MEDICO-BIOLOGICAL SCIENCES
ORIGINAL ARTICLES
EVALUATION OF THE EFFECTIVENESS OF ANTI-OSTEOPOROSIS DRUG IN THE ACTIVATION OF THERANKL/OPG CYTOKINE SYSTEM IN EXPERIMENTAL MODEL OF OSTEOPOROSIS IN COMBINATION WITH DIABETES MELLITUS TYPE II
Mamina N.Sh., Bairamov A.A., Karonova T.L., Timkina N.V., Amrakhov M.V., Kuznetsova N.N., Shabanov P.D., Novikov Vasilii Egorovich
Abstract: Objectives. The purpose of the study was to evaluate the processes of osteogenesis, according to the assessment of markers of bone remodeling in blood serum at the stages of treatment of experimental osteoporosis and in its combination with a model of type 2 diabetes mellitus Methods. The study was carried out on an experimental model of osteoporosis in 50 female rats, followed by the induction of type 2 diabetes in some of these rats, using biochemical methods to analyze markers of osteoporosis in blood serum. Results. Based on the results of the study of the content of bone remodeling markers, a dependence of the anti-osteoporosis activity of a composite drug based on succinic acid salts on impaired glucose metabolism in diabetes was revealed. The new drug is highly effective in monotherapy and in combination with vitamin D3 in activating osteogenesis processes in experimental osteoporosis was leveled by metabolic disorders and induction of type 2 diabetes. Conclusion. The new drug was shown to be highly effective in activating osteogenesis processes in an experimental model in female rats and the dependence of the pharmacological effectiveness of the anti-osteoporosis drug on metabolic disorders such as type 2 diabetes.
Keywords: osteoporosis, experimental model, bone remodeling, osteogenesis markers, anti-osteoporosis agent, type 2 diabetes
CLINICAL AND ESTIMATED EFFECTIVENESS OF SUCCINATE-CONTAINING DRUGS IN THE TREATMENT OF PATIENTS WITH ASTHENIC SYNDROM
Buznik G.V., Shabanov P.D.
Abstract: Objective. To analyze the effectiveness of treatment of asthenic disorders in patients with asthenic disorders based on biochemical analyzes of oxidation/antioxidation systems. Methods. In 683 patients with asthenic syndrome due to traumatic, stressful, toxic influences and excessive physical activity, the presence of correlations between the effectiveness of drug treatment with metabolic correctors containing (Mexicor, Cytoflavin, Metaprot Plus) and not containing (Emoxipin, Riboxin, Metaprot) succinate in their structure (composition) was studied. Laboratory parameters of lipid peroxidation (concentrations of diene conjugates and malonic dialdehyde) and antioxidant defense systems (superoxide dismutase activity, reduced glutathione content) were examined in all patients over time. Results. A higher clinical effectiveness of course (over 2-3 weeks) administration of succinate-containing metabolic protectors (Mexicor vs Emoxypine, Cytoflavin vs Riboxin, Metaprot plus vs Metaprot) in eliminating or reducing asthenic syndrome in surgical patients and victims with associated injuries, in patients with neurotic and stress-related disorders, in patients who have suffered a closed brain injury, in patients with a developed dependence on alcohol in the post-abstinence period and in high-achieving athletes under excessive loads were established. These data are confirmed by laboratory studies of the lipid peroxidation system (diene conjugates, malonic dialdehyde) and antioxidant protection (superoxide dismutase activity, reduced glutathione content). Succinate-containing drugs reduced lipid peroxidation to a greater extent and restored antioxidant protection. Conclusion. Oxidation/antioxidation indicators should be considered as an objective and fairly reliable criterion when assessing the effectiveness of antiasthenic drugs.
Keywords: asthenic syndrome, metabolic therapy, effectiveness, succinate-containing drugs, lipid peroxidation, antioxidant systems
SUCCINATE-CONTAINING PREPARATIONS IN THE THERAPY OF ASTHENIC DISORDERS DUE TO BRAIN TRAUMA
Buznik G.V., Zarubina I.V., Shabanov P.D.
Abstract: Objective. Evaluation of the effectiveness of succinate-containing drugs in the treatment of asthenic symptom complex in patients who have suffered closed craniocerebral trauma. Methods. In 116 patients who suffered a single closed craniocerebral injury, men and women aged from 18 to 45 years (average age was 29.8±3.4 years), with illness duration from 3 months to 6 years (average 4.1±1.4 years) we conducted a double-blind, placebo-controlled, randomized comparative study in pairs of the effectiveness of succinate-free and succinate-containing drugs (Emoxipin vs Mexicor, Riboxin vs Cytoflavin and Metaprot vs Metaprot plus). All patients were divided into 8 groups of 13-15 people each, receiving various treatment regimens in accordance with the clinical trial protocol. The course of prescription of drugs (Emoxipin/Mexicor, Riboxin/Cytoflavin and Metaprot/Metaprot plus and placebo) was 15 days. To objectify the study and formalize clinical indicators, the MAST scale was used; color method for assessing the emotional state of M. Luscher; method for determining a simple visual motor reaction; proofreading test using A.G. Ivanov-Smolensky tables and finding numbers using Schulte tables; memory research using A. Luria’s method for memorizing 10 words. The oxidative (content of malonic dialdehyde and diene conjugates) and antioxidant (superoxide dismutase activity, reduced glutathione content) status of patients during the treatment period was also examined in the blood. Results. A course of treatment of patients with the consequences of closed brain injury using succinate-free (Emoxipine, Riboxin, Metaprot) and succinate-containing (Mexicor, Cytoflavin and Metaprot plus) drugs reduced the disturbances of the asthenic symptom complex to varying degrees. A significant positive therapeutic effect was recorded for Metaprot plus > Cytoflavin > Metaprot > Mexicor (substances are arranged in descending order of activity), that is, succinate-containing drugs showed a greater positive effect compared to succinate-free metabolic drugs (Emoxipine and Riboxin). The therapeutic effect of metabolic protectors was to reduce weakness, exhaustion, manifestations of autonomic dysfunction, improve mood and sleep, reduce anxiety and depression. Conclusion. Consequently, succinate-containing metabolic protectors (Mexicor, Cytoflavin, Metaprot plus), when administered in a course of 2 weeks, exhibit a pronounced antiasthenic effect, which consists in normalizing the mental state and improving the somatic health of patients who have suffered a brain injury. The antiasthenic effect of these drugs is generally higher than the therapeutic effects of similar drugs, the structure of which does not contain succinic acid (Emoxipin, Riboxin, Metaprot).
Keywords: closed craniocerebral injury, asthenic syndrome, metabolic therapy, effectiveness, succinate-containing drugs
PREPARATION OF GENOMIC LIBRARIES AFTER SATURATING TRANSPOSON MUTAGENESIS TO SEARCH FOR GENES AFFECTING THE FITNESS COST OF ANTIBIOTIC-RESISTANT BACTERIA E. COLI
Shatalova R.O., Zakharova M.V., Kolosova E.S., Pozdnyakova-Filatova I.Y., Tarlachkov S.V., Nagornykh M.O.
Abstract: Objectives. Development of conditions for carrying out transposon mutagenesis and obtaining libraries for further genome-wide analysis on antibiotic-resistant E. coli mutants. Methods. E. coli resistant mutants to quinolone antibiotics (nalidixic acid and ciprofloxacin) were selected using in vitro selection on the appropriate antibiotics. Analysis of mutations in genes conferring resistance to quinolone antibiotics was carried out using PCR analysis, sequencing and the VectorNTI program. Construction of growth curves for antibiotic-resistant E. coli clones, as well as determination of MICs, were carried out using nalidixic acid and ciprofloxacin. Transposon mutagenesis and preparation of clone libraries was carried out using an optimized procedure for E. coli bacteria. Results. Using in vitro selection, E. coli resistant clones to quinolone antibiotics were selected. Mutations conferring resistance to quinolone antibiotics were analyzed and mapped using Sanger sequencing. A comparative analysis (construction of growth curves, determination of MIC) of resistant clones containing different mutations and their combinations was carried out. Using selected clones, optimal conditions were selected for carrying out saturating transposon mutagenesis and obtaining genomic DNA library preparations suitable for further genome-wide analysis. Conclusion. As a result of this work, methods for conducting transposon mutagenesis and obtaining libraries for genomic analysis of its results on antibiotic-resistant forms of E. coli were optimized. The quality of the libraries obtained in this way meets the requirements for conducting a genome-wide study of the functional role of E. coli genes using the Tn-seq method.
