REVIEWS
Novel coronavirus infection (COVID-19) is a highly contagious respiratory disease caused by the SARS-CoV-2 coronavirus. COVID-19 is known to affect both the respiratory, digestive, excretory, and nervous systems. The incidence of chronic effects of the novel coronavirus infection is now on the rise. This paper is aimed to review the epidemiology, pathogenesis and components of post-COVID asthenia. Material and methods. Sixty-three references published between 2005 and 2023 and indexed in the PubMed, CyberLeninka, Russian Citation Index, Semantic Scholar, and Google Scholar databases were included in this review. Results. The study revealed the most common symptoms of post-COVID asthenia are fatigue, muscle weakness, shortness of breath, sleep disturbances, anxiety or depression, impaired memory and cognitive functions (“foggy brain”), hyposmia, and reduced work performance. One of the specific symptom complexes for post-COVID is asthenovegetative syndrome, the incidence of which according to the meta-analysis ranged from 13.1 to 72.8 %, with a cumulative percentage of 45 ± 0.05 % (95 % confidence interval 0.31–0.54). Conclusions. Nowadays, post-COVID asthenia is becoming extremely severe. It is necessary to review in detail the available data on the epidemiology and components of post-COVID asthenia in order to develop an adequate strategy for post-COVID management.
Epidemics of Filovirus Hemorrhagic Fevers demonstrate an increase in incidence, a reduction in the intervals between outbreaks, the emergence of a risk of infection spreading to non-endemic regions in recent years. Filovirus infections are associated with high mortality due to the complexity of pathogenesis, the variety of spread routes, and severe and often irreversible clinical manifestations. The review contains information reflecting modern ideas about the taxonomy and structure of the genome of filoviruses, epidemiology, pathogenesis, clinical presentation, diagnosis, methods of treatment and immunoprophylaxis of hemorrhagic fevers. According to the latest revision of family Filoviridae taxonomy by the International Committee on Taxonomy of Viruses (ICTV), the family includes eight genuses, 15 species and 16 viruses. The genome is represented by a negative RNA strand that includes seven genes encoding seven structural proteins. The area of infections includes Africa, South and Central Europe, Southeast Asia, China. The natural reservoir of filoviruses is the fruit-bats mammals. The infectious process is based on the aberrant production of proinflammatory cytokines. There are three periods of the disease: prodromal, generalization and terminal. The main method for diagnosing filovirus infections is recognized as a reverse transcription-polymerase chain reaction in real time. Etiotropic therapy is based on the use of monoclonal antibodies against viral glycoprotein. The World Health Organization has approved two vaccines against Filovirus Infections for use. Several vaccines approved for use have been developed and registered on the territory of the Russian Federation and China.
Splenectomy (removal of the spleen) and splenorrhaphy (spleen suturing) remain the leading treatments for patients with severe organ injuries. These surgeries require a thorough understanding of the anatomy of the spleen. The aim of the study was to present modern data on organometric parameters (length, width, thickness and volume) of the spleen in individuals of different sex, age and physique. Within the study we conducted a systematic search and analyses of sources in bibliographic databases Scopus, Web of Science, PubMed and Russian Science Citation Index (RSCI). The statistical software R (version 4.1) was used. As a result of meta-analysis, it was found that the weighted mean values of length, width and volume of the spleen are: 10.46 cm, 6.43 cm, and 205.43 cm3, respectively. The researchers observed a tendency for the its length to increase as body length increases. It is also found that spleen volume is significantly greater in males (254.20 cm3) than in females (185.11 cm3). Understanding of the actual organometric characteristics of the spleen will contribute to the improvement of methods of early diagnosis of diseases, objective assessment of treatment and prevention of its pathology and, as a consequence, to the improvement of the quality of medical care.
Bronchial asthma is a growing burden on the health system worldwide, mainly affecting population of low-income countries. The widespread growth of morbidity has a significant negative impact on the quality of life of patients. The lack of radical treatment of asthma for many years can be explained by a lack of understanding of the mechanisms of its development. Currently, the heterogeneity of bronchial asthma is recognized, which is reflected in numerous risk factors. Advances in various aspects of the pathogenesis of this complex disease contribute to the development of new and more effective therapeutic approaches. Understanding the phenotyping and endotyping of asthma is an important aspect on which the effectiveness of a particular biological drug depends. Timely diagnosis and well-chosen therapy prevent the progression of the disease and allow achieving a long-term remission of bronchial asthma. The long-term history of studying the disease etiopathogenesis has brought progressive changes in the effectiveness of its treatment. The purpose of this work is to review the phenotypic features of bronchial asthma, as well as individualized treatment methods for severe asthma, prognostic and monitoring biomarkers of biological drugs. The search was conducted using PubMed, and EMBASE databases. The following keywords were used: “bronchial asthma”, “asthma phenotypes”, “asthma endotypes”, “asthma biomarkers”.
Cardiovascular diseases (CVD) remain one of the main problems in most countries of the modern world. In this connection, maintaining adherence to the treatment and prevention of CVD is a priority in the fight against diseases of the cardiovascular system. According to the WHO, insufficient adherence to treatment is an urgent medical problem. Approximately 35 % of patients cancel taking medications within a year after an acute cardiovascular event, which leads to a threefold increase in the risk of complications. The purpose of the review is to highlight the problem of low adherence in the aspect of CVD and highlight the main methods of increasing adherence to treatment. This article reflects the main aspects of adherence management, considers the factors leading to a decrease in the level of disease control, identifies the causes of low adherence, and identifies methods for increasing adherence to treatment in patients with CVD.
