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Acta Biomedica Scientifica

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Vol 9, No 1 (2024)
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DEPUTY EDITOR IN CHIEF’S PREFACE

INTERNAL DISEASES

12-22 567
Abstract

Lysophosphatidic acid (LPA) is a biologically active lipid mediator that regulates a number ofsignaling pathways involved in the pathogenesis of bronchial asthma. Attention to studying the relationship of LPA with LPA receptors (LPARs) and ion channels with transient receptor potential (TRP) is caused by their role in the initiation and development of bronchial obstruction, which suggests the development of new effective strategies for the treatment of bronchial asthma through blocking LPA synthesis and/or regulation of the activity of the ligand-receptor relationship.

The aim of the review. To summarize ideas on the role of lysophosphatidic acid and its receptors in the pathogenesis of bronchial asthma based on the analysis of articles published in English in 2020–2023 from the PubMed database.

Conclusion. The review summarizes recent literature data on the chemical structure, biosynthetic pathways and LPA receptors. It presents the information on the role of LPA, LPARs andTRP channels inthepathogenesis of bronchial asthma; summarizes the bronchial asthma therapeutic strategies targeting LPA, LPARs, andTRP channels. The review highlights not only a new perspective on understanding the mechanisms of initiation of asthmatic reactions, but also possible ways to manage them at the stage of correction of their development.

DEMOGRAPHY

23-31 894
Abstract

Background. The increasingly complex structure of modern society and systemic changes associated with the processes of digitalization and mediatization are raising the issue of preserving the health of the younger generation, which is the most receptive and vulnerable group to external impact.

The aim of the study. Based on survey data, to carry out an analysis of social factors influencing the development of eating disorders in girls.

Materials and methods. The method of collecting information was an online survey of girls aged 18 to 25 years old, conducted in Yekaterinburg in the spring of 2023 (n  =  205). Using in-depth interviews, 8  girls were interviewed to  clarify the  social factors in the formation of eating disorders.

Results. In girls’ assessments, distorted body image, fear of weight gain, and orthorexia are the signs of eating disorders. Social factors influencing the formation of  an  ideal body image and  eating disorders are  social media, circle of  contacts, as well as the external environment, which causes psychological and physical stress. Despite the negative perception of the content of communities promoting anorexic bodies, girls are well aware of the published materials. The main tool for achieving the standard model of a girl’s physicality is dietary practices, food restrictions and calorie counting, despite the recognition of the negative consequences of their use.

Conclusion. Eating behavior for girls is one of the leading tools for achieving an ideal body, ideas about which are formed today by social media, as well as the immediate social environment, including the  opposite sex. Communities on  social networks can serve as  a  source for  development of  deviant eating attitudes, on  the  one hand, and a real driving force in providing assistance and support to young people with signs of eating disorders, on the other hand. We believe that online consultations with specialists and the development of a parental culture of health protection can have a significant impact on the development of harmonious, health-protecting eating habits.

CARDIOLOGY

32-41 1044
Abstract

The role of arginine in the development of primary arterial hypertension continues to be clarified up to the present moment. During natural metabolic processes in cells, methylated forms of arginine are produced – symmetric (SDMA) and asymmetric (ADMA) dimethylarginine. ADMA is a nitric oxide synthase inhibitor and is now considered a well-established marker for endothelial dysfunction. SDMA is not a nitric oxide synthase inhibitor, but may indirectly reduce nitric oxide production through competitive interaction with cellular L-arginine.

Currently, arginine preparations are practically not used for the treatment of primary arterial hypertension. This was the rationale for the given scientific review. The article summarizes the information available in the literature (2018–2022) on the pathogenetic mechanisms of  the  relationship between arginine and  the  development of impaired vascular tone. We used PubMed and RSCI databases for our review. Using keywords, 1784 publications were found over the past 5 years. The final selection criteria were time frame and matching keywords. The review provides data on the increased ADMA concentrations in experimental hypertensive animals and individuals with essential hypertension. The role of arginine metabolites in the genesis of endothelial dysfunction and arterial hypertension and the prospects for the therapeutic use of this compound are discussed.

42-52 565
Abstract

Background. Increase ofthe epicardial adipose tissue (EAT) thickness isassociated with development of inflammation and cardiovascular complications, however, there is no data on the relationship between EAT thickening and the number of immunosuppressive regulatory T lymphocytes.

The aim. To study the number of circulating T regulatory lymphocytes and nuclear translocation ofthe FoxP3 transcription factor in patients with stable coronary heart disease (CHD) depending on the epicardial adipose tissue thickness.

Materials and methods. We examined 30 patients with chronic stable CHD. The EAT thickness was measured by echocardiography. Patients were divided into groups depending on the presence and absence of EAT thickening above 5 mm (groups 1 and 2, respectively). Imaging flow cytometry was used to determine the number of T regulatory lymphocytes and the level of FoxP3 nuclear translocation. The concentration of cytokines and high sensitivity C-reactive protein (hsCRP) was determined using enzyme-linked immunosorbent assay in blood serum.

