[The treatment of tuberculosis under current conditions].

AIM: Study of the current state of problems of treatment of patients with tuberculosis based on literature data and their own experience. MATERIALS AND METHODS: In the Russian Federation, the number and proportion of patients with co-infection with HIV/tuberculosis continues to increase against the background of improvement in the main epidemiological indicants for tuberculosis. In 2017, 20.9% of newly diagnosed tuberculosis patients had HIV infection. The combination of the two infections significantly complicates the further improvement of the situation with tuberculosis, and the appearance of drug-resistant strains of Mycobacterium tuberculosis sometimes completely neutralizes the results of chemotherapy. The article describes the schemes of modern tuberculosis chemotherapy taking into account HIV/tuberculosis co-infection, as well as MDR in combination with surgical treatment methods, as well as analyzes the data of epidemiological monitoring of treatment of 1115 tuberculosis patients newly diagnosed in 2017 in Moscow, 360 tuberculosis patients with MDR MBT (cohort 20132014), the results of treatment with the use of new chemotherapy regimens for tuberculosis (bedaquiline, linezolid, moxifloxacin) in 36 patients, the effectiveness and safety of surgical methods in 192 patients. RESULTS: The application of new individualized anti-TB chemotherapy schedules in patients with HIV co-infection/tuberculosis with MDR-MBT has allowed to improve the treatment efficacy. The surgical intervention combined with modern chemotherapy regimens in patients with HIV/tuberculosis co-infection with MDR MBT has been proved to be effective and safe, contributes to the improving the results of treatment for this category of patients. CONCLUSION: The confluence of two global problems of co-infection HIV/TB and MDR TB, significantly prevents from the end of the tuberculosis epidemic in the world. At the same time, advances in the development and implementation of new anti-TB drugs and surgical treatment methods give hope for significant progress for resolving this situation.

Combined NMR and computational study for azide binding to human manganese superoxide dismutase.

Human manganese superoxide dismutase (MnSOD) labeled with 3-fluorotyrosine (Tyf) was complexed with the (15)N-labeled inhibitor azide ([(15)N(3)(-)]). The sample was characterized by solid-state NMR (SSNMR) spectroscopy ((19)F-MAS and (15)N-CPMAS). Employing (19)F-(15)N-REDOR spectroscopy, we determined the distances between the fluorine label in Tyrosine-34 and the three (15)N-nuclei of the azide and the relative orientation of the azide in the binding pocket of the MnSOD. A distance of R(1)=4.85A between the (19)F-label of Tyf34 and the nearest (15)N of the azide and an azide-fluorotyrosine Tyf34 angle of 90 degrees were determined. These geometry data are employed as input for molecular modeling of the location of the inhibitor in the active site of the enzyme. In the computations, several possible binding geometries of the azide near the Mn-complex were assumed. Only when the azide replaces the water ligand at the Mn-complex we obtained a geometry of the azide-Mn-complex, which is consistent with the present NMR data. This indicates that the water molecule ligating to the Mn-complex is removed and the azide is placed at this position. As a consequence the azide forms an H bond with Gln143 instead with Tyf34, in contrast to non-(19)F-labeled MnSOD, where the azide is hydrogen bonded to the hydroxy group of Tyr34.