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Vol 23, No 4 (2023)
- Year: 2023
- Articles: 10
- URL: https://journals.eco-vector.com/MAJ/issue/view/8374
- DOI: https://doi.org/10.17816/MAJ.234
Analytical reviews
Pathogenesis of neuropsychic complications of new coronavirus infection
Abstract
Infection caused by the SARS-CoV-2 coronavirus is characterized by neurological and mental complications in a significant number of patients, which are based on disruption of the permeability of the blood-brain barrier, penetration of pro-inflammatory cytokines into the brain, neuroinflammation and coagulopathy. Studies of the brains of patients who died during an acute period of the disease showed a presence of foci of perivascular inflammation containing macrophages and, in a small number, CD8+ T cells. Microglial cells, mast cells, macrophages, and endothelial cells are involved in the development of neuroinflammation. Microglial nodules were observed in brain tissue samples, indicating neurophagia and neuronal loss. Some SARS-CoV-2 proteins, in particular the S protein, have pathogenic properties towards neurons. Biochemical markers in the cerebrospinal fluid of COVID-19 patients — NfL (neurofilament light chain) and GFAp (glial fibrillary acidic protein) indicate axonal destruction and astrocyte damage. Many patients with COVID-19, develop autoantibodies to self-antigens, including some CNS receptors, and encephalitis due to immune dysfunction and molecular mimicry. In patients with Alzheimer’s disease and Parkinson’s disease, coronavirus infection increases the symptoms of these diseases. The purpose of the review is summarizing the literary data for the analysis of immunopathogenesis of neuropsychic complications of acute coronavirus infection (COVID-19) and post-COVID syndrome.
5-20
Original research
Influence of various light regimes on some circadian rhythms of transplantable melanoma B16
Abstract
BACKGROUND: Today it is known that disturbance of the lighting regime, expressed both by lengthening of the light period and its reduction, can not only affect the regulation of circadian rhythms of the organism, but also contributes to the initiation of neoplasm growth.
AIM: The aim of the study was to investigate circadian rhythmicity of melatonin level, some micromorphometric indices of tumor cells and expression of genes Bmal1, Clock and Per2 in them in mice with transplanted melanoma B16.
MATERIALS AND METHODS: The study was conducted on 75 mice with subcutaneously transplanted melanoma B16, divided into 3 groups: control group, in which animals were kept under fixed light regime (light/darkness 10/14 hours with light on at 8:00 and off at 18:00), group under dark deprivation conditions, with animals kept under constant light 24 hours a day and group, in which animals were kept in constant darkness. The duration of the experiment was 2 weeks.
RESULTS: It was shown that under conditions of fixed light there are reliable circadian rhythms for all studied parameters, except for the nuclear-cytoplasmic ratio, the circadian rhythms of which was not revealed in any group. Constant darkness leads to rearrangement of all identified rhythms, and constant light causes destruction of all circadian rhythms except the Clock expression rhythm.
CONCLUSIONS: This study shows that light disturbances, whether constant light or constant darkness, lead to significant changes in the structure of the studied circadian rhythms.
21-32
Gene expression of antimicrobial peptides in rat intestine under conditions of chronic stress
Abstract
BACKGROUND: Severe stress causes an array of dysfunctions in the immune, neuroendocrine, cardiovascular, digestive and other systems, resulting in an emergence of various types of pathology. Common manifestations of a chronic stress are the disorders in the gastrointestinal tract, such as irritable bowel syndrome, functional dyspepsia, biliary dyskinesia, dysbiosis, inflammatory processes that determine the development of gastritis and one of the most widespread post-stress pathologies of the gastrointestinal tract — stomach ulcers. The disclosure of the molecular mechanisms of a pathogenesis of diseases associated with gastrointestinal dysfunction related to chronic stress as well as a search for new ways to correct these disorders are important tasks of fundamental and clinical medicine. The present work is focused on evaluating a participation of molecular factors of the innate immunity in intestine, such as antimicrobial peptides secreted by intestinal epithelial cells upon infection, in a response to the chronic stress.
AIM: The aim of the study was to estimate the gene expression of a number of antimicrobial peptides: intestinal α- and β-defensins of laboratory animals (rats) under chronic stress conditions.