Results. Anthropometric indicators of obesity and the severity of atherosclerosis were comparable between groups. In group 2, there was an increase in low-density lipoprotein cholesterol concentration (p = 0.043), ratio of low-density lipoprotein cholesterol tohigh-density lipoprotein cholesterol (p = 0.017) and the concentration ofhsCRP (p = 0.044) andIL-1β (p = 0.005), adecrease in the number and relative count of Tregulatory lymphocytes (p = 0.020 andp = 0.026, respectively), aswellas thenumber of cells withFoxP3 nuclear translocation (p = 0.018) compared togroup1. According tomultiple logistic regression, the concentration ofhsCRP, IL-1β and T regulatory lymphocytes relative count in total were the predictors of EAT thickening (accuracy 80 %; sensitivity 75 %; specificity 84,6 %; AUC = 0.89).

Conclusions. Thickening of epicardial adipose tissue inpatients withcoronary heart disease is associated with a decrease in the number of T regulatory lymphocytes andFoxP3 nuclear translocation inthem in presence of comparable anthropometric parameters of obesity and the severity of coronary atherosclerosis.

MICROBIOLOGY AND VIRUSOLOGY

53-63 554
Abstract

Klebsiella pneumoniae (Kp) species complex is a genetically and ecologically diverse group of bacteria that causes a wide range of infections in humans and animals.

The aim. To carry out biological characterization and genotyping based on the study of different loci of Klebsiella pneumoniae clinical isolates.

Materials and  methods. The  object of  the study was  three Klebsiella pneumoniae clinical isolates from different biotopes of patients from a regional children’s multidisciplinary hospital. We used a complex of bacteriological, molecular genetic and bioinformatic methods. Genotyping of the isolates was carried out using the Pasteur Institute service for strains of the K. pneumoniae species complex.

Results. All strains were sensitive to antimicrobial drugs from carbapenem (imipenem, meropenem) and  tetracycline groups (tigecycline), and  demonstrated high sensitivity to the Klebsiella polyvalent bacteriophage. The antibiotic resistance of the Kp ODKB-16 and ODKB-81 isolates to seven and eight antimicrobial drugs, respectively, was registered

Based on  the results of  multi-locus sequence typing, all  strains were assigned to  Kp1  phylogroup, K2  type and  differed in  sequence type, scgMLST629  profile and KL type. Kp ODKB-16 strain was identified as ST-65, scgST-11107, KL2; ODKB-07 strain – as ST-219, scgST-6401, KL125KL114; ODKB-81 strain – as ST-86, scgST-2800, KL2KL30. The virulence gene clusters AbST, CbST, YbST, SmST, and RmST have been characterized only in the genome of the Kp ODKB-16 isolate, allowing it to be characterized as highly virulent with multidrug resistance (MDR). Additionally, genes responsible for the synthesis of types 1 and 3 fimbrial adhesins were registered in all strains, and ter operon loci were identified only in Kp ODKB-16. Resistome analysis showed that all strains had 2b genotype. Plasmids were found in the genomes of Kp ODKB-81 (IncI2) and ODKB-16 (IncFIA + IncFIB + IncHI1B).

Conclusion. We used a comprehensive framework for genomic taxonomy of clinical isolates, which can contribute to the unification of global and regional peculiarities of the developing and microevolution of bacterial pathogens.

MORPHOLOGY, PHYSIOLOGY AND PATHOPHYSIOLOGY

64-72 2872
Abstract

Background. Indole and its derivatives are widely used in all areas of pharmaceutical production. The toxicometry of indole compounds has been sufficiently studied. At the same time, there is still no information on the toxic effect on individual organs and systems during long-term intake of most compounds.

The aim. To carry out an experimental study of the toxic effect of indole and its derivative 1-benzylindole on the functional state of the heart and blood values.

Materials and  methods. The  work was  carried  out on  46  white rats, divided into groups: control group (n = 22); animals receiving indole once a day for 1 month (n = 12); animals receiving 1-benzylindole once a day for 1 month (n = 12). The substances were administered intragastrically 5 days a week. The condition of the animals was assessed by integral parameters, peripheral blood parameters and biochemical serum tests, and morphological data.

Results. Administration of indole and 1-benzylindole caused an increase in the electrical activity of the atria, a decrease in the duration of the QRS complex, and a statistically significant decrease in  blood pressure and  body temperature compared to the control group. The intake of indole and 1-benzylindole decreased the number of red blood cells and hemoglobin, increased the activity of aspartate aminotransferase and alanine aminotransferase, and increased the concentrations of urea, total cholesterol and triglycerides in the blood. Against the background of long-term exposure to indole and 1-benzylindole, dystrophic disorders, hypertrophic and atrophic changes in individual fibers with a pronounced congestion of the microcirculatory vessels were revealed in the heart of rats.