Obesity is one of the most acute issues of medicine at the present stage due to the steady increase in morbidity, high risk of complications and comorbid conditions that entail significant financial costs. At the same time, many different etiopathogenetic factors are involved in the formation of obesity. The article presents a literature review concerning the main risk factors and etiologic aspects of the development of overweight and obesity in adults and children. The most relevant pathogenetic mechanisms are considered, including imbalance of adipokines (decrease in adiponectin level and increase in leptin content), formation of low activity chronic inflammation as a result of proinflammatory cytokines, changes in the features of neuroimmune-endocrine interactions, the impact of chronic stress on the human body, vitamin D deficiency, disorders of the “gut – brain” axis, quantitative and qualitative changes in the composition of intestinal microbiota. The main therapeutic approaches and surgical methods in the treatment of obesity are presented. The data available in the literature at the present stage on methods of rehabilitation of patients with obesity, as well as persons with excess body weight, indicating the need for a comprehensive approach and combination of lifestyle modification, physiotherapeutic methods, psychological counseling to achieve positive results are summarized.
The literature review is devoted to the problem of exogenous-constitutional obesity and the role of oxidative stress (OS) in this form of obesity. The issues of modern diagnostics and pathogenesis of exogenous-constitutional obesity are considered. The results of various studies devoted to the study of OS in obesity in both laboratory animals and humans are presented. Excess body weight is often accompanied by increased OS and subclinical systemic inflammation. The need to correct the antioxidant status of the body is a topical issue, an important part of which is an individual approach to the selection of agents and dosages in order to reduce the negative impact of free radicals at the cellular level. A significant problem is the lack of a single standard for determining OS parameters, which requires standardized laboratory equipment, in this regard, the choice of a specific method is a responsible step for a research specialist. In this area, there are still many questions that require more detailed study.
Gold nanoparticles have unique physical, chemical and optical properties, due to which they are used to develop promising drugs: radiosensitisers, X-ray contrast media, agents for photothermal therapy, drugs for targeted delivery. In each case, the choice of nanoparticle parameters is determined not only by the field of application, but also by the biodistribution in the living organism: blood circulation time and accumulation in target organs and tissues, including the tumor. For long blood circulation, nanoparticles should avoid phagocytosis by liver macrophages. The aim of this review was to systematise information on the influence of gold nanoparticle parameters on their pharmacokinetic properties and biodistribution in intact and tumor-bearing small laboratory animals. Size, shape and stabilising coating were considered. Smaller nanoparticles tend to circulate longer in the bloodstream and accumulate more slowly in the liver. Various coatings such as citrate, bovine serum albumin or polyethylene glycol are used to protect nanoparticles against aggregation, opsonisation and phagocytosis. The influence of nanoparticle shape on biodistribution is not completely understood; presumably, it is less important than size and coating. In general, the available data indicate that gold nanoparticles with a diameter of up to 50 nm with a polymer coating have optimal pharmacokinetic properties for biomedical application.
BIOMEDICINE
Intrauterine hypoxia (IUH) changes the postnatal heart development and contributes to the individual susceptibility to cardiovascular diseases, also by impairment of protein-synthetic function of cardiomyocytes (CMC). Non-opiate analogues of leu-enkephalin, peptides NALE (Phe–D-Ala–Gly–Phe–Leu–Arg) and G (Phe–D-Ala–Gly–Phe–Leu–Gly), cytoprotectors with the wide spectrum of biological activity, improve the state of the CMC nucleo-nucleolar apparatus in neonatal age after IUH. The aim of the study was to analyze the parameters of CMC nucleo-nucleolar apparatus in mature albino rats, exposed to IUH and to the neonatal administration of peptides-analogues of leu-enkephalin. Material and methods. The offspring of Wistar rat females, subjected to hypobaric exposure (15–19 days of gestation, pO2 = 65 mm. Hg, duration – 4 hours), received from day 2 to day 6 of life daily intraperitoneal injections of NALE and G peptides (100 µg/kg), as well as NALE in combination with non-selective NO synthase blocker L-NAME (50 mg/kg), after that they were withdrawn from the experiment in mature age (60 days). The animals of control group and the comparison group received an equal volume of isotonic sodium chloride solution. The karyo- and nucleolometric parameters of CMC, and also the CMC nucleoli number were analyzed in heart sections, stained by using AgNOR method. Results and their discussion. IUH induced the significant decrease in nucleoli number of the CMC of both heart ventricles, and also led to the impairment of karyo- and nucleolometric parameters of the CMC in the mature offspring. Administration of NALE peptide in dose of 100 µg/kg in neonatal period corrected the posthypoxic changes of the CMC nucleonucleolar apparatus. Neonatal administration of non-selective NO-synthase blocker (L-NAME, 50 mg/kg) obviated the registered effects of NALE. The correction of delayed posthypoxic changes, similar to the effects of NALE, was observed after administration of its arginineless analogue– the G peptide. Conclusions. The cardioprotective effect of NALE is partially mediated by L-arginine – a potential donator of nitric oxide. Non-opiate analogues of leu-enkephalin – the NALE and G peptides, might be considered as perspective cardioprotective substances with the delayed activity, preventing the long-term consequences of the IUH.
