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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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 5237

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 4804

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 4954

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 5128

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 4487

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

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VIEWS 4789

Reutov AA, Aronov MS, Kushel YuV

Iatrogenic arteriovenous fistulas make up only 0.22% of all fistulas. This article reports a postoperative arteriovenous fistula in a female patient who initially presented with a vestibular schwannoma and was operated using the retrosigmoid approach. Undesired clinical symptoms developed after the patient had been discharged home, and included pulsatile tinnitus, which intensified when the patent tilted or turned her head. The diagnosis was established based on cerebral angiography findings during the second hospital stay. This case report describes complications of retrosigmoid craniotomy, clinical manifestations of the arteriovenous fistula and successful fistula embolization.

Received: 2018-01-19

Published online: 2018-08-15

DOI: 10.24075/brsmu.2018.034

Comments 0

VIEWS 4463

Gaydina TA, Dvornikov AS, Skripkina PA, Arutyunyan GB

Nevus sebaceous of Jadassohn (NSJ) is a benign skin lesion, a hamartoma typically localized to the face or scalp and equally common in men and women. Pluripotent epithelial cells that give rise to NSJ provide a favorable environment for benign and malignant tumors to form in the nevus. Because of the possibility of malignant transformation, NSJ should be removed after puberty. If surgery is impossible, long-term observation is indicated. In this work we present two cases of successful NSJ treatment with the CO2 laser in young patients.

Received: 2018-05-05

Published online: 2018-08-14

DOI: 10.24075/brsmu.2018.033

Comments 0

VIEWS 5192