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Vol 31, No 2 (2023)

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Original study

Voluntary Consumption of Sodium Glutamate Solution as a Factor of Depression-Like Behavior in Adult Rats: an Experimental Study

Parot'kin D.O., Bogdanova N.G., Nazarova G.A., Sudakov S.K.

Abstract

INTRODUCTION: Use of sodium glutamate solution with food is a widely spread practice. The glutamate-ergic system has been shown to directly participate in the mechanisms of depression, however, up to the moment, no data have been found to evidence that use of sodium glutamate causes depression.

AIM: To study the effect of intake of sodium glutamate on the formation of depression-like behavior in male rats.

MATERIALS AND METHODS: Formation of depression-like behavior was evaluated in male rats of Wistar line with 230 g–250 g weight at the beginning of the experiment in the situation of ‘inescapable swimming’ according to the method of R. D. Porsolt, and of ‘hanging by the tail’ according to T. A. Voronina. In the course of the experiment, the rats of the experimental group consumed 1.1% sodium glutamate solution daily for 30 days, the control animals drank water. During the experiment, the rats were kept in individual cages and had free access to water. The animals of the control group (n = 7) had only water in the drinking bowls. The animals of the experimental group (n = 7) were given water in one drinking bowl and 60 mМ (1.1%) sodium glutamate solution (Henan Lotus Flower Gourmet Powder Cо., LTD, China) in the other.

RESULTS: Consumption of 1.1% sodium glutamate solution for 30 days led to reduction of the time of active movements and to increase in the number of periods of immobilization in animals in both tests. Besides, in the tests for depression-like behavior of animals, increased rhythmologic index of depression was found in the group of rats receiving sodium glutamate solution.

CONCLUSION: Based on the results of study, it was found that chronic voluntary consumption of 60 mM (1.1%) sodium glutamate solution for 30 days provokes the formation of depression-like behavior in rats.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):169-176
pages 169-176 views

Free Radical Oxidation and Metabolic Processes of Cartilage and Bone Tissues in Animals with Surgical Model of Posttraumatic Osteoarthrosis

Belova S.V., Zubavlenko R.A., Gladkova E.V., Babushkina I.V., Ul'yanov V.Y.

Abstract

INTRODUCTION: Posttraumatic osteoarthrosis (PTOA) resulting from injuries of connective-tissue components of the joint, is accompanied by formation of free radicals activating chondro- and osteoresorption, which leads to fragmentation of biopolymers of the extracellular matrix of the joint tissues.

AIM: To study the peculiarities of free radical oxidation and metabolic processes of cartilage and bone tissues in animals with a surgical model of PTOA of the knee joint.

MATERIALS AND METHODS: The study was conducted on 31 rats (11 intact animals and 20 animals with PTOA model). The metabolic processes of the connective tissue were evaluated by the changes in the content of biomarkers of the cartilage (hyaluronan, aggrecan) and bone (fibroblast growth factor-23, osteprotegerin, sclerostin, osteocalcin) tissues. The condition of the free radical oxidation processes was evaluated by the level of lipid hydroperoxides, and the activity of antioxidant system by the parameters of the total antioxidant and thiol statuses.

RESULTS: In rats with the PTOA model, an increase in cartilage tissue biopolymers aggrecan and hyaluronan (p < 0.001) was noted with a negative change in the marker of bone formation (a tendency to increase in the content of osteocalcin) and markers of regulation of bone homeostasis (increased fibroblast growth factor-23, p < 0.001), with a tendency to decrease in the content of osteoprotegerin and sclerostin, in comparison with intact animals of the control group. In parallel with this, an increase in lipid hydroperoxides (p < 0.01) in the systemic bloodstream was detected with a decrease in the thiol status index (p < 0.01) with preserved normal total antioxidant activity (p > 0.05).

CONCLUSION: The data of the conducted study evidences intensification of free radical oxidation and derangement of metabolic processes in the bone and cartilage tissues in animals with a surgical model of PTOA of the knee joint. A negative change in the metabolism of the bone tissue was manifested by the loss of balance of remodeling processes, and metabolic disorders in the cartilage tissue consisted in the destruction of its biopolymers in conditions of intensification of free radical oxidation processes and relative tension of the thiol system with the total antioxidant activity remaining within the physiological norm. The established facts are promising from the point of view of using the studied biomarkers both for the identification of pathogenetic triggers of PTOA of the knee joint, and for the determination of the direction of therapeutic measures.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):177-184
pages 177-184 views

Functional Activity of Reciprocal Inhibition of α-Motor Neurons of Antagonistic Muscles in Different Types of Muscle Contractions of Submaximal and Maximal Force

Gladchenko D.A., Bogdanov S.M., Roschina L.V., Chelnokov A.A.