To date, about 70 drugs based on regulatory peptides have been registered, including proline-containing ones, such as the nootropics Semax and Selank. Further study of the properties of glyproline peptide sequences is relevant in order to describe their neuroprotective properties and the possible development of new drugs based on them. The purpose of the study was to compare the effects of three glyproline peptides on the morphometric characteristics and proliferative activity of brain cells in albino rats. Material and methods. Sexually mature Wistar male rats were intraperitoneally injected with the peptides Thy-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP), Arg-Pro-Gly-Pro (RPGP) and Pro-Gly-Pro-Leu (PGPL) at a dose of 0.1 mg/kg for 5 days. The intact animals that received 0.9 % sodium chloride solution in equivolume served as controls. Morphocytometry was performed on preparations of the right hemisphere of the brain after staining with hematoxylin and eosin. The dimensional (area of bodies, nuclei, and nucleoli) and numerical (number of nucleoli) characteristics of cells were assessed. We examined the parameters of neurons and gliocytes in five localizations (the second and fifth layers of the anterior parietal lobe, the second and fifth layers of the proprietal lobe, field CA1 of the hippocampus). Using immunohistochemical staining, the proliferation intensity was determined (marker Ki-67, clone MIB1). Results. The TKPRPGP peptide changed the morphometric parameters of nervous tissue cells and the gliocyte proliferation index to a greater extent than RPGP and PGPL. In our experiment, the proliferative activity of neurons is maximally influenced by glyproline PGPL. The arginine-containing compound RPGP activates the proliferative activity of gliocytes. Leucine-containing PGPL, to a greater extent, changes the morphometric parameters of neurons. Conclusions. Both studied tetrapeptides affect the morphometric characteristics and proliferative activity of nervous tissue cells when administered five times intraperitoneally at a dose of 0.1 mg/kg. When comparing glyprolines, a more pronounced effect was observed after the administration of PGPL.
Lithium salts are known to treat bipolar disorder. Their high potential as neuroprotective agents in cerebral ischemia determines relevance for preclinical studies for the registration of new drugs based on them. Aim of the study was to investigate the toxic properties and local tolerability with an assessment of the toxicokinetics of the developed lithium chloride preparation for injection in dwarf pigs with repeated intravenous administration. Material and methods. Lithium chloride (solution, for intravenous administration 4.2 %) has been administered to minipigs (control and 3 experimental groups of animals of 3 males and 3 females) for 28 days at doses of 12.6; 29.4 and 63 mg/kg. General toxicity, local irritation, and basic pharmacokinetic parameters (Cmax, AUC0-24, MRT, T1/2, Vss, and Cl) were evaluated. Serum lithium ion concentration was estimated colorimetrically using quinizarin. Results and discussion. Toxic properties of the test drug were revealed, expressed in a change in the clinical state (vomiting after administration, inhibition of behavior and feed refusal), body weight negative dynamics, clinical and laboratory changes, shortening of the “QT” interval, accompanied by abnormalities according to the pathomorphological study results (focal infiltration with single renal tubular necrosis areas, kidneys fibrosis, replacement of thyroid tissue with adipose tissue). There were no signs of locally irritating effects of the test product. To evaluate toxicokinetic parameters, a bioanalytical assay (calibration range – from 0.17 to 5.45 μg/mL) was developed and validated, which is not inferior by its characteristics to the commercial reagent kits. According to the results of biomaterial analysis no lithium accumulation in the pig’s body was found with repeated use of the test drug. Doses of the drug that provide toxic concentrations of lithium (above 3 μg/ml) in the minipig’s serum were identified. The NOAEL was 12.6 mg/kg and the LOAEL was 29.4 mg/kg. Conclusions. The comprehensive approach to the consideration of toxic manifestations and toxicokinetics, including its analytical component of studies of this kind, was noted. The obtained results should be taken into account to assess the benefit/risk ratio in the clinical use of lithium chloride injection.
Reactive oxygen metabolites and antioxidants, as well as the redox-sensitive signaling Nrf2-dependent pathway, play a dual role in the formation, growth and progression of malignant neoplasms. The aim of the study was to investigate the ability of the original synthetic monophenolic antioxidant of combined action to influence tumor growth in vivo and the side effects of cytostatic use. Material and methods. Lewis lung carcinoma (LLC) was used as an experimental model of malignant growth. The study was performed on 120 female C57Bl/6 mice, which were divided into 12 groups; the animals were weighed weekly. Mice of the corresponding groups received intragastrically a solution of sodium 3-(3′-tert-butyl-4′-hydroxyphenyl)propylthiosulfonate (TS-13) (100 mg/kg body weight), a suspension of tert-butylhydroquinone (tBHQ) or a solvent (0.9% NaCl solution) throughout the experiment. 28 days after the start of TS-13 and tBHQ administration, mice were implanted intramuscularly with a suspension of LLC cells at a dose of 2×105 cells/mouse; on the 7th and 14th days of tumor development, a solution of doxorubicin was administered intraperitoneally twice at a cumulative dose of 8 mg/kg body weight (4/5 LD10). On the 35th day of tumor growth, the animals were removed from the experiment, the tumor was extracted, weighed and its linear dimensions were determined; the tumor mass coefficient and volume were calculated, respectively. The spleen mass coefficient was also estimated. Results and discussion. On the 7th and 14th days of tumor growth, the body weight of animals receiving TS-13 and tBHQ was statistically significantly greater than that of other tumor carriers. Administration of TS-13 to mice inhibited tumor growth as effectively as doxorubicin, and more significantly when used in combination; tBHQ did not exert an independent inhibitory effect, and did not enhance its effect in combination with the cytostatic. Doxorubicin significantly reduced the spleen mass coefficient, while TS-13 and tBHQ statistically significantly reduced the effect of the cytostatic. Monotherapy with doxorubicin was accompanied by hair loss on the dorsal surface (8 animals out of 10), while no alopecia was observed with the combined administration of the cytostatic with TS-13 and tBHQ. Conclusions. Monophenol TS-13, a direct antioxidant and inducer of the Keap1/Nrf2/ARE system, is comparable to doxorubicin in terms of its antitumor effect. The use of TS-13 allows to significantly reduce the negative manifestations associated with malignant growth and the side effects of chemotherapy, such as cachexia, splenotoxity, and alopecia.
