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Vol 105, No 6 (2024)

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Theoretical and clinical medicine

Laboratory and instrumental parameters associated with the long-term mortality risk in patients after myocardial infarction

Mushikhina N.A., Gorbatenko E.A., Teploukhova A.I., Yaroslavskaya E.I., Larionova O.N.

Abstract

BACKGROUND: The risk of death remains high in patients who survive 1 year after myocardial infarction (MI).

AIM: To identify the laboratory and instrumental parameters of myocardial remodeling associated with long-term mortality in patients 1 year after MI.

MATERIAL AND METHODS: The study included 184 patients who survived 1 year after MI. Group 1 included living patients who were followed up for 5 years after MI (n = 160). group 2 comprised patients who had died by the 5-year mark (n = 24). Inflammation and myocardial dysfunction biomarkers and echocardiographic parameters reflecting types of left ventricular remodeling, linear dimensions of cardiac cavities, wall thickness, chamber volumes, and systolic ventricular function were retrospectively analyzed. After analyzing the distribution of numerical data, the Student’s t-test or Mann–Whitney U test and χ2 test for categorical variables were applied. A logistic regression model was developed. This model was validated and assessed for reliability using the receiver operator characteristics curve, Hosmer–Lemeshow goodness-of-fit test, and bootstrap method.

RESULTS: Patients in group 2 were older (p = 0.007) and more likely to experience ST-segment elevation MI during hospitalization (p < 0.001). One year after the MI, a complex pattern of N-terminal brain natriuretic propeptide level changes was observed, with a decrease in group 1 and an increase in group 2. The end-diastolic volume index (p = 0.014) and left ventricular asynergy size were higher (p = 0.043) and the ejection fraction was lower (p = 0.015) in group 2 than in group 1. The model for predicting 4-year mortality in patients who survived MI during the first year includes parameters such as the left ventricular end-diastolic volume index, N-terminal pro-brain natriuretic peptide level, and presence of concentric left ventricular hypertrophy.

CONCLUSION: In patients who survive 1 year following MI, long-term mortality risk is associated with parameters reflecting left ventricular remodeling and heart failure development.

Kazan medical journal. 2024;105(6):869-878
pages 869-878 views

Left ventricular systolic function in patients with myocardial infarction and iron deficiency during correction with iron supplements

Khastieva D.R., Tarasova N.A., Valeeva I.K., Khasanov N.R.

Abstract

BACKGROUND: Iron deficiency is associated with worse contractile function of the heart in patients after myocardial infarction.

AIM: To study the contractile function of the left ventricle in patients with myocardial infarction and iron deficiency for 12 months while taking iron supplements.

MATERIAL AND METHODS: The study included 83 patients with myocardial infarction and iron deficiency. The average age was 62.0±11 years. The patients underwent drug correction of iron deficiency by parenteral administration of iron carboxymaltose or oral administration of iron sulfate. After 3 months, the patients were divided into two groups depending on the compensation of iron deficiency. The first group consisted of 58 (70%) patients with compensated iron deficiency, the second group — 25 (30%) patients with persistent deficiency. The patients underwent echocardiography with assessment of the left ventricular ejection fraction and the total index of its myocardial mobility in the first 24 hours after hospitalization, after 3, 6 and 12 months. Comparison of mean values was performed using the Mann–Whitney U-test. Differences in indicators were considered statistically significant at p <0.05.

RESULTS: In the first 24 hours after hospitalization for myocardial infarction, the ejection fraction did not differ in patients: in the first group — 48% [45; 54], in the second — 53% [48; 54] (p=0.07). In the first group, an increase in the ejection fraction was found compared to the baseline value: 53% [46; 58] (p <0.001) 6 months after myocardial infarction, 55% [48; 58] (p <0.001) after 12 months. In the second group, the ejection fraction after 3, 6 and 12 months did not differ from the baseline. The total myocardial mobility index on the 1st day after myocardial infarction did not differ between the groups: 1.25 [1.19; 1.62] in the first group and 1.25 [1.12; 1.56] in the second group (p=0.3). Its decrease was found in the first group: 1.19 [1.06; 1.56] (p <0.001) after 6 months and 1.12 [1.0; 1.44] (p <0.001) after 12 months. In the second group, the values of the total myocardial mobility index after 3, 6 and 12 months did not differ from the initial ones.

CONCLUSION: Iron deficiency compensation is associated with improved left ventricular systolic function within 12 months after myocardial infarction.

Kazan medical journal. 2024;105(6):879-886
pages 879-886 views

Features of inspiratory muscle functional state in patients with heart failure with preserved ejection fraction

Ivanov K.M., Silkina T.A., Baykina N.G.

Abstract

BACKGROUND: Chronic heart failure contributes to multiorgan dysfunction, including skeletal muscle impairment.

AIM: This study aimed to assess the strength and electrical activity of inspiratory muscles in patients with chronic heart failure with preserved left ventricular ejection fraction.