Abstract

INTRODUCTION: Currently, the results of investigation of different types of spinal inhibition in isometric voluntary contraction of muscles have been published. There are separate reports devoted to the role of recurrent and presynaptic inhibition in the regulation of isometric and anisometric voluntary contractions of submaximal and maximal strength.

AIM: To evaluate the effect of the type and strength of muscle contraction with and without performing Jendrassik maneuver on the manifestation of reciprocal inhibition of α-motor neurons of antagonistic muscles of the lower leg.

MATERIALS AND METHODS: The study involved 8 healthy men aged 20–22 years. Reciprocal inhibition was evaluated by suppression of the amplitude of testing H-reflex of m. soleus in conditioning stimulation of n. peroneus profundus, and of testing stimulation of n. tibialis with 3 msec interval between stimuli. Reciprocal inhibition was recorded in concentric, eccentric and isometric contractions with 50% and 100% of maximal voluntary contraction (MVC) with and without Jendrassic maneuver.

RESULTS: In performing concentric, eccentric and isometric contractions of lower leg muscles with increase in strength from 50% to 100% of MVC, the activity of reciprocal inhibition decreased. Reciprocal inhibition was most evident in concentric contraction with 50% of MVC strength, less evident in eccentric contraction and was lowest in isometric contraction. With the maximal strength, reciprocal inhibition was most expressed in isometric contraction, less expressed in concentric contraction and was weakest in eccentric contraction. With Jendrassik maneuver, reduction of reciprocal inhibition was more expressed in different types of MVCs in comparison with parameters obtained with 50% of MVC. Using Jendrassic maneuver with 50% and 100% of MVC effort, strongest reciprocal inhibition was recorded in isometric contraction, weaker inhibition in concentric contraction and weakest in eccentric contraction. The effect of Jendrassik maneuver was manifested by weakening of reciprocal inhibition in concentric and eccentric contraction of submaximal force, and by its enhancement in isometric contraction.

CONCLUSION: Variability of manifestation of reciprocal inhibition of α-motor neurons of antagonistic muscles of lower leg in different types of muscle contractions of submaximal and maximal strength is associated with the fact that the pool of segmental motor neurons of m. soleus is controlled not only by a wide spectrum of excitatory cortico- and reticulospinal influences, but also by other kinds of inhibition, thus providing coordinated motor actions.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):185-194
pages 185-194 views

Therapeutic Drug Monitoring in Uncontrolled Arterial Hypertension: Result of the Pilot Part of Study

Seleznev S.V., Yаkushin S.S., Mylnikov P.Y., Tranova Y.S., Shchul'kin A.V., Yakusheva E.N., Nikulina N.N.

Abstract

INTRODUCTION: Despite the recently established evidence-based and systemic approach to treatment for arterial hypertension (AH), not in all cases its control can be achieved.

AIM: To conduct a comparative analysis of the concentration of antihypertensive drugs (AHTDs) in blood serum of patients with controlled and uncontrolled AH.

MATERIALS AND METHODS: Fifty six patients were included. Inclusion criteria: age ≥ 18 years, signing of informed consent, established diagnosis of AH, regular intake of any two of study antihypertensive drugs (lisinopril, amlodipine, valsartan) and also of indapamide at stable doses, for women — adequate contraception. According to the results of daily monitoring of the arterial pressure (AP), patients were divided into two groups: the first group — controlled hypertension (AP < 140/90 mmHg; n = 39), the second — uncontrolled hypertension (AP ≥ 140/90 mmHg; n = 17). The mean age of patients in the first group was 65.03 ± 10.80 years, in the second — 63.50 ± 8.31 (p = 0.576). In the first group, women prevailed (64.1% vs. 35.3%, p = 0.047) and the mean body mass index was lower (26.30 ± 1.38 kg/m2 vs. 32.20 ± 4.15 kg/m2, p = 0.02). In patients of both groups, venous blood was taken in fasting condition in the morning and 2 hours after intake of AHTDs to assess their concentration by high-performance liquid chromatography. The analytical range for lisinopril, indapamide, amlodipine was 5–500 ng/ml, for valsartan — 10–10,000 ng/ml.