The study of the viability of the spermatogenic epithelium in case of toxic lesions and their correction in experiment is a key factor for understanding the possibilities of restoring reproductive function in conditions of increasing technogenic pollution. The purpose of the study was to evaluate the level of pathomorphological changes in the testes of Wistar rats and the intensity of steroidogenesis upon administration of Escherichia coli lipopolysaccharide (LPS) endotoxin and subsequent correction of intoxication by administration of oxidized dextran. Material and methods. Three groups of Wistar rats were formed, intraperitoneal administration: 2 ml of 0.9 % NaCl solution (n = 5, control); E. coli LPS at a dose of 50 μg/kg body weight (n = 5); E. coli LPS at the same dose, followed by the introduction of 2 ml of a 2 % solution of oxidized dextran (OD) (n = 5). The content of testosterone in the blood serum and pathomorphological changes in the testes were assessed. Results and discussion. The administration of LPS led to moderate hypotrophy of the spermatogenic epithelium due to a decrease in the numerical density of spermatocytes and spermatogonia (by 22.4 and 26.6 %, respectively); a decrease in the numerical density of Leydig cells by 14.5 % and testosterone levels by 2.3 times (in 80 % of animals, testosterone levels ranged from 4.3 to 2.0 nmol/l). The injection of OD after LPS caused an increase in seminiferous tubule diameter and the spermatogenic epithelium height (by 2,9 и 3,3 %, respectively), in numerical density of spermatocytes and spermatogonia (by 16.8 and 14.6 %, respectively) compared to LPS; increase in the ratio of the number of spermatocytes to spermatogonia (by 6.8 %) compared to the control. The numerical density of Leydig cells increased by 4 %, the testosterone level increased by 1.7 times (in 60 % of animals the testosterone level varied from 12.7 to 37.3 nmol/l) compared to LPS. Conclusions. A single administration of OD after acute exposure to E. coli LPS endotoxin initiated the onset of restoration of the histological structure of the spermatogenic epithelium of the seminiferous tubules.
Thermal burns are one of the common types of human injuries, causing in severe cases an extensive immune response both locally in the wound and having a systemic effect. The search for new means of local treatment of burn wounds remains an urgent task. The aim of this study was to investigate the wound healing properties of recombinant granulocyte-macrophage colony-stimulating factor (ryGM-CSF) and its prolonged chimeric form with human apolipoprotein AI (ryGM-CSF-apoAI) on the model of burn injury in rats. Material and methods. ryGM-CSF and ryGM-CSF-apoAI obtained by expression in yeast P. pastoris were used in this work. The study was performed on 27 Wistar rats, which were modeled burns of III degree. The wound-healing effect of recombinant cytokines was evaluated morphologically, and the expression of cytokine genes - markers of the course of the wound process and angiogenesis - was measured. Results and discussion. ryGM-CSF is known to accelerate wound healing. Human rGM-CSF on the rat burn model showed both the properties of a cytokine influencing angiogenesis, increasing the number of vessels, and being a foreign protein stimulated the immune response, increasing prolonged the number of lymphocytes and supporting inflammation. The chimeric form of cytokine ryGM-CSF-apoAI reduced inflammation, accelerated the change of wound healing phases and, as a consequence, reduced the number of neutrophils by 16 days. Unexpectedly, it induced maturation of vessels, which in this case had normal lumen, size, and were lined with endothelium. The ratio Angpt1 and Angpt2 gene mRNA content was 2-fold higher when ryGM-CSF-apoAI was used, compared to control and ryGM-CSF administration. Conclusions. With xenogeneous administration, recombinant human GM-CSF prolongs inflammation due to early lymphocytic response to foreign protein and increased neutrophil content at later wound healing periods. The chimeric form ryGM-CSF-apoAI reduces cytokine immunogenicity by promoting earlier replacement of neutrophils by macrophages and fibroblasts and stimulates maturation of high-grade blood vessels.
The purpose of the study was to assess the involvement of the polyamine system in the implementation of the cytoprotective effect of non-opiate analogues of leu-enkephalin under conditions of oxidative stress. Material and methods. Rat pulmonary fibroblasts were incubated with the NALE peptide (Phe–D-Ala–Gly–Phe–Leu–Arg, 0.1 μM) and its structural analogue peptide G (Phe–D-Ala–Gly–Phe–Leu–Gly, 0. 1 µM), some series - with difluoromethylornithine (DFMO, 2 mM). Oxidative stress was modeled by adding H2O2 (100 μM) to the culture medium. The morphometric parameters of the nucleo-nucleolar apparatus of fibroblasts, the proliferative activity of cells, and the features of p53 expression were studied on monolayers. Results. Incubation of fibroblasts with hydrogen peroxide leads to a stress response of cells, as evidenced by the complete absence of mitotic activity, a significant decrease in cell culture density, an increase in the area of nuclei and an increase in the proportion of p53 + fibroblasts. Incubation with the ornithine decarboxylase synthesis blocker DFMO caused a deterioration in the condition of the cell culture: the mitotic index decreased, and the number of p53 + fibroblasts increased even more significantly. Pre-incubation (before adding H2O2) with NALE and G peptides reduced, but did not completely eliminate, the negative effect of hydrogen peroxide on cell culture. Preliminary co-incubation of cell monolayers with peptides and DFMO showed a more pronounced cytoprotective effect in OS. Thus, in the series with NALE, the indicators of the proportion of p53 + fibroblasts, culture density, and size of fibroblast nuclei did not differ from the control parameters; a significant increase in the total area of nucleoli in cell nuclei was recorded. In the series with peptide G, the indicators of the proportion of p53 + fibroblasts, the size of fibroblast nuclei, the number and total area of nucleoli were similar to the control indicators, and a significant increase in the cell culture density was revealed, compared to the control. Conclusions. The results of the study indicate a direct cytoprotective effect of peptides - non-opiate analogues of leu-enkephalin, including conditions of blockade of the polyamine system.