Keywords: transposon mutagenesis, antibiotic resistance, genomic libraries
REVIEWS
NEURON-SPECIFIC PROTEINS AS MARKERS OF BRAIN DAMAGE IN DIABETES MELLITUS
Bykov Yu.V., Baturin V.A
Abstract: Objective. To analyze the results of scientific studies dedicated to detection of neuron-specific proteins (NSP) serving as biomarkers of brain damage in diabetes mellitus (DM). Methods. Papers related to the topic were found using the PubMed, Scopus and eLibrary databases, and a literature review was performed. From the body of selected papers, the most impactful Russian and foreign publications published over the last 15 years were used for analysis. Results. Diabetic encephalopathy (DE) is one of the most severe and long-lasting complications of DM. Neuropsychological tests used to diagnose DE are far from perfect, that’s why there is an ongoing active search for laboratory markers specific to this complication. NSP are markers that reflect brain damage in numerous neurological and psychiatric disorders, and may be viewed as indicators of DE in DM. The most significant NSP for detecting brain damage are the S100 protein, glial fibrillary acidic protein, neuron-specific enolase, myelin basic protein, and brain-derived neurotrophic factor. These NSP were found to be elevated in both type 1 and type 2 DM, which confirms the occurrence of DE in these diseases. Discussion. Inclusion of NSP as part of the diagnostic toolkit in DM would allow doctors to diagnose DE and take steps towards its correction in a timely manner, minimizing the severity of brain dysfunction and improving patients’ quality of life.
Keywords: diabetes mellitus, diabetic encephalopathy, neuron-specific proteins
PROTEASOME SYSTEM OF THE CELL. PARTICIPATION IN PROTEASOME PATHOGENESIS OF DISEASES
Bon E.I., Maksimovich N.Ye., Zimatkin S.M., Belokon S.S., Kokhan N.V., Petuhov Z.A
Abstract:
Objective. Description of the morphofunctional characteristics of proteasomes and their participation in the pathogenesis of diseases. Methods. There are two main approaches for the isolation and purification of intracellular proteasomes: biochemical and affinity. The biochemical method uses various techniques such as stepwise salting, ultracentrifugation, and chromatography. The second method, affinity-based, is based on the use of a special HTBH peptide that contains histidines, a site for cleavage by TEV protease and a biotin-like sequence. This peptide forms a strong bond with avidin, which allows efficient and rapid purification of proteasomes within a few hours. Results. Proteasomes are multi-subunit proteases that reside in the cytosol. Their ubiquitous presence and high content in compartments reflects their central role in cellular protein metabolism. Conclusion. Studies of the proteasome over the last quarter century have provided a profound insight into its structure and function, which has greatly contributed to our understanding of cellular life. However, many questions remain to be elucidated.
Keywords: proteasome, cell, protein, apoptosis, proteasome subunit, protein complex
PRINCIPLES OF CHOOSING ANTIMICROBIAL THERAPY FOR INFECTIVE ENDOCARDITIS IN THE ABSENCE OF ETIOLOGICALLY SIGNIFICANT PATHOGENS
Danilov A.I., Slivkin M.D., Fomin S.G., Trubinal L.V.
Abstract: Objective. To highlight the issues of choosing antimicrobial therapy for infectious endocarditis in the absence of etiologically significant pathogens. Methods. Based on the approved recommendations, the most significant criteria for choosing antimicrobial therapy for culture-negative infectious endocarditis are presented. Results. The established practice in domestic healthcare during the appointment of antimicrobial therapy does not always correspond to modern recommendations. Practitioners often neglect the rules for conducting bacteriological research, in particular the need to take biological material before prescribing antimicrobial therapy. In this regard, the problem of identifying etiologically significant pathogens and the correct choice of antimicrobial therapy for infectious endocarditis in the Russian Federation is extremely relevant. Conclusions. To date, in the Russian Federation, there is extremely insufficient data reflecting the actual practice of managing patients with culture-negative infectious endocarditis. In this regard, it is extremely important to conduct multicenter studies and the subsequent implementation of their results into clinical practice.
Keywords: culture-negative infective endocarditis, bacteriological examination of blood, risk factors, antimicrobial therapy, clinical practice
USE OF ORAL ANTICOAGULANTS IN PATIENTS WITH COVID-19: CURRENT SEARCHES AND CONTRADICTIONS
Petrov V.I., Shatalova O.V., Stetsckiy N.P., Klikova M.S., Komissarova I.A.
Abstract: Objective. To analyse the efficacy and safety (based on data from large randomized trials) of oral anticoagulants at different doses in patients with COVID-19 after hospital treatment. Methods. Completed RCTs on the topic of therapy with oral anticoagulants in COVID-19 patients after hospital treatment were reviewed. Such resources like PubMed, Cochrane Library, Embase, Clinical Trials and UpToDate were used. The search was performed by keywords: COVID-19 and coagulopathy; COVID-19 and rivaroxaban, COVID-19 and thrombosis, COVID-19 and anticoagulants. Results. The results of completed RCTs on oral anticoagulant therapy in patients with COVID-19 demonstrate that prolonged prophylaxis with oral anticoagulants after hospital treatment can reduce the risks of VTE and improve the course of the disease (primarily in patients with ≥2-3 points on the IMPROVE VTE scale and elevated D-dimer level). At the same time, in dispensary practice, there is a tendency to over-prescribe anticoagulants, especially with a mild course of COVID-19. Conclusion. Based on the analysis of large completed RCTs on the topic of prolonged prevention of VTE in patients with COVID-19, it can be concluded that using of oral anticoagulants reduces the risk of thromboembolic complications in patients with COVID-19 after hospital treatment, improves clinical outcomes and prognosis for life. At the same time, the use of rivaroxaban at a dose of 20 mg per day increased the risk of clinically significant bleeding, while not improving the prognosis, and the use of anticoagulants for mild COVID-19 in patients receiving outpatient treatment was probably inappropriate.
Keywords: COVID-19 and coagulopathy, COVID-19 and rivaroxaban, COVID-19 and anticoagulants, COVID-19 and thromboembolism, COVID-19 and mortality
CLINICAL MEDICINE
ORIGINAL ARTICLES
GASTROESOPHAGEAL REFLUX DISEASE AND CHRONIC BRONCHOPULMONARY DISEASES. THE NEED FOR 24-HOUR pH IMPEDANCE MEASUREMENT
Gorbacheva E.M., Ilyushina I.V., Slonchakova D.M., Shadrina N.E., Dekhnich N.N., Punin A.A.
Abstract: Objective. To summarize and present materials on the results of the use and effectiveness of the method of 24-hour pH-impedance measurement for the diagnosis of GERD. To highlight the issues of the general presentation of this research method, the methodology of the 24-hour pH impedance measurement procedure, as well as to assess the prospects of this technique and its diagnostic potential, in particular, the current state and development opportunities in the Russian Federation. Methods. Analysis of more than 20 papers, including individual clinical studies, some meta-analyses, conference materials and a number of historical monographs on the use, benefits and conditions of the 24-hour pH-impedance measurement procedure. Results. The data testifying to the high efficiency of 24-hour pH impedance measurement in the diagnosis of GERD, in particular, in bronchopulmonary diseases, are demonstrated. Outpatient reflux monitoring with pH-metry is the only study that can assess the relationship of reflux symptoms with the development of reflux-associated bronchial asthma. Esophageal pH monitoring is indicated before deciding on antireflux surgery for GERD, usually in patients with discontinued treatment, to confirm the association of symptoms with reflux [13]. The ability of the method to fix high and gas reflux is indispensable for the diagnosis of GERD occurring with atypical symptoms (chronic cough, pharyngitis, regurgitation, etc.) [2]. Information about the methodology and development of 24-hour impedance measurement in world medicine, as well as information about trends in the study of this method in Russia, is presented. Conclusion. 24-hour impedance measurement can be recommended for the diagnosis of GERD and related pathological processes. The current experience of using pH-impedance measurement of the esophagus allows us to consider this method the most accurate and modern in the diagnosis of GERD. In this regard, it is advisable to widely introduce pH-impedance measurement into the practical activities of general practitioners and gastroenterologists to optimize the diagnosis and treatment of GERD [10].