RESULTS: In the first group, equilibrium concentration of lisinopril was 2.67 times higher (p = 0.053), and concentration of indapamide in 2 hours after intake was 1.83 times higher (р = 0,084); when normalized to the dose, the differences were leveled out (p > 0.05). Concentrations of amlodipine and valsartan did not differ between the groups both before and 2 hours after intake (p > 0.05). In 3 of 39 (7.7%) patients with controlled hypertension and in one of 17 patients (5.9%, p = 1.0) with uncontrolled hypertension, AHTDs were detected in blood serum, which were not administered to them.

CONCLUSIONS: Results of the pilot part of the study (n = 56) demonstrated the absence of difference between the mean concentrations of the study AHTDs in the blood serum of patients with controlled and uncontrolled AH, and in some cases the presence of traces of AHTDs not administered by the doctor.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):195-202
pages 195-202 views

A comparative Hygienic Evaluation of Balance of Lipid Components in the Diet of Medical University Students

Lopukhova I.V., Korolev A.A., Nikitenko E.I., Denisova E.L., Kirpichenkova E.V., Fanda E.A., Petrova E.S.

Abstract

INTRODUCTION: A balanced diet provides the optimal level of metabolism and is one of key modifiable factors of the primary prophylaxis of chronic non-infectious diseases. Excess of the common fat in the diet is the most common alimentary imbalance in nutrition of the population.

AIM: A comparative characteristics of the level of the alimentary intake and of the main alimentary sources of lipid components in medical university students.

MATERIALS AND METHODS: For quantification of entry of lipid components, the method of triple 24-hour reproduction was used. The data on actual nutrition were acquired and analyzed using a specialized questionnaire developed for the given study.

RESULTS: A comparative analysis of levels of intake of the common fat, saturated and polyunsaturated fatty acids did not identify any statistically significant differences in women and men in both groups the main sources of the common fat and saturated fatty acids were hard cheese, milk chocolate, sausage products, chicken eggs, butter and mayonnaise. The main contribution to the required level of polyunsaturated fatty acids, irrespective of gender, were made by sunflower oil, fish, mayonnaise, nuts, seeds, pizza and olive oil.

CONCLUSION: The level of intake of common fat with the diet exceeds the physiological demand in 95.3% of women and 94.8% of men. A share of saturated fatty acids made more than 10% of the energy value in 92% of female respondents and in 94% of male respondents, which is associated with the excessive quantity of the sources of hidden fat in the diet of students of the two comparison groups, such as hard cheese, milk chocolate and sausage products. In 45% of students, owing to the presence of oils, fish, mayonnaise and nuts in their diet, the level of entry of polyunsaturated fatty acids met the physiological demand.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):203-210
pages 203-210 views

Testing of Medico-Sociological Toolkit for Evaluation of Quality of Organization and Affordability of Dental Orthopedic Care

Uspenskaya I.V., Tishkina L.N., Peshkov M.V.

Abstract

INTRODUCTION: The issues of accessibility, quality of organization and satisfaction of Russian citizens with dental orthopedic care (DOC) are insufficiently studied and covered in the literature, which increases the relevance of the topic of our study ‘Scientific Substantiation of Criteria and Pa-rameters of Accessibility and Quality of Organization of Dental Orthopedic Care’. For this study, a medico-sociological toolkit is tested, which presents a questionnaire of 36 questions developed by the authors for evaluation of the quality of organization of DOC and of its affordability for the population.

AIM: To test the medico-sociological toolkit by evaluating the filling out of the questionnaire by patients.

MATERIALS AND METHODS: The questionnaire was developed on the basis of ethical and de-ontological principles with taking into account the quality management standards (ISO 9001:2015). In a comparative analysis and evaluation of affordability of DOC, the level of family income of patients was expressed in relative parameters — minimum living wages. The pilot study was conducted on the basis of an enlarged dental clinic with surveying 41 patients who received DOC.

RESULTS: Filling out of the questionnaire by patients of a dental clinic was evaluated in part of the study of affordability and the study of satisfaction with the quality of DOC organization — 7 and 12 questions, respectively. Positive results of testing of the medico-sociological toolkit are presented.