Conclusion. Indole and 1-benzylindole in case of long-term intake lead to functional disorders of the cardiovascular system, which cause the development of arterial hypertension, coronary heart disease, and atherosclerotic vascular lesions. Preventive measures in industries with possible contact with indole and its derivatives should include regular medical examinations of workers with mandatory monitoring of electrocardiography and advanced indicators of general and biochemical blood tests.

73-84 482
Abstract

Wound healing is  a  spatiotemporal and  highly regulated process that is  divided into  four continuous and  overlapping stages: hemostasis, inflammation, repair (proliferation) and remodeling. All stages are controlled by various body systems and depend on the regulatory role of immune and stem cells. Despite significant progress in  understanding the  cellular and  molecular mechanisms of  inflammation, the role of the immune microenvironment in the regeneration process remains unclear. On the one hand, the critical importance of the cellular and molecular components of the immune system in the reparative response of tissues, including the degree of scarring, restoration of structure and function of organs, has been proven, and on the other hand, little data is presented on the loss of tissue regeneration ability associated with  the  immune competence evolution. The  review presents the  key cellular and molecular mechanisms of the immune response and of the stem cells participation soft tissue repair process during their interaction with the extracellular matrix. An analysis of the latest scientific data on the participation of components of  the  immune microenvironment and  of  stem cells in  soft tissue repair process was  carried  out based on  the  publications presented in  Google Scholar, Medline, PubMed, Scopus and Web of Science. It has been shown that the nature of this response and its duration have a significant impact on the outcome of repair – from incomplete recovery (scarring or fibrosis) to full regeneration. It is indicated that various types of immune and stem cells take part in the soft tissue repair and remodeling processes, and their interaction must be precisely controlled. The review data may provide the basis for the development of new therapeutic approaches for soft tissue repair through immune regulation or the use of stem cells and extracellular vesicles.

85-95 462
Abstract

Background. Studying the functional state of the body of adolescents when they preform cognitive activity using electronic devices is of great importance due to the introduction of information and computer technologies into the educational process. Identifying the characteristics of the reactivity of students’ bodies when performing cognitive activities in  a  digital environment will contribute to  both optimization of learning and health protection.

The aim. To study the autonomic regulation of heart rate, electrodermal activity, cerebral circulation and the level of cortisol in saliva when adolescents performed a cognitive test on electronic devices (tablet, laptop) and on paper.

Materials and  methods. Using analysis of heart rate variability, electrodermal activity, rheoencephalography and enzyme-linked immunosorbent determination of cortisol in saliva, цe examined 48 adolescents while performing a cognitive activity on electronic devices.

Results. When adolescents perform cognitive activity using electronic devices, we can register changes in heart rate variability, electrodermal activity and cerebral circulation. Cognitive activity in a digital environment causes an increase in sympathetic effect ontheheart rate with adecrease inparasympathetic activity, anincrease inthe integrative indicator ofgalvanic skin response, invascular tone and adecrease in the cerebral blood flow intensity. One in four adolescents experiences anticipatory stimulation of the endocrine system before taking a cognitive test. Correlation analysis revealed alarge number of correlations between the studied indicators both in the initial state and during cognitive activity.

Conclusion. A large number of correlations, both in the initial state and during the cognitive test, between heart rate variability and cortisol concentration, cerebral circulation parameters indicate the preservation of a rigid system of neurovegetative and humoral regulation of heart rate when using electronic devices compared to paper-based media.

ONCOLOGY

96-106 624
Abstract

Background. Treatment for malignant brain gliomas includes surgery, radiation therapy, and chemotherapy with temozolomide. However, this complex treatment does not prevent tumor relapses and progression, which is caused by the activity of tumor cells and a high mutational burden. Researchers are experimenting with different intensity of focused ultrasound (FUS) in the treatment of glioblastoma (GBM). FUS has shown encouraging results in clinical studies.

The aim of the study. This review presents brief information on the history of the development of  the studied method, the  results of  its  application in  experiments and   clinical trials, as  well  as the  main possible directions for  its  implementation in  neuro-oncology, in  particular, for  the  treatment of  glioblastomas, depending on parameters, including frequency, power, pulse duration and duty cycle.

Methods. We carried out an analysis and interpretation of existing publications; for the search, we used the PubMed database and the keywords “focused ultrasound, glioma, HIFU, LIFU”, as  well  as Yandex and  Google search engines and  the  same keywords in Russian.

Results. Low-intensity FUS can be used to temporarily open the blood-brain barrier (BBB), which limits the diffusion of most macromolecules and therapeutic agents into the brain. High-intensity FUS can cause tumor ablation due to a hyperthermic effect, and also stimulate an immunological attack of tumor cells, activate sonosensitizers to exert a cytotoxic effect on tumor tissue, and can increase the sensitivity of tumors to radiation therapy. Histotripsy causes tumor ablation through acoustic cavitation.

Conclusion. Focused ultrasound is a promising potential treatment for gliomas. Further study in the form of clinical trials should determine the optimal ultrasound parameters to achieve effective treatment for patients with malignant brain tumors.