Keywords: 24-hour impedance measurement, gastroesophageal reflux disease, heartburn, bronchopulmonary diseases
CLINICAL CASE OF IDIOPATHIC PULMONARY HYPERTENSION
Shnyreva A.V., Tsareva V.M., Rogutsky B.S.
Abstract: Objective. To give a brief description of the structure of the incidence of pulmonary hypertension in the Smolensk region, as well as to present and analyze a rare clinical case of idiopathic pulmonary arterial hypertension. Methods. A retrospective analysis of clinical case histories of patients diagnosed with pulmonary hypertension for 2013-2023 was carried out on the basis of the departments of general and emergency cardiology of the Smolensk Regional Clinical Hospital. The analysis included 32 case histories. To study the clinical case and LAC, a detailed analysis of the medical documentation of several medical institutions, data from laboratory and instrumental research methods was performed. Results. The article presents a rare clinical case of primary arterial pulmonary hypertension. Patient A. was diagnosed with high pulmonary hypertension at the age of 20. In February 2018, the patient was hospitalized for the first time at the FSBI "NMIC of Cardiology" of the Ministry of Health of the Russian Federation, where idiopathic pulmonary hypertension was diagnosed according to the results of a comprehensive examination (EchoCG, lung scintigraphy). The patient underwent catheterization of the right parts of the heart, according to the results of which SDLA = 102 mmHg, cf. DLA = 77 mmHg, DLA= 6 mmHg. Taking into account the severity of the condition, the patient initiated LAG-specific therapy with an endothelin receptor antagonist - macitentan. In July 2018, there was a deterioration in health, the patient was re-hospitalized in the "NMIC of Cardiology" of the Ministry of Health of the Russian Federation. It was decided to escalate the LAG-specific therapy and administer riocigcate. Due to the high risk of thromboembolic complications, the patient was prescribed warfarin. The patient was discharged with improvement. In 2019, after undergoing acute respiratory viral infection, the patient's condition worsened, and therapy was corrected to triple LAG-specific therapy with the addition of selexipag in the "NMIC Cardiology". In 2020, the patient was taken in severe condition to the SOCB in the ARO after surgical treatment of apoplexy of the right ovary. Conclusions. This clinical example should alert doctors of all specialties in relation to this pathology in order to improve the prognosis of patients with ILAG.
Keywords: primary pulmonary hypertension, idiopathic pulmonary arterial hypertension, Aerza disease
GASTRITIS AND DUODENITIS IN OUTPATIENT PRACTICE AS A REFLECTION OF DYSPEPSIA SYMPTOMS
Zhestkova T.V., Esakova E.M., Efanova L.V., Kryutchenko E.P., Razzhivina E.G.
Abstract: Objective. To assess the prevalence of gastritis and duodenitis in the structure of the general morbidity of the population geographically attached to the city clinic over 5 years of observation. Methods. Data from the annual reports of the city clinic for 2018-2022 were retrospectively studied. Anonymized complaints were summarized, 100 patients with an established main diagnosis according to ICD-10 code K29.3 - K29.7. Results. The incidence of code K29.0 - K29.9 over five years of observation was 1.8±0.2%, of which the proportion of newly diagnosed cases was 6.5±1.0%. In the structure of morbidity, the diagnosis prevailed: unspecified gastritis (K29.5) - 76.7±4.0%. The complaints of patients treated with the established diagnosis according to code K29.0 - K29.9 were: pain - 84% of cases, nausea - 67%, feeling of heaviness in the epigastrium after eating - 63%, heartburn - 61%, belching - 58%. Of all biopsies of the gastric mucosa performed per year, non-cardiac gastric cancer was detected in 6.6±0.1% of cases. A significant increase in the proportion of patients aged ≥60 years with an established diagnosis of gastritis and/or duodenitis was revealed, and the age of patients with diagnosed non-cardiac gastric cancer was 66.4±1.1 years. Conclusions. Gastritis and duodenitis remain common outpatient nosology, associated in clinical practice primarily with subjective symptoms - pain and dyspeptic symptoms.
Keywords: gastritis, dyspepsia, duodenitis, morbidity
DYNAMICS OF VENTRICULAR RHYTHM DISORDERS DURING REHABILITATION MEASURES IN HYPERTENSIVE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE OF DUST ETIOLOGY
Ignatenko G.A., Mukhin I.V., Sochilin A.V.
Abstract: Objective. To analyze the influence of two rehabilitation programs on the dynamics of ventricular arrhythmias in hypertensive patients with chronic obstructive pulmonary disease (COPD) of dust etiology. Methods. The study included 108 hypertensive patients (all men) with dust COPD. Using a random sampling method, they were distributed into 2 comparable observation groups. Patients of group 1 received only a basic rehabilitation cardio-respiratory complex, and representatives of group 2 additionally received daily sessions of interval normobaric hypoxic therapy (INBHT) for 15 days. For quantitative analysis of ventricular arrhythmias, 24-hour ECG monitoring was performed. To conduct 15-day sessions of INBGT, a hypoxicator “Bio-Nova 204AF” (scientific and technical association “Bio-Nova”, Russia) was used. Statistical processing of the results was carried out using the Statistica 6.0 program. Results. The total frequency of ventricular arrhythmias during initial ECG monitoring in group 1 was 63.6%, in group 2 - 62.3%, respectively (p>0.05). The first place in the groups of patients in terms of frequency was taken by class 1 according to Lown-Wolf as modified by Ryan M. (43.6 and 43.4%, respectively, p>0.05). The second place in frequency was taken by class 2 (20.0 and 18.9%, respectively, p>0.05). Under the influence of two rehabilitation programs in patients with class 1, there was a tendency to increase by 1.9% (p>0.05) in group 1 and, on the contrary, decrease by 7.6% in group 2 (p<0.05). At stage 2, the difference in class 1 frequency between patient groups was 9.7%. The initial incidence of class 2 was 20.0 and 18.9%, respectively (p>0.05). In group 1, there was a tendency to reduce the frequency of class 2 by 1.8% (p>0.05), and in group 2, a significant decrease by 5.7% (p<0.05) compared with similar values. The difference between groups at stage 2 was 5.0%. Conclusion. The average incidence of ventricular arrhythmias of classes 1 and 2 in hypertensive patients with dust COPD was 63%. Traditional rehabilitation measures did not have a significant effect on the incidence of ventricular arrhythmias. The rehabilitation program with INBHT made it possible to significantly reduce the incidence of class 1 and 2 in patients with combined hypertensive-respiratory pathology without the additional use of antiarrhythmic drugs.
Keywords: ventricular arrhythmias, dynamics, hypertensive patients, dust COPD, rehabilitation
CORRECTION OF MYOCARDIAL ELECTRICAL INSTABILITY IN VENTRICULAR RHYTHM DISORDERS WITH TYPE 2 DIABETES MELLITUS
Mukhin I.V., Zubritsky K.S., Miminoshvili V.R.
Abstract: Objective. The choice of tactics for correcting electrical instability of the myocardium and analysis of factors influencing the prognosis of ventricular arrhythmias in patients with type 2 diabetes mellitus (type 2 DM). Methods. The study included 133 patients with type 2 diabetes with ventricular arrhythmias, which were classified according to Lown B. and Wolf M. (1971). The patients were randomized into 3 observation groups. The entire study period was divided into 3 stages. Patients of group 1 (n=44) received amiodarone and a beta-blocker (BAB). Representatives of the 2nd group (n=45) received the same treatment, but in combination with meldonium. Representatives of group 3 (n=44) received treatment with amiodarone, BAB, and trimetazidine. All patients underwent ECG, 24-hour cardiac monitoring, and echocardiography. Results. The frequency of classes of ventricular arrhythmias among the examined patients was different. Thus, the frequency of class III was 54.9%, class IVA - 26.3%, class IVB - 11.3%, class V - 7.5%. Potential causes of electrical instability of the myocardium are hypoglycemia, postprandial hyperglycemic “peaks”, silent myocardial ischemia, post-infarction cardiosclerotic changes, left ventricular hypertrophy, left ventricular diastolic dysfunction, insulin resistance, hyperinsulinemia. In group 1, the dynamics of class III frequency was characterized by a significant decrease from stage to stage. In group 2, the frequency of the same class also decreased, however, between stages 1 and 2 in the form of a trend, then between stages 2 and 3 in the form of a statistically significant decrease. In group 3, on the contrary, a significant difference was noted between the stages and, unlike groups 1 and 2, in this group there was not a decrease in frequency, but, on the contrary, its increase. The frequency of class 4A in groups 1 and 2 did not change, while in group 3 it had a significant decrease both compared to the initial and intermediate values. The frequency of classes 4B and 5 did not change in all groups. Conclusion. In patients with type 2 diabetes with ventricular arrhythmias, the frequency of class III was 54.9%, class IVA - 26.3%, class IVB - 11.3%, class V - 7.5%. Potential causes of the occurrence/maintenance of ventricular arrhythmias are: hypoglycemia, postprandial hyperglycemic “peaks”, BMI, left ventricular hypertrophy, post-infarction scar changes, left ventricular diastolic dysfunction, insulin resistance and hyperinsulinemia. Trimetazidine as a component of complex antiarrhythmic therapy made it possible to significantly more effectively reduce the frequency of classes 3 and 4A, and the antiarrhythmic effect increased with long-term use of the drug. Cardioprotectors as components of a comprehensive antiarrhythmic program did not have a statistically significant effect on the frequency of high-grade ventricular arrhythmias.