MATERIAL AND METHODS: Eighty patients of both sexes aged 45–74 years were included and divided into three groups: group 1 comprised 24 patients with chronic heart failure classified as NYHA functional class II, group 2 included 20 patients with NYHA class I chronic heart failure, and group 3 (control group) involved 36 patients without chronic heart failure. All participants underwent evaluation for serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a 6-minute walk test, assessment of inspiratory muscle strength, and surface electromyography of inspiratory muscles during three loading tests. The significance of intergroup differences was assessed using the Mann–Whitney and Pearson χ2 tests.

RESULTS: When stratified by sex, women in group 1 had 31.5% lower maximal inspiratory pressure than those in the control group (p = 0.006). The patients in group 1 demonstrated a smaller increase in diaphragm electromyography amplitude during the first test—sustained inspiratory effort at 30% intensity for 15 seconds—by 27.9% (p = 0.010), 26.1% (p = 0.025), and 40.7% (p = 0.033) at 5, 10, and 15 seconds, respectively. In the second test—sustained inspiratory effort at 50% intensity for 5 seconds—electromyography amplitude decreased by 32.6% (p = 0.041) at 5 seconds. In the third test—sustained inspiratory effort at 70% intensity for 5 seconds—the reduction was 42.8% (p = 0.009) at 5 seconds compared with the control group. Additionally, a more pronounced decrease in electromyography frequency was observed during the first test—by 24.2% (p = 0.048) and 24.7% (p = 0.030) compared with the control group—indicating fatigue. In the accessory inspiratory muscles, electromyography amplitude gain was higher in group 1 than in the control group, showing activation of additional motor units: in the external intercostal muscles during the first test, by 31.7% (p = 0.032) and 37.9% (p = 0.044) and by 28.9% (p = 0.048) and 43.1% (p = 0.036) during the second test; and in the sternocleidomastoid muscle during the first test by 66.1% (p = 0.033) and 49.4% (p = 0.043) and by 128.6% (p = 0.032) during the second test.

CONCLUSION: Surface electromyography with loading tests revealed diaphragm fatigue and increased activation of accessory inspiratory muscles in patients with NYHA class II chronic heart failure.

Kazan medical journal. 2024;105(6):887-894
pages 887-894 views

Differential expression of the SLC34A2 gene in different histological subtypes of ovarian carcinomas

Nurgalieva A.K., Fetisov T.I., Kuzin K.A., Shakirova E.Z., Kiyamova R.G.

Abstract

BACKGROUND: Patients with ovarian carcinoma exhibit varying degrees of sensitivity to chemotherapy. Consequently, enhancing the effectiveness of treatment requires a comprehensive evaluation of tumor characteristics, including the histological subtype.

AIM: To identify novel molecular markers of ovarian cancer by analyzing the expression of candidate genes, namely, BAX, SLC34A2, MUC16, CD300A, and XKR8, in ovarian carcinomas of different histological subtypes.

MATERIAL AND METHODS: Real-time polymerase chain reaction was used to analyze BAX, SLC34A2, MUC16, CD300A, and XKR8 gene expressions in 33 carcinomas, considering histological subtypes. Tumor samples from patients with ovarian carcinoma were obtained from the Blokhin National Medical Research Center of Oncology (Moscow) and Republican Clinical Oncological Dispensary (Kazan). The samples were divided into three groups according to histological subtype: high-grade (n = 16) or low-grade (n = 6) serous ovarian carcinomas, endometrioid ovarian carcinomas (n = 8), and mucinous ovarian carcinomas (n = 3). Further analysis was performed using microarray data from the Gene Expression Omnibus database to determine the expression levels of selected candidate genes in various ovarian carcinoma histological subtypes of ovarian carcinomas. The dataset included 4 samples of normal ovaries and 95 samples of ovarian carcinomas of different histological subtypes, including serous (n = 41), endometrioid (n = 37), and mucinous (n = 13) subtypes. Statistical data analysis was conducted using Prism software. Nonparametric Dunn’s test was employed to compare gene expression among patient groups.

RESULTS: Low-grade serous ovarian carcinomas demonstrated increased SLC34A2 gene expression (p = 0.0257) compared with mucinous ovarian carcinomas. Additionally, bioinformatic analysis revealed increased SLC34A2 gene expression in serous (p = 0.0023) and endometrioid (p = 0.0355) ovarian carcinomas compared with normal ovarian tissues.

CONCLUSION: The SLC34A2 gene may be used as a molecular marker to differentiate histological subtypes of ovarian cancer and therapeutic target for low-grade serous ovarian carcinoma.

Kazan medical journal. 2024;105(6):895-905
pages 895-905 views

Association of spleen-derived stem-like cells with hematogenous metastasis development

Andryukhova E.S., Tashireva L.A., Afanasyev S.G., Zavyalova M.V., Perelmuter V.M.

Abstract

BACKGROUND: Spleen status has been associated with survival in patients with carcinoma, potentially mediated by the effects of immunosuppressive hematopoietic cells in the spleen.

AIM: This study aimed to investigate the composition and quantity of hematopoietic stem-like cells in the spleen and their relationship with hematogenous metastases in patients with varying carcinoma types.

