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Vol 30, No 3 (2022)

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Original study

Intracellular Location and Function of Nuclear Factor of Erythroid Origin 2 (Nrf2) in Modeling Oxidative Stress in vitro

Abalenikhina Y.V., Erokhina P.D., Seidkuliyeva A.A., Zav’yalova O.A., Shchul’kin A.V., Yakusheva E.N.

Abstract

INTRODUCTION: Nuclear factor E2-related factor 2 (Nrf2) is a member of cap‘n’collar (CNC) family of subfamily of leucine zipper transcription factors that regulates cell protection against toxic substances and oxidants.

AIM: To determine location, mechanism of activation and role of Nrf2 in conditions of oxidative stress in vitro.

MATERIALS AND METHODS: The study was performed on human colon adenocarcinoma cell line (Caco-2). Oxidative stress (OS) was modeled by adding hydrogen peroxide (Н2О2) at concentrations of 0.1 µМ–100 µМ to the nutritive medium and incubation for 24 and 72 hours. In assessment of Nrf2 function, its inhibitor ― AEM1 ― was added to cells at a concentration of 5 µМ. The extent of OS development was determined using photometric methods by the concentration of protein SH-groups and carbonyl derivatives of protein, and the activity of superoxide dismutase (SOD). Viability of cells was assessed by the results of cytotoxic test (MTT assay), the amount of Nrf2 in the cytoplasm and nucleus was determined by heterogenous ELISA method.

RESULTS: Incubation of Caco-2 cells with Н2О2 resulted in decrease in the level of protein SH-groups and increase in the concentration of carbonyl derivatives of protein. In incubation with H2O2 at concentrations of 0.1 µМ–10 µМ for 24 hours and 10 µМ for 72 hours, the activity of SOD increased. At concentrations of Н2О2 of 50 µМ and 100 µМ (24 hour and 72 hour), SOD activity and viability of cells decreased. Exposure to Н2О2 led to translocation of Nrf2 from the cytoplasm into nucleus. Direct correlation dependence was revealed between concentration of protein SH-groups and the amount of Nrf2 in the cytoplasm in incubation with H2O2 for 24 hour (r = 0.44, р = 0.03), 72 hour (r = 0.34, р = 0.05). The amount of Nrf2 in the nucleus positively correlated with SOD activity in the cytoplasm on exposure to H2O2 for 24 hour (r = 0.77, р = 0.0001) and 72 hour (r = 0.36, р = 0.06). In inhibition of Nrf2 in conditions of exposure to H2O2, the viability of cells decreased to a larger extent.

CONCLUSION: Hydrogen peroxide induces the nuclear translocation of Nrf2, which promotes activation of antioxidant enzyme SOD and preserves viability of cells of OS conditions in vitro.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):296-304
pages 296-304 views

Study of Electrophysiological Properties of Atrioventricular Node in Permanent Cardiac Pacing under Influence of Trimetazidine Dihydrochloride

Smirnov V.N., Staroverov I.N., Gridin A.N.

Abstract

INTRODUCTION: Dual-chamber cardiac pacing permits to maintain permanent atrial-ventricular synchronization. Physiological sequence of propagation of the impulse from atria to ventricles is provided with an artificial delay analogous to delay of propagation of excitation through the atrioventricular (AV) node of a heathy individual. The delay interval is formed so that to minimize stimulation of the right ventricle. This preserves the left ventricular ejection fraction, reduces the risk of development of the chronic heart failure (CHF) and of atrial fibrillation, and increases functional abilities of the patient. On the other hand, critical increase in the atrioventricular delay leads to pacemaker syndrome: impairment of circulation function, shortness of breath, reduced tolerance to exercise, dizziness, syncopal state. The question of the influence of the permanent electrical pacing on the AV node conduction remains unsolved.

AIM: To study the effect of trimetazidine dihydrochloride on the AV node conduction in conditions of permanent cardiac pacing, to determine the effect of cardiac pacing on the AV node in the studied time period.

