Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Rustamova YK, Imanov GG, Azizov VA

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.

Received: 2018-01-16

Published online: 2018-09-17

DOI: 10.24075/brsmu.2018.042

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VIEWS 4005

Avetisova KG, Kostyuk SV, Kostyuk EV, Ershova ES, Shmarina GV, Veiko NN, Spiridonov DS, Klimenko PA, Kurtser MA

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.

Received: 2018-03-15

Published online: 2018-09-15

DOI: 10.24075/brsmu.2018.041

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VIEWS 4324

Shur KV, Umpeleva TV, Bekker OB, Maslov DA, Zaychikova MV, Vakhrusheva DV, Danilenko VN

Evolution of Mycobacterium tuberculosis have lead to the development of a number of lineages that have unique phenotypes and genotypes and are associated with certain geographical regions. Thus, compared to the reference strains of M. tuberculosis, Beijing and LAM genotypic lineages, which are the most common in the world, are highly virulent and transmissible. However, the extensive use of antibiotics over the past 50 years has caused the next evolutionary leap, which yielded new, epidemiologically dangerous sublineages: Beijing-B0 in Russia, Beijing-modern-4 in China and KZN in South Africa. This study aimed at investigating the effect the immune dysfunction predictors registered in patients have on the severity of tuberculosis (TB) developing after contracting M. tuberculosis Beijing-B0. We compiled a sample of patients with newly diagnosed TB caused by M. tuberculosis Beijing-B0, searched for the immune-suppressing diseases/conditions in their medical history and developed their immunograms. No connection was found between the state of the immune system and the characteristics of the disease we considered.

Received: 2018-06-02

Published online: 2018-08-24

DOI: 10.24075/brsmu.2018.040

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VIEWS 3860

Maslov DA, Bekker OB, Shur KV, Vatlin AA, Korotina AV, Danilenko VN

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.

Received: 2018-05-30

Published online: 2018-08-23

DOI: 10.24075/brsmu.2018.039

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VIEWS 3607

Danilenko VN, Zaychikova MV, Dyakov IN, Shur KV, Maslov DA

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.

Received: 2018-06-05

Published online: 2018-08-23

DOI: 10.24075/brsmu.2018.038

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VIEWS 3738

Nikiforova AI, Abramov DD, Zobkova GU, Goriainova AV, Semykin SYu, Shubina J, Donnikov AE, Trofimov DYu

Cystic fibrosis (CF) is one of the most common monogenic disorders of humans. The knowledge of population frequency of a mutant genotype causing a monogenic disease helps to optimize DNA testing and to reduce its costs and time required for the procedure. This article presents the results of a retrospective study of the CFTR gene in 191 children with mixed manifestations of CF. To screen for 24 most common mutations, we used the diagnostic PCR panel; minor mutations were detected by next generation sequencing. The diagnostic panel allowed us to identify 18 typical CFTR mutations, including F508del (allelic frequency of 54.7%), dele 2,3 (21kb) (7.3%), 2143delT (3.4%), 2184insA (3.4%), 1677delTA (2.4%), N1303K (2.1%), 3849+10kbC>T (2.1%), E92K (2.1%), G542X (1.6%), W1282X (1.6%), S1196X (1.3%), R334W (1.0%), 394delTT(0.8%), 3944delGT (0.8%), 3821delT (0.5%), 2789+5G>A (0.5%), 621+1G>T(0.3%), and 2183AA>G (0.3%). Sequencing revealed the presence of 24 potentially pathogenic CFTR variants in the sample. We also discovered 8 minor CFTR variants previously unseen in Russian patients with CF, including 4 new CFTR mutations: p.Glu819Ter, p.Gln378Ter, p.Val1360Phefs, and p.Lys1365Argfs.

Received: 2018-07-10

Published online: 2018-08-23

DOI: 10.24075/brsmu.2018.037

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VIEWS 3702

Lyadova IV, Panteleev AV, Nikitina IYu, Radaeva TV

Development of new tuberculosis (TB) vaccines and host-oriented therapy requires understanding mechanisms mediating protective antituberculous immunity. Antigen-specific Th1 lymphocytes have long been considered as the main correlate of TB protection. However, recent data do not confirm this concept. This article discusses debatable issues concerning the role for Th1 lymphocytes in antituberculous immunity, as well as their use as correlates of protection in preclinical and clinical studies assessing the effectiveness of new candidate TB vaccines.

Received: 2018-05-29

Published online: 2018-08-21

DOI: 10.24075/brsmu.2018.036

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VIEWS 3364

Kunafina TV, Chuchalin AG, Belevsky AS, Mescheryakova NN, Kalmanova EN, Kozhevnikova OV

Patients with chronic obstructive pulmonary disease (COPD) are unable to do physical exercises included into standard pulmonary rehabilitation programs. Neuromuscular electrical stimulation (NMES) is a good alternative for such patients as it does not aggravate shortness of breath. The aim of this work was to assess the effect of short-term NMES of the quadriceps femoris muscle on the physical activity of patients with COPD. Our prospective open randomized study was carried out in 36 patients distributed into two groups. The main group was administered NMES for 10 days. On day 10 clinical and functional parameters, as well as adverse events, were evaluated. On admission to hospital, the groups did not differ in terms of the studied parameters. Following the treatment course, the main group significantly improved their step count and electromyography results (418.5 (86.0; 815.0) vs. 226.7 (48.0; 660.0), p = 0.02, and 463.0 (122; 804) vs. 210.5 (64; 481), p = 0.0001, respectively). The patients scored much less on the Mmrc and Borg scales and the CAT-test: 22.8 (18.0; 34.0) vs. 28.4 (26.0; 34.0), p = 0.00007; 2.7 (2.0; 4.0) vs. 3.1 (3.0; 4.0), p = 0.03; and 6.3 (5.0; 7.0) vs. 7.2 (6.0; 9.0), p = 0.0002, respectively. No adverse events were registered in the main group. Based on the obtained results, we conclude that shortterm NMES of the quadriceps femoris muscle improves physical activity, the quality of life and ability to do physical exercise in patients with COPD providing them with a good alternative to standard rehabilitation programs.

Received: 2018-05-19

Published online: 2018-08-17

DOI: 10.24075/brsmu.2018.035

Comments 0

VIEWS 3492