MATERIAL AND METHODS: Forty patients with carcinomas of the stomach, gastroesophageal junction, pancreas, splenic flexure of the colon, sigmoid colon, kidney, ovary, and uterus were examined. The subgroup with hematogenous metastases (15 patients) included 7 cases of gastric cancer, 1 of gastroesophageal junction cancer, 4 of colon cancer, 1 of pancreatic cancer, 1 of renal cancer, and 1 of ovarian cancer. The subgroup without hematogenous metastases (13 patients) comprised 6 cases of gastric cancer, 4 of gastroesophageal junction cancer, 1 of colon cancer, 1 of pancreatic cancer, and 1 of uterine cancer. Formalin-fixed, paraffin-embedded spleen tissue sections were analyzed using multiplex tyramide signal amplification, a modified immunohistochemistry technique, with antibodies to CD45, CD34, CD133, TIE2, VEGFR1, CD90, and CD11b. Data are presented as median (Me) and interquartile range (Q1–Q3). Differences between groups were assessed using the Mann–Whitney U test. ROC analysis was employed to evaluate the prognostic significance of the parameters. P < 0.05 indicated significant differences.

RESULTS: Multiparametric analysis of spleen tissue identified 20 phenotypes within the continuum of hematopoietic stem cells and cells with hematopoietic/angiogenic potential, exhibiting phenotypic diversity. Across all carcinoma types, the number of CD45CD34+CD133TIE2VEGFR1 stem-like cells in lymphoid follicles was lower in patients with hematogenous metastases: 43.313 (0.00–85.393) and 110.034 (83.050–197.915), respectively (p = 0.03). The number of stem-like cells with the CD45CD34+CD133TIE2VEGFR1 phenotype was lower in the group of patients with gastric cancer and hematogenous metastases (31.092 [0.000–37.987]) than in the group without hematogenous metastases (119.962 [103.486–258.533]) (p = 0.001). In contrast, the number of hematopoietic progenitor cells with the CD45+CD34CD133+TIE2VEGFR1 phenotype identified in the lymphoid follicle was higher (7901.164 [5705.314–8563.807] vs 4670.894 [3328.607–6473.649]) (p = 0.035), as well as the number of CD45+CD34CD133+TIE2+VEGFR1+ cells detected in the red pulp of the spleen (131.396 [35.701–167.521] vs 21.524 [6.123–30.117]) (p = 0.02).

CONCLUSION: The number of spleen-derived cells with the phenotypes CD45CD34+CD133TIE2VEGFR1, CD45+CD34CD133+TIE2VEGFR1, and CD45+CD34CD133+TIE2+VEGFR1+ is associated with hematogenous metastasis.

Kazan medical journal. 2024;105(6):906-916
pages 906-916 views

Analysis of plasma hemostasis and the role of microvesicles in the coagulation process in patients with COVID-19

Gracheva E.S., Abdullina R.R., Mustafin I.G., Abdulganieva D.I.

Abstract

BACKGROUND: Coagulopathies in COVID-19 are an important aspect in the pathophysiological mechanisms, clinical picture of the disease, and occurrence of delayed complications.

AIM: To study plasma hemostasis using turbidimetry, thromboelastography, and the role of microvesicles in the coagulation process in patients with COVID-19.

MATERIAL AND METHODS: The study used blood samples from patients of the temporary infectious diseases hospital based on the State Autonomous Healthcare Institution “Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan” in Kazan (n=213) in the period from June to August 2020. Patients were divided into two groups according to the severity of the disease: the first group — moderate COVID-19 (n=138), the second group — severe COVID-19 (n=75). Patients were treated according to the protocols of the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation, version 7. The blood of healthy donors (n=20) was used as a control group. Plasma hemostasis was assessed using dynamic turbidimetry (measured lag period — Lag, polymerization rate — V, maximum optical density at a given wavelength — Amax) and thromboelastography (determined coagulation activation time — R). Statistical processing of the results was performed using IBM SPSS Statistics 26.0. The groups were compared using the nonparametric Mann–Whitney U-test. Statistical processing of the results following standart normal distribution was performed using the Student's t-test. Differences were considered significant at p <0.05.

RESULTS: Severe COVID-19 was characterized by an increase in the lag period (9.4±0.8 min relative to the control 6.2±1.2 min; p <0.0001), a decrease in the polymerization rate (1.12±0.71 OD units/s relative to the control 3.93±2.3 OD units/s; p <0.0001) and a decrease in the maximum optical density of the clot (0.576±0.17 OD units relative to the control 1.625±0.433 OD units; p <0.0001). In moderate cases, a shortening of the lag period was noted (3.8±1.1 min relative to the control 6.2±1.2 min; p=0.0004), the maximum optical density of the clot was lower than the control (1.412±0.351 OD units at 1.625±0.433 OD units, respectively; p=0.0007). In patients with moderate disease severity, a 1.6-fold reduction in coagulation activation time was noted relative to the control group. In patients with severe disease, coagulation activation time was increased by 1.5 times relative to the control. After adding microvesicles to the samples, this parameter decreased by 2.12 times in patients with a moderate course of the disease (16.9±1.1 min and 8±0.6 min; p <0.0001), and by 1.44 times in patients with a severe course of the disease (10.8±0.9 min and 7.5±0.5 min; p <0.0001).

CONCLUSION: Moderate COVID-19 is characterized by signs of hypercoagulation, which can lead to the development of thrombotic complications; severe disease is accompanied by hypocoagulation, which contributes to hemorrhagic complications.

