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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Komarova EF, Zhukovskaya ON, Lukbanova EA, Yengibaryan MA, Vashenko LN, Kharagezov DA, Pozdnyakova VV, Ushakova ND, Shatova YuS, Przhedetsky YuV

Most cancer drugs used in a clinical setting are insufficiently effective and insufficiently safe. This prompts the search for novel substances to fight cancer. The aim of this study was to explore the effects of dihydrobromide 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo[1,2-a] benzimidazole (RU-185) on the growth and metastasis of experimentally induced transplantable Lewis lung carcinoma (LLC). Fifty-five C57/Bl6 male mice (weight 18–20 g) were subcutaneously inoculated with LLC cells. The tested substance (0.5 ml) was administered intragastrically at 50, 220, and 500 mg/kg (groups 1, 2 and 3, respectively) once a day for 10 days starting at 48 h after inoculation. The control group received normal saline. Intragastric administration of the tested substance resulted in significantly longer survival in group 2 only (162.3%) and in the significant reduction of tumor size on day 1 after treatment in all groups. After the end of treatment, tumor sizes in groups 2 and 3 were 3.4 and 1.3 times smaller, respectively, on day 7 and 2.2. and 1.3 times smaller, respectively, on day 14 than in the control group (р < 0,05). The growth delay rate was sustained in group 2 by day 14 after the end of treatment; tumor regression was observed in 20% of the animals. The number of metastases in the lungs was lower in groups 1 and 2 than in the control group (2.6 and 3.1-fold, respectively), and the metastasis inhibition was 68.1% and 80%, respectively. The tested substance RU-185 has an anticancer effect in mice: it results in longer survival, slower growth of the primary tumor and fewer lung metastases of Lewis lung carcinoma.

Received: 2021-06-01

Published online: 2021-06-25

DOI: 10.24075/brsmu.2021.031

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

Lipid-lowering drugs affect standard lipoproteins. However, we have no knowledge of changes in other plasma lipids upon treatment. The study was aimed to assess the dynamic changes in cholesterol, high- and low-density lipoproteins (HDL and LDL), triglycerides, and sphingolipids against the background of lipidlowering therapy in patients with premature coronary artery disease, atherosclerosis and hypercholesterolemia. A total of 18 patients were enrolled (the average age was 53 ± 6.7 years): in group 1, six patients received starting statin doses; group 2 included six patients, who failed to achieve LDL target levels against the background of treatment with starting statin doses, and received escalated statin doses; seven patients in group 3 failed to achieve LDL target levels against the background of treatment with maximum tolerated doses of statins and ezetimibe, and received alirocumab. Sphingolipid levels were assessed by mass spectrometry. In group 1, the decreased levels of ceramide Cer 14:1 (p = 0.046) and sphingomyelins SM 22:1, SM 22:0, SM 24:0 (p = 0.028) were observed. There were no significant changes in the levels of total cholesterol, LDL-C, HDL-C, and triglycerides. In group 2, the significantly decreased levels of total cholesterol (p = 0.028), LDL (p = 0.043), sphingomyelins SM 18:1, SM 24:1 and SM 26:1, and ceramide Cer 16:1 (p = 0.028) were observed. The level of Cer 22:1 significantly increased (p = 0.028). In group 3, total cholesterol decreased by 36.2%, and LDL-C (p = 0.018) decreased by 60.1% compared to baseline (ΔLDL-C = –2.67 ± 3.12); the elevated levels of ceramide Cer 22:1 (p = 0.028) were observed. It has been shown, that decreased sphingomyelin levels are associated with statin therapy and correlate with decreased levels of LDL-C. No significant dynamic changes in ceramides and ceramide risk against the background of statin therapy were observed, however, PCSK9 inhibitor added to therapy reduced the Cer 16:0/24:0 ratio.

