Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

Scopus

SCImago Journal & Country Rank

Log In Registration RU

Maslov DA, Bekker OB, Alekseeva MG, Kniazeva LM, Mavletova DA, Afanasyev II, Vasilevich NI, Danilenko VN

Tuberculosis (TB) is the world’s deadliest bacterial infection. Its causative agent Mycobacterium tuberculosis evolves into rapidly spreading multidrug-resistant and extensively drug-resistant (MDR and XDR) strains, which complicates the treatment. Therefore, the use of novel target-specific chemical compounds is crucial for the development of effective antituberculosis agents. Serine/threonine protein kinases (STPKs) of M. tuberculosis are currently considered as attractive drug targets. In turn, aminopyridines and aminopyrimidines that have not been used for TB treatment so far exhibit inhibitory activity towards STPKs. In this study we screened 192 aminopyridine- and aminopyrimidine-based compounds using the Mycobacterium smegmatis aphVIII+ test system designed to screen for active STPKs inhibitors. First, we selected 53 compounds with subinhibiting concentrations of up to 100 nmol/disk. Of them, 22 showed STPKs-inhibiting activity in the test system, which was confirmed in vitro on the M. tuberculosis PknA protein with a maximum of 26.9 ± 6.1 %. Toxicity testing was performed in vitro on human embryo fibroblasts using the MTT-assay. Ultimately, 3 relatively active and relatively non-toxic STPKs inhibitors were selected for further research as drug candidates for MDR-TB treatment.

Received: 2017-01-30

Published online: 2017-03-13

DOI: 10.24075/brsmu.2017-01-04

Comments 0

VIEWS 6684

Chagina IA, Perevarova YuS, Perevarov VV, Chaplin AV, Borisova OYu, Kafarskaya LI, Afanas'ev SS, Aleshkin VA

The pathogenic mechanism used by Corynebacterium diphtheriae is attributed to the ability of the diphtheria toxin to disrupt protein synthesis in human cells. Diphtheria toxin production is regulated by the DtxR protein. The latter is involved in the iron-mediated repression of the toxin gene and coordinates activities of other genes essential for the survival of C. diphtheriae. The DtxR-encoding gene occurs in both toxigenic and non-toxigenic strains; therefore it can be used to analyze the population structure of the species. In our work we have studied 45 strains of C. diphtheriae isolated in the Russian Federation in 2010–2015. These strains were analyzed to reveal that gene dtxR is a highly conservative region of С. diphtheriae genome that can be found in all members of the studied species. The majority of the discovered polymorphisms were synonymous (16 of 18 single nucleotide polymorphisms identified). In spite of the low phylogenetic signal, the allelic variant of dtxR was associated with the strain’s phenotype (biovar, toxigenicity). The obtained data indicate the presence of aggressive negative selection aimed to maintain the existing protein sequence in the population. Based on the results, we recommend dtxR polymerase chain reaction as an additional technique for pathogen identification, which is especially relevant considering the increasing prevalence of the disease associated with non-toxigenic C. diphtheriae strains.

Received: 2017-02-02

Published online: 2017-03-11

DOI: 10.24075/brsmu.2017-01-03

Comments 0

VIEWS 5985

Gordeev AB, Lyubasovskaya LA, Rodchenko JV, Dubodelov DV, Mukosey IS, Kochetkova TO, Nikitina IV, Ionov OV, Zubkov VV, Trofimov DYu, Priputnevich TV

Staphylococcus epidermidis is a member of the normal bacterial flora of humans capable of causing potentially dangerous diseases in neonates with very or extremely low birth weight. The number of genes responsible for virulence and antibiotic resistance may vary in different S. <i>epidermidis</i> strains. We sequenced isolates of S. <i>epidermidis</i> to explore genetic diversity of 14 strains circulating in the Neonatal Intensive Care Unit of Kulakov Research Center for Obstetrics, Gynecology and Perinatology. Among the studied strains, 8 sequence types were identified, the most frequent being ST2 and ST59, both of which belong to the clonal complex CC2. Of 14 studied strains, 10 were of CC2 type. The studied strains revealed a variety of genes responsible for antibiotic resistance. We found 15 genes that provided resistance to aminoglycosides, beta-lactam antibiotics, fusidic acid, macrolides, lincosamides, streptogramin B, tetracycline, and trimethoprim. We identified a number of genes associated with virulence (<i>aae, atlE, aap, embp</i>), whose frequency in the studied isolates was varied. The insertion element IS256 was detected in 9 strains, and 7 strains revealed the presence of the <i>ica</i>-operon responsible for the biosynthesis of the biofilm matrix proteins.

Received: 2017-02-02

Published online: 2017-03-11

DOI: 10.24075/brsmu.2017-01-02

Comments 0

VIEWS 5999

Makarov VV, Khromov AV, Gushchin VA, Tkachuk AP

Each new emerging infection may become a big challenge to the medical community. Changing environment, tropical deforestation, melting of the Antarctic ice, growing population density and uncontrolled use of antibiotics provoke emergence and evolution of pathogens. Epidemics caused by new strains of the influenza virus, respiratory syndromes associated with coronaviruses, outbreaks of hemolytic Escherichia coli infections and antibiotic-resistant superbacteria are hazards to humans. Among high-priority measures for pathogen control that are yet to be taken is development of fast and accurate techniques for pathogen identification. Our review looks at the cases of new infections registered in the 21st century and explores feasibility of next generation sequencing for the detection and identification of new pathogens.