CONCLUSION: In the course of the pilot study, the Questionnaire was tested, no primary cor-rections were required. The algorithm of processing and analysis of the primary materials of the planned medico-sociological study was determined.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):211-220
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Prognostic Significance of Cardiac Fat Deposits in Patients with Coronary Heart Disease

Uryasyev O.M., Solov’yeva A.V., Cheskidov A.V., Filimonova A.A., Nikiforova E.А.

Abstract

INTRODUCTION: Obesity is one of the leading risk factors for the development of cardiovascular diseases. At present, of the greatest scientific interest are local deposits of adipose tissue as a possible morphological substrate for the development of this group of diseases. Along with the traditional risk factors, one more risk factor for a poor prognosis of cardiovascular disease can be a change in the thickness of the epicardial fat (EF) and of the interatrial septum (IAS) in case of its lipomatosis.

AIM: To study the significance of EF and of IAS thickness as markers of cardiovascular risk in coronary heart disease.

MATERIALS AND METHODS: The study involved 116 individuals with coronary heart disease (55 men (47%) and 61 women (53%), mean age — 68 [61; 72] years). Thickness of EF and IAS was evaluated by the method of echocardiography. The frequency of poor outcomes was evaluated using Kaplan–Meier method, ROC-curve analysis. The differences were considered statistically significant at p < 0.05.

RESULTS: In the group of patients with unstable angina, the threshold value of IAS thickness was 0.7 cm (p < 0.001), and of EF thickness — 0.8 cm (÷2 = 10.89, p = 0.001), in the group of patients with myocardial infarction — 0.7 cm (p < 0.001) and 0.8 cm (p < 0.001), respectively. In the group of patient with unstable angina, IAS thickness > 0.7 cm (÷2 = 10.3, p = 0.0013) and EF thickness > 0.8 cm (÷2 = 10.89, p = 0.001) demonstrate a poor prognosis in comparison with the parameters below the threshold values. In the group of patients with myocardial infarction, IAS thickness > 0.7 cm (÷2 = 8.4, p = 0.005) and EF > 0.8 cm (÷2 = 9.66, p = 0.0019) demonstrate poor prognosis in comparison with the parameters below the threshold values.

CONCLUSION: In unstable angina and myocardial infarction, the value of IAS thickness > 0.7 cm (p = 0.0013 and p = 0.005, respectively) and of EF thickness > 0.8 cm (p = 0.001 and p = 0.0019, respectively) present a poor prognosis compared to lower values. It is recommended that EF and IAS thickness be determined in echocardiography as an additional marker for a poor prognosis in coronary heart disease.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):221-230
pages 221-230 views

Criteria of Formation of Fatty Liver Disease in Individuals of Different Age Groups in the Long-Term Period after Minimally Invasive Cholecystectomy

Ambartsumyan A.R., Chumak B.A., Deryagina L.E., Batskov S.S., Pyatibrat E.D.

Abstract

INTRODUCTION: Despite the technical advance in medicine and the use of minimally invasive laparoscopic techniques, complications of cholecystectomy considerably reduce the quality of life of the operated patients. Development of the most common and severe complication — fatty liver disease (FLD) — is difficult to predict due to numerous factors that influence its formation.

AIM: To identify prognostic criteria of formation of FLD in the long-term period after cholecystectomy and to scientifically substantiate their significance.

MATERIALS AND METHODS: To identify prognostic criteria of formation of FLD in the long-term period after minimally invasive cholecystectomy, 330 patients (159 men and 171 women) who underwent surgical treatment, were examined. Anthropometric data, hemodynamic parameters were evaluated, autonomic index was calculated. US evaluation of choledoch and Elastography of the liver, magnetic resonance tomography of the liver and magnetic resonance cholangiopancreatography were performed. Using chromatography-mass-spectrometry, microbial markers of parietal microbiome of the intestine were determined.

RESULTS: Parameters of body mass index indicate the interrelation between the formation of FLD and increased body mass in patients of older age. In the first group with FLD, sympathetic status prevailed, and in the control group of the same age, parasympathicotonia was predominating. At the older age, in the second and third subgroup, the autonomic regulation did not influence the formation of FLD. The choledoch diameter in men and women with FLD of the first age subgroup was greater relative to patients of the control group and of the preoperative period and also relative to older patients of the same group. In the long-term period after cholecystectomy in the group with fatty liver disease, the opportunistic microflora prevailed over essential one, and aerobic microflora — over anaerobic one. Besides, increased amount of fungi and viruses was noted, as well as a change in the distribution of obligate microflora due to decrease in the content of eubacteria and predomination of lactobacteria over bifidobacteria in the parietal layer of the intestine. In the individuals of older age, reduction of the obligate and increase in the opportunistic microflora including aerobic one, was noted.