MATERIALS AND METHODS: Modeling of a chronic stress was performed by daily forced swimming of laboratory animals in cold water. An expression of α- and β-defensin genes was evaluated using a real-time polymerase chain reaction.
RESULTS: We found an increase in the level of expression of the rat α-defensin-5 and β-defensin-3 genes in response to chronic stress, while the expression of β-defensin-2 gene was not changed compared to the control.
CONCLUSIONS: Considering that changes in the concentration and spectrum of peptides with antibacterial activity, caused by prolonged stress, can contribute to modification of the composition of the intestinal microbiota, the data obtained can expand our understanding of the molecular basis of the pathogenesis of diseases associated with disorders in the composition of microbiota under stress.
33-42
Morphological assessment of the ovarians after single and fractional local electron iradiation
Abstract
BACKGROUND: When malignant neoplasms of the pelvic organs are irradiated, healthy ovarian tissues can get into the irradiation area. So, among all physico-chemical factors, ionizing radiation is the most common cause of ovarian failure, which has a negative impact on fertility. Conducting research in this area is especially important in connection with the active introduction of electron therapy in the protocols for the treatment of malignant neoplasms of the small pelvis with the need to find ways to prevent and treat post-radiation ovarian lesions. In addition, one of the main tasks of modern radiobiology is the creation of experimental animal models in order to reveal the mechanisms of radiation exposure with subsequent extrapolation of the results obtained to humans in order to level the side effects of radiation therapy and select optimal doses.
AIM: The aim of the study was a morphofunctional assessment of the ovaries after local electron irradiation in single and fractional modes.
MATERIALS AND METHODS: Wistar rats (n = 30) were divided into three groups: I — control (n = 10); II (n = 10) — subjected to a single local irradiation with electrons at a dose of 2 Gy; III (n = 10) — subjected to fractional local irradiation with electrons in a total dose of 20 Gy.
RESULTS: After a single local irradiation with electrons at a dose of 2 Gy, multiple hemorrhages and a decrease in the number of growing follicles with a discontinuous theca layer, which were unevenly distributed over its volume, were noted in the ovary. A statistically significant difference in the number of follicles was revealed: a decrease in the number of primordial, primary, secondary and tertiary follicles and an increase in atretic follicles. The most pronounced difference in the number of follicles between the studied groups was found in the group of fractional electron irradiation at a dose of 20 Gy: the smallest number of primordial and the largest number of atretic follicles with signs of post-radiation fibrosis.
CONCLUSIONS: The most profound damage to the ovary develops after exposure to fractional electron irradiation at a total dose of 20 Gy compared with a single exposure to ionizing radiation at a dose of 2 Gy: a reduced number of follicles, a decrease in the area and thickness of the cortical substance, as well as the thickness of the ovarian tunica, in combination with the growth of the connective tissue.
43-52
Mathematical modeling of biomechanical elastic and hyperelastic properties of the myocardium
Abstract
BACKGROUND: The study of mechanical properties of biological tissues is extremely informative and is one of the most important areas of biomechanics. Knowledge of these aspects of biological objects based on experimental data can become a source of new medical and technical solutions for the reconstruction of organs and the development of replacement materials.
AIM: Passive mechanical properties of isolated myocardium are compared with linear, bilinear, exponential and the most common hyperelastic models (neohookean, Mooney–Rivlin, Ogden, Yeoh, polynomial and Veronda–Westmann).
MATERIALS AND METHODS: Literature data on mechanical tests of autopsy material obtained from mongrel dogs were used as initial data. To search for the most advanced calculation algorithms the computer algebra system was used, the Mathcad 15.0 software package and the multifunctional finite element analysis application ANSYS 2022 R2 were used. Direct comparison of models was made based on mathematical statistics.