MATERIALS AND METHODS: The study involved 86 patients. The AV node activity was assessed by antegrade intraoperative determination of Wenckebach point on the basis of electrocardiography data in 24–48 hours after pacemaker implantation, in 6–8 hours, 7, 14, 9 and 180 days after intake of trimetazidine dihydrochloride and in 7, 14, 21 and 30 days after its cancellation. To compare the extent of influence of the studied drug on the AV node activity, the patients were divided to three groups depending on the basic pathology: group 1 ― patients with the sick sinus node syndrome (n = 38, 44.2%); group 2 ― patients with II degree AV block (n = 25, 29.1%); group 3 ― patients with III degree AV block (n = 23, 26.7%).

RESULTS: Trimetazidine dihydrochloride improved the electrophysiological properties of the AV node in the first and second groups: increase in the mean value of Wenckebach point antegrade in the first group was in total 3.26% (р = 0.022), in the second group 4.68% (р = 0.001). In the third group of patients no improvement was noted, but it should be said that under the action of this drug, in 4 of 23 patients with III degree AV block, antegrade AV conduction appeared (р = 0.236).

CONCLUSION: Trimetazidine dihydrochloride has a positive effect on the AV node activity as early as in 6–8 hours of intake, which reaches maximum in 3 weeks. Cardiac pacing had no effect on AV node within the follow-up period (6 months).

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):305-312
pages 305-312 views

Prospects of Hyaluronidase Therapy in Novel COVID-19 Infection with Damage to Lungs

Solov’yeva A.V., Korshunova L.V., Shurpo E.M., Namestnikova A.S.

Abstract

INTRODUCTION: In recent years, the production and regulation of synthesis of hyaluronic acid in COVID-19 has been actively studied. Hyaluronan plays a significant role in development of severe lung damage in COVID-19 and is a potential therapeutic target the action on which will probably improve prognosis for patients with COVID-19.

AIM: To study prospects of using bovhyaluronidaze azoximer in complex treatment of patients with COVID-19 with lung damage at the inpatient stage.

MATERIALS AND METHODS: Thirty five patients (6 men and 29 women) aged 58.9 ± 12.9 years hospitalized with COVID-19 infection, were examined. Capillary blood saturation (SpO2) was 80.1 ± 8.6%, the volume of lung damage in X-ray computed tomography (X-ray CT) was 45.1 ± 19.4% on the right and 40.0 ± 19.5% on the left. All the patients received treatment according to the “Temporary Guidelines: prevention, diagnosis and treatment of novel coronavirus infection. Ver. 14 (27.12.2021)”. Besides, as part of complex treatment for COVID-19, bovhyaluronidaze azoximer was administered intramuscularly on the 21.9 ± 6.8th day of illness with a course of 10 injections (once in 3 days).

RESULTS: In the course of comprehensive treatment including bovhyaluronidaze azoximer, increase in SpO2 was recorded: in 7 patients ― after 1 injection (4.2 ± 1.7%), in 24 ― after 2 injections (5.4 ± 0.6%), another 4 patients did not show any significant increase in SpO2 after the first two injections. Increase in SpO2 after the 1st injection inversely correlated with age (r = -0.34; p < 0.05) and the initial saturation (r = -0.38; p < 0.05). Increase in SpO2 after the second injection correlated with the day of illness on which treatment with bovhyaluronidaze azoximer began (r = -0.36; p < 0.05).

CONCLUSION: Use of bovhyaluronidaze azoximer in complex treatment for COVID-19 with the lung damage at the inpatient stage can be effective in younger patients with more expressed initial reduction of SpO2, and also in case of administration of the drug in the early stages of the disease. The data obtained in the pilot study, dictate the necessity of studying the level of hyaluronic acid in blood of patients with COVID-19 and lung damage and its role in risk stratification of such patients.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):313-322
pages 313-322 views

Complex Neuropsychiatric and Laboratory-Instrumental Diagnostics in Determination of Tactics of Therapeutic Management of Patients with Spinal Muscular Atrophy: Regional Experience

Gayduk A.Y., Cumming P., Chernikova V.V., Vlasov Y.V., Smirnova D.A.