Keywords: electrical instability of the myocardium, ventricular arrhythmias, type 2 diabetes mellitus
PAROXYSMS OF ATRIAL FIBRILLATION DURING PLANNED CARDIAC SURGERY UNDER CARDIOPULMONARY BYPASS
Gulyaeva-Seltsovskaya E.P., Dhif I., Mols A.A., Simonyan A.O., Chomakhidze P.Sh., Kopylov F.Yu., Komarov R.N.
Abstract: Objective. To identify the incidence and predictors of the development of atrial fibrillation paroxysms that occur in the perioperative period during planned interventions on the aorta and heart valves under cardiopulmonary bypass. Methods. The study included 200 patients who underwent elective cardiac surgeries on the heart valves, thoracic aorta, including Ozaki-operation and `Russian Conduit`, coronary artery bypass grafting or mammary coronary artery bypass grafting, and had no history of AF. A complete preoperative examination was performed. Results. AF paroxysms were registered in 19 patients (9.5%) of all patients included in the study, of which 78.95% of episodes were asymptomatic. The majority (80%) of paroxysms occurred in the first 5 days after surgery. Episodes of AF have been regarded as the main cause of 66,7% of all non-fatal myocardial infarctions (MI) in the perioperative period and 50% of fatal MI. Patients with AF were significantly more likely to suffer from a history of hypertension, diastolic myocardial dysfunction of the 2nd degree, as well as with initial hypokalemia. Among the ECHOCG data, the development of perioperative episodes of AF was associated with an increase in the left atrial volume index of more than 37 ml/m2, as well as a decrease in the left atrial ejection fraction below 40%. Conclusion. 9.5% of patients after elective interventions on the aorta and heart valves developed episodes of AF that required medical cardioversion. Multivariate analysis identified predictors of arrhythmia development, which determine the group of patients requiring continuous ECG monitoring for at least 5 days after surgery.
Keywords: aorta, heart valves, surgery, atrial fibrillation, perioperative risk
CONDITION OF THE CARDIOVASCULAR SYSTEM IN PATIENTS WITH ANEMIC SYNDROME
Emomzoda I.Kh., Odinaev Sh.F., Rajabzoda M.E., Faizulloev H.T., Tursunov R.A.
Abstract: Objective. The purpose of the study is to identify disorders of the cardiovascular system and myocardial contractile function in patients with anemic syndrome. Methods. The work is based on the results of a cardiological examination and inpatient treatment of 120 patients with anemia of varying degrees, having functional and organic disorders of the cardiovascular system. The study was conducted for the period from 2019 to 2023 in the departments of the Republican Clinical Center of Cardiology in Dushanbe. Results. In patients with a mild degree of anemic syndrome, the following changes were identified: arterial hypertension was recorded in 6 (15.0%) patients, decreased levels and stable hypotension were recorded in 6 (15.0%) patients. According to ECG recordings, no heart rhythm disturbances were detected in patients of this group, and the heart rate in this group of patients had a stable tendency towards moderate tachycardia. In patients with moderate anemic syndrome, arterial hypertension was recorded in 11 (27.5%) patients, stable hypotension was observed in 8 (20.0%) patients. Extrasystole was detected in 3 (7.5%), sinus tachycardia - in 18 (45.0%), bradycardia - in 5 (12.5%) patients. Examination of patients with severe forms of anemic syndrome revealed various deviations from the functioning of the cardiovascular system. More than half of the group of 22 (55.0%) patients with severe anemia had sinus tachycardia, while bradycardia was recorded in 9 (22.5%). Elevated blood pressure figures were noted in 21 (52.5%) patients, various rhythm and conduction disturbances were observed in 33 (82.5%) patients, which were recorded in the form of extrasystoles, bundle of His branch blocks, disturbances in repolarization processes, subendocardial myocardial ischemia and other violations. Conclusion. In patients with iron deficiency anemia of moderate and severe severity, myocardial remodeling disorders are formed, which is manifested by a violation of the segmental (local) diastolic function of the left and right ventricles, dilation of the heart cavities, hypertrophy of the left ventricular myocardium, the interventricular septum against the background of a global decrease in myocardial contractility.
Keywords: iron deficiency anemia, cardiovascular system, myocardial function, anemic syndrome
EFFECT OF SACUBITRIL/VALSARTAN ON SYSTEMIC MARKERS OF INFLAMMATION AND FIBROSIS DEVELOPMENT IN PATIENTS WITH HFpEF AND ADVANCED LEFT VENTRICULAR HYPERTROPHY
Gvozdeva A.D., Filatova A.Yu., Svirida O.N., Sobolevskaya M.S., Zakiev V.D., Ageeva S.F., Masenko V.P., Ageev F.T., Ovchinnikov A.G.
Abstract: Objective. To assess the effect of angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) on markers of inflammation and fibrosis,clinical status andleft ventricular (LV) diastolic functionin patients with heart failure with preserved ejection fraction (HFpEF) and advanced concentric LV hypertrophy (LVH). Methods. The open-label, prospective study included 61 patients with HFpEF in NYHA functional class II-III and moderate/severe hypertensive concentric LVH (LV mass index ≥132 g/m2 for men or ≥109 g/m2 for women). The participants were randomized to receive S/V (100-400 mg/day, n=30) or individualized therapy (that includes ACE inhibitors or ARBs, n=31) for 6 months. All patients underwent an echocardiographic study, assessment of quality of life, a 6-minute walk test (6MWD) and assessment of pro-inflammatory (high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1)) and pro-fibrotic markers (C-terminal type I procollagen propeptide (PIСP), N-terminal type III procollagen propeptide (PIIINP), growth differentiation factor-15 (GDF-15), galectin-3, soluble ST2 (sST2), osteopontin), NT-proBNP at baseline and after 6 months. Results. After 6 months, S/V showed an increase in 6MWD and a decrease in the Minnesota Quality of Life Questionnaire scores (p <0.05 compared to the control group). S/V showed a decreasein LV mass index, LA volume and E/e' ratio (p <0.05). After 6 months of taking S/V, there was a decrease in hsCRP level (by 28% [-54; -16]; % p <0.001), osteopontin (by 17 % [-63 - -3] %; p=0.046) and NT- proBNP (by 27% [-43 - -24] %; p < 0.001) levels compared with the control group. There was an inverse correlation between hsCRP level and 6MWD (r=-0.44; p=0.002); positive correlation between hsCRP level and Minnesota Quality of Life Questionnaire score (r=0.35; p=0.013) and NT-proBNP (r=0.44; p=0.001). Conclusions. In patients with HFpEF and advanced LV hypertrophy, treatment with S/V was associated with an improvement in exercise capacity and quality of life, a decrease in LV myocardial mass and an improvement in LV diastolic function, as well as a decrease in NT-proBNPlevel. The positive clinical and hemodynamic effects of sacubitril/valsartan may be associated with the anti-inflammatory and antifibrotic effects because treatment with S/Vwas associated with a decrease inhsCRP andosteopontin levels. Changes in hsCRP correlated with changes in 6MWD, quality of life, and NT-proBNP level.