One of the promising areas of regenerative technologies is the stimulation of proliferative activity of stem cells and, accordingly, the rate of their self-renewal, by exposure to nanosecond repetitive pulsed microwave radiation (RPMs). The article presents data on the effect of nanosecond RPMs on the rate of division of mesenchymal stem cells from the femur of Wistar rats. Material and methods. Data are presented on the effect of nanosecond repetitively pulsed microwave radiation carrier frequency of 9.4 GHz, pulse repetition rate of 13 Hz, 50 pulses, peak power flux density of 140, 210, and 310 W/cm2, absorbed energy value in 50 pulses at a depth of 1 cm, respectively 699, 1049 and 1549×10–6 J/cm3 on the division rate of mesenchymal stem cells from the femur of laboratory rats Wistar. The effect of the exposure was assessed by the change in the number of cells in the culture 24 and 72 hours after a single irradiation with RPMs with different intensity. Results. Depending on the intensity of RPM, both an increase and inhibition of cell division rate were observed, that is, the response had a phasic character. The most pronounced stimulating acceleration of cell division is exerted by RPMs with a peak power flux density of 140 W/cm2, and the effect is realized at the maximum rate after 24 h. Conclusions. The most probable biophysical and physiological mechanisms for the formation of the effects of changes in the rate of self-renewal of stem cells induced by RPMs are considered.
Long-term alcohol abuse causes psycho-emotional and cognitive impairment, including severe dementia. Oxidative stress is considered one of the main mechanisms in the cognitive disorders pathophysiology caused by long-term alcoholism. In this regard, the search for substances capable of correcting mitochondrial dysfunction and oxidative stress that arise as a result of prolonged ethanol consumption is relevant. Of particular interest in the complex treatment of alcoholic encephalopathy is Chinese hyssop (Lophanthus chinensis), used in Tibetan and Mongolian traditional medicine for liver diseases, as well as a means of improving the functional state of the body and metabolism, slowing down the aging process. Material and methods. Alcohol intoxication was modeled in Wistar rats by per os administration of a 40 % ethanol solution in a volume of 10 ml/kg for six weeks. The L. chinensis dry extract at a dose of 100 mg/kg was administered to animals per os starting from the third week, an hour after ethanol. On day 45, the content of malondialdehyde (MDA), reduced glutathione (GSH), activity of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, NADH dehydrogenase and succinate dehydrogenase complex, concentration of ATP werei determined spectrophotometrically in the animal brain homogenate. Results. It was found that L. chinensis extract increases the activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase (by 10 %, р = 0.016, by 31 %, р = 0.001, by 30 %, р = 0.041, by 29 %, р = 0.009, respectively) and GSH content (by 24 %, р = 0.019), and also reduces the concentration of MDA (by 20 %, р = 0.014) in brain tissue. A decrease in the intensity of oxidative stress enhances the functioning of enzymatic complexes I (by 23 %, р = 0.017) and II of the mitochondrial respiratory chain (by 72 %, р = 0.001) and increases the ATP content (by 23 %, р = 0.029) in the rat’s brain. Conclusions. L. chinensis extract exhibits antioxidant effects and stimulates energy processes in neurodegenerative processes in the brain caused by long-term alcoholism.
Glyprolines have a wide range of pharmacological effects, including antioxidant effects. This can be used to correct functional and morphological disorders of the brain after traumatic brain injury (TBI) by inhibiting secondary damage, the prevention of which is the main way to improve TBI outcomes. The aim of the study was to investigate the level of apoptosis in the cells of the proper parietal lobe (PPL) and the CA1 field of the hippocampus of mature male Wistar rats after mild TBI and a course of glyproline RPGP (Arg-Pro-Gly-Pro). Material and methods. Rat brain tissues (n = 38) were used in the experiment. Mild TBI was modeled by free fall of a load. After the injury, the animals received intraperitoneal RPGP peptide at a dose of 0.1 mg/kg, dissolved in 0.9% NaCl solution or NaCl solution. The level of apoptosis in brain tissues was assessed by the expression of p53 antigen using immunohistochemistry. Results. On the 22st day after TBI, the number of glial cells that entered into apoptosis in layer II of the proper parietal lobe (PPL) of the Wistar rat brain increases. In animals subjected to simulated TBI and receiving RPGP intraperitoneally at a dose of 0.1 mg/kg for 21 days, the level of apoptosis did not increase. Conclusion. It was found that after a course of RPGP administration against the background of TBI, the level of apoptosis in neuroglial cells decreases.
CLINICAL MEDICINE
Introduction. Classical trigeminal neuralgia is caused by the compression of the trigeminal nerve root and often requires surgical intervention due to the maladaptive intense pain syndrome. Both arteries and veins are considered compressing vessels, however, the role of venous compression in the development of neuralgia remains undefined. The aim of the study was to investigate the effectiveness of microvascular decompression in the treatment of trigeminal neuralgia caused by venous compression, considering the use of various surgical tactics. Material and methods. A retrospective analysis of surgical outcomes in 70 patients who underwent microvascular decompression for trigeminal neuralgia at the Federal Neurosurgical Center (Novosibirsk, Russia) between 2017 and 2021 was conducted. The study included 46 women and 24 men aged 23–82 years with unilateral facial pain. Brain MRI was performed preoperatively to evaluate neuroimaging picture and to clarify the relationships between the trigeminal nerve root and adjacent vessels. The surgical results were assessed during follow-up using the Barrow Neurological Institution (BNI) scale. Results. The study showed that venous neurovascular compression is frequently found in trigeminal neuralgia patients undergoing microvascular decompression in 26.9 % of cases. Various operative strategies were used when venous compression was detected, with high short-term success rates and lower recurrence rates. Long-term monitoring indicated pain relief in 71.4 % of cases (BNI I–II) and pain recurrence in 28.6 % of cases (BNI III, IV, V). Conclusion. This study highlights the effectiveness of microvascular decompression in treating classical trigeminal nerve neuralgia caused by venous compression and emphasizes the importance of individual surgical tactics based on the characteristics of the adjacent veins to achieve optimal results.