Abstract

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare hereditary disabling disease and the most common hereditary cause of infant deaths. The timely comprehensive diagnosis of SMA permits to plan therapeutic tactics and preserve the quality of patients’ life. One of the objectives of the given work is a review of the actual literature data on etiopathogenesis, clinical presentation, valid diagnosis and modern effective tactics of SMA management.

AIM: To evaluate the management tactics of patients with SMA taking into account neuropsychiatric symptoms, to analyze problems of proposal and organization of measures aimed at improvement of the quality of medical care, on the basis of the practical experience of the Samara region and with consideration of the current state of the problem.

MATERIALS AND METHODS: In the work, the data of the archive of Seredavin Samara Regional Clinical Hospital were analyzed, 132 medical histories of 77 patients were processed with discharge dates from January 2008 to February 2022 with the following diagnoses (according to the code of the International Classification of Diseases and Health Related Problem, 10th revision (ICD-10)): G12.0 (spinal muscular atrophy, type I [Werdnig–Hoffmann disease], G12.1 (other hereditary SMA), G12.8 (other SMA and related syndromes) and G12.9 (unspecified SMA). The analysis of the results of clinical, laboratory, instrumental and neuropsychiatric diagnostic methods was performed in comparison with the tactics of therapeutic management of these patients. For statistical processing of the data, methods of descriptive statistics were used.

RESULTS: Socio-demographic data. As of February 2022, 58 patients were registered (mean age 38.4 (41.3) years, of them 32 (55.2%) were individuals of female gender including 21 children (mean age 12.3 (7.4) years, 14 (24.1%) girls), with the following diagnoses according to ICD-10: G12.0 (n = 7; 12.0%; only children), G12.1 (children: n = 14; 24.1%; adults: n = 29; 50.0%), G12.8 (n = 6; 10.3%; only adults), G12.9 (n = 2; 3.4%; only adults). Clinical data. Motor disorders from a mild proximal lower paraparesis (n = 13; 22.4%) to pronounced tetraparesis (n = 7; 12.0%). The study of mental status was limited to evaluation of the state of consciousness and effectiveness of contact. Data on therapy. Until 2021, symptomatic therapy of SMA was conducted in the region, since March 2021, 8 children (13.8% of the total sample) aged 7.3 (8.8) years received nusinersen, another 8 children (13.8%) aged 9.5 (6.9) years received risdiplam; parents of 3 more children (5.2%) refused taking drugs. Of adult patients (n = 37; 63.8%; 35.3 (23.6) years) with confirmed SMA 5q (n = 10; 17.2%, 35.3 (19.0) years), 1 patient received nusinersen, the rest 9 patients (15.5%) did not receive therapy, 3 (5.2%) were achieving the right to receive drugs (at the moment of the analysis).

CONCLUSION: The data analysis revealed deficit of early SMA diagnosis (at the moment of the diagnosis, all the patients were already having pronounced symptoms), of assessment of affective and cognitive disorders, monitoring of treatment effectiveness (absence of validated scales for motor skills assessment), and also showed low availability of treatment for adult patients, which requires reorganization of care of patients with SMA in the region taking into account the revealed factors).

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):323-334
pages 323-334 views

Characteristic Features of Impact of COVID-19 Pandemics on Mental Health of Population of Different Countries: Results of Cross-Sectional Online Studies in Albania, India, Iran and Nigeria

Dashi E., Vahdani B., Chepure A., Hayatudeen N., Kumari P., Farhang S., Ramalho R., Patil I., Majidi M., Ransing R., Metaj E., Baba Musami U., Fisayo A., Metu I., Ungratwar A., Rehman S., Alikaj V., Numbere T., Adiukwu F.