107-115 753
Abstract

Aspects of  modern medicine cover a  huge number of  diseases, including postcastration syndrome, which occurs as a result of endocrine testicular dysfunction in men. The relevance of this condition is great, since it is caused by many reasons and is the basis for an inferior life in men. The review shows the impact of this disease on the quality of life and the methods for its treatment. When writing this review, we used data on castration methods and its correction based on materials published in the eLibrary and PubMed databases. The search was carried out using the keywords: “castration”, “post-castration syndrome”, “prostate cancer”. With castration, there is a decrease in serum testosterone levels, as androgens stimulate the growth of prostate cancer. Today, hormone therapy is an alternative to castration in the treatment of prostate cancer. Surgical castration is the gold standard; it can suppress tumor cell proliferation and induce tumor apoptosis, but it causes significant impairment of  quality of  life. The  article presents characteristics of  medications, indications, contraindications and side effects of hormone therapy. The quality of life of men with testosterone deficiency is clinically associated with the development of metabolic syndrome, manifested by obesity, hepatic steatosis and type 2 diabetes mellitus. Numerous studies by domestic and foreign scientists confirm the effect of castration in men on their body, which increases the risk of stroke, depression, cognitive disorders and Alzheimer’s disease. Thus, despite the significant advances of modern medicine in the treatment of malignant diseases of prostate, post-castration syndrome remains a completely unexplored problem, which indicates the need for further study and the development of effective therapy.

OPHTHALMOLOGY

116-128 636
Abstract

Background. Melatonin is an endogenous regulator of intraocular pressure (IOP), but its effectiveness as a drug for glaucoma treatment is limited.

The  aim of  the  study. To develop and  to  validate a  virtual screening method to identify bioisosteric analogs of melatonin that are promising for study as agents that reduce intraocular pressure.

Results. A database containing structural and experimental affinity information for 48 individual reference compounds was created. Risk assessments for mutagenic, carcinogenic, irritant and reproductive toxicity were performed in DataWarrior based on substructural analysis and identification of fragments that are markers of relevant toxicity. A virtual screening of 2457 structures was carried out and 25 compounds from the selected ones were experimentally studied for their effect on intraocular pressure (IOP) in intact rats. 10 of the 25 prioritized compounds were found to significantly reduce IOP; compound RU-398 reduced IOP by 40 %, K-165 – by 40.9 %, and RU-615 reduced glaucoma by 33.3 %.

Conclusion. The  effectiveness of  virtual screening after experimental validation was 40 %. The identified active compounds are promising for further study and development as the agents for the treatment of glaucoma.

129-135 401
Abstract

Background. Accommodation disorders in  children with  hypermetropia is  one of  the  main factors in  emmetropization disorders and  maintenance of  image defocusing. The most severe changes in accommodation are observed in children with anisometropia and hyperopia.

The  aim of  the work. To  evaluate the  changes in  the  accommodative function of the eye in children with hyperopia, amblyopia, who underwent refractive laser surgery (RLS), as  well  as in  children with  spectacle and  contact lens correction in combination with pleoptic treatment.

Methods and materials. Group 1 consisted of 30 children after RLS; group 2 consisted of 29 children who had spectacle correction; group 3 consisted of 26 children who had soft contact lens correction; all children received pleoptic treatment. Clinical examination included the analysis of objective reserves of relative accommodation (RRA) and objective accommodative response (OAR) with an open field autorefractometer, and the results of accommodation measurement.

Results. In 1.5 years, statistically significant changes were observed in the coefficient of accommodation response (CAR) of the amblyopic eye between the groups 1 and 2 – 0.12 ± 0.02 and 0.00 ± 0.1 relative units, respectively (p = 0.01). Similar statistically significant changes were obtained in OAR and objective RRA of the amblyopic eye. OAR in the group 1 was –2.1 ± 0.67 dpt, in the group 2 – –1.38 ± 0.19 dpt (p = 0.01). At the end of the observation, the OAR in the group 1 was –2.1 ± 0.67 dpt, the objective RRA – –2.1 ± 0.67 dpt; in the group 2 the OAR was –1.38 ± 0.19 dpt (p = 0.01), the objective RRA – –1.38 ± 0.19 dpt (p = 0.01). There were no statistically significant changes in these parameters of the amblyopic eye between the groups 1 and 3.

Conclusion. There was an  improvement of  accommodation disorders in  children with anisometropia, hyperopia and  amblyopia after refractive laser surgery and in children with contact lens correction. Due to a decrease in the refractive indices of the amblyopic eye, the values of CAR, OAR and objective RRA after refractive laser surgery tended to be closer to the normal values.

136-141 477
Abstract

The  aim. To  present a  clinical case of  surgical treatment of  parasitic invasion of the vitreous body caused by dirofilaria.

Material and methods. One patient with intraocular dirofilariasis got operated underwent surgical treatment including vitrectomy, phacoemulsification with implantation of an intraocular lens. At the stage of vitrectomy, a whole helminth was removed from the vitreal cavity using collet tweezers for subsequent typing. The uncorrected visual acuity of the right eye at the time of treatment was 0.4, of the left eye – 0.45.