Keywords: neprilysin, natriuretic peptide, sacubitril, heart failure with preserved ejection fraction
ELECTROENCEPHALOGRAPHY INDICATORS OF CHILDREN WHO HAVE SUFFERED CHRONIC INTRAUTERINE HYPOXIA AND ARE BROUGHT UP IN SOCIAL INSTITUTIONS
Udovenko A.A., Shestakova V.N., Evseev A.V., Sosin D.V., Glushchenko V.A., Morozova A.A., Indyukova E.D., Lyamec L.L.
Abstract: Objective. To identify the features of the main indicators when registering background EEG in primary school-age children living in social institutions and minors who have suffered chronic intrauterine hypoxia in the antenatal period. Methods. The study involved students of the initial stage of general education (n=75). Of these, 45 children made up the main observation group who experienced chronic hypoxia in the antenatal period. The comparison group included children who did not have chronic intrauterine fetal hypoxia (HVUG). The background EEG was recorded using the Mizar-EEG-202 electroencephalograph. For the analysis of the background EEG data, sections without the presence of artifacts were used, which were divided into epochs of 2.56 seconds, with a total duration of at least 30 seconds. The values of the relative EEG power were determined for the examined groups. Mathematical processing of materials was carried out using application programs on a personal computer. Results. As a result of the examination, the main indicators of alpha, beta, delta and theta rhythms of the background EEG in the main observation group and the comparison group were determined. It was found that the indicators of the maximum and average amplitude of the alpha rhythm in the left and right leads in both observation groups were within normal values (norm 20-100 MV) (p>0.05). The dominant frequency and asymmetry of the alpha rhythm between the right and left hemispheres did not exceed the limits of the norm, and there were no significant differences in them (p>0.05). The amplitude of the beta rhythm in children with HVUG was significantly more often (p≤0.05) recorded at the upper limit of the norm, and also significantly higher (p≤0.05) than in children without HVUG in the anamnesis. There were no significant differences in the registration of the delta rhythm and its average amplitude indicators between the main observation group and the comparison group (p>0.05). The average value of the theta rhythm amplitude was significantly higher (p≤0.05) in the main group than in the comparison group. Conclusions. According to the data of the study, beta activity in children with HVUG is higher than in children without HVUG, and is at the upper limits of the norm, which characterizes the activity of the network of gabaergic inhibitory neurons of the neocortex, and is expressed in a higher level of external excitatory impulse and relatively strong intracortical inhibition. Theta activity in children with HVUG during background EEG recording indicates a stronger emotional arousal.
Keywords: schoolchildren of the initial stage of education, chronic intrauterine hypoxia, electroencephalogram indicators
FEATURES OF PEPTIC ULCER IN ADOLESCENTS AGAINST THE BACKGROUND OF CONNECTIVE TISSUE DYSPLASIA
Osovetskaya Yu.L., Kildiyarova R.R., Legonkova T.I., Chervyakova Ya.I., Shtykova O.N.
Abstract: Objective. To determine the relationship between gastric and/or duodenal ulcers and phenotypic manifestations of connective tissue dysplasia (CTD) in children. Methods. The study involved 53 children aged 10 to 17 years with peptic ulcer of the stomach and duodenum at the Morozov Children's City Clinical Hospital. The patients were divided into two groups: the main group - 33 patients with signs of CTD and the comparison group - 20 patients without signs of CTD. The diagnosis of peptic ulcer was verified clinically and endoscopically; DST was established based on the presence of primary and secondary signs recommended by the Federal Clinical Guidelines for Connective Tissue Dysplasia. To compare the two groups, the method of correlation analysis was used; error values p<0.05 were taken as the borderline level of statistical significance. Results. In all observed children, the diagnosis of peptic ulcer was verified clinically and endoscopically; concomitant diseases were gallbladder dyskinesia in 41.5%, functional constipation - 32.1%, iron deficiency anemia - 26.4% of cases. In the main group, ulcerative defect was observed more often in the stomach - in 75.8%, less often - in the duodenum - 24.2%. In the comparison group, all children (20 people) had duodenal ulcer. It should be noted, that during the formation of an ulcerative defect in the duodenum in the presence of DST, the occurrence of “mirror” ulcers was noted in 12.1%, in the absence of such phenomenon in the comparison group. In children of the main group, the disease manifested itself at an earlier age - from 11 years, in the comparison group - 12.5 years. In both groups, a direct strong relationship was found between age and the severity of pain (r=0.74, p=0.001) and asthenic syndromes (r=0.82, p=0.001). But in the main group, medium and strong correlations were noted between pain and asthenic syndrome and signs of connective tissue dysplasia (r is from 0.6 to 0.95, p<0.01). Conclusion. According to our observations, the presence of DST in adolescents with peptic ulcer disease increases the severity of pain, asthenic and upper dyspeptic syndromes, which is confirmed by reliable average and strong correlations. An ulcerative defect is formed more often in the stomach compared to patients without DST, which is characterized by damage to the duodenum. The presence of phenotypic signs of DST should be considered an indicator of the prognosis of a more severe course of ulcerative pathology in adolescents.
Keywords: connective tissue dysplasia, adolescents, peptic ulcer of the stomach and duodenum
CHARACTERISTICS OF THE PHYSICAL AND NEURO-MENTAL DEVELOPMENT OF PRESCHOOL CHILDREN WITH CHRONIC ADENOIDITIS
Sultanov I.S., Boboshko I.E.
Abstract: Objective. The purpose of the study was to identify the features of the physical and neuropsychic development of children aged 4-7 years of different types of psychosocial constitution with chronic adenoiditis. Methods. The study was performed on the basis of the otorhinolaryngological department of the regional children's hospital in the city of Vladimir. Questioning of parents of children suffering from chronic adenoiditis was conducted. The division of children according to the type of orientation of mental activity was carried out jointly with a psychologist and a teacher on a nine-point scale. Children whose expert assessment of the direction of mental activity fluctuated in the range of 1-3 points ("inward orientation") were assigned to the "introvert" subgroup, 7-9 - to the "extrovert" subgroup ("outward orientation"). The sample of children was as follows: extroverts made up 36.8% of the total number of children, introverts 37.9%, centrovers 28.3%. All children underwent an assessment of physical development with in-depth somatometry and somatoscopy, an assessment of neuropsychic development with in-depth psychometry. Results. Introverts with chronic adenoiditis were characterized by a microsomatic type with a lack of body weight, a decrease in fine motor skills, activity in social contacts, and passive social activity. Extroverts were characterized by meso- and macrosomatic types with overweight, low rates of social activity, a decrease in large-motor endowment and visual memory. In children of intro- and extroverts with chronic adenoiditis, the leveling of the strengths and the aggravation of the weaknesses of the physical and neuropsychic organization are shown, which characterizes the characteristics of the health and socialization of the child as a whole. Conclusion. Clinical and functional differences in the course of chronic adenoiditis in intro- and extroverts are the basis for creating differentiated approaches to medical and social support.
Keywords: chronic adenoiditis, psychosomatic constitution, introverts, extroverts, resistance reduction
WANDERING SPLEEN TORSION WITH NECROSIS IN CHILDREN
Labuzov D.S., Stepanov V.N., Abrosimova T.N., Kiselev I.G., Melnikova V.M., Artyomenkova E.I.
Abstract: Objective. To present a description of our own rare clinical observation of a wandering spleen with its torsion, necrosis, and compression of the descending colon in a child. Methods. Information analysis of clinical observation of the wandering spleen torsion with necrosis and compression of the descending colon in a child was carried out. Results. A 4-year-old girl was admitted with abdominal pain and palpable tumor syndrome, vomiting, stool retention over three days. Based on clinical and echographic data, the preliminary diagnosis was made: "palpable tumor" syndrome, colonostasis and suspected colonic abnormalities. After preparation, irrigography was performed: the middle third of the descending colon was persistently displaced by a 6-cm mass adjacent to the colon. Repeated ultrasound scan revealed reveaced 94×43 mm mass in the projection of the middle third of the descending colon, no blood flow, spleen was in a typical place. Intraoperative findings were atypically located spleen with necrosis and omentum wrapping. Splenectomy and resection of adjacent omentum were performed. Post-splenectomy manifestations of post-splenectomic hyposplenism occurred in the postoperative period. Conclusions. The child had the rarest pathology - spleen volvulus with its necrosis and compression of the descending colon. The present clinical case and publications in medical literature show that a wandering spleen remains a difficult diagnostic problem, especially in children.
