ISSN Print 2713-2757    ISSN Online 2713-2765
Extreme Medicine
SCIENTIFIC AND PRACTICAL REVIEWED JOURNAL OF FMBA OF RUSSIA

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Original research Changes in some immunological parameters after COVID-19: general trends and individual characteristics
Glazanova TV, Shilova ER, Efremova YS, Chubukina JB, Bessmeltsev SS
The specifics of individual immune reactions after COVID-19 have not been studied sufficiently. This study aimed to describe the changes in indicators of cellular and humoral levels of immunity after COVID-19, and gage general trends and individual characteristics. We sampled blood of 125 unvaccinated COVID-19 patients (29 men and 96 women, median age 53 years) 1 to 4 months after recovery, and determined the relative content of T-lymphocytes (CD3+), B-lymphocytes (CD19+), and cells with late activation markers (CD3+HLA–DR+) in them using flow cytometry. With the help of ELISA, we have registered the level of circulating immune complexes, which can be medium molecular weight (CICmed) and low molecular weight (CIClow), and the content of antibodies to SARS-CoV-2. In the mild course group, significant differences from the normal values (p < 0.001) were found for T cells (growth, 74.4 ± 1.2% vs. 68.6 ± 1.1%) and B cells (decline, 10.2 ± 0.7% vs. 13.9 ± 0.9%). In the moderately severe course and severe course groups, the level of CD3+HLA–DR+ lymphocytes was increased (7.7 ± 0.4% and 15.7 ± 2.5%, respectively, versus 3.9 ± 0.8% in the control group; p < 0.01). All the examined patients had high levels of CIClow (2.6-2.9-fold increase) and CICmed (1.6–1.8-fold increase). The protective level of antibodies to SARS-CoV-2 above 150 BAU/ml was registered in about 50% of the mild group participants, 75% of the moderately severe group members, and 100% of patients who had the disease in a severe form. We detected no connections between immune disorders and clinical features of the course of the disease and the period thereafter, with the exception of abdominal syndrome peculiar to the acute stage of the disease. The article also describes a clinical case of detection in the early post-COVID-19 period of a pathological clone characteristic of B cell chronic lymphocytic leukemia, and its subsequent disappearance and normalization of the immunophenotype as registered during a follow-up 1.5 years after recovery. The persistent immunological shifts should be taken into account when assessing the risks of reinfection and possible complications.
Received: 2024-04-02
Published online: 2024-06-30
DOI: 10.47183/mes.2024.028
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Original research Secondary hyperparathyroidism associated with vitamin D deficiency in young highly trained athletes
Isaeva EP, Okorokov PL, Zyabkin IV
Vitamin D deficiency that remains non-compensated for a long time is associated with high risk of rickets in children and osteomalacia in adults, myopathies and low-energy fractures, as well as secondary hyperparathyroidism (SHPT). SHPT represents one of the main mechanisms, through which vitamin D deficiency can contribute to pathogenesis of low-energy fractures. The study was aimed to assess the calcium and phosphorus metabolism state and the bone tissue metabolism markers in highly trained athletes with SHPT, as well as the prevalence of SHPT in elite sports. The study involved 527 young athletes aged 12–18 years (average age 15.2 years) doing 32 sports. The group with SHPT included 16 children (11 girls and 5 boys) with the average age of 15.0 years. The control group with normal levels of parathyroid hormone consisted of 511 children (254 boys and 273 girls) with the average age of 15.2 years. The studied subgroups were matched by age (p = 0.678). Girls predominated in the group with SHPT (р = 0.02). SHPT associated with vitamin D deficiency was revealed in 3% of young highly trained athletes, it was more prevalent among girls. The SHPT development does not result in alteration of the calcium and phosphorus metabolism indicators, however, it is accompanied by the increase in bone resorption markers, β-CrossLaps and total alkaline phosphatase. Many aspects related to vitamin D deficiency in SHPT are currently poorly understood, and there are no clinical guidelines on the cholecalciferol replacement therapy. Large-scale clinical trials are required to determine the optimal threshold values of 25(ОН)D3 and the powerful and effective treatment regimens for young athletes having SHPT associated with vitamin D deficiency.
Received: 2024-05-23
Published online: 2024-06-30
DOI: 10.47183/mes.2024.033
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Original research Effect of sodium bicarbonate or hydrochloric acid intragastric administration on gut-derived endotoxemia in rats receiving cyclophosphamide myeloablative conditioning
Vakunenkova OA, Zolotoverkhaja EA, Pechurina TB, Schäfer TV, Ivnitsky JuJu
Toxic effects of the myeloablative cyclophosphamide (CP) doses include damage to the gastrointestinal tract. This is manifested by gastrointestinal stasis, cytostatic drug-induced damage to the small intestinal mucosa, and acute gut-derived endotoxemia. The study was aimed to identify causal relationships between gastrointestinal stasis, enterocytopenia, and acute gut-derived endotoxemia in the rat model of the CP myeloablative conditioning. We assessed the effects of the intragastrically administered 0.48 М sodium bicarbonate (NaHCO3) solution or the 0.1 М hydrochloric acid (HCl) solution on the indicators of gastrointestinal stasis, enterocytopenia, portal blood levels of endotoxin, ammonia, urea, and urinary indican excretion. The stomach overfilled with chyme, decreased alkaline phosphatase and cholinesterase activity in the small intestinal tissues, 4.4-fold increased endotoxin levels, 4.6-fold increased urea levels, twofold increased portal blood plasma creatinine levels, and twofold increased urinary indican excretion were observed three days after intravenous administration of CP in a dose of 390 mg/kg. Intragastric administration of NaHCO3 or HCl partially prevented gastric stasis, but not acute gut-derived endotoxemia. Administration of NaHCO3, not HCl, prevented enterocytopenia in the duodenum. Acute gut-derived endotoxemia resulted mainly from the more intense release of the cecal microflora waste products into blood. Testing the use of sodium bicarbonate intragastric administration combined with the enteral detoxification and/or options for suppression of colonic microflora vegetation for prevention of the myeloablative cytostatic therapy complications is promising.