Received: 2017-02-03

Published online: 2017-03-11

DOI: 10.24075/brsmu.2017-01-01

Comments 0

VIEWS 6419

Lipengolts AA, Budaeva JA, Blaickner M, Cherepanov AA, Menkov MA, Kulakov VN, Grigorieva EYu

In vivo quantitative determination of high-Z elements such as iodine gadolinium, gold, etc. is an important issue for contrast enhanced radiotherapy (CERT) that aggravates its clinical implementation. X-ray computed tomography (CT) could be a reliable, convenient and universal method for this task. The aim of this study was to demonstrate the feasibility of iodine quantification with CT in a tissue equivalent phantom, meeting the demands for CERT. The results show a linear relationship between iodine concentration and radiopacity on tomographic images expressed in Hounsfield units (HU) over an iodine concentration range of 0.5–50 mg/ml. Furthermore, iodine quantification with CT proofed to be suitable for CERT since the deviation between CT- derived and actual iodine concentration does not exceed 5 % in the concentration range of 10–50 mg/ml. More significant deviations were observed for concentrations below 5 mg/ml with up to 80 %, which is still acceptable for CERT since the corresponding error for the absorbed dose in that range is less than 2.8 %. X-ray beam hardening within the tissue equivalent object does not significantly influence the accuracy of iodine quantification. The placement of iodine water solutions at the surface or in the centre of a visualized object during iodine quantification leads to a less than 2 % change in the determined iodine concentration.

Received: 2016-12-01

Published online: 2017-01-19

DOI: 10.24075/brsmu.2016-06-03

Comments 0

VIEWS 5868

Abramov DD, Belousova MV, Kadochnikova VV, Ragimov AA, Trofimov DYu

This article continues a series of works estimating carrier frequencies of mutations associated with the development of common monogenic disorders in the Russian population. The study aimed to establish the frequency of GJB2 and GALT mutations in first-time blood donors. Genotyping of 1000 first-time blood donors who identify themselves as Russians and permanently reside in the Russian Federation detected 37 carriers of GJB2 mutations associated with sensorineural hearing loss (carrier frequency in the sample was 3.7 %, or 1 : 27) and 6 carriers of GALT mutations associated with galactosemia (carrier frequency in the sample was 0.6 %, or 1 : 167). In one carrier, concurrent mutations were detected; thus, in total 42 carriers of GJB2 and GALT mutations were detected (carrier frequency in the sample was 4.2 %, or 1 : 24).

Received: 2016-12-06

Published online: 2017-01-19

DOI: 10.24075/brsmu.2016-06-04

Comments 0

VIEWS 5939

Nizamutdinov II, Korostin DO, Ilinsky VV, Rakitko AS

The principle of inheritance of multifactorial traits (MTs) relies on the presence of a considerable number of genetic markers, with each marker contributing to the probability of developing those traits. This work proposes an algorithm for the selection of DNA markers that could be used to devise a prognostic test system for the assessment of individual predisposition to MTs. The method is based on the selection of genetic markers that have demonstrated a statistically significant association with an MT in question and have been described as functionally significant polymorphisms that affect MT development. If the functional significance of a polymorphism has not been described so far, then to be reliably associated with an MT, this polymorphism is expected to achieve genome-wide significance in one of the studies and such significance must be confirmed in an independent sample. Works used to assess the association of genetic markers with MTs are expected to meet the proposed criteria depending on the study type.

Received: 2016-12-16

Published online: 2017-01-19

DOI: 10.24075/brsmu.2016-06-05

Comments 0

VIEWS 5968

Kharina DS, Poletaeva TA, Kondakov AK, Mosin DYu, Znamensky IA

The number of patients suffering from diabetes mellitus (DM) is increasing necessitating the development of new strategies for early detection of the disease. Here, radionuclide imaging may be a promising diagnostic technique. We have conducted a retrospective analysis of medical records and scintigrams of patients with type 2 diabetes (n = 83) and impaired glucose tolerance (n = 52) to evaluate the effectiveness of dynamic renal scintigraphy and myocardial perfusion scintigraphy at rest (single-photon emission computed tomography, SPECT) in detecting coronary and renal angiopathies. The control group consisted of patients with normal levels of blood sugar. To evaluate the functional state of the renal parenchyma, we conducted a qualitative analysis of patients’ scintigrams and renographic curves; the glomerular filtration rate (GFR) was evaluated using Gates and Cockroft-Gault methods; myocardial scarring was evaluated using perfusion SPECT images synchronized with ECG. The functional activity of the renal parenchyma was shown to decrease significantly in patients with type 2 DM (Pearson’s chi- squared test was applied, p-value was 0.03). With Gates method applied, GFR in both experimental groups was significantly lower than in the controls (Mann-Whitney U was calculated; p-value was 0.0004 and 0.0002, respectively). In patients with type 2 DM, GFR was lower than in patients with impaired glucose tolerance (p = 0.0004). With Cockroft–Gault method applied, we observed the same GFR pattern; however, the difference between patients with impaired glucose tolerance and the controls was insignificant (p = 0.08). The correlation between GFR values obtained using different methods was moderate in all groups (Spearman’s rank correlation coefficient rs = 0.53, with p = 0.038).

Received: 2016-11-25

Published online: 2017-01-19

DOI: 10.24075/brsmu.2016-06-06

Comments 0

VIEWS 5764