Keywords: children, wandering spleen, congestion
MAGNETIC RESONANCE IMAGING AS A DIAGNOSTIC STEP IN THE ASSESSMENT OF THE ALCOHOLIC NATURE OF DIFFUSE LIVER DISEASE
Lozbenev F.S., Morozova T.G
Abstract: Objective. To evaluate the possibilities of magnetic resonance imaging in assessing the alcoholic nature of diffuse liver diseases. Methods. From 2019 to 2023 patients with ALD who were treated in the gastroenterological department of the OGBUZ "Clinical Hospital No. 1" were examined. The preliminary clinical diagnosis was established according to the anamnesis, CAGE test, clinical and laboratory parameters, among the patients there were 76 men and 52 women. Comparison group included 57 patients with other pathology of the gastrointestinal tract and absolutely healthy - 10 patients. Results. Upon admission and monitoring of patients, a high correlation between DWI quantitative indicators and elastography and an average correlation with biopsy data was established. The diagnostic and prognostic significance of the developed DWI criteria for liver MRI in patients with ALD at admission for quantitative assessment was carried out. When comparing the results of a qualitative assessment of DWI of the liver during MRI with the data of the CAGE test, the results of a survey of patients and relatives about the use of alcoholic beverages, a high correlation was established between the restriction of diffusion in the liver during MRI and continued intake of alcoholic beverages. Conclusion. 1. Quantitative indicators of DWI MRI allow to establish the clinical form of ALD: ACD for steatosis is 2.67 [2.62; 2.90] ×10-3mm2/s, for steatohepatitis - 2.15 [2.10; 2.20] ×10-3mm2/s, for hepatitis - 1.75 [1.73; 1.80] ×10-3mm2/s, for cirrhosis - 1.18 [1.15; 1.31] ×10-3mm2/s (AUROC 0.985, (95% CI 0.945-0.912)). 2. Qualitative parameters of DWI liver MRI (with/without diffusion restriction) predict continued alcohol intake in patients with ALD in all clinical forms (AUROC 0.997, (95% CI 0.973-0.998)). 3. In patients with ALD, a high correlation was noted with a decrease in liver ACD and negative clinical and laboratory dynamics (r=0.884); high correlation with an increase in ACD and positive clinical and laboratory dynamics (r=0.885).
Keywords: diffusion-weighted images, magnetic resonance imaging, alcoholic liver disease
REVIEWS
LARYNGOPHARYNGEAL REFLUX IN CHILDREN, ADULTS AND PALLIATIVE PATIENTS: PROBLEMS AND PROSPECTS OF DIAGNOSTICS
Razuvaeva Yu.Yu., Ledneva V.S., Leonova V.V., Leonov S.A., Ulianova L.V., Razuvaev O.A.
Abstract: Objective. To study the problem of laryngopharyngeal reflux in children, adults and palliative patients, including epidemiology, etiopathogenesis, clinical picture, differential diagnosis of gastroesophageal and laryngopharyngeal reflux, diagnostic possibilities, drug and non-drug treatment, as well as consequences. Methods. Review of modern domestic and foreign literature on current methods of diagnosis and treatment of laryngopharyngeal reflux in adults, children and palliative patients, in particular clinical recommendations, original articles, including databases Elibrary.ru, Pubmed, Сyberleninka.ru. Results. Currently, laryngopharyngeal reflux (LPR) is a global problem, with maximum detectability occurring in developing and developed countries. LPR is an independent risk factor for diseases of the respiratory tract mucosa, which is a dynamic process of destruction and change of mucosal barriers, which is based on complex mechanisms of interaction between the reflux agent and the mucous membrane. Typical symptoms of LPR include hoarseness of voice, mild dysphagia, prolonged cough, pain when swallowing and a feeling of a foreign body in the larynx. Despite the similarities between LPR and gastroesophageal reflux disease (GERD), these are two different forms of the disease. The Horvath scale is a new promising method of diagnosis, assessment of the severity and type of LPR to determine the dynamics of therapy. Treatment of LFR includes lifestyle modification, as well as long-term use of proton pump inhibitors (PPIs). Conclusion. Laryngopharyngeal reflux is an independent disease and can be combined with gastroesophageal reflux disease, but in this case it is confirmed by the data of daily PH-metry. The Horvath scale is a new promising method of diagnosis, assessment of the severity and type of LPR to determine therapeutic tactics.
Keywords: laryngopharyngeal reflux, children, adults, diagnostics, gastroesophageal reflux, palliative patients
PHARMACEUTICAL SCIENCES
ORIGINAL ARTICLES
STUDYING CHARACTERISTICS OF ADSORPTION OF VINPOCETENE ON COLLOID PARTICLES OF IRON HYDROXIDE SOL
Polkovnikova Yu.A.
Abstract: Objective. To study the adsorption characteristics of vinpocetine on colloidal particles of iron hydroxide sol in order to evaluate various criteria for the efficiency of vinpocetine adsorption on liposomes. Methods. As an adsorbent for reference, an iron (III) hydroxide sol obtained by a chemical reaction was used. To determine the characteristics of adsorption of vinpocetine on colloidal particles of iron (III) hydroxide sol, the equilibrium concentration of vinpocetine in a dispersion medium was determined at various initial concentrations of vinpocetine. The separation of the dispersion medium from colloidal particles was carried out using column chromatography. Quantitative determination of vinpocetine in eluates was carried out by spectrophotometry. The calculated values of adsorption of vinpocetine on sol particles were used to determine the constants of the Freundlich and Langmuir equations. Results. The constants of the Freundlich equations (1/n 0,61401±0,20755; k, mol/kg 49,24816±22,19217) and Langmuir (A∞, mol/kg 0,26566±0,12997; b, mol/kg 0,26566±0,12997; b, mol/kg l 6,21445×10-5±12,556×10-5) were calculated. Conclusion. The data obtained in the course of the work showed that the limiting adsorption of vinpocetine on liposomes is significantly lower than that for the adsorption of vinpocetine on colloidal particles of iron hydroxide sol (III). The constant b of the Langmuir equation is less than that for adsorption on iron (III) hydroxide sol particles, which indicates a fairly effective adsorption of vinpocetine by liposomes at a low concentration.
Keywords: adsorption, vinpocetine, reference adsorbent, iron hydroxide, column chromatography
PHARMACOLOGICAL STUDIES OF AZOXIMER BROMIDE SYRUP
Khamidov M-E.Kh., Ogai M.A., Losenkova S.O., Abisalova I.L.
Abstract: Objective. To study the pharmacological activity of azoximer bromide in the composition of the drug syrup developed by the authors in comparison with the dosage form of the tablet azoximer bromide in a model of dexamethasone immunosuppression. Methods. To create a model of immunosuppression, dexamethasone (JSC "PFC Obnovleniye", Russia) was used intraperitoneally at a dose of 40 mg/kg for 5 days. For therapeutic purposes, male rats were administered orally at a dose of 2 mg/kg body weight for 7 days with 0.1% drug syrup azoximer bromide. Animals in the comparison group received a crushed tablet form of azoximer bromide at a dose of 2 mg/kg also for 7 days. After euthanasia of the animal under anesthesia (chloral hydrate at a dose of 300 mg/kg), venous blood was taken from the right side of the heart, the organs of the immune system were extracted: thymus, spleen, adrenal glands. For histological studies, sections of rat organs were made using a sled microtome. Statistical processing of the results was carried out using the Statistica 10 package. The significance of differences in medians across groups was calculated using the Mann-Whitney test. Results Based on the results of comparative pharmacological studies, it was found that the dosage form "azoximer bromide syrup 0.1%" at a dose of 2 mg/kg of rat weight has an immunomodulatory effect in the model of dexamethasone immunosuppression, comparable to the effect of the dosage form "azoximer bromide tablets 12 mg" at a dose of 2 mg/kg. Conclusion. Therapeutic administration of azoximer bromide syrup 0.1% at a dose of 2 mg/kg of rat weight for 7 days contributed to the improvement of blood parameters, bringing them closer to the values of the intact group. Histological studies of the thymus, spleen and adrenal glands of animals from the groups of tested dosage forms (syrup and tablets) did not reveal pathological changes.
