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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Malgina NV, Dolgina TYu, Epifanova AD, Rodoman GV

Due to advances in medical science, the frequency of surgical interventions that once ended in end-stoma formation has decreased significantly. An ostomy is a life-saving surgery performed when there are no other options. Unfortunately, the number of patients with life-threatening conditions requiring colostomy or ileostomy is growing. A stoma in itself is a cause of social alienation; stoma-associated complications reduce the quality of life and debilitate the patient. The aim of this study was to assess the effectiveness of hybrid intraperitoneal mesh repair of paracolostomy hernia using a modified EUROQOL 5D-5L questionnaire. Sixty patients with paracolostomy hernias included in the study were divided in 2 groups (30 persons per group). The experimental group (10 (33%) men and 20 (67%) women) and the control group (11 (37%) men and 19 (63%) women) were comparable in terms of sex (р = 0.787) and age (66.5 (62.2; 72.0) years vs. 65.0 (61.25; 71.75) years, respectively; р = 0.246). Patients included in the control group underwent a classic Sugarbaker procedure; the experimental group underwent hybrid intraperitoneal mesh repair. The quality of life of the patients was evaluated before surgery and then 1 and 2 years after surgery using a modified EUROQOL 5D-5L questionnaire. Hybrid intraperitoneal mesh repair proved to be effective in the early and late postoperative periods. Based on the significant improvement of the patients’ quality of life after hybrid intraperitoneal mesh repair, we conclude that this technique is an effective surgical treatment for paracolostomy hernias.

Received: 2021-07-10

Published online: 2021-08-17

DOI: 10.24075/brsmu.2021.037

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VIEWS 2383

Osikov MV, Ageeva AA, Fedosov AA, Ushakova VA

The development of novel local therapies for thermal burns (TB) and their pathogenetic rationale are a pressing challenge. Melatonin (MT) is an endogenous factor of hemostasis regulation with pleiotropic potential. The aim of this study was to assess some parameters of tissue regeneration, the functional state of mast cells and the levels of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the experimentally induced TB treated with the original MT-enriched dermal film (DF). A second-degree burn (3.5% of the total body surface area) was modelled by exposing a patch of skin to hot water. Applications of 12 cm2 DF enriched with 5 mg/g MT were performed every day for 5 days. The following parameters were calculated: the wound area, the rate of wound epithelization, the number of MC in the wound, the intensity of degranulation, and the levels of MMP-9 and VEGF expression. Over the course of treatment, the absolute wound area shrank by 35%, its epithelization rate increased, the number of MC rose, their functional state changed, and the expression of ММР-9 and VEGF increased. A negative correlation was established between the wound area and the expression of ММР-9 and VEGF, as well as between the wound area and the degranulation coefficient. Applications of MT-enriched DF resulted in the reduction of the wound area, higher epithelization rate, an increase in the total MC count and degranulation intensity on days 5 and 10; it also led to a reduction in the total MC count and a loss in degranulation intensity on day 20 (166.87 (154.95; 178.78) un/mm2 vs. 464.84 (452.92; 476.76) un/mm2) in the group of intact animals), an increase in MMP-9 expression on day 5 (14.20 (11.30; 18.10) vs. 3.30 (2.20; 4.40) in the intact group), an increase in VEGF expression on days 5 and 10 (33.00 (30.20; 34.90) vs 25.40 (22.20; 29.30) in the intact group), and a reduction in MMP-9 expression on days 10 and 20 after thermal injury.

Received: 2021-06-28

Published online: 2021-08-07

DOI: 10.24075/brsmu.2021.035

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VIEWS 2507

Plotkin DV, Vinogradova TI, Reshetnikov MN, Ariel BM, Zyuzya YuR, Zhuravlev VYu, Sinitsyn MV, Bogorodskaya EM, Yablonsky PK

The prevalence of tuberculous peritonitis that has been observed in the recent decades is the result of lymphohematogenous spread of Mycobacterium tuberculosis (MBT) from lungs and other extrapulmonary sources. It is still unclear why certain organs and anatomical regions get involved in the inflammatory process during generalization of the tuberculosis infection. Why do some cases develop into peritoneal tuberculosis and other into kidney tuberculosis? Thus study aimed to investigate the pathogenesis of tuberculous peritonitis in a reproducible biological model. Tuberculous peritonitis was modeled in 18 rabbits (10 in the test group, 8 in control) by intraperitoneal inoculation of the MBT suspension. In order to suppress peritoneal macrophages and major cytokines, test group rabbits were injected with the TNFα inhibitor and iron (III) hydroxide sucrose complex before being infected, while control group rabbits received no immunosuppressive drugs. Autopsy of the control group animals revealed changes characteristic of pulmonary tuberculosis in 37.5% of cases, with no damage to other organs and systems registered. Conversely, test group rabbits had the signs of tuberculous peritonitis in their abdominal cavities. The results of this study suggest that it is the local immunity of an anatomical area that largely determines whether a secondary focus of extrapulmonary tuberculosis infection will develop there or not. For the peritoneum, a smaller pool of peritoneal macrophages and weaker cytokine production is a necessary and sufficient condition to have tuberculous peritonitis developing therein.

