agent may be used to monitor the progress of treatment. DST has a high specificity--healthy individuals had a negative response to DST while the Mantoux test was positive in many cases. The high specificity of DST was suggested by the fact that the persons vaccinated with (this caused BCG ostitis) had a negative reaction to DST while the Mantoux test was positive in all cases BCG-vaccinated BCG. The findings warrant the use of DST for the differential diagnosis of tuberculosis and BCG-associated complications and the possibility of differentiating postvaccinal and infection allergy in children and adolescents.

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.

A combined, including urodynamic, study was made in 129 patients with abnormal reservoir function of the urinary bladder (UB). Of them, 82 patients had nephrotuberculosis (NT). Cystoscopy was made in 93 patients, endovesical multifocal biopsy of the bladder wall-- in 23. Correction was conducted with alpha-adrenoblocker alfusozine. In NT, sensory functional disorders of UB prevail (60%). The degree of fibrous-inflammatory involvement of the bladder wall by biopsy findings and severity of urodynamic disorders do not correlate (r0.03). Miction recovered in 81.5% patients with NT taking alfusozine. Ileocystoplasty (n = 20) was made in treatment failure and total UB fibrosis. Long-term pathogenic action of specific infection on the neuroreceptor system of the UB may cause defects in its activity. Complex urodynamic investigations of the lower urinary tracts in NT patients identify the type of the disorder and help in making choice of pharmacological or surgical correction. Alfusoxine is a drug of choice in UB hypersensitivity.

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.

The experimental studies have provided strong evidence that the efficacy of etiotropic therapy for tuberculosis can be enhanced by applying a number of antimicrobial agents having different mechanism of action, which belong to cephalosporins, macrolides, aminoglycosides, fluoroquinolones. The basis of the mechanism responsible for potentiation of activity of essential tuberculostatic drugs for potentiation of activity of essential tuberculostatic drugs is enhanced inhibition of the viability of a microbacterial population, prevented development of drug resistance in tuberculosis mycobacteria, and increased function of macrophages.

Cephalosporin antibiotics cefamezin (I generation drug sensitive to beta-lactamase) and cefotaxime (III generation drug resistant to beta-lactamase) have been tested for antituberculous activity. The latter was found dependent on resistance to mycobacterial beta-lactamase. A minimal inhibiting concentration of cefotaxime was similar to that of etambutol and tisamid. Cefotaxime also enhanced tuberculostatic and bactericidal effect of isoniazid and rifampicin. Combination cefotaxime+isoniazid+rifampicin proved more effective than cefotaxime+etambutol+tisamid. The effectiveness against tuberculosis of the beta-lactamase resistant cephalosporin points to the validity of further research for active phthisiatric drugs among III generation cephalosporins.

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.