Kazan medical journal. 2024;105(6):917-925
pages 917-925 views

Lymphocyte apoptosis in patients with coronavirus infection COVID-19

Khaertynov K.S., Boichuk S.V., Anokhin V.A., Galembikova A.R., Evdokimova A.E.

Abstract

BACKGROUND: Lymphopenia in patients with coronavirus infection COVID-19 is associated with the risk of developing severe forms and unfavorable outcome. One of the reasons for the development of lymphopenia is apoptosis.

AIM: Evaluation of the severity of peripheral blood lymphocytes' apoptosis in patients with moderate and severe COVID-19.

MATERIAL AND METHODS: A total of 42 patients with COVID-19 aged 37 to 90 years were examined. They were hospitalized at the Republican Clinical Infectious Diseases Hospital named after Professor A.F. Agafonov, Kazan, from October 24, 2021 to March 1, 2022. In 13 patients, the lung lesion volume ranged from 10 to 25% (CT-1), in 20 — from 25 to 50% (CT-2), in 9 — from 50 to 75% (CT-3). Ribonucleic acid of the SARS-CoV-2 virus was isolated from the nasopharynx in 35 (83%) patients. COVID-19 was moderate in 14 patients, and severe in 28 patients. The control group consisted of 10 conditionally healthy people of the same age. Lymphocyte apoptosis was assessed by quantifying hypodiploid cells by changing the intensity of their staining with propidium iodide using flow cytometry. To determine the reliability of differences in indicators between the compared groups, the Mann–Whitney U-test was used, and when comparing percentages, the χ2 criterion was used. The reliability of differences was established at p <0.05.

RESULTS: It was found that patients with COVID-19 had significantly higher lymphocyte apoptosis activity compared to the control group. The median of the studied indicator in patients with COVID-19 was 39.3%, while in the control group it was 15.1% (p <0.001). The severity of lymphocyte apoptosis correlated with the severity of the disease: the highest rates were recorded in patients with severe COVID-19 (p=0.02). Moreover, lymphocyte apoptosis >55% was associated with the risk of death (p=0.03). A moderate correlation was established between lymphocyte apoptosis rates and blood ferritin levels (Spearman coefficient p=0.39, p <0.05).

CONCLUSION: Coronavirus infection COVID-19 was accompanied by an increase in the activity of peripheral blood lymphocyte apoptosis; the highest apoptosis rates were recorded in patients with severe COVID-19.

Kazan medical journal. 2024;105(6):926-935
pages 926-935 views

Features of hematological indices in cataract in the dynamics of surgical treatment

Smirnova O.V., Zinkina T.O.

Abstract

BACKGROUND: Cataracts are a prevalent ophthalmological condition that frequently results in blindness.

AIM: To study hematological indices in men aged >40 years with different types of cataracts before and after surgical treatment.

MATERIAL AND METHODS: The study included 25 (25 eyes) patients with cortical opacities, 19 (19 eyes) with total opacities, 26 (26 eyes) with nuclear opacities, and 30 (30 eyes) with subcapsular opacities. Of these patients, 43 (43 eyes) had incipient cataracts, 39 (39 eyes) had immature cataracts, and 18 (18 eyes) had mature cataracts. The control group comprised 30 individuals. The patients underwent complete ophthalmological examinations and hematological index evaluations. The following integral hematological indices were calculated according to generally accepted formulas: lymphocyte index (lymphocytes/neutrophils); leukocyte intoxication index; and neutrophil-to-lymphocyte, neutrophil-to-monocyte, lymphocyte-to-monocyte, lymphocyte-to-eosinophil, and leukocyte-to-erythrocyte sedimentation rate ratios. Statistical analysis was performed using the Statistica 10 software. The nonparametric Kruskal–Wallis and Mann–Whitney tests were used to evaluate differences between the groups. The significance level for testing scientific hypotheses was set at p < 0.05.

RESULTS: Unidirectional changes in hematological indices were detected in all degrees of cataract maturity pre- and post-surgery. Specifically, the lymphocyte-to-eosinophil ratio decreased (1.4–2.0; p = 0.01), whereas the neutrophil-to-monocyte (1.3–2.1; p = 0.04), lymphocyte-to-monocyte (1.4–2.5; p = 0.02), and leukocyte-to-erythrocyte ratios increased (2.9–6.8; p = 0.01). In immature cataracts, the intoxication index, as determined by hematological indices, exhibited a twofold increase in surgical treatment dynamics. Multidirectional changes in hematological indices were found in cortical and subcapsular lens opacities and unidirectional changes in nuclear and total opacities.

CONCLUSION: Patients with nuclear and total cataracts show the most significant abnormalities in the cell population ratio according to hematological indices, thus constituting a high-risk group for complications.

Kazan medical journal. 2024;105(6):936-945
pages 936-945 views

Anatomical features of the parotid gland in men depending on cranial shape

Abduvosidov K.A., Chernyavsky V.I., Shestakova V.G., Yusufov A.A., Smirnova A.D.

Abstract

BACKGROUND: In vivo analysis of the morphometric parameters of the parotid gland in the context of various cranial shapes is a promising approach, as it enables the systematization of the existing knowledge of the parotid gland anatomy.