CONCLUSIONS: Age, autonomic regulation and body mass have a significant influence on the formation of FLD in the long-term period after cholecystectomy. In the group of older patients, the influence of the autonomic regulation is lower, and increase in body mass is higher than in younger individuals.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):231-242
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Analysis of Risk Factors of Venous Thromboembolic Complications and of Different Variants of Anticoagulant Therapy in Patients with New Coronavirus Infection

Kalinin R.E., Suchkov I.A., Agapov A.B., Mzhavanadze N.D., Povarov V.O., Nikiforov A.A.

Abstract

INTRODUCTION: A new coronavirus infection (NCI) is characterized by catastrophic coagulopathy with development of thrombotic and hemorrhagic complications. The choice of an optimal anticoagulant in these patients remains an important issue.

AIM: To evaluate risk factors for venous thromboembolic complications (VTEC), effectiveness and safety of different variants of anticoagulant therapy (ACT) in patients with NCI.

MATERIALS AND METHODS: A prospective study was conducted that involved 370 patients with NCI: group 1 — patients who received low molecular weight heparin (LMWH) — 190 people, group 2 — patients who received unfractionated heparin (UFH) — 123 people, group 3 — patients who took direct oral anticoagulants (DOAC) — 57 individuals. Clinical and anamnestic data, frequency of thrombotic and hemorrhagic complications were evaluated. The study was approved by the Local Ethics Committee and was registered on ClinicalTrials.gov. platform.

RESULTS: The existence of chronic venous diseases increases the risk of development of venous thromboembolism (VTE) in patients with NCI 6.433 times (95% confidence interval (CI) 2.167–19.093)) (р = 0.001), use of UFH instead of LMWH or DOAC — 3.542 times (95% CI 1.149–10.916) (р = 0.028), use of artificial lung ventilation (ALV) — 5.925 times (95% CI 2.034–17.26) (р = 0.001), high D-dimer level — 2.024 times (95% CI 1.231–3.33) (р = 0.005). The level of C-reactive protein and ferritin decreased in all patients in the course of treatment for NCI, with the lowest levels in patients receiving LMWH (С-reactive protein — 5.8 (1.7–15.0) mg/l, р = 0.004; ferritin — 364 (324–497) µg/l, р = 0.001). Lower fibrinogen levels were recorded in patients of group 1 compared to groups 2 and 3 (2.43 (1.9–3.52) g/l versus 3.37 (2.8–4.92) g/l and 4.1 (2.8–5.25) g/l, respectively, р = 0.002). A high frequency of pulmonary embolism with unspecified source was recorded in patients receiving UFH — 11.4% of cases, with this, the frequency of using ALV in the group with UFH was evaluated as high — 21% of cases.

CONCLUSION: Risk factors of VTEC in patients with NCI are both factors typical of VTEC in general (obesity, chronic vein diseases, elevated D-dimer level), and factors specific of NCI (ALV, hypoventilation). Effective and safe anticoagulants in this group of patients are LMWH that demonstrated low frequency of development of VTEC and of hemorrhagic complications.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):243-254
pages 243-254 views

Evaluation of Cytotoxicity of Gold Glyconanoparticles of Human Colon Adenocarcinoma Cells

Chernykh I.V., Kopanitsa M.A., Shchul'kin A.V., Yakusheva E.N., Ershov A.Y., Martynenkov A.A., Lagoda I.V., Volkova A.M.

Abstract

INTRODUCTION: Use of metal nanoparticles is a promising trend in oncotherapy.

AIM: To evaluate cytotoxicity of gold nanoparticles (GNPs) modified with fucose, lactose and galactose residues, on Caco-2 cells.

