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Biomedical subjects

V A Krasnov

Publications and source records attributed to V A Krasnov.

At least 19 recordsLinked to original sources

Novel conjugate of moxifloxacin and carboxymethylated glucan with enhanced activity against Mycobacterium tuberculosis.

Mycobacterium tuberculosis is an intracellular pathogen that persists within macrophages of the human host. One approach to improving the treatment of tuberculosis (TB) is the targeted delivery of antibiotics to macrophages using ligands to macrophage receptors. The moxifloxacin-conjugated dansylated carboxymethylglucan (M-DCMG) conjugate was prepared by chemically linking dansylcadaverine (D) and moxifloxacin (M) to carboxymethylglucan (CMG), a known ligand of macrophage scavenger receptors. The targeted delivery to macrophages and the antituberculosis activity of the conjugate M-DCMG were studied in vitro and in vivo. Using fluorescence microscopy, fluorimetry, and the J774 macrophage cell line, M-DCMG was shown to accumulate in macrophages through scavenger receptors in a dose-dependent (1 to 50 microg/ml) manner. After intravenous administration of M-DCMG into C57BL/6 mice, the fluorescent conjugate was concentrated in the macrophages of the lungs and spleen. Analyses of the pharmacokinetics of the conjugate demonstrated that M-DCMG was more rapidly accumulated and more persistent in tissues than free moxifloxacin. Importantly, therapeutic studies of mycobacterial growth in C57BL/6 mice showed that the M-DCMG conjugate was significantly more potent than free moxifloxacin.

Animals↗

[The clinicobiological status of patients with pulmonary tuberculosis concurrent with chronic hepatitis B and/or C].

Examination was made in 155 patients, including 60 patients were diagnosed as having hepatitis, hepatic lesion being first detected by a screening survey for markers of hepatitis. The antipyrine test was carried out. Patients with slow and rapid hydroxylation were identified. No changes were found in the biotransformation functions of the liver in patients with pulmonary tuberculosis 6 months after intravenous intermittent chemotherapy twice a week from the beginning of therapy; however, there was inhibition of the activity of monooxygenases and a two-fold increase in the number of patients with slow hydroxylation among patients with concomitant chronic hepatitis B and/or C. The best results of chemotherapy were found in tuberculous patients with slow hydroxylation: they less frequently underwent surgical interventions since decay cavities were therapeutically closed.

Biomarkers↗

[Molecular and genetic characterization of rifampicin- and/or izoniazid-resistent strains of M. tuberculosis, isolated in Novosibirsk and Tomsk regions].

The purpose of the work was to study rifampicin- and izoniazid-resistent strains of M. tuberculosis, circulating in Western Siberia, by VNTR and IS6110 typing. The authors also studied genetic causes of resistance to these antibiotics and undertook a search of new VNTR loci, displaying polymorphism in genomes of closely related clonally-disseminated variants of Mycobacterium tuberculosis in W-Beijing family model analysis.

Antitubercular Agents↗

[The forced oscillation techniques in the detection of bronchial obstruction in patients with pulmonary tuberculosis].

Clinical trials of the forced oscillation (FO) technique could identify criteria for bronchial obstruction: viscosity airway resistance (VAR) (R(fo), R(in), R(ex)), and its frequency dependence. VAR studies promoted detection of bronchial patency in further 21.9% of the patients who had no bronchial obstruction, as evidenced by spirography (SG) and F-FEV curve recording. To improve the diagnosis of impaired bronchial patency, it is expedient to explore VAR by the FO technique along with the routine methods (SG and F-FEV curve recording).

Adolescent↗

[KatG Ser3 15Thr mutation as the main reason of isoniazid resistance in Mycobacterium tuberculosis isolated in the Novosibirsk and Kemerovo Regions].

KatG Ser3 15Thr mutation is one of the main reasons of resistance to isoniazid in Mycobacterium tuberculosis isolates. The frequency rate of the above mutation among isoniazid-resistant isolates made 94% in Novosibirsk Region and 93% in Kemerovo Region. The use of PCR-restriction fragment length polymorphism (PCR-RFLP) can be regarded as an adequate method for rapid screening of isoniazid resistance in Mycobacterium tuberculosis isolated in the West-Siberian Region.

Adolescent↗

[Specific features of the course of pulmonary tuberculosis concurrent with liver pathology].

