[Preclinical and clinical trials of the new tuberculosis drug perchlozon].

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.

[Enucleation, formation of cyto- and karyoplasts, and their fusion with neuronal body].

In this research that was performed on isolated neurons of mollusk Lymnaea stagnalis, using neuron enucleation, the cytoplast was obtained which was then fused with another neuron resulting in cybrid formation. The experiments performed have shown that the isolated neurons are able to fuse with each other, forming binuclear neurons; also, like all other cells, they could be enucleated with the formation of cyto- and karyoplasts and, after fusion, they can form cell body-cytoplast, cytoplasts-karyoplast, and other complexes. This is associated with the appearance of all doubtless indicators of fusion described for fusion of nerve cell bodies. This work demonstrates the possibility to artificially fuse the amputated neuroplasm fragment with neuronal cell body--the metabolic center of another cell. Theoretically, this means that in vivo amputated neuronal process also can be fused with a novel cell.

[Ultrastructure of the caudal mesenteric ganglion neurons during early development in kittens].

Electron microscopy was used to study the peculiarities of the development of nervous elements in the sympathetic caudal mesenteric ganglion (CMG) in the cat from the moment of birth until the end of the second month of life. The discordance in the rate of maturation of both neurons and their endings was observed. In newborn kittens, mature neurons, glial cells and synapses were observed together with many immature ones. In 14-day-old animals, the proportion of immature neurons decreased, while destruction of neurons was observed more frequently in this age. In CMG of the animals of all the age groups, axodendritic synapses were found most frequently and axosomatic synapses were observed more rarely. Finally, the ultrastructure of CMG in kittens become comparable to that of adult animals at the age of 60 days.

[Glio-neuronal and glio-glial syncytial cytoplasmic connections in peripheral nerve trunks of the crayfish Astacus leptodactylus].

The paper considers various aspects of glial sheaths of neuritis in the crayfish peripheral nerve trunks and roots. There are revealed dotted glio-neurite tight junctions and a varicose deformation of the intercellular glio-neurite cleft. Rupture of membranes in the area of contact leads to formation of the glio-neurite pore (less than 10 nm) that is enlarged and forms wide (up to 240 nm) syncytial perforations. At the edge of perforation, either remnants of tight junctions are present or damaged membranes that fuse and are rounding. The lumen of perforations always contains residual membranous bodies in the form of vesicles. Their deviation from the median line can indicate a mutual translocation of substances of the glio- and neuroplasm. In the adjacent layers of the multilayer glial sheath there is noted a similar phenomenon of formation of the glio-glial syncytial connection terminating by fusion of neighbor glial layers, which is terminated by fusion of neighbor glial layers into the single lamina. The process begins from the varicose deformation of interglial clefts, which appears as a result of massive formation of dotted and expanded tight membranous contacts. As a result of transformation of ellipsoid varicose deformations into the spherical ones, syncytial pores (less than 10 nm) between them are formed, which are enlarged and break the paired gliolemmas into fragments. As a result, the adjacent glial layers are united. Since this process in intact animals occurs on the background of undamaged nerve structures, a suggestion is put forward about its reversibility and the functional nature.

Syncytial cytoplasmic anastomoses between neurites in caudal mesenteric ganglion cells in adult cats.

The fact that most published data on syncytial cytoplasmic anastomoses are based on the autonomic nervous system in the early postnatal period of development, when many nerve fibers are poorly ensheathed by glia or have no glial sheaths at all, has led to the assumption that these anastomoses do not exist in adults because of the significant development of the glia and glial insulation of individual neurites from each other. We tested this assumption using electron microscopic studies of the caudal mesenteric ganglion in adult cats. A high level of glial ensheathing of neurites was observed. However, syncytial pores were seen between contacting neurites lacking glial sheaths in almost every specimen. This is the first report describing axodendritic synapses with perforations in the presynaptic zone outside the synaptic specializations in the autonomic nervous system. It is suggested that although syncytial cytoplasmic connections are seen in adult animals, they do not contradict the neuron theory.

Development of rat stellate ganglion neurons containing membrane-bound muscarinic receptors and purinoreceptors.

The aim of the study reported here was to investigate the locations and morphometric characteristics of neurons in the stellate ganglion (SG) containing muscarinic cholinoreceptors and purinoreceptors in rat pups of different ages (neonatal, 10, 20, 30, 60, and 180 days) using immunohistochemical methods. The results showed that in all animals, most neurons were immunoreactive to M1 cholinoreceptors and P2X2 and P2X6 purinoreceptors from birth. Sections showed isolated neurons containing P2X3 purinoreceptors, the numbers of which increased from day 10 of life to day 20 and then decreased again. During ontogenesis, the proportions of neurons expressing M1 cholinoreceptors and P2X2 and P2X6 purinoreceptors did not change significantly. Thus, by the moment of birth, muscarinic synaptic transmission already occurred in the SG in rats, while the final set of purinoreceptors in the neurons of this sympathetic ganglion formed by age 30 days.

