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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Andreevskaya SN, Smirnova TG, Larionova EE, Andrievskaya IYu, Chernousova LN, Ergeshov A

The lack of simple, rapid diagnostic tests for isoniazid-resistant rifampicin-susceptible tuberculosis infection (Hr-TB) can result in low treatment efficacy and further amplification of drug resistance. Based on the clinical data, this study sought to estimate the prevalence of Hr-TB in the general population and characterize the phenotypic susceptibility and genetic determinants of isoniazid resistance in M. tuberculosis strains. Molecular-genetic and culture-based drug susceptibility tests were performed on M. tuberculosis isolates and M. tuberculosis DNA obtained from the patients with pulmonary TB undergoing treatment at the Central Tuberculosis Research Institute between 2011 and 2018. The tests revealed that Hr-TB accounted for 12% of all TB cases in the studied sample. Hr-TB strains were either resistant to isoniazid only (45%) or had multiple resistance to 2–6 anti-TB agents. Resistance to isoniazid was caused by mutations in the katG gene. Based on the literature analysis and our own observations, we emphasize the importance of developing simple molecular drug susceptibility tests capable of detecting simultaneous resistance to rifampicin and isoniazid and the necessity of their translation into clinical practice.

Received: 2019-12-11

Published online: 2020-01-12

DOI: 10.24075/brsmu.2020.001

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VIEWS 4095

Rogozhina AA, Minushkina LO, Alessenko AV, Gutner UA, Shupik MA, Kurochkin IN, Maloshitskaya OA, Sokolov SA, Zateyshchikov DA

Development of modern methods for metabolome assessment, such as gas chromatography–mass spectrometry, allows one to expand the knowledge about the features of lipid metabolism in various clinical conditions. The study was aimed to investigate lipidome features in patients with different probability of family hypercholesterolemia (FH). The study involved 35 patients: 15 men (42.9%) and 20 women (57.1%) with dislipidemia or early cardiovascular diseases which manifested below 55 in men and 60 in women (average age of patients was 49.8 ± 9.96). The family dislipidemia probability was evaluated using the Dutch Lipid Clinic Network Score. In 10 patients the probability of FH was low (score 1–2), 22 patients had possible FH (score 3–5). Three patients had probable or definite FH (score 6 in 2 patients, score 9 in one patient). Determination of molecular species of sphingomyelins, ceramides and sphingoid bases (sphingosine, sphinganine) as well as galactosylceramide was carried out using gas chromatography–mass spectrometry. In patients with definite/probable FH the sphingosine level was significantly higher compared with patients having low probability of FH (144.36 ± 107.863 and 50.14 ± 62.409 ng/ml; р = 0.01). In patients with FH, an increase in the proportion of long chain sphingomyelin SM 18 : 1/22 : 0 as well as a significant increase in the level of long chain ceramides with С 20 : 1 and С 22 : 1 was determined. Positive correlation of low-density lipoproteins and sphingosine level (r = 0.344; p = 0.047) together with negative correlation of high-density lipoproteins (HDL), sphinganine (r = –0.52; p = 0.002), and galactosylceramide level (r = –0.56; p = 0.001) were detected. Thus, in patients with high probability of FH the lipidome changes were observed, which could be considered the cardiovascular risk markers.

Received: 2019-11-30

Published online: 2019-12-27

DOI: 10.24075/brsmu.2019.090

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VIEWS 3333

Ivanova GE, Melnikova EV, Shmonin AA, Verbitskaya EV, Belkin AA, Bodrova RA, Lebedev PV, Maltseva MN, Prokopenko SV, Prosvirnina MS, Sarana АM, Stakhovskaya LV, Suvorov AYu, Khasanova DR, Shamalov NA