The study was undertaken to reveal clinical, biochemical, morphological, and immunological features of pulmonary tuberculosis concurrent with liver pathology. Patients with pulmonary tuberculosis who suffered from liver diseases were found to have more marked clinical signs, such as subfebrile temperature, weight loss, elevated levels of aminotransferases and gamma-glutamyltransferase. Morphological studies of liver biopsy specimens indicated that the rates of necrosis and inflammatory infiltration were higher in patients with chronic hepatitis C (CHC) and chronic hepatitis B (CHB) and CHC and substantially lower in CHB and alcoholism. Impaired immunity involved primarily the phagocytic link.

Adult↗

[On early transfer of new cases of pulmonary tuberculosis to outpatient treatment].

Based on 228 clinical cases, the authors propose procedures for complex two-stage (inpatient and outpatient) treatments of new cases of pulmonary tuberculosis by using intermittent intravenous chemotherapy that makes it possible to have a high therapeutic effect in a short space of time, to reduce the duration of hospital treatment substantially, to on the average 2-4 months, and to ensure controlled chemotherapy at the outpatient stage.

Adult↗

[Modalities of complex therapy in different categories of patients with pulmonary tuberculosis].

The paper proposes the standards of combined treatment involving intermittent intravenous bactericidal chemotherapy for different groups of patients. It describes treatment regimens at the inpatient stage, defines the scope and time of control examination and correction of a treatment protocol by taking into account the pattern, phase, and dissemination of a process and the duration of the disease.

Antitubercular Agents↗

[Treatment of patients with destructive pulmonary tuberculosis and nonspecific purulent endobronchitis].

Imozymase treatment should be started from the first hospital days in patients with destructive pulmonary tuberculosis concurrent with nonspecific purulent endobronchitis. Two-week ultrasound inhalations with imozymase in a dose of 1 ml (60 PU) may rapidly abolish not only the nonspecific inflammatory bronchial process, but also accelerate the attenuation of symptoms of intoxication, the time of abacillation, cavernous closure, and preparation for surgical interventions.

Administration, Inhalation↗

[Role of surgical treatments in patients with fibrocavernous pulmonary tuberculosis].

Three hundred and seventy patients operated on at the Institute Surgical Clinic underwent 638 surgical interventions: 356 and 282 in Groups 1 and 2 patients, respectively. Intraoperative complications occurred in 24 (3.8%) cases, in 6.5% of the patients operated on. Twenty-two complications were successfully eliminated, 2 patients died. Postoperative complications were established in 25 (14.8%) of the 169 patients of Group 1 and in 12 (6.0%) of the 201 patients of Group 2. The incidence of complications largely depended on the type of an operation. Complications were observed in 8 (36.4%) of the 22 patients undergone pulmonectomy. The active phase of a specific process as a surgical risk factor is prime consideration. In patients operated for emergency indications in the phase of an non-arrested exacerbation of tuberculosis, pleuropulmonary complications occur 2.5 times as frequently as those in patients with relative process stabilization.

Adult↗

[Outlooks for promoting antituberculosis care for the Siberian population].

An analysis of the TB situation in three Siberian territories, i.e. the Kemerovo, Omsk and Tomsk Regions, is presented. Conclusions pertaining to the key specific features were made and a correlation between an epidemic level tension, on the one hand, and an efficiency of the anti-TB activity management, on the other hand, was established. The conclusions were considered as a precondition for setting up a management structure in the sphere of the anti-TB activity that would accumulate the achievements of home phthisiology and of modern methodological and methodical management approaches. Results of elaborations of Novosibirsk Research Institute of TB Issues, which are related with establishing an anti-TB management system in Siberia, are presented; such system would comprise aims, functions, a structure and the key management components. Supposedly, the described approach is expected to optimize the efficiency and good results in the anti-TB management activity at all levels with the resources being distributed and used on the rational basis.

Attitude to Health↗

[The genetic diversity of Mycobacterium tuberculosis and an assessment of risk factors of tuberculosis spread in Russia's Siberian region by molecular epidemiological methods].