RESULTS: Among the first group of models, the results closest to the experimental data were demonstrated by the exponential model R = 0.9958/0.9984 (in the longitudinal/transverse direction with respect to the myocardial fibers), the lowest accuracy was demonstrated by the linear model R = 0.9813/0.9803. Young’s moduli of linear, bilinear and exponential models and material constants of hyperelastic models are determined. The coefficient of elastic anisotropy of the myocardium, defined as the ratio of the elastic moduli of the linear model measured along and across the direction of the fibers, is equal to 2.18, which is very different from the literature data for the myocardium of the human heart. Deformation along the fibers of the heart muscle is more energy-consuming in the direction along the fibers than in the transverse direction (3.81 and 2.52 mJ/cm3). The most accurate hyperelastic models turned out to be the 2nd order polynomial model R = 0.9971 and the 3rd order Yeoh model R = 0.997. The largest deviations and the lowest correlation coefficient between the experimental and model data were demonstrated by the simple neohookean model R = 0.974 with a single parameter μ. The numerical values of the parameters of hyperelastic models obtained by calculation methods used practically did not differ from each other (≤2.16%).
CONCLUSIONS: The study demonstrated the importance of selecting the correct mechanical model for isolated myocardium. The data obtained can be useful in virtual interventions (simulations) for predicting outcomes and supporting clinical decisions, developing replacement materials and structures made of them for reconstructive operations on heart structures.
53-68
Cytotoxic effects of nerve growth factor and its combinations with chemotherapeutic drugs on anaplastoc astrocytoma, glioblastoma and medubloblastoma cells in vitro
Abstract
BACKGROUND: Currently, the effectiveness of the treatment of malignant tumors using surgical resection, radiotherapy and chemotherapy is insufficient. Therefore, new research is needed to find alternative molecules with antitumor effects. It is known that nerve growth factor (NGF) inhibits invasion, migration, and angiogenesis of tumor cells. Studying the effects of NGF on brain tumors, as well as its combinations with chemotherapy drugs used in medicine, may contribute to the development of new treatment regimens for malignant neoplasms in the central nervous system.
AIM: The purpose of this study is an exploration the molecular and cellular mechanisms of anticancer effects of individual and combined preparations of NGF and chemotherapeutic drugs on brain tumor cells (gliomas C6, U251, anaplastic astrocytoma, glioblastoma and medulloblastoma).
MATERIALS AND METHODS: The study was performed on rat glioma C6, human U251 glioma cell lines, as well as on primary cells of anaplastic astrocytoma (n = 9), glioblastoma (n = 9) and medulloblastoma (n = 38) patients. The cytotoxicity of chemotherapeutic drugs, NGF and their combinations against tumor cells was assessed using the MTT assay. The expression of TrkA and p75 receptors on anaplastic astrocytoma, glioblastoma and medulloblastoma cells was assessed by immunofluorescence analysis using anti-TrkA and anti-p75 monoclonal antibodies.
RESULTS: Nerve growth factor exhibits in vitro cytotoxic activity that exceeds the activity of chemotherapy drugs towards rat glioma C6, human U251, anaplastic astrocytoma (AA), glioblastoma (GBM) and medulloblastoma cells. The cytotoxic activity of NGF in combination with chemotherapy drugs is significantly higher than the activity of the individual NGF drug against medulloblastoma cells, while against anaplastic astrocytoma cells it is comparable to the indicators of the isolated action of NGF, and lower for glioblastoma cells. The effectiveness of the cytotoxic effect of the combinations NGF + cisplatin and NGF + temozolomide (TMZ) on AA and GBM cells correlates with both the expression of TrkA, p75 receptors, and their coexpression, indicating that expression indicators can be considered as markers of tumor cell sensitivity to NGF.
CONCLUSIONS: The data obtained allow us to consider NGF as a potential anticancer drug for the treatment of brain tumors. Thus, NGF can act as a potential anticancer drug for the development of new therapeutic regimens for brain tumors.
69-84
Clinical research
Immune response and laboratory markers in the spectrum of severity of COVID-19
Abstract
BACKGROUND: Serum antibodies to SARS-CoV-2, when measured early after disease onset, may add value to the diagnosis of COVID-19.
AIM: To examine the levels of serum antibodies to SARS-CoV-2 and laboratory blood parameters in hospitalized patients with COVID-19 of varying severity.
MATERIALS AND METHODS: In this retrospective cohort study, we examined laboratory markers of inflammation in patients with acute COVID-19 during the 1st week of hospitalization. The levels of serum antibodies to SARS-CoV-2 were studied using commercial test systems.