Received: 2021-05-24

Published online: 2021-06-23

DOI: 10.24075/brsmu.2021.030

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Schegolev AI, Tumanova UN

This article analyzes the literature on SARS-CoV-2 persistence in the corpses of patients infected with COVID-19, possible routes of viral transmission from the bodies and biosafety measures to prevent the spread of the infection. SARS-CoV-2 persists for quite long in the tissues and bodily fluids of decedents with COVID-19 and on various surfaces. The longest viability of the virus is on stainless steel and plastic surfaces that come in contact with the infected body. Autopsies on decedents with COVID-19 must be performed at specially conditioned facilities. Medical and forensic pathologists and other mortuary workers must adhere to stringent biosafety requirements.

Received: 2021-05-31

Published online: 2021-06-18

DOI: 10.24075/brsmu.2021.029

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Maksimov GV, Sashkina TI, Faskhutdinov DK, Slatinskaya OV, Saldusova IV, Zaychenko OV

Currently, biophysical studies are of great interest, the results of which are important for development of a method for diagnosis of the cells and tissue condition to be used in clinical practice. The study was aimed to use a non-invasive optical method (Raman spectroscopy) for assessment of changes in the composition and conformation of the molecules of the patient’s mandibular cells and tissues. This approach was proposed to increase the informativeness and effectiveness of studying the composition of autografts harvested for augmentation of alveolar processes with bone tissue deficiency (elective bone grafting). In the course of the study the bone tissue samples obtained from three patients aged 51–73 (two men and one woman) were assessed. Raman signals were detected, indicating the presence of phosphate groups and carbonate ions (such as СО3–2) of the inorganic bone components. Raman bands indicating the presence of collagen, red blood cell hemoglobin, proteins (C–N bonds), lipids (С–Н groups of fatty acids and phosphate groups of phospholipids), as well as their OH groups may be considered the markers of periosteum tissue. The general possibility was suggested of studying single cells of autografts using the markers, indicating the presence of collagen, hemoglobin, proteins, lipids (С–Н groups of fatty acids of lipids; phosphate groups of phospholipids), and their OH groups. According to the authors, the results obtained can provide a basis for development of the new method for diagnosis of autograft bone using the combination of Raman spectroscopy and light guides.

Received: 2021-05-13

Published online: 2021-06-17

DOI: 10.24075/brsmu.2021.028

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Poydasheva AG, Sinitsyn DO, Bakulin IS, Suponeva NA, Piradov MA

Repetitive transcranial magnetic stimulation (rTMS) is an alternative treatment option for patients with drug-resistant trigeminal neuralgia (TN). However, the effect of rTMS is variable. The aim of this study was to find neuroimaging biomarkers of clinical efficacy of navigated rTMS. Seventeen patients with TN (14 women and 3 men, median age 56 years) received 10 sessions of high-frequency rTMS of the motor cortex contralateral to pain side. The data were analyzed for correlations between functional connectivity (FC), the grey matter (GM) volume and the reduction in pain intensity. Positive correlations were established between the reduction in average pain intensity and GM volume in caudate nuclei in both hemispheres (p(unc) = 0.03), both cerebellar hemispheres (p(unc) = 0.002) and the postcentral gyrus contralateral to pain side (p(unc) = 0.005); between the reduction in peak pain intensity and GM volume in the caudate nucleus contralateral to pain side (p(unc) = 0.04) and the cerebellar hemisphere ipsilateral to pain (p(unc) = 0.03). Significant positive correlations were discovered between the reduction in average pain intensity and FC between the thalamus contralateral to pain side, the postcentral gyrus and the insular operculum (both ipsilateral to pain side; (p(FWE) = 0.018), as well as between the cingulate cortex and the anterior cingulate cortex ipsilateral to pain (p(FWE) = 0.017), between the contralateral subcallosal gyrus and the cerebellar hemisphere ipsilateral to pain (p(FWE) = 0.018). A negative correlation was established for FC between the contralateral putamen and the occipital lobes in both hemispheres (p(FWE) = 0.001). Our findings may spur the development of individual predictors of rTMS efficacy in patients with chronic pain.

