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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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: 2019-12-25

DOI: 10.24075/brsmu.2019.086

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VIEWS 4572

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: 2019-12-20

DOI: 10.24075/brsmu.2019.085

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VIEWS 4998

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

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VIEWS 5626

Osipova ZM, Shcheglov AS, Yampolsky IV

Bioluminescent systems are increasingly being used for the development of highly sensitive optical imaging techniques in vivo. However, it is necessary to inject expensive and unstable synthetic substrates (luciferins) before each analysis for most of the systems applied. Autonomous bacterial and fungal bioluminescent systems, that recently have become available for implementation in eukaryotic cells, in our opinion, may be developed into an effective tool in new technologies of bioluminescent imaging.

Received: 2019-12-03

Published online: 2019-12-19

DOI: 10.24075/brsmu.2019.083

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VIEWS 6214

Churov AV, Siutkina AI, Mamashov KY, Oleinik EK

Despite the considerable progress in the therapy of autoimmune pathologies, the existing methods are associated with the risk of serious adverse events. We think that regulatory T cells hold great promise for the therapy of disorders caused by a breakdown in immunological self-tolerance. This article aims at estimating the possible challenges facing Treg-based clinical approaches and offers solutions to the technical issues associated with the use of these cells in the therapy of autoimmune diseases.

Received: 2019-11-25

Published online: 2019-12-18

DOI: 10.24075/brsmu.2019.082

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VIEWS 4751

Kumar V, Frolov MA, Dushina GN, Shradqa AS, Bezzabotnov AI, Abu Zaalan KA

The uveoscleral outflow as an alternate route of aqueous drainage is of great interest in glaucoma surgical treatment. A cyclodialysis cleft allows one to create a direct connection between the anterior chamber (AC) and the suprachoroidal space (SCS) which is the key element of uveoscleral outflow. The purpose of the study was to evaluate the safety and effectiveness of reverse meridional cyclodialysis ab interno (RMCai) in decreasing intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) and refractory glaucoma (RG). Fourteen patients who exhibited POAG and RG (11 men and 3 women, age 77.3 ± 7.8 years) were included in the study. All patients underwent RMCai with the help of custom-designed spatula. The spatula, inserted through a clear corneal incision, was used to detach the ciliary body from the scleral spur to create a 2.0–2.5 mm wide and 6.0–6.5 mm deep cleft. Outcome measures were IOP change, use of hypotensive medication(s), complications, and need for a second surgery. Decrease in IOP by more than 20% and IOP between 6 and 21 mmHg without hypotensive medication constituted complete success. Similar changes in IOP with medication constituted partial success. Need for second surgery constituted failure. The follow-up period was >3 months. Baseline IOP and hypotensive medication use were 22.0 ± 8.5 mmHg (95% confidence interval (CI), 17.6–26.4) and 2.6 ± 0.9 (95% CI, 2.2–3.1). At 3, 6, 12, 18, and 24 months, complete success was achieved in 64.3%, 77.8%, 55.6%, 37.5%, and 40% of patients respectively; partial success — in 14.3%, 22.2%, 44.4%, 50.0%, and 60.0%. Four patients required a second surgery. Failure occurred because of cleft closure by fibrosis. It was concluded that RMCai is safe and effective in decreasing IOP in POAG and RG patients.

Received: 2019-11-27

Published online: 2019-12-16

DOI: 10.24075/brsmu.2019.081

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VIEWS 4773

Oleynik AA, Ivanova NE, Oleynik EA, Ivanov AYu

The rate of mortality and disability associated with aneurysmal subarachnoid hemorrhage (SAH) is high. Patients with multiple cerebral aneurysms (MCA) require repeated surgeries more often and they are likely to develop aneurysms de novo and suffer their rupture. This study aimed to apply the International Classification of Functioning (ICF) to assess the quality of life (QOL) of MCA patients after endovascular treatment, late postoperative period. The study involved patients who underwent endovascular treatment and had multiple (>2) cerebral aneurysms (141 people). All patients underwent 1–6 endovascular surgeries; complications developed in 7.1% (10/141) of cases. The patients' QOL was assessed against the ICF 6 to 24 months post-surgery. We found that at such time points treatment results deteriorate in a number of domains, namely those associated with pain, memory, motor coordination, limb strength. Patients with ruptured aneurysms showed worse results for locomotion-related domains than patients with unruptured aneurysms (p < 0.05), in patients with aneurysms having a pseudotumor type of flow, by domains associated with dysfunction of the cranial nerves responsible for innervation of the eye muscles (p < 0.001) (p < 0.001). Patients with ruptured MCA were more active in the late post-surgery period, which was revealed by comparing that period's data to the baseline pre-surgery records (p < 0.05). The severity of activity disorders depended on surgery complications, patient age (p < 0.05), complications that developed during the acute SAH stage (p < 0.001).

Received: 2019-11-19

Published online: 2019-12-13

DOI: 10.24075/brsmu.2019.080

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VIEWS 4752

Hamad A, Chumakov SP

Recombinant herpesviruses can be used as oncolytic therapeutic agents and high packaging capacity vectors for delivering expression cassettes into the cell. Herpesvirus saimiri is a gamma-herpesvirus that normally infects squirrel monkeys but also has a unique ability to infect and immortalize human lymphocytes while allowing them to retain their mature phenotype and functional activity. Recombination of the Herpesvirus saimiri genome in permissive cells is impeded by its resistance to chemical transfection and electroporation. The aim of this study was to develop an effective method for incorporating expression cassettes into the genome of Herpesvirus saimiri without having to transfect a permissive cell culture. Transfected HEK-293T cells expressing glycoproteins of the measles virus vaccine strain were co-cultured with permissive OMK cells infected with Herpesvirus saimiri. Cell fusion and formation of syncytia stimulated recombination between the viral genome and the expression cassette; this allowed us to obtain a recombinant Herpesvirus saimiri variant without chemical transfection in permissive cells. The genetically modified virus expressed a selectable marker and retained its ability to persist in the cell in the latent state; it also caused immortalization of primary lymphoid cells. The proposed approach allows engineering recombinant Herpesvirus saimiri strains carrying a variety of expression cassettes in its genome.

Received: 2019-11-11

Published online: 2019-12-11

DOI: 10.24075/brsmu.2019.079

Comments 0

VIEWS 4812