AIM: This work aimed to identify the anatomical features of the parotid gland in men with different cranial shapes based on the head computed tomography (CT) and magnetic resonance imaging (MRI) findings.

MATERIAL AND METHODS: A retrospective study was conducted based on the analysis of head CT and MRI findings from 92 men. Based on the cranial shape, the sample was divided into the following groups: dolichocranes (n = 30), mesocranes (n = 32), and brachycranes (n = 30); chamaecranes (n = 19), orthocranes (n = 47), and hypsicranes (n = 26); and tapeinocranes (n = 33), metriocranes (n = 30), and acrocranes (= 29). Based on the facial shape, three groups were identified: euryenes (n = 29), mesenes (n = 33), and leptenes (n = 40). A morphometric study of the parotid gland was performed, measuring dimensions in three planes and calculating the gland volume using the ultrasonographic method for measuring internal organ vo­lumes. Statistical analysis was performed using nonparametric methods, including the Kruskal–Wallis test, the Mann–Whitney test with Bonferroni correction, and Spearman’s correlation.

RESULTS: The sagittal dimension of the parotid gland in the men increased significantly from brachycranics (4.22 cm on the right, 3.99 cm on the left) to dolichocranics (4.77 cm on the right [p = 0.0001], 4.57 cm on the left [p = 0.0001]). A decrease in the frontal dimension of the gland was observed from brachycranics (3.43 cm on the right, 3.47 cm on the left) to dolichocranics (2.49 cm on the right [p = 0.0001], 2.47 cm on the left [p = 0.0001]). With regard to viscerocranium shapes, a significant diffe­rence in the vertical dimension of the gland was identified (6.12 cm on the right, 6.18 cm on the left in euryenes; 6.98 cm on the right [p < 0.0001], 6.95 cm on the left [p < 0.0001] in leptenes). The frontal dimension decreased significantly from euryenes (3.42 cm on the right, 3.53 cm on the left) to leptenes (2.51 cm on the right [p < 0.0001], 2.58 cm on the left [p < 0.0001]).

CONCLUSION: In men, the sagittal dimension of the parotid gland varies significantly depending on the shape of the neurocranium as determined by the cranial index; the frontal dimension of the gland changes depending on both the neurocranial and viscerocranium shapes.

Kazan medical journal. 2024;105(6):946-956
pages 946-956 views

Experimental medicine

Proliferation and apoptosis in the colonic epithelium of rats after electron irradiation

Saakian S.V., Mimuni A.F., Karakayeva E.B., Gotovtsev K.K., Demyashkin G.A.

Abstract

BACKGROUND: Electron irradiation is one of the most promising modalities for the treatment of malignant colonic neoplasms.

AIM: To evaluate the morphology of apoptosis and proliferation in the colonic epithelium of animals after local fractional electron irradiation at a focal dose of 25 Gy.

MATERIALS AND METHODS: Two groups of Wistar rats were used: group 1, control (n = 10); and group 2, experimental (n = 20). The experimental group was exposed to local electron irradiation at a focal dose of 25 Gy in fractions of 5 Gy on days 1, 3, 5, 7, and 9. Colonic fragments were examined using light microscopy, and immunohistochemical reactions were performed using antibodies to the Ki-67 and caspase-3 antigens. The wall thickness and diameter of the serous mucosal membrane were measured in micrometers. Morphological changes were evaluated using a scoring system. Results were analyzed using the Kolmogorov–Smirnov test, Student’s t-test, Mann–Whitney U-test, and Fisher’s test.

RESULTS: Macroscopic examination of the colon of rats in the experimental group revealed mucosal hyperemia without significant destructive changes. Furthermore, microscopic examination showed insignificant lesions of the colonic mucosa and decreased goblet cells compared with the control group (63.17% ± 1.87% vs. 21.64% ± 1.37%, respectively; p = 0.009). The number of caspase-3-positive epithelial cells increased (28.7% ± 8.2% vs. 14.5% ± 3.9%, p = 0.027). The proliferative index (Ki-67) in colonic crypts decreased after local fractional electron irradiation at a total focal dose of 25 Gy compared with the control group (11.14% ± 6.23% vs. 19.45% ± 5.12%, p = 0.013).

СONCLUSION: Local fractional electron irradiation of rats at a total focal dose of 25 Gy was found to induce weak degenerative and dystrophic changes in the epithelium and a decrease in goblet cells while preserving regenerative potential in the colon.

Kazan medical journal. 2024;105(6):957-964
pages 957-964 views

The role of physical exercise in modulating hemostatic parameters under hypobaric hypoxia

Alekseeva O.V., Ulitina O.M., Moiseeva T.G.

Abstract

BACKGROUND: Exposure to multiple extreme environmental factors disrupts the function of multiple organ systems, including the hemostatic system. Identifying safe and effective strategies to enhance the body’s adaptive capacity can help mitigate or prevent stress-related consequences.

AIM: This study aimed to assess the response of the hemostatic system to a single 24-h exposure to hypobaric hypoxia and evaluate the potential of preconditioning with physical exercise to correct associated abnormalities.