MATERIALS AND METHODS: Cells were cultured to a monolayer with GHPs in concentrations of 10 µg/ml–600 µg/ml for particles with fucose, 10 µg/ml–900 µg/ml for particles with lactose and 10 µg/ml–550 µg/ml for particles with galactose. As non-tumor cells, Caco-2 cells were used after differentiation into small-intestine enterocytes (incubation time — 21 days). The cytotoxicity of GNPs was evaluated in MTT-test after incubation with cells for 2 hours, 8 hours and 24 hours. A comparison drug was fluorouracil in concentrations of 50 µg/ml–2000 µg/ml. The half-maximal inhibitory concentration (IC50) was calculated in GraphPad Prism 8.4.3 program.

RESULTS: IC50 for GNPs with fucose for tumor cells was 582 ± 29 and 336 ± 36 µg/ml after incubation for 2 hours and 8 hours, respectively; for GNPs with lactose — 769 ± 50 and 515 ± 45 µg/ml, for GNPs with galactose — 467 ± 299 and 299 ± 28 µg/ml. For differentiated cells, IC50 for all types of GNPs was higher than for tumor cells after incubation for 2 and 8 hours: for particles with fucose — 530 ± 3 and 410 ± 15 µg/ml; for particles with lactose — 831 ± 7 and 639 ± 14 µg/ml; for particles with galactose — 511 ± 21 (p = 0.018) and 376 ± 36 µg/ml, respectively. After 24-hour incubation of Caco-2 cells with fucose, IC50 did not differ for tumor and differentiated varieties. For other GNPs, IC50 for tumor cells was higher than for differentiated cells. Fluorouracil showed cytotoxicity for tumor cells with IC50 2108 ± 19 and 1764 ± 193 µg/ml after 2 hours and 8 hours of incubation, respectively. For differentiated cells, IC50 of fluorouracil was 1694 ± 102 µg/ml after 2-hour incubation and 1694 ± 102 µg/ml after 8-hour incubation. There were no differences between IC50 of fluorouracil for differentiated and tumor cells with equal incubation time.

CONCLUSION: GNPs with fucose, lactose and galactose have a cytotoxic effect on human colon adenocarcinoma cells and in the activity are superior to fluorouracil.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):255-264
pages 255-264 views

Expression of FOXP3 of Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer: Its Relationship to Histopathological Parameters and Overall Survival

Hagone S., Bharat P.U., Gupta A., Nitin G.

Abstract

BACKGROUND: Forkhead box P3 protein (FOXP3) is expressed in both tumor cells and tumor-infiltrating lymphocytes (TILs) and is reported to be associated with differences in clinical outcomes. Recent literature shows that FOXP3 positive (FOXP3+) T regulator cells (Tregs) influence anti-tumor immunity in solid tumors.

АIM: To explore FOXP3+ Tregs expression related to various prognostic factors in breast carcinoma (BC) in the central Indian population. Our study is also helpful in correlating the role of FOXP3+ Tregs in the survival of invasive ductal BC with different histopathological presentations.

MATERIALS AND METHODS: This is a retrospective and prospective observational study in which FOXP3+ Tregs was counted in the peritumoral area by immunohistochemistry in 47 consecutive cases of BC operated on and diagnosed already. The patients were followed for 48 to 69 months for disease progression.

RESULTS: High-grade tumors are prevalent (n = 30) in the study area irrespective of the stage of clinical presentation. Patients who could adhere to their treatment plan remained free of adverse outcomes until the end of our follow-up period of 69 months (p = 0.001). No molecular subtype in our study showed specific predilection towards a high Tregs count in the peri-tumoral area. No other clinical or pathological parameters significantly correlated with FOXP3 +Treg count, including overall survival and disease-free survival.

CONCLUSION: The study shows that luminal human epidermal growth factor receptor 2 negativ and human epidermal growth factor receptor 2 enriched BC show comparatively high FOXP3+ Tregs count. There is no relation with tumor grade, TNM stage, important immune markers, or overall survival and disease-free survival.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):265-272
pages 265-272 views

Comparative Analysis of Gene Expression Profile in Tumor and Healthy Tissue in Patients with Colorectal Cancer

Mertsalov S.A., Kulikov E.P., Strel'nikov V.V., Kalinkin A.I., Shumskaya E.I., Piskunov R.O.

Abstract

INTRODUCTION: Colorectal cancer (CRC) is a sure leader among malignant neoplasms (12.3%), without taking into account gender. Five-year survival rate in stage I CRC is 91%, in stage IV — 14%. The currently existing treatment methods are helpless to significantly reduce mortality the approaches should be personalized and include the use of molecular genetic methods.