Advances in pediatric surgery, intensive care, and anesthesiology have significantly improved the outcomes of surgical treatment of full-term and premature infants with intestinal malformations and necrotizing enterocolitis (NEC). The main challenges in treating children of this complex group today lie in improving diagnostics, choosing treatment tactics, and ensuring the postoperative period. Monoamine oxidase (MAO) is a mitochondrial enzyme that catalyzes oxidative deamination of biogenic and xenobiotic monoamines, including those in intestinal wall cells and tissues. It can be a prognostic and diagnostic marker of the effectiveness and rate of intestinal recovery in the postoperative period, and also serve as a point of application for pharmacological correction. The aim of the study is to determine the activity of intestinal MAO in children of the first year of life with surgical pathology. Material and methods. The study included 24 patients with colon and small intestine pathologies, aged from 1 day to 3 months, who were treated at the Chelyabinsk Regional Children’s Clinical Hospital from October 2022 to May 2024. MAO-A and MAO-B activity was studied by spectrophotometry in intestinal homogenates obtained at the proximal resection margin. Results and discussion. Intestinal samples obtained from patients with diseases accompanied by pronounced inflammatory changes (NEC stage IIIA–IIIB, enterostomy closure after NEC III, intestinal neuronal dysplasia (IND), Hirschsprung’s disease) showed a significant decrease in the activity of the MAO-A isoform. A decrease in MAO-B activity was demonstrated in intestinal wall samples obtained from children with confirmed diagnoses of Hirschsprung’s disease and intestinal neuronal dysplasia, as well as in premature infants with surgical stages of NEC. The highest activity of both enzyme isoforms was found in sigmoid colon samples without pathological changes in patients with anal and rectum atresia.
According to international research data, COVID-19 increases the risk of developing hypertensive and metabolic disorders. Aim of the study was to assess the risks of hypertensive and metabolic disorders in pregnant women with COVID-19 and to identify potential markers of these conditions. Material and methods. The study involved 265 pregnant women, infected in the first, second, and third trimesters of pregnancy, and uninfected with COVID-19, from 2020 to 2022. Spectrophotometric methods were used to evaluate blood level of glucose, total cholesterol, high- and low-density lipoprotein (LDL), and triglycerides. ELISA was used to measure content of oxidized LDL and apolipoprotein B (apo B). Results. Gestational arterial hypertension (GAH) developed more frequently in women with COVID-19 infected in the second trimester compared to those infected in the third trimester (15.7 and 6.1 % cases, respectively, p = 0.044). Gestational diabetes mellitus (GDM) was more commonly diagnosed in pregnant women with COVID-19 than in those uninfected (17.2 and 4.0 % cases, respectively, p = 0.015), particularly in those infected in the second and third trimesters (17.6 and 18.9 %, respectively). Pregnant women with COVID-19 showed an increase in glucose levels by 1.14 times (p = 0.001), oxidized LDL by 1.24 times (p = 0.042), and apo B protein by 1.14 times (p = 0.025) in blood serum. Conclusions. Infection with COVID-19 in the second trimester of pregnancy increases the risk of GAH by 2.56 times, and in the second and third trimesters, the risk of GDM by 4.3 times. Increase of glucose, oxidized LDL, and apo B content in blood serum may have prognostic significance in the development of hypertensive disorders.
Arterial spin labeling (ASL) allows the assessment of tissue perfusion and has advantages such as non-invasiveness and the ability to repeat examinations multiple times. This enables dynamic monitoring without contrast administration. This technique requires additional pre- and post-processing, complicating result acquisition. A promising trend is the assessment of brain perfusion changes for diagnosing ischemic stroke. Aim of the study was to evaluate a comprehensive dynamic perfusion change in the brain in patients in the early post-stroke recovery period and conditionally healthy volunteers by the ASL. Material and Methods. A prospective observation of two groups was performed. The control group included 20 conditionally healthy volunteers aged from 18 to 25 years (21.8 ± 2.65 years) (mean ± standard error of the mean), the study group ‒ 20 patients with verified ischemic stroke aged from 40 to 70 years (59.4 ± 9.2 years) on days 1–3, 7–10, and three months after disease onset. Perfusion indicators of gray and white matter of the lobes of the cerebral hemispheres (parietal, occipital, frontal, temporal) in visually intact areas of the brain were integrally evaluated. Perfusion values were also calculated in ipsilateral and contralateral regions of interest relative to the stroke focus. Results and discussion. The stroke focus shows a nonlinear dynamic of changes, starting from 19.86 ± 5.69 ml/100 g/ min on days 1–3, increasing to 27.57 ± 4.86 ml/100 g/min on days 7–10, and decreasing to 14.48 ± 3.66 ml/100 g/min by the 3–4 month, remaining low compared to visually intact areas and the control group. Perfusion in the visually intact area of the ipsilateral hemisphere in relation to the stroke focus is significantly (p < 0.05) reduced by 4–5 % on days 1–3 and 7–10 compared to other regions of interest. Meanwhile, there is a gradual increase in perfusion values in all analyzed regions from the first to the third examination. Conclusions. The ASL method allows for the quantitative assessment of the dynamics of cerebral perfusion in the early recovery period, with a significant (p < 0.001) reduction in tissue blood flow in the ischemic focus relative to the analyzed regions of interest and the control group. The intact area in the ipsilateral hemisphere in relation to the stroke focus shows dynamic growth from hypoperfusion to normoperfusion, which is related to the involvement of the brain as a whole organ.