[Roncoleukin in enhancing the efficiency of complex therapy for infiltrative pulmonary tuberculosis in adolescents].

Seventy-eight patients, aged 15.69 +/- 0.15 years, who had infiltrative pulmonary tuberculosis, were examined. Roncoleukin was given intravenously in 20 patients of them (Subgroup 1a), in an indirect lymphotropic fashion in 30 patients (Subgroup 1b); 28 adolescents were treated with the conventional treatments (Group 2). A decay phase was recorded in 33 (66%) from Group 1 and in 16 (57.1%) from Group 2. On admission, all 78 (100%) patients had immunological disorders that required immunomodulation. Roncoleukin caused positive clinical and X-ray changes that were more pronounced in Subgroup 1b: bacterial excretion cessation was recorded in 100% of patients in Subgroup 1a (p < 0.05); in 94.4% in Subgroup 1b (p < 0.05), and in 68.7% in Group 2; decay cavities closed in 69.2, 60, and 37.5% in Subgroups 1a and 1b and Group 2. At the same time, the duration of a procedure considerably reduced, which positively affected adolescents' compliance.

[Syncytial cytoplasmic anastomoses between the neurites of caudal mesenteric ganglion cells in adult cats].

Since the majority of the published data on syncytial cytoplasmic anastomoses relate to the autonomic nervous system in the early postnatal period of development, when many nerve fibers are still poorly covered by glia or have no glial sheaths at all, it was suggested that such anastomoses were not present in adults due to the significant development of glia separating individual neurites from each other. To check this assumption, we have performed an electron microscopic study of the adult cat dorsal caudal mesenteric ganglion. The cell neurites were found to be frequently covered by glial sheaths. However, almost in every sample, the syncytial pores were detected between the contacting neurites lacking glial covering layers. Sometimes serial syncytially connected neurites were seen. Axo-dendritic synapses with presynaptic perforations outside the synaptic specializations were described in the autonomic nervous system for the first time. These observations therefore provide evidence of syncytial cytoplasm connections in normal adult animals, however this does not reject the neuronal doctrine.

The problem of neuronal syncytical connection in disease.

The membranes of neuron profiles adjacent to each other in the caudal mesenteric ganglion were examined electron microscopically during the first 3 days after crossing of the preganglionar or postganglionar branches. The contacting membranes were thinned and perforated, and neuron-to-neuron syncytial connections were forming. Multiple connections were formed between the nerve processes and terminals in the synapse. The pre- and even postsynapses were clear in pronounced perforations.

[Monitoring of chemotherapy in patients with pulmonary tuberculosis by the blood bacteriostatic activity-determining test].

The paper gives the results of studies to determine blood bacteriostatic activity (BBA) in the use of a patient's autostrain and semiliquid medium versus the clinical and laboratory parameters of the course of a process in 101 patients with pulmonary tuberculosis. There is evidence for the relationship of the BBA to the sensitivity to isoniazid and the structure of drug resistance. The zero values of BBA correspond to the severest course of the disease. The efficiency of treatment is much higher in patients with high and moderate BBA. The latter's determination using the semiliquid medium permits an objective evaluation of the efficiency of chemotherapy, identification of patients with a poor prognosis, and then choice of an individual treatment regimen on day 7 after the test just before obtaining the data on drug sensitivity.

[Development of rat stellate ganglion neurons, containing membrane muscarinic and purinoreceptors].

The aim of this study was to determine the localization and morphometric characteristics of the stellate ganglion (SG) neurons containing muscarinic and purinoreceptors in rats of different ages (newborn, 10-, 20-, 30-, 60-, and 180-day-old) using the immunocytochemical methods. The results obtained indicated that in all the animals studied, the major part of neurons contained immunopositive P2X2, P2X6 purinoreceptors and M1 cholinoreceptors since birth onwards. A few of the neurons containing P2X3 purinoreceptors were detected in all the stages of postnatal development; these neurons were scarce in rats up to 10 days of life, after which their number increased to reach a maximal value in 20-day-old animals and then declined again. No significant changes were found in the proportion of neurons expressing M1 cholinoreceptors and P2X2, P2X6 purinoreceptors during the ontogenesis. Thus, the muscarinic synaptic transmission was already present in SG of rats by the time of their birth, while the final set of purinoreceptors on the neurons of sympathetic ganglion was formed by the age of 30 days.

[Immunogenetic aspects of the course and treatment of pulmonary tuberculosis].