AIM: To perform a comparative evaluation of expression profile of samples of tumor and healthy colon tissue in CRC.

MATERIALS AND METHODS: The material for the study was 19 samples of tumor tissue taken from the pathologically altered colonic mucosa of 19 patients with CRC, and 7 samples of ‘healthy’ tissue taken 10 cm–12 cm distally or proximally from the visual boundary of the tumor. Biopsy materials were homogenized using a mechanical method. The quality and quantity of ribonucleic acid in the eluted solution were evaluated using IMPLEN nanospectrophotometer (Germany). Gene expression was evaluated using microchip kit SurePrint G3 HumanGeneExpv3 ArrayKit (Agilent, USА). Microchips were scanned on InnoScan 1100 AL apparatus (США) with subsequent image processing in Mapix Software program (USA).

RESULTS: The analysis of expression profile demonstrated 505 differentially expressed genes, 337 of which showed reduced expression and 168 — enhanced expression in the tumor material. The highest expression was demonstrated by genes bound with miRNA: hsa-miR-29b-3p and hsa-miR-1-5p, and also genes Н19, FOXQ1, INHBA, MMP1, CDH3, CXCL2, MDFI, THBS2. On the contrary, genes TMIGD1, GUCA2B, ZG16, AQP8, SLC4A4, CDKN2B-AS1, CA4, СА1 demonstrated a low expression in the tumor material. Expression of genes responsible for functioning of signal pathways: IL-17, NF-kappa B, TNF, was increased in tumor samples. Genes responsible for signal pathways Fatty acid degradation, Drug metabolism — cytochrome P450, Metabolic pathways, Fatty acid metabolism and Steroid hormone biosynthesis, showed reduced expression.

CONCLUSION: Significant differences were found in the expression profile of tumor and healthy tissue in patients with CRC. A comparative analysis of gene enrichment and the data of the international databases permitted to identify a number of terms, genes, clusters that can be used in future in search for predictors of prognosis and of response to treatment.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):273-282
pages 273-282 views

Clinical reports

Surgical Treatment of Pulmonary Embolism Associated with COVID-19: First-Hand Experience

Fedorov S.A., Zhurko S.A., Pichugin V.V., Chiginev V.A., Maximov A.L., Kulkarni S.V.

Abstract

INTRODUCTION: Venous thromboembolic complications occupy one of the central positions in the structure of complications associated with CoronaVirus Disease 2019 (COVID-19). Characterized by high epidemiological threshold values, as well as an atypical clinical picture, they determine the need for new approaches to early diagnosis and active treatment. Surgical treatment of pulmonary embolism in itself is an extremely controversial method of reperfusion of the pulmonary arterial bed. Concerning pulmonary embolism associated with a new coronavirus infection, we did not find a single clinical case reported in the available literature. The article considers a clinical case of surgical treatment of pulmonary embolism against the background COVID-19 infection, demonstrates a comprehensive approach to treatment and describes peculiarities of the clinical picture.

CONCLUSION: Based on the presented case, one should note the importance of the anticoagulant therapy in a group of people with a virus-specific intervention to prevent recurrence of thromboembolic complications. Complex surgical treatment in combination with the proposed methods of anesthesiological support are the methods of choice in a group of people at intermediate-high and high risk of early cardiac death.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):283-292
pages 283-292 views

Reviews

Analysis of Cognitive Functions and Neurophysiological Processes in Adaptation of Human to Conditions of the Arctic Region

Murtazina E.P., Korobeynikova I.I., Poskotinova L.V., Karatygin N.A., Pertsov S.S.