RESULTS: In 47% of hospitalized patients with COVID-19, during the first week of hospital stay, IgM and IgG antibodies to SARS-CoV-2 were detected, both in the case of a positive and negative PCR test. An average positive cor- relation of detected IgM and IgG with antibodies to the receptor-binding site of the S-protein of the SARS-CoV-2 virus is shown. In total, IgM and IgG antibodies to SARS-CoV-2 were most often detected in patients with a favorable course of the disease. Laboratory parameters in patients with moderate and severe COVID-19 were characterized by a significant increase in the level of serum C-reactive protein, an increase in the neutrophil-leukocyte ratio and fibrinogen level, in comparison with data from patients with a mild course of the disease. In mild cases of infection, a moderately negative correlation was revealed between the levels of antibodies to SARS-CoV-2 and NLR.
CONCLUSIONS: Detection of antibodies to SARS-CoV-2 in the early stages of hospitalization may be a predictor of a favorable outcome of the disease and serve as an additional criterion for the diagnosis of COVID-19 along with PCR analysis.
85-94
Long-term consequences of COVID-19 in hospitalized patients over 75 years old
Abstract
BACKGROUND: The COVID-19 pandemic remains an urgent medical and socio-economic problem. The symptoms, signs and complications of COVID-19 in the acute phase of the disease are now well known, while the long-term consequences of the disease continue to be studied.
AIM: The aim of this study was to study the frequency, clinical manifestations of “prolonged” COVID-19 and post-covid syndrome in advanced and old ages people treated in a hospital.
MATERIALS AND METHODS: The study included patients aged over 75 years old diagnosed with COVID-19 who were treated in two multidisciplinary hospitals in Moscow in 2021–2022: 94 patients aged 75 to 94 years, including 75.5% of women. At the stage of inpatient treatment, patients were interviewed and medical records were analyzed with registration of demographic data, comorbidities, clinical symptoms and signs of the disease, laboratory markers, complications, and treatment outcome. After 1 and 12 months. after discharge, among the survivors, they were interviewed by telephone interview using a special questionnaire with registration of complaints, repeated hospitalizations and complications of COVID-19, assessment of their psycho-emotional state and identification of cognitive-behavioral disorders.
RESULTS: In 70.2% of cases, the disease proceeded in a severe and extremely severe form. The majority of patients before COVID-19 had chronic diseases, most often arterial hypertension (85.9%), chronic heart failure (45.7%) and diabetes mellitus (27.2%). Hospital mortality was 22.6%. Poll after 1 month performed in 41/70 surviving patients (58.6%). Among the symptoms, the most common were fainting (41.5%), palpitations (36.6%), constipation (34.1%), the appearance or increase of shortness of breath (31.7%). Almost every day, 14.6%, 12.2% and 14.6% of the respondents experienced stress, anxiety and apathy. Difficulties in performing hygiene procedures, self-care, dressing were observed in 19.5, 12.2 and 12.2% of cases, respectively; 36.6% experienced severe problems when walking long distances. Poll after 12 months performed in 34/70 people (51.4%). Among the symptoms, the most frequently recorded were behavioral changes (32.4%), increased blood pressure (26.5%), problems with vision (26.5%) and hearing (23.5%). Psycho-emotional disorders were detected less frequently: 2 patients (5.9%) experienced daily stress, 1 respondent (2.9%) was worried about strong agitation and apathy. Difficulties in dressing, performing hygiene procedures, self-care were experienced by 32.4, 29.4 and 8.8% of patients; 20.6% experienced severe problems when walking long distances.
CONCLUSIONS: The conducted study indicates a high prevalence of symptoms of “prolonged” COVID-19 and post-covid syndrome in elderly people and the duration of their persistence, which may limit their functional activity and negatively affect the quality of life.
95-106
History of medicine
107-112
V.A. engelhardt and V.S. Ilyin: their role in the development of biochemical science in the second half of the XX century
Abstract
The paper is devoted to two well known scientists V.A. Engelhardt and V.S. Ilyin, who were at the head of department of biochemistry, Institute of Experimental Medicine, one from 1944 to 1952, the other from 1952 to 1976. Presented are their most famous investigations, which enriched Russian and the world science. Both had to work in very hard period for our country and science, both being a model of high moral and so they wun victory.
113-124
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор). Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.