The paper presents the clinical, X-ray, and laboratory characteristics of patients with pulmonary tuberculosis. Both general regularities and differences in the frequency of alleles of the HLA-DQB1* locus have been revealed in the groups of patients with pulmonary tuberculosis as compared with healthy individuals. There are specificities associated with the risk of pulmonary tuberculosis and the variants of the course of infection; thus, allele 05 of the HLA-DQB1* locus is positively associated with the incidence of tuberculosis. Specificity 03 of the HLA-DQB1* locus has been ascertained to be associated with the poor course of the disease. The most pronounced immunological changes have been observed in patients with the poor course of the disease, who are the carriers of specificity 05 of the HLA-DQB1* locus. The totality of immunological parameters and the data of genetic studies provide a basis for using the selective immunomodulator rIL-2 (roncoleukin) in the most seriously ill patients who are carriers of specificity 05.

[A role of the HLA-DRB1* genotype in the complex therapy of pulmonary tuberculosis].

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.

Indicators of neuritis growth and retraction in tissue culture and histological specimens.

The dynamics of structural processes in cultured neurons was studied by time-lapse video recording and compared with the diversity of morphological structures in fixed preparations. Ellipsoid terminal structures indicate not the growth, but growth arrest of neurites and the start of their retraction (retraction bulbs). Only growth cones can be the indicators of neuritis growth and development. Autotomy of individual terminals is a normal process, but does not indicate neural pathology. The "neuroplasm protuberances" on fixed preparations do not indicate neuroplasm extrusion, but reflect an extreme state of retracting processes. The formation of varicosities results not from swelling, but from redistribution of the neuroplasm and often accompanies its contraction. Disruption of neural contacts and complete invagination of neurites into the cell body are not indicative of the neuron death. These cells can form new processes and make new interneuron contacts.

[Combined therapy of pulmonary tuberculosis by using recombinant interleukins]. / Kompleksnaia terapiia tuberkuleza legkikh s primeneniem rekombinantnykh interleikinov.

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) (p < 0.05), 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 (p < 0.05).

[Therapy strategy in the treatment of patients with drug-resistant pulmonary tuberculosis]. / Taktika lecheniia bol'nykh lekarstvenno-ustoichivym tuberkulezom legkikh.

The article contains a clinical- X-ray- and laboratory description of 56 patients with tuberculosis (disease length ranging from 2 to 5 years), who, during the previous treatment stage, received a therapy in compliance with the generally accepted methods and without any effect. All patients discharged bacteria. Drug-resistance to 3 and more preparations was registered in all patients. A complex approach to the therapy of patients with destructive pulmonary tuberculosis is suggested, within the study, with regard for the presence of multidrug-resistance of Mycobacterium tuberculosis (MBT), for a degree of inactivation of isoniazid and for a degree of bacterial-static activity of patient's blood, which provides for a higher treatment efficiency.

[Blood bacteriostatic activity in patients with respiratory tuberculosis]. / Bakteriostaticheskaia aktivnost' krovi u bol'nykh tuberkulezom organov dykhaniia.

Vertical diffusion on the Löwenstein-Jensen medium was used to study blood bacteriostatic activity (BBA) in 174 patients with respiratory tuberculosis in relation to the drug resistance of isolated Mycobacterium tuberculosis (MT) strains and to the course of a tuberculous process. There was a clear relationship of BBA to the sensitivity of MT cultures to isoniazid: BAC was high and moderate in 90.8-98.2% of cases if strain drug sensitivity was present and low or null in 98% with drug resistance. The high and medium values of BBA correlated with the clinical indices "improvement" and "significant improvement". Patients with zero and lower values of BBA and isoniazid resistance showed a progressive specific process in 22.0% of cases. Estimation of total BBA by using liquid media is the most informative method.

[Structural and functional changes in sympathetic ganglia following endotoxin and alpha1-antitrypsin exposure]. / Strukturno-funktsional'nye izmeneniia v simpaticheskikh gangliiakh pri deistvii v organizme éndotoksina i al'fa-antitripsina.

Structural and functional organisation of sympathetic ganglia under conditions of endotoxemia was studied in white rats, cats, and dogs. Submicroscopic characteristics of the changes occurring in the rat prevertebral sympathetic ganglia after endotoxin administration or application of endogenous proteinase inhibitor alpha 1-antitrypsin, were assessed as well as ultrastructural bases of the febrile rat ganglionic responses to antipyretic drug administration. Effects of endotoxin on synaptic transmission in inferior mesenteric plexus' ganglia of cats and on electrical activity in inferior mesenteric plexus' ganglia of dogs, were electrophysiologically demonstrated.

[Morphofunctional mechanisms of responses of sympathetic ganglia to the high external temperature and pyrogen exposure]. / Morfofunktsional'nye mekhanizmy reaktsii simpaticheskikh gangliev na deistvie vysokoi vneshnei temperatury i pirogenov.

Reactive changes of structural and functional organization of pre- and paravertebral sympathetic ganglia were studied in experimental fever and under the effect of high temperatures using electron microscopy and histochemical methods. Changes in histochemical and ultramicroscopic characteristics of neuroglial complex, synaptic apparatus and of histohematic barrier were demonstrated. Correlation between those changes and the dose and duration of the challenge was established.