Received: 2024-05-01
Published online: 2024-06-30
DOI: 10.47183/mes.2024.035
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Original research Computational phantom for the dosimetry of the red bone marrow of a 10-year-old child due to incorporated beta-emitters
Sharagin PA, Tolstykh EI, Shishkina EA
Bone-seeking radionuclides, in particular 89,90Sr, could get into the environment in the course of various anthropogenic radiation incidents. From there they enter a human body with food and water. This leads to red bone marrow (RBM) internal exposure. These elements were present in the composition of radioactive releases into the Techa River in 1950s, and are the major source of RBM exposure for the residents of the riverside settlements. RBM dose estimation relies on dosimetric modeling which comprises the development of 3D computational phantoms of the skeleton parts. By imitating the energy transfer in these phantoms, the conversion coefficients from the radionuclide activity in a bone to the dose rate in RBM are evaluated. The given study is yet another step in the research aimed at the elaboration of a set of computational phantoms of the skeleton for people of various age. The objective is to develop a computational phantom of a skeleton of a 10-year-old child to estimate dose to RBM due to incorporated beta-emitters. Original SPSD (stochastic parametric skeletal dosimetry) approach was used to create the phantoms. According to this method the skeleton sites containing RBM were divided into smaller segment of simple geometric shape, for which voxel phantoms were generated. The parameters for phantom generation were based on published research data. They included^ linear dimensions of bones, thickness of the cortical layer, characteristics/properties of the bone micro-architecture, density and chemical composition of the modelled media and the percentage of RBM content in bones. Generated computational phantom of the skeleton sites with active hematopoiesis of a 10-year-old child consists of 38 phantom-segments. Linear dimensions of the segments were from 3 to 88 mm, cortical layer thickness: 0.2–2.2 mm.
Received: 2024-05-20
Published online: 2024-06-29
DOI: 10.47183/mes.2024.032
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Original research In vitro assessment of immunogenicity in chondrocytes obtained from the B2M knockout induced pluripotent stem cells
Barinova AA, Pikina AS, Golubinskaya PA, Ruchko ES, Eremeev AV
Today, the cell-based technologies are one of the instruments used for the cartilage tissue repair. Creation of a universal hypoimmunogenic cartilage tissue graft from the differentiated derivatives of induced pluripotent stem cells (iPSCs) might solve the problem of the lack of the cartilage cell product. However, currently there is little data on immunogenicity of such tissue-engineered preparations. The study was aimed to create a cartilage implant from the differentiated derivatives of the B2M-deficient iPSCs and assess its immunogenicity. The previously developed protocol was used to ensure differentiation of both wild-type and B2M knockout iPSCs into chondrocyte-like cells. After quality control of the resulting cell lines by conducting polymerase chain reaction and immunocytochemical assessment, the resulting cell lines were co-cultured with the peripheral blood mononuclear cells of a healthy donor. When co-cultivation was over, activation and degranulation of CD8+ T cells was assessed by flow cytometry analysis based on the CD69 and CD107a expression on the cell surface, respectively. The iPSC-derived chondrocytes expressed the cartilage tissue markers. Flow cytometry analysis revealed no substantial differences in immunogenicity between the derivatives of wild-type and B2M knockout iPSCs, as well as from the cartilage tissue cells of a healthy donor. Immunogenicity of chondrocyte-like cells was higher than that of hypoimmunogenic non-edited iPSCs. The B2M knockout iPSCs demonstrated a trend towards greater activation of CD8+ T cells. Thus, the B2M knockout in the iPSC-derived chondrocytes had no significant effect on the tissue immunogenicity. It is necessary to further edit the genes encoding MHC II and CD47 to obtain a less immunogenic product.
Received: 2023-11-15
Published online: 2024-02-05
DOI: 10.47183/mes.2024.001
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Original research Combined matrices and tissue-engineered constructs made of biopolymers in reconstructive surgery of ENT organs
Daykhes NA, Diab KhM, Nazaryan DN, Vinogradov VV, Reshulskiy SS, Machalov AS, Karshieva SSh, Zhirnov SV, Osidak EO, Kovalev AV, Hesuani YuD
Microtia is a combined congenital malformation with the prevalence of one case per 10,000–15,000 newborns, which accounts for 50% of all congenital malformations. Treatment of microtia is a challenging task. Numerous solutions have been proposed, however, none of these options guarantee good functional and aesthetic outcome. High hopes for solving the problem are placed on advances in reconstructive surgery. The study was aimed to determine the possibility of using advanced biocompatible endoprostheses manufactured using the tissue engineering technologies. Two closely related male 2-year-old minipigs of the Sus salvanius breed underwent implantation of bioengineered implants manufactured by combined 3D bioprinting with application of the collagen solution containing autologous cartilage tissue cells under the temporal fascia. The samples were collected 3 months later. Histological examination and immunohistochemistry showed that the implanted endoprosthesis initiated the development of regenerated connective tissue and its own vasculature in 100% of cases, thereby ensuring cell viability and integrity of biological structures; furthermore, no facts of the endoprosthesis rejection or resorption were reported. We have concluded that the developed implant manufacturing method is promising and can provide the basis for creation of domestic porous ear implants based on biocompatible polymeric materials, hydrogels, and autologous cellular material. It is necessary to further test the auricular implant using biological models.
Received: 2023-12-20
Published online: 2024-03-25
DOI: 10.47183/mes.2024.007
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