Results. The  postoperative period had no  signs of  an  active inflammatory reaction. 4 months after surgical treatment, at a follow-up visit, visual acuity of the left eye reached 1.0. According to the parasitological study, a female Dirofilaria repens was identified. In the postoperative period, the areas of pronounced chorioretinal atrophy in the peripheral parts of the retina were visualized, which may be a consequence of mechanical contact of the parasite or the toxic effects of its metabolic products.

Conclusion. This  clinical example demonstrates the  possibility of  infection with the  ocular form of  dirofilariasis in  a  region that is  atypical for  the  presence of this helminth. Despite the positive outcome of the disease, in the presented patient, the long-term presence of the parasite in the vitreal cavity led to the formation of chorioretinal atrophy in the peripheral retina, which confirms the need for timely diagnosis and surgical treatment.

142-150 441
Abstract

Demodicosis occupies a leading position among all dermatoses. According to ICD-10, it is not distinguished as a separate disease; it belongs to the class of parasitic diseases. The relevance of studying the problem of ophthalmodemodecosis is caused by its high prevalence and contagiousness, chronic course, an open issue of the role of the Demodex mite in the occurrence of inflammatory eye diseases, as well as the lack of effective methods for treating and preventing this pathology. In addition, Demodex causes discomfort and contributes to the occurrence of cosmetic defects, which in turn worsens the patient’s quality of life.

The aim. To present a review of the literature data and our own results of laboratory diagnostics of ophthalmodemodecosis.

Materials and methods. The article presents clinical cases of demodectic eyelid lesions with different disease outcomes in case of similar treatment. Laboratory diagnostics included drawing up an acarogram. Epilated eyelashes were used as a material for detecting mites on eyelids. Counting of individuals was carried out using light microscopy; all forms of mite development were taken into account. The work presents the statistics on the frequency of examination of patients with suspected demodicosis at different times of the year, confirming the seasonality of this disease. The literature review included data on the history of studying the Demodex mite, existing hypotheses and theories about its pathogenesis, as well as the information on domestic and foreign methods of treating ophthalmodecosis, including modern hardware techniques.

Results. Demodex mites play a significant role in the development of blepharitis and blepharoconjunctivitis. It is important to consider that demodicosis can occur against the background of inflammatory eye diseases of another etiology. Therapy for  ophthalmodemodecosis currently remains complex, lengthy and  ineffective. When assessing the results of an acarogram, any detected stages of a mite are clinically significant, and there isn’t a direct relationship between the number of detected mites and the severity of clinical manifestations in all cases.

PSYCHOLOGY AND PSYCHIATRY

151-160 732
Abstract

Background. Math anxiety is a state of fear and anxiety that an individual experiences when interacting with mathematical problems. Currently, there is a lack of questionnaires to measure mathematical anxiety for Russian-speaking schoolchildren.

The aim. The study analyzed the factor structure and psychometric properties of the Abbreviated Math Anxiety Scale (AMAS).

Materials and methods. The study involved 1,198 schoolchildren in grades 10–11. The psychometric properties of the AMAS were analyzed.

Results. AMAS demonstrated bifactor structure: subscales of Learning Math Anxiety (LMA) and Math Evaluation Anxiety (MEA) and general scale of Math Anxiety. The bifactor model demonstrated the best fit indices. Analysis confirmed reliable internal consistency (Cronbach’s alphas for LMA  =  0.82, MEA  =  0.75, total AMAS  =  0.95). External validity of AMAS has been confirmed. LMA showed lower scores than MEA. The distribution of scores on the general AMAS scale was shifted to low values. Girls showed higher scores on all scales of the questionnaire. The analysis also confirmed measurement invariance for both boys and girls.

Conclusion. Based on the analysis, we can conclude that the AMAS is a valid tool for assessing mathematical anxiety in high school students.

161-176 571
Abstract

Studying stress factors of childbirth intentions is an important parameter in population development policy making. There is no data on the comparison of the relative importance of different types of determinants and stress inducing factors of parenting in the scientific literature.

The aim. To study the factors determining the ideas about the stressfulness of the parental role among modern youth.

Methods. The  sample consisted of  364  students with no  parenting experience. Three groups were identified, differing in their orientation towards having children: a group with a focus on single-child parenting (257 people); group with childfree focus (32 people); group with a focus on multi-child parenting (75 people). The following methods were used: socio-demographic questionnaire; “Parental Stress Scale” (J.O. Berry, W. Jones, 1995; adapted by Yu.V. Misiyuk, I.V. Tikhonova, 2022); “Intensive Parenting Attitudes Questionnaire (M. Liss, H.H. Schiffrin, V.H. Mackintosh, H. Miles-McLean, M.J. Erchull, 2013; adapted by Yu.V. Misiyuk, 2022); express version of the “World Assumptions Scale” (R. Yanoff-Bulman; modified by M.A. Padun, A.V. Kotelnikova; author’s semi-structured interview.