Received: 2021-06-30

Published online: 2021-08-04

DOI: 10.24075/brsmu.2021.036

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VIEWS 2635

Guselnikova VV, Sufieva DA, Tsyba DL, Korzhevskii DE

Recently, fluorescence microscopy becomes more available, presenting new opportunities to face several challenges of experimental biology and medicine. The study was aimed to assess the effectiveness of fluorescence microscopy for the identification of amyloid deposits in human tissues. Post-mortem samples of the myocardium (n = 12) and cerebral cortex (n = 8) obtained from subjects of both sexes aged 60–98 with verified amyloidosis were used as a material for the study. The specimens were stained using 11 different histochemical dyes and subsequently analyzed by light and fluorescence microscopy. Qualitative and quantitative analysis has shown that Thioflavin T is the most effective stain for fluorescence detection of β- and transthyretin amyloid in human tissues. Congo red staining is highly effective for the detection of transthyretin amyloidosis, however, it is ill-suited for the identification of β-amyloid plaques. It has been found that the ability of Congo red to exhibit fluorescence when binding to amyloid fibrils can be used for verification of amyloid deposits instead of the traditional polarized light microscopy. As has been first noted, methyl violet can selectively bind to β-amyloid with fluorescent complex formation. In addition, methyl violet treatment effectively reduces the autofluorescent background in the nervous tissue. This makes methyl violet staining a promising diagnostic tool for Alzheimer's-type pathology.

Received: 2021-07-12

Published online: 2021-07-31

DOI: 10.24075/brsmu.2021.034

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VIEWS 2630

Nikiforova MA, Siniavin AE, Shidlovskaya EV, Kuznetsova NA, Gushchin VA

Infected SARS-CoV-2 virus occurs not only through contact with an infected person, but also through surfaces with wich the illnes has contacted. The problem of preserving an infectious virus over time capable of infecting remains actual. We evaluated the SARS-CoV-2 viability preservation on different model surfaces over time. Ceramic tiles, metal (aluminum foil), wood (chipboard), plastic and cloth (towel) were used as model materials. Assessment of the presence of SARS-CoV-2 RNA was carried out by quantitative RT-PCR. Viable virus was determined by tissue culture assay on 293T/ACE2 cells. It was found that the SARS-CoV-2 RNA was detected on all studied surfaces for 360 minutes, but a significant decrease RNA by 1 log10 copies/ml was detected after contact of the virus with cloth (towel). While the viability of the virus was completely lost after 120 minutes. Type of experimental surface significantly affects viability preservation.

Received: 2021-06-25

Published online: 2021-07-13

DOI: 10.24075/brsmu.2021.033

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VIEWS 3088

Lomova NA, Chagovets VV, Dolgopolova EL, Novoselova AV, Petrova UL, Shmakov RG, Frankevich VE

Neonates born to mothers with COVID-19 are at risk for infection, they may have high risk of complications during the neonatal period, and long-term health consequences. The study was aimed to define the amino acid profile of blood plasma and amniotic fluid in patients with COVID-19 in order to assess the relationship between the COVID-19 infection during the antenatal period, and metabolomic alterations in the “intrauterine” patient. The levels of 31 amino acids in the samples of amniotic fluid and cord blood plasma of pregnant women with COVID-19, obtained during delivery, were assessed by high-performance liquid chromatography-mass spectrometry. The index group included 29 patients with confirmed diagnosis of COVID-19, and the control group included 17 healthy women with uncomplicated pregnancies. There were significant (p < 0.05) differences in the concentrations of eight amino acids between the studied groups. Logistic regression models were developed (sensitivity 0.84; specificity 1) making it possible to define, whether the assessed amniotic fluid was obtained from COVID-19 patients. Significant differences in the concentrations of four amino acids were observed in the umbilical cord blood. The models developed made it possible to define whether the studied cord blood plasma belonged to controls or to COVID-19 patients (sensitivity and specificity 1). Three amino acids were detected, and their levels were significantly different in COVID-19 patients simultaneously in two points (amniotic fluid and cord blood plasma), depicting the fetal metabolome in a holistic manner. The impact of the virus on those infected results in pronounced metabolomic alterations in the amniotic fluid and the fetal cord blood plasma, which may lead to impaired programming of protein production, but never show up at birth.

Received: 2021-05-24

Published online: 2021-06-29

DOI: 10.24075/brsmu.2021.032

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VIEWS 2781

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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VIEWS 2618

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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VIEWS 2695