MATERIAL AND METHODS: The experiment involved 60 sexually mature male rats. Group 1 (n = 24) served as the control. Rats in group 2 (n = 12) underwent daily 2-h treadmill walking at a speed of 6–8 m/s for 30 days. Those in group 3 (n = 12) were exposed to a single 24-h hypobaric hypoxia episode by placing the rats in a hypobaric chamber at 0.55 kgf/cm2, simulating an altitude of 6,500 m above sea level. Group 4 rats (n = 12) received a 2-h daily exercise regimen for 30 days prior to a 24-h exposure to hypobaric hypoxia. Platelet aggregation activity, plasma coagulation, and the activity of anticoagulant and fibrinolytic systems were evaluated in all groups using diagnostic test kits (Technologia-Standart, Russia). Statistical analysis was performed using the software Statistica 10. Data were tested for statistical significance of differences using the Student t test and the nonparametric Mann–Whitney U test.

RESULTS: A 24-h hypobaric hypoxia activated both the platelet and plasma arms of hemostasis, as shown by significantly shortened platelet aggregation time (p = 0.000), silica clotting time (p = 0.006), and prothrombin time (p = 0.008). Additionally, antithrombin III levels significantly declined (p = 0.000) and fibrin-lysis time lengthened (p = 0.001) relative to those of the controls. Preconditioning physical training followed by hypoxic exposure resulted in hypocoagulation, manifested as a significant prolongation of platelet aggregation time (p = 0.000), silica clotting time (p = 0.011), kaolin clotting time (p = 0.000), and prothrombin time (p = 0.000). Furthermore, antithrombin III concentration significantly increased (p = 0.000) and fibrin clot lysis time significantly decreased (p = 0.002) relative to those of the untrained animals exposed to hypoxia alone.

CONCLUSION: A single episode of hypoxic stress is characterized by hypercoagulation at all stages of the coagulation cascade, accompanied with suppression of plasma anticoagulant and fibrinolytic activity, which is mitigated by prior physical training.

Kazan medical journal. 2024;105(6):965-973
pages 965-973 views

Reviews

Possibilities of gene, cellular and pharmacological approaches to correct age-related changes

Kitaeva K.V., Solovyeva V.V., Filin I.Y., Mukhamedshina Y.O., Rizvanov A.A.

Abstract

Improvement of the human habitat has led to an increase in average life expectancy. Long life goes hand in hand with old age, which reduces the quality of human life and it is an acute social problem. Thus, the search for approaches that can improve the quality of life, the ability to live it without age-related diseases is an extremely urgent task. Aging of the body begins with the aging of cells, in which the activation of the aging process occurs through the induction of specific signaling pathways, which irreversibly divides the life of any cell into “before and after”. Aging cells are able to influence their microenvironment, secreting more inflammatory signaling molecules and inducing pathological changes in neighboring cells. The accumulation and long-term preservation of aged cells lead to deterioration of the condition of tissues and organs, and ultimately to a decrease in the quality of life and an increased risk of death. Among the most promising approaches to the correction of aging and age-related diseases are pharmacological, gene and cell therapy. Increasing the expression of aging suppressor genes, using certain populations of native and genetically modified cells, as well as senolytic drugs can help delay aging and associated diseases for a more distant future. This review examines currently studied approaches and achievements in the field of anti-aging therapy, in particular gene therapy using adeno-associated vectors and approaches based on cell therapy.

Kazan medical journal. 2024;105(6):974-986
pages 974-986 views

Intestinal microbiota as a fundamental basis for homeostasis, general pathology and aging

Sozinov A.S., Anikhovskaya I.A., Zhdanov R.I., Markelova M.M., Morozov S.G.

Abstract

Intestinal microbiota is a kind of satellite organ that performs digestive and protective functions, a supplier of molecules vital for homeostasis processes, involved in metabolic processes and determining the activity level of adaptive systems, including immunity. Immunity works both for and against the host, which is predetermined by the very nature of adaptive immunity and its interaction with the innate link of the immune system. The key element of this interaction is endotoxin molecules, or lipopolysaccharides, the concentration of which in the general bloodstream determines the activity level of adaptive (mediated by innate) immunity, which operates in a stochastic mode. This provides both antitumor protection and self-destruction of the body based on autoimmune damage. Over the past 35 years, there has been a powerful breakthrough in the field of understanding the mechanisms of interaction between the intestinal microbiota and the host organism. Interesting data have been obtained and published that have not yet been fully systematized and understood. The methodology for studying the biological role of lipopolysaccharides in clinical settings developed by Russian scientists was based on the ability of agents for reducing their blood levels to increase the effectiveness of the treatment and preventive process. In particular, it made it possible to establish the involvement of the lipopolysaccharide factor in the pathogenesis of a number of diseases. The phenomenon of systemic endotoxinemia discovered by Russian researchers is a process of controlling the activity of adaptive systems (including the immune system) with the participation of the hypothalamic-pituitary-adrenal system by means of intestinal endotoxins. We see the following issues for wide discussion in the clinical community: (1) determining the directions for finding agents for normalizing systemic endotoxinemia indicators as the basis of preventive medicine, including pro- and prebiotics, entero- and hemosorbents, hepatoprotectors, immunopreparations, chaotropic effects (plasmapheresis, blood irradiation); (2) clinical and experimental models for studying diseases associated with intestinal microbiota; (3) creation of a research protocol to establish the age range of integral indicators of systemic endotoxinemia (the level of lipopolysaccharides and the activity of antiendotoxin immunity that resists endotoxin aggression); (4) ways to understand the mechanisms of development of endotoxin tolerance accompanying aging and its overcoming.