Results. We  analyzed the  ideas about  the  stress that  is  associated with fulfilling the  parental role. Parameters that potentially act as  the  factors determining the stressfulness of parenthood are considered. The specificity of ideas on parental stress and its determinants is analyzed in accordance with the dominant orientation towards childbearing.

Conclusion. Ideas about the stressfulness of the parental role are determined by objective (age, status of personal relationships, education) and subjective (assessment of family relationship, attitudes towards the need to stimulate the child’s development, essentialism and  satisfaction from  raising children) factors, but  subjective ones have the greatest weight. The specificity of the determination of ideas about parental stress depending on the orientation towards childbearing has been revealed.

PHARMACOLOGY AND PHARMACEUTICS

177-191 544
Abstract

Background. Determining changes in the content of monoamine neurotransmitters and their metabolites in brain structures is a necessary part of studying the pharmacodynamics of  antiparkinsonian drugs. A  method for  the  joint determination of norepinephrine, adrenaline, dopamine, serotonin, 5-hydroxyindole-3-acetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid in rat brain tissue has not previously been developed.

The aim of the study. To develop and to validate a method for the quantitative determination of norepinephrine, adrenaline, dopamine, serotonin, 5-hydroxyindole3-acetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid in rat brain tissue using high-performance liquid chromatography in combination with tandem mass spectrometry (HPLC-MS/MS).

Materials and  methods. A method for  determining monoamine mediators and their metabolites was developed using the HPLC-MS/MS method. Brain tissue homogenates were prepared using a  mechanical hand-operated homogenizer. The  effect of  various antioxidants on  the  stability of  norepinephrine, adrenaline, dopamine and 3,4-dihydroxyphenylacetic acid in the test samples was studied.

Results. Chromatographic separation of sample components was carried out using two Synergi Max RP (20 × 2.0 mm, 2.5 µm) and Synergi Fusion RP 80Å (250 × 4.6 mm, 4 µm) chromatographic columns. Elution was carried out in a gradient mode using a  mobile phase based on  methanol and  a  0.1% solution of  formic acid in  water. To prepare homogenate batches, the samples were diluted with a solution of internal standards in methanol. A 5% aqueous solution of ascorbic acid was chosen as an antioxidant stabilizer.

Conclusion. The  developed methodology has been fully validated and meets the requirements of Russian and international guidelines. The chosen stabilization method allows samples of brain homogenates to be stored for 30 days after collection.

PHTHISIOLOGY

192-202 531
Abstract

Background. Despite the visible successes of domestic phthisiology at the present time, the problem of medical rehabilitation of patients with tuberculosis remains relevant. In recent years, approaches to medical rehabilitation of patients with various diseases have changed significantly, which entail the need to consider a complex of rehabilitation measures for patients with tuberculosis from the perspective of the Procedures for organizing medical rehabilitation in adults and children and their integration into phthisiatric practice.

The aim. To study the organizational aspects of medical rehabilitation of patients with respiratory tuberculosis in the world and the Russian Federation.

Methods. We carried out an analysis of domestic and foreign literature, regulatory documents on the organization of rehabilitation for tuberculosis patients for 2018–2023 in electronic databases PubMed/Medline, Google Scholar using terms “tuberculosis, pulmonary/rehabilitation” in English and Russian languages.

The  results show a  growing amount of  factual information demonstrating the positive effect of pulmonary rehabilitation in patients with respiratory diseases, including tuberculosis. The analysis revealed defects in the organization of the medical rehabilitation system in the structure of medical care for tuberculosis patients in the Russian Federation. This concerns problems of routing, phasing, organizational models, human and material resources, standardization of the main components of the rehabilitation process, the significance and effectiveness of certain rehabilitation measures, which leads to low availability of rehabilitation care for tuberculosis patients. Deficiencies in the regulatory framework prevent the integration of medical rehabilitation into the practice of TB services.

Conclusion. Modern issues of organizing rehabilitation care for patients with tuberculosis require further study and  improvement. The  development of  a  system of medical rehabilitation of patients with tuberculosis helps to increase the effectiveness of treatment, to reduce the number of complications, disability, mortality due to tuberculosis, and to increase the duration and quality of life of patients.

EXPERIMENTAL RESEARCHES

203-213 415
Abstract

Background. There  is growing interest in  determining the  role of  melatonin in the regulation of proliferation and apoptosis of ovarian cells at various diseases and destabilizing influences. It is believed that the choice between the implementation of  a  cell  death or  survival program determines the  ratio of  anti-apoptotic and pro-apoptotic proteins.

The aim. To identify the effect ofmelatonin onthe expression ofanti-apoptotic Bcl-2 and pro-apoptotic Bad and the Bcl-2/Bad ratio in the ovarian luteocytes of Wistar rats in the acute (day 3) and recovery (days 7 and 14) periods after a single exposure to experimental hyperthermia.