Abstract

INTRODUCTION: The aim of the work is analysis of one of the most important problems of the modern biomedical science — problem of studying the processes of human adaptation to a complex of climatic and geographic factors and conditions of the Far North in the period of increased necessity in realization of the economic, industrial and defense activity of the government. The review presents the data of scientific study of cognitive functions and neurophysiological changes in people permanently living in or arriving to the Arctic zone. In the first part, the factors are considered that evidence different disorders in memory, concentration, efficiency of performing simple and complex cognitive tasks by test persons in conditions of low temperature, seasonal photoperiodicity, a particular working regime, such as rotational team method, etc. The age-related peculiarities of dynamics of the cognitive processes in children and adolescents living in the Arctic region are considered. The second part of the article presents analysis of scientific data on changes of electrophysiological parameters of the brain structure activity under the influence of individual or complex factors of Arctic conditions. In particular, changes of the encephalographic rhythms, evoked potentials, hemispheric asymmetry and parameters of autonomic regulation of the heart rate variability in the initial condition and on exposure to the factors of the Far North, are described. A necessity of individual typological analysis of the adaptation process characteristics depending on the initial regulatory peculiarities, neurophysiological characteristics of people, duration of their stay in the mentioned conditions, is emphasized. Inconsistency or ambiguity of the presented data indicate the importance of using a complex approach to scientific research which should include systemic analysis of the dynamics of neurophysiological characteristics and parameters of achieved effectiveness of modeled or professional activity in the Arctic conditions.

CONCLUSION: The paper substantiates the necessity of elaboration of personalized methods of increasing the adaptive reserves of people working and living in the Arctic zones; one of these may be modern systems based on biocontrol with feedback from physiological systems of a human. Besides, it is noted that application of the principles of the theory of the functional systems formulated by academician P. K. Anokhin, can contribute to deeper understanding of adaptation processes, changes of cognitive and professional abilities, their neurophysiological support in the Arctic conditions.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):293-304
pages 293-304 views

Endovascular Recanalization Methods in Treatment of Chronic Lower Limb Ischemia: Modern State of Problem

Gaibov A.D., Nematzoda O., Rakhmonov D.K., Davlatov R.K., Kalmykov E.L.

Abstract

INTRODUCTION: The problem of treatment of patients with chronic lower limb ischemia (CLLI) remains extremely important to date. This is first of all due to increase in the number of patients with chronic obliterating diseases of peripheral arteries, which hold one of the leading positions in the structure of morbidity and disability of the population over 60 years. The progression of the disease with development of critical CLLI leads to amputation of the limb within five years in a third of patients. The first line therapy for CLLI is endovascular interventions both stand-alone and with use of hybrid approach, especially in patients with critical CLLI. In many cases of multi-level, especially multifocal lesions of arterial vessels, the choice of revascularization tactics is not yet completely defined.

CONCLUSION: In recent years, there has been a trend of using endovascular revascularization technologies in continued stenosis and occlusions of the lower limb arteries. However, there is an essential need to study their long-term results, as well as to clarify the indications for stenting in critical CLLI.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):305-316
pages 305-316 views

Complex Approach in Examination of Function of the Knee Joint in Patients with Osteoarthritis

Fedoseyev A.V., Chekushin A.A., Tishkin R.V., Dobychin A.N., Zenkin G.Y., Prints A.D., Melyokhina M.S., Tkachik A.V., Zubov A.A.

Abstract

INTRODUCTION: Osteoarthritis (OA) of the knee joint (KJ) is a common problem. The basic factors impairing the function of the KJ are pain and restriction of movement. Evaluation of function of the KJ in OA is an indispensable part of the diagnostic and treatment process. There exists a problem of a quantitative evaluation of pain and restriction of movement of the KJ in OA, associated with the absence of a single standard for evaluation of the KJ function. In the article, the data are given on the modern possibilities for evaluation of the KJ function in OA. The KJ function is evaluated in clinical examination, functional tests, numerous functional questionnaires, as well as with the use of devices for record of movements. Clinical picture of OA of the KJ is evaluated in the clinical examination which includes diagnostic tests, evaluation of the volume of movement, force of muscles, with conclusions about the phenotype of the disease. Functional tests recommended by OARSI (Osteoarthritis Research Society International) are preferable for express-testing, but not all of them have reference values. Functional questionnaires for evaluation of the KJ function exist in many variants, which impedes their choice and interaction between specialists, and they are characterized by different labor intensity in use. There exists a diversity of devices for evaluation of function of the KJ, some of which are expensive, require special rooms, training of the specialist, and take considerable time. Others are simpler in use and inexpensive, but give less reliable results.

CONCLUSION: The authors showed the possibilities of a comprehensive evaluation, described the problem of the lack of a single standard for investigation of the KJ function. A conclusion is made about the necessity to develop a software-hardware complex that maximally satisfies the criteria of objectivity, accessibility and quickness of use for evaluation of function of the KJ in OA.

I.P. Pavlov Russian Medical Biological Herald. 2023;31(2):317-328
pages 317-328 views


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