Keywords: azoximer bromide, syrup, tablets, intact group, dexamethasone immunosuppression
DEVELOPMENT OF METHODS FOR ISOLATING CARBAMAZEPINE FROM BIOLOGICAL OBJECTS
Habieva N.A., Lyust E.N., Timerzyanov M.I.
Abstract: Objective. To develop methods for isolating carbamazepine from biological fluids (blood, urine) and biological tissues (liver, kidney). Methods. To study the extraction of carbamazepine from aqueous solutions, a liquid-liquid extraction method was used on standard carbamazepine solutions with a concentration of 10 mcg/ml. Organic solvents were used as extractants: hexane, chloroform, diethyl ether, methyltretbutyl ether, ethyl acetate, a mixture of chloroform-propanol-1 (9:1), extraction was carried out from an alkaline medium (pH 9-10). An experiment to develop a technique for isolating carbamazepine from blood and urine was carried out using model mixtures of urine and blood with a concentration of carbamazepine of 1, 10, 100 mcg/ml. Chloroform and methyltretbutyl ether were tested as extractants, the pH was 9-10. When studying the conditions for isolating carbamazepine from the tissues of internal organs, the liver and kidneys of intact laboratory animals (rats) were used to prepare model mixtures. To prepare the model mixtures, the biological sample was homogenized in distilled water (1:4) using an ultrasonic homogenizer. 250, 500, 1000 ml of carbamazepine aqueous solution with a concentration of 100 mcg/ml was added to 10 g of tissue homogenate (the introduced amount was 25, 50, 100 mcg). To extract the target substance from the tissue homogenate, water and acetonitrile acidified to pH 2 were tested. Next, the extraction was carried out with an organic solvent (chloroform, methyltretbutyl ether). The quantitative determination of carbamazepine in extracts from biological objects was carried out by high-performance liquid chromatography (HPLC). Results. The data obtained showed that chloroform and methyltretbutyl ether are promising for the development of methods for sample preparation of biological objects based on liquid-liquid extraction. Carbamazepine is more fully extracted from biofluids by chloroform. The results of studying the conditions for isolating carbamazepine from biological tissues (liver and kidney) showed that acidified polar solvents (water, acetonitrile) are effective as isolating agents for carbamazepine. Conclusion. It has been established that acetonitrile is the optimal solvent at the stage of carbamazepine isolation from biological tissues, and it is more expedient to use chloroform as an extractant to extract the substance from solutions.
Keywords: forensic chemical examination, carbamazepine, biological fluids, biological tissues, isolation, extraction, chloroform, acetonitrile
INVESTIGATION OF BIOLOGICALLY ACTIVE SUBSTANCES AND ANTIPLATELET ACTIVITY OF UNDERGROUND ORGANS OF RASPBERRIES (RUBUS IDAEUS L.)
Guljaev D.K., Belonogova V.D., Krylova I.D., Julmuhametova G.R., Kurbanova Ch.S.
Abstract: Objective. Determination of the content of biologically active substances and antiplatelet activity of raspberry ordinary rhizomes with roots. Methods. The determination of the sum of polyphenolic compounds was carried out with the Folin-Ciocalteu reagent. Quantitative determination of the tannin content was carried out in accordance with the requirements of the State Pharmacopoeia. Determination of the content of procyanidins in raspberry ordinary rhizomes with roots was carried out using acid cleavage of procyanidins to anthocyanidins by the Porter method. In vitro experiments were performed on the blood of healthy male donors. The study of the effect on platelet aggregation was carried out using the Born method. Results. According to the results of qualitative reactions, saponins, phenolic compounds, tannins and polysaccharides were found in ordinary raspberry rhizomes with roots. According to the results of quantitative determination, it was found that the main group of biologically active substances in rhizomes with raspberry roots are tannins (9.76±0.95) and saponins (4.94±0.35). It was found that the dry aqueous extract of raspberry ordinary rhizome with roots exhibits antiaggregational activity (Table 3), which is manifested by an elongation of the lag period and a decrease in platelet aggregation. Conclusion. In rhizomes with raspberry roots, tannins of the hydrolyzable group predominate. Dry aqueous extract of raspberry ordinary rhizome with roots has an antiplatelet effect, superior in strength to acetylsalicylic acid.
Keywords: red raspberry, rhizomes with roots, tannins, saponins, dry extract, antiplatelet activity
DEVELOPMENT AND VALIDATION OF METHODS FOR QUANTITATIVE DETERMINATION OF CAROTENOIDS AND CHLOROPHYLLS OF SEA BUCKTHORN LEAVES
Kovaleva N.A., Trineeva O.V., Kolotneva A.I.
Abstract: Objective. The aim is to develop and validate a spectrophotometric method for the quantitative determination of carotenoids and chlorophylls in sea buckthorn leaves. Methods. The object of the study is dried (humidity not more than 10%) leaves of sea buckthorn. The development of a technique for the spectrophotometric determination of carotenoids and chlorophylls was carried out on the basis of the determination of similar compounds in the leaves of stinging nettle. Validation was carried out in accordance with the State Pharmacopoeia XIV edition. Results. When selecting the optimal degree of grinding, raw materials of 5 fractions were used, and with a decrease in the particle size, the yield of carotenoids and chlorophylls increased. When choosing an extractant, we compared the yield of substances during extraction with ethyl alcohol at concentrations of 70 and 96% vol., but the best yield was observed when using ethanol 70% vol., since, according to the literature data, carotenoids and chlorophylls are better extracted with water-alcohol mixtures. When choosing the time, an increase in the yield of substances in the extraction was observed with an increase in the duration of extraction with a maximum at 45 minutes. With an increase in the extraction ratio to 2, the yield of carotenoids and chlorophylls increased, decreasing when using a 3-fold extraction. The influence of the filter material is associated with the possible clogging of the pores of the paper filter with the accompanying macromolecular substances and the adsorption of target substances on the surface of these compounds. The validation of the method was carried out according to such criteria as precision at the level of convergence, limit of detection, limit of quantification, linearity, analytical area of the method, specificity. Conclusion. The optimal degree of grinding, at which the maximum yield of carotenoids and chlorophylls from raw materials is observed, is 0.5-1.0 mm; extraction is recommended to be carried out with ethyl alcohol 70% vol. at a ratio of raw material: extractant 1: 200 for 45 minutes twice. The developed method is valid and suitable for spectrophotometric determination of carotenoids and chlorophylls in sea buckthorn leaves.
Keywords: sea buckthorn leaves, chlorophylls, carotenoids, spectrophotometry, validation
RESPONSE SURFACE METHODOLOGY IN THE QUANTITATIVE DETERMINATION OF POLYSACCHARIDES IN THE ROOTS OF THE POLYGONATUM OFFICINALE
Makarova D.Yu., Novikova E.K., Alexandrova L.Yu.
Abstract: Objective. Application of the response surface methodology in the quantitative determination of polysaccharides in the roots of the Polygonatum officicnale to find the optimal hydromodule and time in ultrasonic extraction. Methods. The object of the investigation is the crushed roots of the Polygonatum officinale harvested in the Republic of Crimea; quantitative determination of polysaccharides is carried out according to the OFS.1.2.3.0019.15 "Determination of sugars by spectrophotometric method" according to the method with picrin reagent; to find the optimal values of the hydromodule and the time of ultrasonic extraction, the software for processing statistical data "Minitab" is used: at the first stage, an experimental plan consisting of 13 experiments is created, at the second stage a regression model is derived and the significance of each parameter is established, at the third stage the obtained data are optimized and the theoretical yield of polysaccharides is determined. Results. For the highest yield of polysaccharides, a hydromodule equal to 1:60 and a time equal to 15 minutes are found. The theoretical yield of polysaccharides is 13.73%, the practical yield is 13.86%. Conclusion. The optimal values of the hydromodule and time in the quantitative determination of polysaccharides in the roots of Polygonatum officinale due to the methodology of the response surface are selected.
Keywords: response surface methodology, polysaccharides, the roots of the Polygomatum officinale
VALIDATION OF A METHOD FOR THE QUANTIFICATION OF ANTOCIANINS IN ARONIA MICHURINA LEAVES
Pugacheva O.V., Trineeva O.V., Panova K.E.