Methods. Warming up took no  more than 17  minutes. Melatonin was injected subcutaneously (0.1 mg in 0.2 ml of physiological solution) for 3 days after experimental hyperthermia. Comparison groups included rats with physiological solution injection (control) and  animals after experimental hyperthermia + physiological solution injection. The Bad and Bcl-2 expression was determined immunohistochemically on days 3, 7 and 14 after experimental hyperthermia + physiological solution or melatonin injection.

Results. On the day 3 after experimental hyperthermia, the effect of the hormone was not detected. A week after experimental hyperthermia + melatonin injection, the Bad expression area decreased more significantly than in rats after experimental hyperthermia + physiological solution injection, which led to an increase in Bcl-2/ Bad ratio. This indicated an increase in anti-apoptotic protection, blocking the development of the internal apoptosis pathway at this time. 2 weeks after experimental hyperthermia + physiological solution injection, the Bcl-2 area decreased more significantly than the Bad area. As a result, the Bcl-2/Bad ratio decreased almost 2-fold compared to the control group. This indicated the activation of the “mitochondrial branch” of luteocyte apoptosis. 2 weeks after experimental hyperthermia + melatonin injection, the Bad and Bcl-2 areas decreased synchronously, which restored Bcl-2/ Bad to control values.

Conclusion. The  melatonin injection after experimental hyperthermia shifts the ratio of Bcl-2/Bad expression areas towards an increase in anti-apoptotic Bcl2 already a  week after the  recovery period and  promotes earlier normalization of Bcl-2/Bad to physiological levels (as early as 2 weeks after experimental hyperthermia + melatonin injection).

214-221 398
Abstract

Background. The presence of increased manganese concentrations in soils and water intakes areas for drinking and household purposes in a number of the Russian Federation subjects indicates the  chronic influence of this metal on all segments of the population. This situation is aggravated by violation of the optimal nutrition principles, which leads to changes in the organism absorption of micronutrients. In this regard, the study of the elemental status of an organism against the background of manganese exposure is of particular importance.

The aim. To study the effects of subchronic exposure to manganese on the mineral status of Wistar rats.

Materials and methods. To  conduct the study, 20  mature rats were selected, from which two groups were formed – control (n = 10) and experimental (n = 10). Animals in the control group received a general diet, animals in the experimental group received a diet with additional administration of manganese sulfate at a dose of 1433 mg/kg for 28 days. At the end of the preparatory period, blood and brain samples were taken to determine the content of chemical elements using inductively coupled plasma mass spectrometry and of metal-ligand manganese forms using high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry.

Results. It has been established that subchronic oral exposure to manganese leads to an increase in the content of this microelement in the blood serum and to a decrease in the levels of calcium, potassium, magnesium, iron and copper. In the cerebral cortex, the level of manganese, lead, mercury and strontium increases against the background of a decrease in iron and iodine levels. An increase in the gross content of manganese in blood serum leads to an overload of the main high-molecular carriers and initiates the formation of low-molecular forms of manganese.

Conclusion. Subchronic oral exposure to manganese leads to the accumulation of this microelement in the body of animals and to the development of an imbalance of a number of macro- and microelements.

222-232 430
Abstract

Background. It is known that the protective effect of adaptation and conditioning influence is weakened in animals with metabolic syndrome. Metabolic syndrome may be the basis for the failure of cardioprotection in clinical settings.

The aim of the study. To identify the relationship between disorder in carbohydrate and lipid metabolism and a decrease in the effectiveness of the infarct-limiting effect of moderate chronic normobaric hypoxia; to check the possibility of correcting reduced cardioprotection by normalizing carbohydrate and lipid metabolism.

Methods. The  study included 64  Wistar rats. Metabolic syndrome was  induced by feeding animals a high-carbohydrate, high-fat diet for 84 days. Chronic normobaric hypoxia was carried out for 21 days in the following mode: 12 % O2 : 0.3 % CO2. Metformin at  a  dose of  200  mg/kg/day or  PPARα agonist WY14643 at  a  dose of 1 mg/kg/day were added to the drinking water of rats with metabolic syndrome during adaptation period to hypoxia. A 45-minute coronary occlusion and 120-minute reperfusion were performed, and the infarct size was determined. Indicators of lipid and carbohydrate metabolism, leptin, and adiponectin were studied in the blood serum.

Results. The infarct-limiting effect of chronic normobaric hypoxia was weakened in animals with metabolic syndrome. Infarct size showed a direct correlation with decreased glucose tolerance and serum triglyceride levels. Using metformin therapy did not lead to the restoration of the infarct-limiting effect of chronic normobaric hypoxia, while the  normalization of  lipid metabolism with the  use of  the  PPARα agonist WY14643 corrected the  impairment of  adaptive cardioprotection in  rats with metabolic syndrome.

Conclusion. The  lack of  cardioprotection at  chronic normobaric hypoxia in  rats with  metabolic syndrome is  associated with  impaired carbohydrate and  lipid metabolism. The PPARα agonist restores impaired lipid metabolism and adaptive cardioprotection.