Abstract

BACKGROUND: The coronavirus infection of 2019 (COVID-19) produced an incontestable impact on the mental health of people around the world. This impact is conditioned by a complex interrelation of social, cultural, economic and COVID-19-associated factors. However, insufficient data on comparison of parameters of mental health of the population in different countries limits our understanding of these interrelations.

AIM: To evaluate and compare the frequency of mental health disorders (general problems and problems related to COVID-19) and their correlations in four countries: Albania, India, Iran and Nigeria.

MATERIALS AND METHODS: In this study, the problems of mental health of the population of four countries (Albania, India, Iran and Nigeria) were investigated. The participants were selected in the period from July 07, 2020 to November 13, 2020. The study used a cross-check anonymous online questioning to assess the degree of depression, anxiety and insomnia, which included “Patient Health Questionnaire” (PHQ-9), “Generalized Anxiety Disorder” 7 (GAD-7) questionnaire and Insomnia Severity Index (ISI). To assess the mental health problems associated with COVID-19, the survey included Corona Anxiety Scale (CAS), Obsession with COVID-19 Scale (OCS) and Fear of COVID-19 Scale (FCV-19S). To analyze the data, ꭓ2, Kruskal–Wallis tests and multiple linear regression were used.

RESULTS: In general, the prevalence of general anxiety, depression, insomnia and COVID-19-associated anxiety, was higher among the Iranian population compared to the other three countries. Risk factors for increased anxiety about the new coronavirus infection were fear, depression, trouble and age; however, these factors were different in the four studied countries. The parameter was highest (47%) in the Albanian population and lowest (20%) in India.

CONCLUSIONS: This study shows different prevalence of psychological health disorders during the ongoing pandemics, including problems associated with COVID-19, in different countries. Therefore, healthcare policy and measures adopted in different countries, should be adapted to specific needs of the country rather than be based on the universal global responsive measures.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):335-344
pages 335-344 views

Clinical and Pathomorphological Analysis of Mechanisms of Progression of Dupuytren’s Contracture

Shchudlo N.A., Stupina T.A., Varsegova T.N., Ostanina D.A.

Abstract

INTRODUCTION: The factors and mechanisms of progression and recurrence of the palmar fascial fibromatosis with formation of severe Dupuytren’s contracture, remain insufficiently studied.

AIM: To identify probable mechanisms of progression of the palmar fascial fibromatosis based on the comparative analysis of clinical and morphological characteristics of patients with Dupuytren’s contracture of different extent of severity.

MATERIALS AND METHODS: Objects: medical histories and histological preparations of surgical material of patients with I–II (group 1, n = 121) and III–IV (group 2, n = 135) degree Dupuytren’s contracture. Methods: clinical, histological, statistical.

RESULTS: Clinical markers of hereditary predisposition to Dupuytren’s disease (the percentage of patients under 50 at the time of onset of the disease and the frequency of involvement of both hands) were comparable in the study groups. The incidence of diseases of the circulatory system was reliably higher in group 2: 57.0% against 41.3% (p < 0.01). A prolonged course of the disease (> 8 years) was identified only in half of the patients of group 2. The median of the content of hyperplastic connective tissue in the palmar aponeurosis in patients of groups 1 and 2 was 22.9% and 11.3%, respectively (p < 0.001), interquartile range 0%–67.8% and 0%–56.7%, respectively. In the capillary network and in the intima of larger vessels, CD34-positive endothelium was identified in patients of both groups. Around the blood vessels supplying fibromatous nodules and cords, cells expressing CD34 were found. Thickness of adventitia and Kernogan index in the arteries perforating the palmar aponeurosis, were higher in group 2.

CONCLUSION: A higher frequency of comorbid diseases of the circulatory system, more evident thickening of adventitia of arteries perforating the palmar aponeurosis, and reduction of their throughput capacity in patients with severe Dupuytren’s contractures indicate the significance of systemic and regional vasogenic mechanisms of progression of the palmar fascial fibromatosis. The content of hyperplastic connective tissue (histological predictor of recurrence) varies individually with each degree of contracture.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):345-356
pages 345-356 views

Morphometric Characteristics of Axial Length of Eye in Population of the Southern Urals (according to “Ural Very Old Study” and “Ural Eye and Medical Study” Research)

Bikbov M.M., Gil’manshin T.R., Israfilova G.Z., Yakupova E.M.

