Published online: 2018-09-19
DOI: 10.24075/brsmu.2018.043
Due to the spreading and increasing drug resistance of pathogens, the search for novel antibiotics is becoming ever more important. Plant-derived polyphenols are a vast and promising class of compounds with a potential to fight infectious diseases. Still, they are not routinely used in clinical practice. No reports on the in vivo studies of these compounds have been presented. The aim of our work was to compare the antimicrobial activity of resveratrol (stilbene), dihydroquercetin and dihydromyricetin (flavonols) extracted from the bark and wood of conifers against the dermatophytes Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Using the radial diffusion assay, we established that dihydroquercetin, resveratrol and dihydromyricetin exhibit high activity against S. aureus even at the smallest possible concentrations of 0.22, 0.15, and 0.15 mM, respectively. In contrast, the highest achievable concentrations of these compounds in the solutions (21.5, 15.5 and 15.0 mM for dihydroquercetin, resveratrol and dihydromyricetin, respectively) have no effect on the growth of P. aeruginosa and C. albicans. These findings suggest that polyphenols derived from conifers could have a potential to be used as a medicine for topical application to treat bacterial infections of the skin caused by S. aureus.
Published online: 2018-09-17
DOI: 10.24075/brsmu.2018.042
The efficacy of cardiac MRI in the diagnosis of hibernating myocardium remains understudied. The existing body of evidence on this matter comes mainly from observational studies carried out in heterogenous (in terms of cardiac pathology) cohorts of patients, which complicates the interpretation of the results. The aim of our study was to evaluate the efficacy of cardiac imaging techniques in 144 patients with a history of myocardial infarction, multivessel coronary artery disease and a low ejection fraction of the left ventricle. All participants underwent stress echocardiography and cardiac MRI examinations. The following parameters were factored into: a) the number of identified segments with abnormal myocardial contractility; b) the transmurality index (scar thickness); c) the volume of the viable myocardium relative to its total mass. The study revealed that on average there were 2.72 ± 0.82 segments with contractile dysfunction per patient. Cardiac MRI was able to detect significantly more hibernating segments than stress echocardiography. On average, the difference in the number of detected segments was 36 (56; 86) at 95% CI and р < 0.01. We established that as the transmurality index increases, the number of hypokinetic segments decreases (r = –0.78; р = 0.0314) while the number of akinetic segments (r = –0.84; р = 0.0282) goes up. This needs to be accounted for when selecting a treatment strategy for such patients. We conclude that cardiac MRI is a more effective and sensitive diagnostic technique in patients with hibernating myocardium that allows detecting significantly more cardiac segments with contractile dysfunction than stress echocardiography. Delayed contrast enhancement is instrumental in estimating the thickness and extent of cardiac fibrosis, the parameters that should be accounted for when deciding on the treatment strategy in such patients.
Published online: 2018-09-15
DOI: 10.24075/brsmu.2018.041
 Placental pathology is accompanied by the activation of apoptosis in the trophoblast and the subsequent increase in the concentrations of microvesicles containing placental (or fetal) DNA accumulating in the maternal blood. Fragments of fetal DNA stimulate the release of nuclear and/or mitochondrial DNA fragments by neutrophils. Therefore, one can expect that complicated pregnancies will be characterized by the dramatic elevation of total cell-free DNA (cfDNA) levels in maternal plasma. The aim of this work was to study the dynamics of plasma cfDNA concentrations and the activity of DNase I, an enzyme involved in the elimination of cfDNA from the bloodstream, in nonpregnant and pregnant women. Our study recruited 40 healthy nonpregnant women, 40 women with uncomplicated pregnancies and 35 women with the intrauterine growth restriction (IUGR) of the fetus. We did not observe the elevation of the total cfDNA concentrations in the patients with complicated pregnancies. Moreover, cfDNA concentrations in their plasma were even lower (though this difference was statistically insignificant) than in healthy pregnant and nonpregnant women. The median values of cfDNA concentrations in the group of healthy nonpregnant women were 75.5 ng/ml; in the group of healthy pregnant women, 78.0 ng/ml; and in the patients with IUGR, it was 42.1 ng/ml. At the same time, we observed a significant increase in DNase I activity in the plasma of women with IUGR. The median DNase I activity in the groups of healthy pregnant and nonpregnant women was 3.0 and 3.4 IU/ml, respectively. In patients with different grades IUGR of the fetus this parameter was as high as 6.3 IU/ml (р < 0.001). Increased DNase I activity in the plasma of women with complicated pregnancies indirectly suggests a transient elevation of circulating cfDNA levels. Our study shows that the high level of activity exhibited by the cfDNA elimination system impedes the analysis of cfDNA concentrations in complicated pregnancies and skews its results. However, if cfDNA, DNase I activity and cfDNA/DNase I ratio were all taken into account, it could be possible to develop a tool for the monitoring of cell death in the mother throughout the entire pregnancy.
Published online: 2018-08-23
DOI: 10.24075/brsmu.2018.039
The spread of multidrug and extensively drug-resistant Mycobacterium tuberculosis urges the development of novel antituberculosis drugs. Previously, we studied the compounds representing the class of substituted imidazo[1,2-b][1,2,4,5] tetrazines capable of inhibiting serine/threonine protein kinases (STPK) in the original M. smegmatis aphVIII+ test-system. To unveil the mechanism of action of drug candidates, it is necessary to search for mutations in the mycobacterial genome that confer resistance to these compounds. The aim of our work was to find and describe such mutations in M. smegmatis strains. We carried out the whole-genome sequencing of 9 mutants resistant to 3 imidazo[1,2-b][1,2,4,5]tetrazines. Seven of 9 mutant strains were found to have the Y52H mutation in the highly conserved mycobacterial gene MSMEG_1601 encoding a protein with an unknown function. Additionally, three of those 7 strains were shown to have two mutations in the MSMEG_1380 encoding a transcriptional regulator. The remaining 2 mutant strains had mutations in MSMEG_0641 and MSMEG_2087 genes encoding transporter-proteins. No mutations were found in STPK genes, meaning that they might be not the primary targets of the studied compounds. Further investigation of MSMEG_1601 function may be of interest as this protein might be the biological target or a part of a new mechanism underlying resistance to antituberculosis drug candidates.
Published online: 2018-08-23
DOI: 10.24075/brsmu.2018.038
In spite of successful measures taken to reduce mortality associated with tuberculosis, this disease is still widely spread. In some Russian regions the number of patients with tuberculosis is no short of the epidemic level. The long-term use of antibiotics, changes in the composition of the human microbiota and a few other factors have contributed to the emergence of drug-resistant and hypervirulent sublineages of Mycobacterium tuberculosis. Insufficient fundamental knowledge of mechanisms underlying the emergence and evolution of M. tuberculosis clones simultaneously resistant to a wide spectrum of antibiotics and exhibiting increased virulence complicates the situation and necessitates a new strategy to combat the disease. The key concepts of this strategy are «superorganism», «microbiota» and «resistome». The emergence of multidrug-resistant (MDR) and extensively resistant (XDR) strains should be addressed in the context of the «superorganism»; among its components are the human body, its microbiota (specifically, the bacteria that affect the immune status), and M. tuberculosis itself. Clinically studied phenotypes and genotypes of MDR/XDR strains are a result of clonal variability that M. tuberculosis develops as part of this «superorganism». Therefore, it is important to focus on the development of vaccines, adjuvants and probiotics with selective immunomodulating and antioxidant properties.