Kazan medical journal. 2024;105(6):987-993
pages 987-993 views

The concept of acute kidney disease and its place in the renal continuum

Sakharov V.S., Menzorov M.V., Denisova A.Y., Kerimova S.F., Matyushina V.V.

Abstract

The paper discusses the concept of acute kidney disease, a relatively new concept in clinical medicine, the introduction of which is due to the presence of kidney diseases that do not meet strict criteria for acute kidney injury or chronic kidney disease. The article presents the criteria and severity stratification of acute kidney disease proposed by the Kidney Disease: Improving Global Outcomes Foundation, interpretation of the criteria and severity stratification by the Scientific Society of Nephrologists of Russia, associations of nephrologists and anesthesiologists-resuscitators of Russia, the National Society of Specialists in Hemapheresis and Extracorporeal Hemocorrection in accordance with the classification system of the Acute Dialysis Quality Initiative group. The role of acute kidney disease in the modern renal continuum is outlined. The article reviews the results of studies of acute kidney disease in patients with septic shock, patients who underwent total joint replacement, myocardial infarction with ST segment elevation and having acute kidney injury, patients with ischemic stroke, after coronary angiography, after acute surgery for type A aortic dissection, which demonstrate the prevalence of acute kidney disease and its outcomes. Despite the fact that acute kidney disease has a high prevalence among patients with various pathologies, worsens the prognosis and increases the risk of death or complications, its significance in modern medicine remains extremely underestimated. The article identifies the most common and studied biochemical markers that can potentially increase the proportion of patients at risk of adverse outcomes when used in clinical practice.

Kazan medical journal. 2024;105(6):994-1002
pages 994-1002 views

Hepatocardial relationships in non-alcoholic fatty liver disease: issues of epidemiology, diagnosis, prognosis

Savzikhanova R.R., Subkhangulova D.O., Khazova E.V.

Abstract

World statistics indicate a steady increase in the prevalence of non-alcoholic fatty liver disease, which correlates with the pandemics of obesity and diabetes, which are quite common in Russia. The commonality of cardiometabolic risk factors, the high global prevalence of non-alcoholic fatty liver disease and atherosclerotic cardiovascular diseases generates the interest of researchers in studying hepatocardial relationships. Currently, non-alcoholic fatty liver disease is positioned as a hepatic manifestation of a multisystem disorder, heterogeneous in underlying causes, manifestations, course and outcomes. The purpose of this review was to analyze hepatocardial relationships based on publications. 76 sources on the epidemiology of non-alcoholic fatty liver disease, published from 2011–2023 in journals indexed in Pubmed and eLibrary, were analyzed. Age and gender aspects of the development of non-alcoholic fatty liver disease were considered. The pathogenetic mechanisms of hepatocardial relationships, which were closely related to systemic inflammation, insulin resistance, metabolic syndrome and its components, were highlighted. The criteria and methods for diagnosing non-alcoholic fatty liver disease and metabolic-associated liver disease were outlined. Recent studies demonstrated the presence of hepatocardial connections, characterized by an increased risk of developing atherosclerosis, cardiomyopathy and rhythm disturbances, changes in the structural and functional parameters and geometry of the heart, as well as diastolic dysfunction, which may precede and/or contribute to the development of chronic heart failure in patients with non-alcoholic fatty liver disease. The article presents data on non-alcoholic fatty liver disease as a new factor associated with the development of adverse cardiovascular events to a greater extent than the outcome of liver diseases themselves, which confirms the need for primary and secondary prevention of cardiovascular diseases in this cohort of patients.

Kazan medical journal. 2024;105(6):1003-1014
pages 1003-1014 views

Social hygiene and healthcare management

Standardization of the physical development research in the pediatric population of the Russian Federation

Popov V.I., Milushkina O.Y., Skoblina N.A., Nikolenko V.N.

Abstract

BACKGROUND: Studying the processes of growth and development in the pediatric population is crucial because of the significance of the pre-nosological approach aimed at primary disease prevention.

AIM: This study aimed to provide the constituent entities of the Russian Federation (RF) with normative data on the physical development of children and adolescents aged 7–17 years.

MATERIAL AND METHODS: An analytical investigation was conducted using the large-scale database, Physical Development of Children, Adolescents, and Youth in the Russian Federation, 2000–2021c, which contains 395,956 observations of physical development (body length and body weight measurements) in children, adolescents, and youth from 49 constituent entities of RF. Constituent entities where regional normative data had never been developed or where the last norms were established 15–20 years ago or earlier were emphasized. At least two constituent entities were analyzed in each federal district. Big data processing was performed using machine learning methods on a PostgreSQL database. A web application was developed featuring tabular data display, histogram generation with customizable parameters, and the publication of data on a map of the RF.