Molecular epidemiology approaches provided for a new interpretation of the TB infection transmission dynamics, contributed to changing the focuses of attention and updated the monitoring practice. On the basis of 101 cases of isolates of Mycobacterium tuberculosis (MBT) complex sampled from 84 patients with pulmonary tuberculosis in the Siberian region, we proved that the independent methods of IS6110 RFLP genetic typing and VNTR-typing by five accurate repeat tandems of ETR A, B, C, D, and E bring about similar results and can be used in studying the MTB clonal structure population in the Siberian region for the purpose of defining the TB infection transmission dynamics. The most widespread genetic types were detected, i.e. Beeijing family strains, the S42 spoligotype, and the 31323 VNTR type, which account for 52.3% of all samples. The general parameters describing the epidemic process intensity were evaluated, i.e. those characterizing the strains (91.6%) and the transmission activity factor (72%). Consequently, each three of the four analyzed TB cases resulted from a recent transmission. However, there is a trend, within the analyzed samples, towards a higher percentage of clusterization in the age group ranging from 40 to 60. Such trend is typical of a prevalence of TB reactivation cases caused by MBT complex strains spread intensively in the discussed territory. As for the clusterized isolates, which are endemic for the territory, such data should be interpreted as a recent transmission only cautiously. 28.5% of the studied isolates are resistant to anti-TB drugs used in medical practice; and 35.7% of them are resistant to izoniazide and rifampicin, therefore, according to the WHO classification they are considered to be poly-antibiotics-resistant (PAR). No strict associations were found between the spectrum of antibiotics-resistance and any of genotypes, however, 30% of PAR strains are 32525 and 42525 types VNTR (spoligotype S1 or Beejing type).

Adult↗

[Molecular genetic characteristics of rifampicin-resistant Mycobacterium tuberculosis isolates in Novosibirsk].

Forty rifampicin-resistant clinical isolates from patients living in Novosibirsk were studied. Six alleles earlier described in the literature were identified by the sequencing technique. The frequency of mutations in the studied samples slightly differs from that earlier reported for other geographic regions: 21 (52.5%) strains carried the mutated codon TTG in position 531 (Ser-->Leu), 7 (17.5%) had GTC in position 516 (Asp-->Val) and 2 (5%) had the GAC substitution in position 526 (His-->Asp), which is prevalent elsewhere. Sequence analysis revealed no mitations in 5 (12.5%) of the 40 isolates although this isolate was repeatedly resistant to rifampicin. VNTR-typing targeted to tandem repeats (ETR A, B, C, D, and E) was carried out to establish a genetic relationship for rifampicin-resistant isolates. Nine genetic types with VNTR-profiles termed as 12322, 32122, 32123, 32124, 32125, 32522, 23524, 12223, 22222, 33433 were revealed. There was no strict correlation between the type of mutation in the rpoB gene and the VNTR-type, which reflects different rates of evolution and the level of selective pressure on these genetic targets. The isolates of VNTR-types 32123 and 32125 with mutations in codon 531, and type 32122 in codons 531, 526, 516 showed a high clustering. This is likely to reflect the recent transmission and clonal dissemination of the epidemic strains of Mycobacterium tuberculosis. Thus, mutations in the rpoB gene did not reduce the virulence and transmissivity of these clones. Twenty-six of 27 clinical isolates selected by rifampicin-resistance were also resistant to isoniazid, which confirms the known fact that rifampicin-resistance may be used as a marker of isoniazid-resistance.

Antitubercular Agents↗

[Surgical treatment of patients with advanced bilateral destructive pulmonary tuberculosis].

The paper analyzes the outcomes of surgical treatment of 135 patients operated on at the Surgery Clinic of the Institute. A set of surgical techniques, including pulmonectomy, collapsosurgical interventions, local cavernous exposures, thoroscopic surgery, thoracic caustic under artificial pneumothorax, was applied. The used system of surgical treatment was found to be beneficial for these patients, as confirmed by fewer surgical (3.0%) and postoperative (7.8%) complications, lower postoperative mortality rates (2.2%), and steady state clinical recovery in 91% and working capacity restoration in 76%.

Adult↗

[Reactions of delayed hypersensitivity in patients with tuberculosis in its dormancy and pandemic].

Comparison of the results of tuberculin diagnosis in patients with tuberculosis during two studies made by the same procedure in 1973 and 1998 showed a marked increase in delayed hypersensitivity, which is indicative of higher sensitization in persons inoculated with Mycobacterium tuberculosis. This appears to be associated with the higher frequency and spread of exogenous reinfections and with the increased virulence of the causative agent.

AIDS-Related Opportunistic Infections↗