The significant prevalence and severe medical and social consequences of comorbidity dictate the need to determine the etiopathogenetic risk factors that contribute to its formation. Purpose of the study: to study the associations of metabolic factors (arterial hypertension, obesity, hyperglycemia, dyslipidemia, hyperuricemia, increased serum concentration of C-reactive protein (CRP) with a high degree of comorbidity in patients with somatic pathology. Material and methods. An analytical retrospective study was carried out including data from the medical records of 5296 patients at a therapeutic clinic, men and women, aged from 18 to 92 years (56.4 ± 0.2 years). Comorbidity was taken into account in the presence of two or more nosologies in one patient, its degree was assessed by the number of nosologies in one patient. The following risk factors were assessed: arterial hypertension, obesity, hyperglycemia, dyslipidemia, hyperuricemia, increased concentration of CRP. The presence of non-alcoholic fatty liver disease (NAFLD) was also taken into account. The association of the considered factors with a high degree of comorbidity was assessed using logistic regression analysis. Results and discussion. The relations have been established between NAFLD, age over 52 years, female gender, as well as the considered metabolic factors with a high degree of comorbidity. NAFLD, age, obesity and hyperglycemia had the strongest associations with comorbidity. NAFLD increased the risk of developing a high degree of comorbidity by 5.6 times (odds ratio (OR) 5.59, 95 % confidence interval (CI) 4.40–7.11), age over 52 years – by 2.6 times (OR 2.60, 95 % CI 2.30–2.95); obesity – by 2.4 times (OR 2.37, 95 % CI 2.08–2.70), hyperglycemia – by 2.1 times (OR 2.05, 95 % CI 1.69–2. 49). Conclusions. The data obtained indicate the importance of NAFLD, as well as metabolic risk factors for CND, in increasing the likelihood of developing a high degree of comorbidity, which must be taken into account when developing programs for the prevention and treatment.
The aim of the study was to evaluate predictors of cardiac conduction disturbance associated with increased risk of temporary and permanent pacemaker implantation after endovascular aortic valve replacement (TAVR). Material and methods. We analyzed patients who underwent surgical treatment for aortic valve replacement by endovascular treatment in Krasnoyarsk Regional Clinical Hospital from January 2018 to May 2023. The total number of people included in the study is 157. Results and discussion. The association between the occurrence of atrioventricular block of II–III degree, left bundle branch block and atrial fibrillation after TAVR implantation, which required temporary pacemaker implantation and permanent pacemaker implantation, was revealed. Atrioventricular block of grade II-III was first detected in 11 (13.3 %) patients after TAVR, left bundle branch block – in 22 (26.5 %) and atrial fibrillation – in 11 (13.3 %). The need for temporary pacing during TAVR was necessary in 35 (23.6 %) patients. 34 (23.0 %) patients had a temporary pacemaker placed within the first 2 days after surgical intervention and 1 patient (0.7 %) after 3 days. Regression analysis revealed 6 significant risk factors for temporary pacemaker implantation: left bundle branch block (p = 0.002), atrial fibrillation (p = 0.030), 1st degree atrioventricular block (p = 0.032), age (p = 0.012), female gender (p = 0.033) and history of acute myocardial infarction (p = 0.024). Permanent pacemaker implantation was performed in 7 (4.5 %) patients in the period from 4 to 20 days, including 6 (85.7 %) patients due to complete atrioventricular block and 1 (14.3 %) patient due to sinus node dysfunction. Permanent pacemaker was implanted to five (3.2 %) patients in the period from 6 months to 3.6 years, including 3 (1.9 %) patients due to complete atrioventricular block and 2 (1.3 %) patients due to sinus node dysfunction. Regression analysis revealed 2 significant risk factors for permanent pacemaker implantation: presence of atrial fibrillation before surgical intervention (p = 0.002; r = 0.160) and presence of left bundle branch block before TAVR (p = 0.037; r = 0.108). Conclusions. Identification of predictors of atrioventricular block of II–III degrees after TAVR will facilitate timely temporary pacing and permanent pacemaker implantation to prevent complications due to bradyarrhythmias.
The purpose of the study is to study the presence and characteristics of socio-psychological problems in adolescents with uncontrolled bronchial asthma (BA). Material and methods. We examined 212 adolescents with BA – patients of the pulmonary allergy center: 90 people with uncontrolled BA (the main group), 22 – with partially controlled asthma and 100 – with controlled asthma (the comparison groups); 136 (64.2 %) boys and 76 (35.8 %) girls; age 14 [13; 15] years (median [lower quartile; upper quartile]). The characteristics of prosocial behavior, the presence and severity of emotional disorders were studied. The values of the total score of the scales of the psychometric questionnaire used (Strengths and Difficulties Questionnaire, SDQ test) were determined. The indicators were assessed in the main and comparison groups, including taking into account age and gender. Results. In the vast majority of those examined, the characteristics of both scales of the questionnaire, regardless of the controllability of asthma, gender and age of adolescents, did not deviate from the norm. The second and third ranking places were occupied by borderline and deviating indicators, respectively. The average values of the total scores of the questionnaire scales were higher in adolescents with uncontrolled BA, both boys and girls. Conclusions. It is necessary to conduct further research aimed at diagnosing socio-psychological problems associated with uncontrolled BA for their timely correction in order to achieve control over the course of asthma, increase the effectiveness of treatment and improve the prognosis in adolescents with this pathology.