Abstract

INTRODUCTION: Currently, ametropias are the most important medical and social problem, which occupies one of the leading places in modern ophthalmology. Determination of the length of the anteroposterior eyeball axis (APEA) in myopia ― a type of ametropia directly associated with increase in the axial length of the eyeball ― is an objective method of its diagnosis and identification of progression. Due to the fact that myopia is a multifactorial disease, the study of correlation relationships of the length of the eyeball seems to be extremely relevant.

AIM: To give a statistical assessment of the peculiarities of the axial length of the eyeball in the population of the Southern Urals, depending on age, gender and the respondents' settlement sites, and to determine the correlation relationships of this parameter.

MATERIALS AND METHODS: The analysis was conducted on the base of Ufa Research Institute of Ophthalmology within large clinical and population studies “Ural Eye and Medical Study” (UEMS) and “Ural Very Old Study” (UVOS). Inclusion criteria: signing of voluntary consent to participation in the project, permanent residence in the territory of study; for inclusion in UEMS ― age from 40 to 85 years, in UVOS ― age above 85. UEMS study involved 5899 respondents, UVOS ― 1526. The study protocol suggested evaluation of 683 criteria, 293 of which were answers of respondents to questions of the questionnaire and the results of the general somatic examination, 355 criteria concerned the results of the ophthalmologic examination, 35 ― of laboratory tests. Axial length of the eyeball was measured by the method of ultrasound echo-biometry (A-scanning) (Ultra-compact A/B/P ultrasound system, Quantel Medical, France).

RESULTS: The mean length of the APEA in the UEMS population was 23.31 ± 1.08 mm, in the UVOS population ― 23.11 ± 1.08 mm (p < 0.001). The length of the eyeball axis was 23.31 ± 1.08 mm in the age group 40-84 years and 23.11 ± 1.08 mm in patients in the age category 85 years and older. The multivariate linear regression analysis in UEMS study showed the highest statistically significant association of APEA length with such factors as age (p < 0.001), height (p < 0.001), presence of arterial hypertension (p = 0.02), education level (p < 0.001 ), intraocular pressure (IOP) (p < 0.001), spherical refractive error (p<0.001), depth of anterior chamber (p < 0.001) and angle of anterior chamber (p < 0.001), mosaicism of the eye fundus in the macular region (p < 0.001), presence of myopic maculopathy (p < 0.001), refractive power of the cornea (p < 0.001), corneal volume (p < 0.001), macular pigment density (p < 0.001), thickness of peripapillary layer of nerve fibers (p < 0.001), presence of the epiretinal membrane (p = 0.01). The multivariate linear regression analysis in UVOS study showed statistically significant association of the APEA length with such factors as height (p < 0.001), education level (p = 0.002), corneal refractive power (p < 0.001), spherical refraction error (p < 0.001).

CONCLUSION: In the population of the Southern Urals, statistically significant association of the length of the eyeball axis with such factors as height, education level, refractive power of the cornea and spherical refractive error, was demonstrated. Besides, in the population of UEMC study, there was also noted association with age, the presence of arterial hypertension, intraocular pressure, the depth of the anterior chamber and the angle of the anterior chamber, mosaicism of the eye fundus in the macular region, the presence of myopic maculopathy, corneal volume, density of macular pigment, thickness of the peripapillary layer of nerve fibers, presence of the epiretinal membrane.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):357-366
pages 357-366 views

Parameters of Functional Lateral Organization of Students of Medical University with Different Levels of Physical Fitness

Mazikin I.M., Lapkin M.M., Akulina M.V., Kulagin P.A.

Abstract

INTRODUCTION: One of the parameters of the functional reserves of the human body is the level of physical fitness, which depends not only on the improvement of various methods used in the education of students in physical culture, but also on the individual characteristics of students, including parameters of their functional lateralization.