Abstract: Objective. Validation of a spectrophotometric method for the quantitative determination of the total anthocyanins in Aronia Michurina leaves. Methods. The object of the research was dried leaves of Aronia Michurina variety "Mulatka" collected on the territory of the Tambov region in 2022-2023; air-shadow drying (moisture content not more than 10%). Raw materials were collected at four stages of plant development: flowering phase, phase of the beginning of fruiting, phase of technical maturity of fruits, phase of the beginning of leaf reddening. Quantification of anthocyanins was made using the developed spectrophotometric technique in terms of cyanidin-3-O-glucoside. Results. The methodology was validated for specificity, linearity, correctness, convergence and interlaboratory precision and can be used for quantitative determination of anthocyanins in Aronia Michurina leaves. Conclusions. With the use of validated methodology, it was established that the optimal harvesting period for obtaining the maximum yield of anthocyanins is the phase of the beginning of leaf reddening (September), at which the content of anthocyanins is 12,77%±0,95%. The high content of anthocyanins allows us to consider Aronia Michurina leaves as a perspective source of biologically active substances of antioxidant properties in purpose of obtaining medicinal preparations on their basis. The obtained data will be used for the chapter "Quantitative Determination" of the project PM for this medicinal plant raw material. The standard of anthocyanins content in terms of cyanidin-3-O-glucoside not less than 5% can be recommended as a parameter for the PM "Aronia Michurina leaves".
Keywords: Aronia mitschurinii, black chokeberry, anthocyanins, cyanidin-3-O-glucoside, quantification, spectrophotometry, validation
DEVELOPMENT OF METHODS FOR OBTAINING AND STANDARDIZING TINCTURES BASED ON MEDICINAL PLANT RAW MATERIALS
Shmygareva A.A., Kurkin V.A., Labkovskay M.V., Dorokhin O.A., Kochukova A.A.
Abstract: Objective. Development of a method for obtaining tinctures based on medicinal plant raw materials with maximum yield of active substances and subsequent standardization. Methods. In order to achieve this goal, the selection of a method for obtaining a correlation between the concentration of the extractant and the extraction time was carried out; the development of methods for standardizing the tincture. As the objects of the study, the leaves of the hanging birch, the grass of the horsetail, the grass of the mountaineer and the herb of St. John's wort were used in a ratio of 30:25:25:25, with the size of particles passing through a sieve with a diameter of 0.5 mm. Thin-layer chromatography and spectrophotometry were used to standardize the resulting tincture. Results. A qualitative analysis of the tincture was carried out using thin-layer chromatography to detect the main active substances, as well as quantitative analysis by spectrophotometric method. At the same time, it was determined that the content of flavonoids in the tincture is 0.46±0.01% (in terms of avicularin). Conclusion. As a result of the conducted research, a method of vacuum extraction with subsequent exposure to ultrasound was proposed, optimal extraction conditions were selected.
Keywords: spectrophotometry, bird highlander, hanging birch, horsetail
BIOSTIMULATION OF FRESH HERBS ALCHEMILLA VULGARIS AND ITS EFFECT ON THE CHEMICAL COMPOSITION AND ANTIOXIDANT ACTIVITY OF JUICE
Cheremnykh E.V., Zorina E.V., Belonogova V.D.
Abstract: Objective. To investigate the effect of low positive temperatures on the chemical composition of the juice of the common herbs of the Alchemilla vulgari s and antioxidant activity. Methods. The object of the study was juice samples obtained from fresh herb Alchemilla vulgaris without biostimulation and after exposure to raw materials at a low positive temperature (+4 ° C) for 7 and 14 days. The qualitative composition of phenolic compounds in juices was established by ascending chromatography on paper. The profile of the phenolic compounds of the juice was established by ultra-efficient liquid chromatography. The content of the dry residue and groups of biologically active substances (BAS) was determined by pharmacopoeial methods, the antioxidant activity (AOA) - 2, 2-diphenyl-1-picrylhydrazyl (DPHG) - by a test. Results. During biostimulation of raw materials, the qualitative composition of phenolic compounds changes, the content of flavonoids and tannins in the juice of herbs Alchemilla vulgaris increases and the AOA increases. The duration of exposure to low positive temperatures on raw materials is essential. Biostimulation for 7 days showed the highest content of phenolic compounds (16 substances were identified) in the juice and an increase in AOA. Conclusions. The process of biostimulation of raw materials has a positive effect on the qualitative and quantitative composition of biologically active substances of fresh herbs Alchemilla vulgaris juice, and contributes to an increase in AOA.
Keywords: juice, biostimulation, Alchemilla vulgaris, antioxidant activity
PUBLIC HEALTH, ORGANIZATION AND SOCIOLOGY OF HEALTHCARE
EPIDEMOLOGIC ANALYSIS OF MALIGNANT NEOPLASMS IN THE PSKOV REGION
Sannikov A.L., Ponomarev A.S., Zelenykh D.V.
Abstract: Objective. To review the dynamics of mortality from malignant neoplasms in the Pskov region and the Russian Federation as a whole, to identify the main risk factors possibly contributing to the occurrence of malignant neoplasms. Methods. The paper analyzes statistical indicators of morbidity and mortality from colorectal cancer, breast cancer, tracheal, bronchial, lung and gastric cancer from 2011 to 2021; it compares the results obtained in the Pskov region with those of the Russian Federation as a whole, as well as the differences between male and female population. The materials and methods used were statistical data associated with cancer mortality in the residents of the Pskov region. Results. Morbidity and mortality from malignant neoplasms in the Pskov region has one of the highest rates in the North-West Federal District in the period from 2011 to 2021, which is probably explained by a number of risk factors such as: demographic features of the Pskov region, the prevalence of smoking, alcoholism, industrial growth, low interest of the adult population in the dispensary, loss of medical personnel and low efficiency of the regional economy. Conclusion. The identified risk factors could probably have an impact on morbidity and mortality rates in the Pskov region. Reorganization and improvement of the efficiency of the regional oncology service, namely the organization of early diagnosis and timely treatment of patients with malignant neoplasms, as well as early detection of malignant neoplasms, are necessary in order to increase the life expectancy of patients.
Keywords: malignant neoplasms, colorectal cancer, breast cancer, trachea, bronchial and lung cancer, stomach cancer, Pskov region
MISCELLANEA
SIGNIFICANCE OF PSYCHOLOGICAL STUDIES IN ASSESSMENT OF STRESS TOLERANCE AND SOCIAL FRUSTRATION IN MEDICAL AND PHARMACEUTICAL STUDENTS AND IN MANAGEMENT OF PHARMACIES’ TEAMS
Ulasen T.V., Starodubtsev N.N., Krikova A.V., Zaitseva V.M.
Abstract: Objective. The aim of our study was to access significance of psychological studies in management of pharmacy teams, as well as to explore correlations of stress resistance and social frustration in medical and pharmaceutical students. Methods. Anonymous psychological testing of sixty-four students of Smolensk State Medical University has been performed. Face-to-face interviewing of pharmaceutical companies’ employees with different forms of ownership in the city of Smolensk was conducted as well. A questionnaire with blocks of questions concerning the microclimate in the teams and relationships between employers and their employees was designed. The questionnaire is a method that provides written answers to a system of questions, each of which is related to the central objective of the study. In the anonymous survey, twenty-five respondents participated including four Heads of Pharmacies (16%), and 21 pharmacists (84%). Results. The article presents results of the study identifying rates of stress, social frustration, aggressive manifestations and the sense of loneliness in medical and pharmaceutical students. The data obtained testify to high stress resistance in the respondents. The correlations between social frustration and hostility, between dissociated loneliness and aggressiveness can be regarded as reliable markers of developing manifestations of social and psychological maladaptation and boost further studies. Collective nature of activities is characteristic of pharmaceutical companies. In this connection, the efficiency of the company’s activity depends on both organizational behavior of employees, and activities of managerial staff. Conclusion. The received data testifies to high stress-resistance in medical and pharmaceutical students. At the same time, the correlations between social frustration and hostility, between dissociated loneliness and aggressiveness should be regarded as possible markers of the development of social and psychological maladaptation manifestations. The structure of company’s management is known to be a form of delegation of formal authorities between employees; the ability of the Head of a pharmaceutical company to estimate the significance and priority of professional tasks facing the company is fundamental. Microclimates of pharmaceutical companies in the city of Smolensk were studied. Employees of the companies constitute certain groups, the joint activities of which are focused on achieving common and coordinated goals aimed at effective financial and economic results.
Keywords: stress, social frustration, maladaptation, pharmaceutical management