Received: 2021-05-18

Published online: 2021-06-12

DOI: 10.24075/brsmu.2021.027

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VIEWS 3341

Radaeva OA, Simbirtsev AS, Kostina YuA, Iskandiarova MS, Mashnina SV, Bessheynov DD, Negodnova EV, Kulyapkin VV

Pathogenetic progression mechanisms in the SARS-CoV-2–essential hypertension (EAH) system are more complex than interaction at the level of angiotensinconverting enzyme 2 (ACE2). The study was aimed to assess the dynamic changes of the IL1 members (IL1β, IL1α, IL1ra, IL18, IL18BP, IL37) blood levels in patients with EAH 10, 30, and 180 days after having COVID-19 in order to define cytokine-mediated mechanisms of EAH progression during the period following infection. The study involved four groups of patients: with a history of EAH and COVID-19 (pneumonia/no pneumonia), with a history of COVID-19 (pneumonia/no pneumonia) and no EAH. Cytokine levels were determined by enzyme immunoassay. The study results demonstrate the prolonged proinflammatory immune response during the period following infection in patients with EAH (retaining higher levels of IL1β, IL1α, and IL18 on days 10, 30, and 180 after recovery (р < 0.001) compared to levels measured prior to SARS-CoV-2 infection). In the group with no EAH, the balance of assayed cytokines was restored on day 30 of follow-up. The two-fold increase of blood IL18 levels in patients, having a history of EAH and COVID-19 and showing no increase in the IL18ВР levels after 30 days of follow up compared to the values measured prior to infection, is associated with cardiovascular complications occurring during the first six months of follow-up. This makes it possible to hypothesize the importance of these immunoregulatory peptides for the pathogenesis of complications and enhances the relevance of further scientific research.

Received: 2021-05-19

Published online: 2021-06-07

DOI: 10.24075/brsmu.2021.026

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VIEWS 3676

Reshetnikov MN, Plotkin DV, Zuban ON, Bogorodskaya EM

The double burden of the novel coronavirus infection and tuberculosis (TB) is a global challenge. The aspects of emergency surgical care for patients with COVID-19 and TB coinfection remain understudied. The aim of this study was to assess treatment outcomes in acute surgical patients with COVID-19 and preexisting TB coinfection. In 2020, our Center delivered surgical care to 465 patients with COVID-19 and preexisting TB; a total of 64 emergency surgeries were performed on 36 (5.6%) patients, of whom 16 had HIV. Thirteen patients (36.1%) were diagnosed with pulmonary TB; 23 patients (63.9%) had disseminated TB. Chest CT scans showed >25% lung involvement in 61.9% of the patients with COVID-19 pneumonia, 25–50% lung involvement in 30.6% of the patients, and 50–75% lung involvement in 5.6% of the patients. By performing abdominal CT, we were able to detect abdominal TB complications, including perforated tuberculous ulcers of the intestine, intestinal obstruction and tuberculous peritonitis, as well as tuberculous spondylitis complicated by psoas abscess. Of all surgical interventions, 28.2% were abdominal, 23.2% were thoracic, 15.6% were surgeries for soft tissue infection, and 32.8% were other types of surgery. Postoperative mortality was 22.2%. We conclude that COVID-19 did not contribute significantly to postoperative mortality among acute surgical patients with TB.

Received: 2021-04-12

Published online: 2021-05-31

DOI: 10.24075/brsmu.2021.025

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Shcheglov AS, Tsarkova AS

Ferroptosis is a form of programmed cell death associated with iron-dependent lipid peroxidation. Novel ferroptosis inducers and suppressors could be instrumental in developing drugs against neurodegenerative disorders and cancer. Prior to embarking on a search for ferroptosis inducers/suppressors, this form of cell death must be studied in living cells and laboratory animals. In addition to two cofactors, luciferase (or photoprotein) of the parchment tubeworm Chaetopterus variopedatus requires the presence of iron ions and hydrogen peroxide or organic hydroperoxides to exert its activity. Therefore, the bioluminescence system of the parchment tubeworm can be used to study ferroptosis in living organisms.

Received: 2021-05-05

Published online: 2021-05-30

DOI: 10.24075/brsmu.2021.024

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