233-240 393
Abstract

The aim of the study. To assess the possibility of correction and prevention of behavioral disorders in rats with metabolic syndrome using a complex phytoadaptogen (CPA).

Material and methods. The experiment was carried out on 30 male Wistar rats randomized into 3 groups: group 1 – control; group 2 – metabolic syndrome (MS); group 3 – treatment of metabolic syndrome using CPA. In groups 2 and 3, animals were on a high-carbohydrate and high-fat diet for 16 weeks. Group 3 received CPA for 14 days in drinking water after 16 weeks of a diet. CPA consists of official tinctures of Glycyrrhiza glabra, Rhodiola rosea, Acantopanax senticosus at a ratio of 1:2:1. Behavior was analyzed through the “open field” test using Realtimer software (Open Science, Russia). Data were analyzed using GraphPad Prism 8.03 software (GraphPad, USA).

Results. The experiment proved that metabolic syndrome is accompanied by increased anxiety (decreased horizontal (p  =  0.017) and  vertical (p  =  0.017) motor activity) and fear (increased periods of immobility (p = 0.011)) in the open field. When corrected with a complex phytoadaptogen, the time spent in the open and closed arms of the maze did not differ statistically significantly from the values of similar control indicators.

Conclusion. Based on the data obtained in the group 3 (no statistically significant differences with control) – decreased manifestations of fear and anxiety (increased orientation and research activity) – we can talk about the effectiveness of complex phytoadaptogens as an anxiolytic. The mechanisms underlying this result remain to be explored, emphasizing the role of the autonomic nervous system, leptin and ghrelin in behavior and the influence of complex phytoadaptogens on them.

EPIDEMIOLOGY

241-250 581
Abstract

Background. Community-acquired pneumonia remains one of the most common and life-threatening forms of pathology among respiratory diseases.

The aim of the study. To identify the features of the epidemiology of communityacquired pneumonia in the conditions of mass immunization against pneumococcal infection in the Irkutsk region.

Materials and methods. We conducted a descriptive epidemiological retrospective study. We studied the incidence of community-acquired pneumonia (including community-acquired pneumonia of bacterial and viral etiology) and mortality from this disease in the Irkutsk region for 2011–2022 according to statistical reporting forms No. 2, No. 5, No. 6, C51.

Results. The incidence of community-acquired pneumonia during the observation period remained at a high level: the long-term annual average rate among the total population was 627.3 [467.8÷786.8]. At the same time, there was a persistent decrease in the incidence of community-acquired pneumonia of bacterial etiology (Tdecrease = 6.8 %). Incidence rates of community-acquired pneumonia of bacterial etiology were distributed unevenly over  the  years and  the  compared population groups. The highest levels were recorded in children in 2018–2019 – 12.3 [10.8÷13.8] and 19.3 [17.8÷20.8], respectively. A decrease in the mortality rate from community-acquired pneumonia among children, adults and in the general population in 2020 was  shown, with a  subsequent increase in  the  rate among adults and  the  general population by  2.5  times. Against the  background of  ongoing immunization of the population against pneumococcal infection, there is a statistically significant decrease in the incidence of community-acquired pneumonia, including communityacquired bacterial pneumonia, and mortality from community-acquired pneumonia among different population groups.

Conclusion. Despite the high incidence of community-acquired pneumonia, a statistically significant decrease in the incidence of community-acquired pneumonia of  bacterial etiology has been shown among children and  adults. The  decrease in mortality from community-acquired pneumonia has continued since the introduction of immunization against pneumococcal infection. The results of the study can be used to optimize epidemiological surveillance and epidemiological control of community-acquired pneumonia at the regional level.

HISTORY OF MEDICINE AND ANNIVERSARIES

251-258 587
Abstract

The article is dedicated to the 500th anniversary of the birth of the greatest physician and scientist of the 16th century Gabriele Falloppio (Fallopius), a  revolutionary morphologist who made an invaluable contribution to the development of science, and one of the founders of fundamental anatomy. Although Falloppio is primarily known as  an  anatomist who  described the  uterine (“fallopian”) tubes, his range of  interests was  much wider, and  his contribution to  anatomy was  substantially more  significant. Fallopius made many important discoveries in  anatomy, and a number of anatomical structures bear his name. Also, Gabriele Falloppio was a talented teacher and a renowned medical practitioner, surgeon and pharmacist. It  should  be especially noted that  Fallopius considered himself an  apprentice of  Andreas Vesalius. There  is no  data confirming the  fact of  their personal acquaintance, but there  is documentary evidence of  short-term correspondence between Fallopius and Vesalius. In  his  famous work “Anatomical observations” (“Observationes anatomicae”, 1561), Fallopius pointed  out Vesalius’ mistakes and  inaccuracies in  anatomical descriptions, subjecting his “De  humani corporis fabrica” to correct criticism. Vesalius’ reply with compliments to Fallopius as a scientist has been preserved. In any case, the undoubted fact is that Fallopius was an adherent of Vesalius’ methods in applied science and the teaching of anatomy, and consistently introduced them into practice throughout his life.



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