PREVENTIVE MEDICINE
Correction of behavioral risk factors (BRFs) as the basic basis of systems for the prevention of chronic non-communicable diseases for various population groups is one of the urgent tasks in the field of public health. Aim of the study was to investigate the prevalence of BRFs for cardiovascular diseases (CVD) among bearing production workers for the subsequent development of preventive measures. Material and methods. A sociological study of behavioral lifestyle factors contributing to the development of CVD (smoking, alcohol consumption, unhealthy diet, low physical activity, irresponsible medical behavior) was carried out in a group of bearing production workers (n = 382), taking into account gender and age differences. Results and discussion. The prevalence of smoking was 39.7 %, with a higher proportion of men smoking than women (42.8 and 22.9 %, respectively, p < 0.001). Alcohol (in moderate quantities) is consumed by 71.5 % of respondents, statistically significantly more often (p < 0.001) by men (75.8 %) than women (58.7 %). The prevalence of physical inactivity was 10.64 % and was more pronounced (p = 0.011) among women compared to men (15.0 and 7.4 %, respectively) and among young people (18–39 years old) compared to middle-aged people (40–65 years old) (p = 0.005). The majority of study participants (82.2 %) do not adhere to healthy eating rules (52.4 % men, 35.8 % women). Insufficient consumption of vegetables and fruits was found (in 30.0 and 34.0 %, respectively), fish (in 80 %), olive oil (in 100 % of those surveyed). 90 % consume excess salt. Low preventive medical activity of workers was revealed, manifested in an unreasonably high assessment of their own health, refusal to see a doctor for therapeutic purposes, self-medication, and neglect of preventive medical examinations. Conclusions. The results of the study indicate the priority of the population direction of preventive measures aimed at correcting the behavioral risk factors of CSD in the working population and increasing motivation for a healthy lifestyle and health-saving behavior.
Epidemiological studies describing the effects of parental radiation exposure on the health of children are highly contradictory. Aim of the study was to analyze the general mortality of offspring whose parents were exposed to occupational radiation at Mayak, the first nuclear power plant in Russia. Material and methods. A retrospective analysis was conducted in a cohort of 19 999 offspring born in 1949–1973, of which 12 836 were born in families of Mayak workers and 7163 were born from non-irradiated parents. General mortality was analyzed taking into account sex, calendar period, nosologies, and doses of external gamma irradiation of the gonads before conception. The standardized mortality ratio (SMR) was calculated in comparison with the national standard, the relative risk (RRisk) was estimated taking into account disease classes and the excess relative risk (ERRisk) with a 95 % confidence interval taking into account the doses of external gamma irradiation of the gonads. Results and discussion. In the main group, 2758 deaths have been registered for the period 1949–2020 (214.9 per 103), which is significantly less than in the comparison group (1689 cases, 235.8 per 103) (p = 0.0006). The most frequently observed diseases were “Injuries and poisoning”, “Diseases of the circulatory system” and “Malignant neoplasms” without significant differences between the groups. The risk of infectious pathology, “Certain conditions of the perinatal period” and “Respiratory diseases” in the comparison group was significantly higher than in the main group. Overall, the RRisk of death was higher in the comparison group for female offspring – 0.78 (0.69–0.88) and for both sexes – 0.89 (0.83–0.95). In many categories of parental age, there was a clear predominance of mortality in the comparison group. The SMR analysis showed that the general mortality from all causes among female offspring in the main group and among male offspring in both groups was statistically significantly lower than in the Russian Federation. The calculation of the ERRisk did not reveal an excess of risk coefficients either overall or in different dose categories. Conclusion. The study results did not indicate an increased risk of death among the offspring of individuals exposed to occupational radiation. Taking into consideration the relatively young age of the observed cohort, further epidemiological monitoring is required.
HEALTHCARE MANAGEMENT
Factors affecting the quality of follow-up (FU) of patients with arterial hypertension (AH) have been evaluated in several large-scale studies by Russian scientists. It was found that the indicators of the process and results of medical care for dispensary patients with AH often did not correspond to the conventional benchmark indicators. The purpose of the study was to identify structure, process, and performance indicators that negatively affect the quality of physician FU of AH patients. Material and methods. The study was performed according to the results of 2022. The level of knowledge of doctors, the scheme of the electronic outpatient card, and equipment for ultrasound diagnostics were studied as structural parameters. To assess the process characteristics, information on home blood pressure (BP) monitoring, patients’ adherence to treatment, availability of current analysis of the FU process were used. Performance indicators included information on normalization of BP and lipid level during the year, about stabilization, regression of the degree of left ventricular hypertrophy and carotid atherosclerosis. The sample of respondents, outpatient records was formed by random method. Results. 58.3 % of respondents were not informed about the possibilities of drug therapy to prevent the damaging effect of AH on target organs. The electronic outpatient cards lacked the templates “Follow-up”, “Stage discharge summary”. The available medical equipment met the needs of FUs by about 50 %. Information on home BP monitoring and patients’ adherence to therapy was available in 8.0 % of cases. Current summarization of FU was performed in 10.0 % of patients, assessment of lipid content dynamics, degree of left ventricular hypertrophy and carotid atherosclerosis was not performed in any case. Data on normalization of BP and lipid levels, data on stabilization, regression of left ventricular hypertrophy and carotid atherosclerosis during a year were actually absent. Conclusions. The identified indicators of structure, process and performance of DN are a probable cause of unsatisfactory quality of physician follow-up of AH patients.
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