RESULTS: At the beginning of the 21st century, specific features of physical development were established among schoolchildren living in various constituent entities of the RF, which allows for the identification of “regional scenarios” that should be considered when developing normative standards. We found that the mean height of 15-year-old boys across the constituent entities ranged from 161.70 ± 0.20 cm in the Kursk Region to 174.55 ± 0.40 cm in the Krasnodar Region (range: 12.85 cm, p = 0.001). In girls, the mean height ranged from 154.60 ± 0.50 cm in the Republic of Tyva to 165.69 ± 0.55 cm in Saint Petersburg (range: 11.09 cm, p = 0.001). The body weight of 15-year-old boys ranged from 50.17 ± 0.70 kg in the Kursk Region to 66.00 ± 0.80 kg in the Khabarovsk Region (range: 15.83 kg, p = 0.001). In girls, the weight ranged from 46.90 ± 0.60 kg in the Chelyabinsk Region to 58.40 ± 0.70 kg in the Khabarovsk Region (range: 8.50 kg, p = 0.001).

CONCLUSION: Forty regional normative standards for the physical development of the pediatric population were developed in a standardized manner, allowing for the consideration of regional characteristics and enabling their practical application in healthcare across the constituent entities of the RF.

Kazan medical journal. 2024;105(6):1015-1022
pages 1015-1022 views

Clinical experiences

Efficiency of chewing load deficiency correction in clinical dental practice

Ksembaev S.S., Salakhov A.K., Saleeva G.T., Musin I.N., Saleev R.A.

Abstract

Weakening of the chewing act, typical for modern humans due to consumption of soft food, causes a deficit of chewing load and has a negative effect on the dental system. To combat hypodynamia of the masticatory apparatus with the aim of preventing destructive processes in its structures, a gnathotraining system was developed, including electrical stimulation of the masticatory muscles themselves in physiological parameters, which develops the effect of “imaginary chewing”, and gnathotraining using chewing gum. In addition, functional training of the masticatory apparatus using chewing exercises was proposed. Considering that chewing gum practically does not compensate for the deficit of chewing load observed in modern society, the staff of the Kazan State Medical University and the Kazan National Research Technological University developed the “Denta Fit” dental trainer and a dental training system. It has been established that dental and jaw training stimulates secretion of saliva, its mineralizing potential, functional resistance of tooth enamel, allows achieving a good level of oral hygiene, reduces the rate of increase in the intensity of dental caries, as well as the severity of muscular-articular disorders of the temporomandibular joints, enhances neuromuscular activity of the masticatory muscles and regional blood flow. In children with permanent bite, dental and jaw training maintains the hydrogen index (pH) of oral fluid at a neutral level and provides, in combination with a toothbrush, optimal hygienic dental care, contributes to the formation of a correct dental occlusion. Thus, the effects of increased neuromuscular activity of the masticatory muscles, as well as regional vascular tone, arising during dental and jaw training, indirectly indicate that the dental and jaw system receives adequate mechanical loads necessary for the normal functioning of all its links. The results of the conducted studies indicate the effectiveness and feasibility of using dental training to improve dental status, which serves as a new approach to the prevention and treatment of dental diseases.

Kazan medical journal. 2024;105(6):1023-1028
pages 1023-1028 views

Malignant melanotic nerve sheath tumor

Agarkova E.I., Maximova N.A., Arzamastseva M.A., Ilchenko M.G., Shatova Y.S.

Abstract

Malignant melanotic nerve sheath tumor, previously melanotic schwannoma, is a rare peripheral nerve sheath tumor composed of melanin-producing Schwann cells, often clinically misdiagnosed as melanoma. It is an uncommon neoplasm with unpredictable biological behavior and varying treatments. Despite its histologic features indicative of benignity, including a low proliferative index, its clinical course is frequently malignant, with a high local recurrence rate and metastatic potential. The distinctive characteristics of malignant melanotic nerve sheath tumor include a relatively young patient age, signs of Carney complex, and psammoma bodies within the tumor. This study presents a case of a patient with malignant melanotic nerve sheath tumor located in the neck with a recurrent clinical course who underwent two surgical procedures. Microscopic and immunohistochemical evaluation of postoperative specimens showed positivity for melanoma markers, absence of psammoma bodies, and low mitotic activity. The clinical course of the disease was malignant, with recurrence developing in the postoperative scar. Diagnosing malignant melanotic nerve sheath tumor is radiologically and pathologically challenging. Multidisciplinary collaboration among the surgeon, radiologist, and pathologist; understanding the lesion’s anatomical context; and close attention to histopathologic findings are critical for establishing an accurate diagnosis.

Kazan medical journal. 2024;105(6):1029-1036
pages 1029-1036 views

Cochrane Review Summaries

Interventions for great saphenous vein incompetence

Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Whing J, Nandhra S, Nesbitt C, Stansby G. Interventions for great saphenous vein incompetence. Cochrane Database of Systematic Reviews. 2021. Issue 8. Art. No.: CD005624. doi: 10.1002/14651858.CD005624.pub4

Kazan medical journal. 2024;105(6):1037-1038
pages 1037-1038 views

Index of authors

Kazan medical journal. 2024;105(6):1039-1042
pages 1039-1042 views

Thank you to all our reviewers in 2024

Kazan medical journal. 2024;105(6):1043-1044
pages 1043-1044 views