Modern papers on treatment and rehabilitation of stroke patients describe the advantages and effectiveness of certain medical rehabilitation types, but these data are not enough to evaluate the efficiency of the whole rehabilitation system. The study was aimed to investigate the potential of the patient-centered problem-oriented multidisciplinary three-stage system for medical rehabilitation of stroke patients. Thestudyincluded 1021 patientsover 18 affected with ischemic or hemorrhagic stroke in the acute phase. All patients had a disability of admission at the time (but no persisting disability in their history). Two models of rehabilitation measures were compared in two consecutive phases of the study. The linear model of rehabilitation assistance was mainly implemented in phase 1, and the multidisciplinary model was implemented in phase 2. The patients’ condition was evaluated using the Modified Rankin Scale (mRS) at the end of rehabilitation. Comparison of the 1st and 2nd phase results demonstrated that the number of patients with mRS score 0–1 in the 2nd phase was lower by 18%. The proportion of patients with positive dynamics was significantly higher in the 2nd phase than in the 1st phase, (16 and 30% respectively). In the 2nd phase there were significantly more patients who demonstrated improvement by 1–4 (mRS score). Thus, the use of a multidisciplinary model provides a significant benefit compared with a linear rehabilitation model.

Received: 2019-11-26

Published online: 2019-12-27

DOI: 10.24075/brsmu.2019.089

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VIEWS 3502

Rakhmatulina MR, Galkina IS

This article describes the contemporary methods of diagnosing sexually transmitted infections, their advantages and disadvantages, indications for use. The authors describe application of quantitative polymerase chain reaction in diagnosing inflammatory diseases and dysbiotic conditions in men and women. This method, which is currently the “golden standard” in urogenital pathology diagnostics, has undeniable advantages over microbiological methods and qualitative polymerase chain reaction: the preanalytical stage requirements (preservation of quantitative ratios between microorganisms or nucleic acids of microorganisms) are not as strict, the risk of contamination from outside environment and subsequent corruption of the results is significantly smaller, the conditions for all microorganisms, including those impossible and hard to cultivate, are the same sensitivity and specificity-wise, it is possible to sample materials and evaluate microbiota (ratios of microorganisms and their groups) and also possible to collect samples non-invasively, the speed of testing is high.

Received: 2019-12-03

Published online: 2019-12-26

DOI: 10.24075/brsmu.2019.088

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VIEWS 2955

Kazakova AV, Uvarova EV, Limareva LV, Lineva OI, Svetlova GN, Trupakova AA

Acute respiratory infections (ARI) are very common in children and often prompt parents to seek medical advice. Increased susceptibility to ARI is caused by a number of factors, including genetically determined imbalances in cytokine production. The aim of this study was to analyze the frequency of 6 clinically relevant polymorphisms of proinflammatory cytokine genes in girls predisposed to recurrent respiratory infections. The study was conducted in girls aged 7–17 years who were undergoing a routine medical checkup. A group of children with frequent respiratory infections was identified. The following polymorphisms were analyzed for possible associations with predisposition to frequent respiratory infections: IL1β T-31C (rs1143627), IL1β T-511C (rs16944), IL1β C-3953T (rs1143634), IL1β G-1473C (rs1143623); IL6 C-174G (rs1800795), and TNFα G-308A (rs1800629). For polymorphism detection, PCR and gel electrophoresis were used. The following alleles were found to be associated with an increased risk for recurrent respiratory infections in girls aged 7–17 years: С-31 (rs1143627) (OR = 2.05; CI: 1.16–3.64; р = 0.013) and С-511 (rs16944) (OR = 3.11; CI: 1.25–7.76; р = 0.013) of the IL-1β gene.

Received: 2019-12-02

Published online: 2019-12-26

DOI: 10.24075/brsmu.2019.087

Comments 0

VIEWS 3106

Mikhaleva LM, Voytkovskaya KS, Fedorov ED, Gracheva NA, Birukov AE, Shidiy-Zakrua AV, Guschin MYu

Barrett’s esophagus (BE) is a pathologically confirmed intestinal metaplasia (CM) of the distal esophagus. BE is recognized as a potential complication of gastroesophageal reflux disease (GERD) and a premalignant condition with a high risk of neoplastic progression. The aim of this study was to compare the morphology of biopsied BE segments and CM segments extending < 1 cm and > 1 cm above the gastroesophageal junction (GEJ), as well as to perform the immunohistochemical analysis of biopsies with BE and CM > 1 cm above GEJ with or without dysplasia. The study recruited 92 patients with GERD: 42 patients with BE, 24 patients with CM > 1 cm above GEJ (С0М1.5–С13M14) and 26 patients with CM < 1 cm above GEJ (С0М0.3–0.8). Comparative analysis of tissue morphology revealed an association between the reactive changes in the epithelium and the severity of esophagitis in all groups. Reactive changes were detected significantly more often in BE segments than in CM segments > 1 cm (Mann-Whitney U, p < 0.05). Eight patients with BE (19.05%) were found to have low-grade dysplasia. One patient with CM > 1 cm above GEJ (4.2%) had high-grade dysplasia with cardiac-type metaplasia and immunohistochemical features of submorphological enteralization. Immunohistochemical testing for the intestinal and gastric markers of cell differentiation revealed the signs of submorphological enteralisation in all esophageal specimens with cardiac and fundic type metaplasia and in the specimens with BE in the areas lacking goblet cells.

Received: 2019-12-03

Published online: 2019-12-26

DOI: 10.24075/brsmu.2019.086

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VIEWS 3028

Dodonova SA, Bobyntsev II, Belykh AE, Andreeva LA, Myasoedov NF

Melanocortins (MCs) are an increasingly studied class of regulatory peptides exerting a wide range of biological effects. All naturally occurring MCs share a His-Phe-Arg-Trp fragment (HFRW) corresponding to the sequence of amino acid residues 6–9 of the adrenocorticotropic hormone (ACTH6-9), which is also a central active component of ACTH. Attaching the Pro-Gly-Pro (PGP) sequence to the C-end of the peptide extends the duration of the peptide’s effect. The aim of this study was to investigate the effects of ACTH6-9-PGP (HFRWPGP) on the spinal and supraspinal mechanisms involved in the nociceptive response in rats and to compare them to those of its structural analog ACTH4-7-PGP (MEHFPGP). ACTH6-9-PGP effects were studied following the intraperitoneal administration of the peptide at doses 0.5, 1.5, 5, 15, 50, 150, or 450 μg/kg 15 minutes before the hot plate and tail flick tests. ACTH4-7-PGP effects were studied under the same conditions at the following doses: 50, 150 and 450 μg/kg. We found that ACTH6-9-PGP administered intraperitoneally at 5 or 150 μg/kg induced a pronounced reduction in pain sensitivity 15 and 45 minutes after the injection (p = 0.04); this effect was implemented via supraspinal mechanisms. In the tail flick test, 150 μg/kg ACTH6-9-PGP increased pain sensitivity, with the participation of segmental spinal mechanisms (p = 0.04). ACTH4-7-PGP did not have any effect on the studied mechanisms of pain sensitivity. Thus, unlike ACTH4-7-PGP, ACTH6-9-PGP can both increase pain sensitivity and exert an analgesic effect.

Received: 2019-12-02

Published online: 2019-12-21

DOI: 10.24075/brsmu.2019.085

Comments 0

VIEWS 3247

Gorbachev DA, Sarkisyan KS

Genetically encodable photosensitizers based on fluorescent proteins produce reactive oxygen species when illuminated with light. Although widely used as optogenetic tools, existing photosensitizers with green fluorescence possess suboptimal properties motivating for a search of new protein variants with efficient chromophore maturation and high phototoxicity. Here we report a mutant of the phototoxic fluorescent protein KillerRed protein with fluorescence in the green part of the spectrum. The mutant variant carries mutations I64L, D114G, and T115S and does not form a DsRed-like chromophore. The protein can be used as a template to create new genetically encodable photosensitizers that are spectrally different from KillerRed.

Received: 2019-12-08

Published online: 2019-12-20

DOI: 10.24075/brsmu.2019.084

Comments 0

VIEWS 3716