AIM: To establish the character of the interrelations between the parameters of functional lateralization and the parameters of physical fitness in medical university students.

MATERIALS AND METHODS: Functional lateralization was determined by both the conventional test methods and by the method of neuro-energo mapping in 120 practically healthy medical university students of male gender aged 18 to 23 years. Physical fitness was assessed in conventional tests for determination of strength fitness, speed-strength fitness, speed endurance. All the data were processed using non-parametric statistical methods and correlation and cluster analysis.

RESULTS: Based on the criterion of physical fitness, young men were divided to two groups: a group with a relatively high level of speed and strength endurance and flexibility (cluster 1, n = 71), and a group with a relatively high level of strength fitness (cluster 1, n = 49). Both the integral (coefficient of lateral organization profile CLOP) and partial parameters (manual and sensory asymmetry) of the functional lateralization were higher in the representatives of cluster 2, with this, the analysis of changes of the permanent potential level (method of neuro-energo mapping) in functional tests showed only an emerging tendency in the differences between the clusters. Also, in cluster 1, weak (r < 0.3, р < 0.05) negative relationships between the parameters of functional lateralization were found in behavioral tests, and between changes in the permanent potential level of the left and right cerebral hemispheres (Td–Ts lead) in load tests. In the representatives of the second cluster, no correlations were found.

CONCLUSION: The results of the performed comprehensive analysis evidence, in the authors’ opinion, the differences in the central-peripheral relationships in the systemic organization of physiological functions that determine non-uniform physical fitness in young men with a relatively high level of speed-strength endurance and flexibility (cluster 1) and those with a relatively high level of strength fitness (cluster 2).

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):367-374
pages 367-374 views

Clinical reports

Case Report of Patient with Posttraumatic Arteriovenous Fistula of Femoral Vessels in the Lower Third of Thigh: Peculiarities of Pathogenesis and Difficulties of Management

Kalinin R.E., Suchkov I.A., Shanaev I.N., Agapov A.B., Khashumov R.M.

Abstract

INTRODUCTION: Pathological communications between the arterial and venous systems have been in the center of attention of surgeons since XVIII century. Despite the achievements of the modern medicine, the diagnosis and treatment of arteriovenous fistulas (AVF) is still quite a difficult problem. The most common location of AVF is the lower limbs ― 17% of cases. Because of the peculiarities of structure and clinical manifestations of posttraumatic AVF, they are diagnosed several years after the injury. Diagnostic errors reach 30%, and unsatisfactory results of surgical treatment are observed in 30% to 70% of cases. The article describes a clinical case of a patient with a rare posttraumatic AVF in the lower third of thigh identified 2 years after fracture of a lower limb. Initially, the patient was delivered to hospital for surgical treatment for varicose vein disease of the left lower limb (C5 in CEAP classification). In the follow-up examination at the department of vascular surgery, a posttraumatic AVF of femoral vessels in the lower third of thigh was found with alterations of central hemodynamics (according to the heart ultrasound data). An attempt of open disconnection of the AVF was undertaken, however, morphological alterations of the walls of femoral vessels caused by a long-existing fistula did not permit this to be done. In result, for effective disconnection of AVF two stages of endovascular treatment were required.

CONCLUSION: This medical case is given by the authors because of the rarity of pathology, atypical clinical manifestations and diagnostic difficulties. This case is also interesting from the point of view of the fact that effective disconnection of AVF required several stages of endovascular treatment.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):375-386
pages 375-386 views

Coronary-Vertebral Collaterals in Takayasu Arteritis: Case Report

Chupin A.V., Zotikov A.E., Kutovaya A.S., Golovyuk A.L., Kharazov A.F., Kul’bak V.A., Kozhanova A.V., Varava A.B., Tiimina I.E.

Abstract

INTRODUCTION: PNonspecific aortoarteritis is a rare autoimmune disease with the involvement and narrowing of the aorta and its branches leading to ischemia of the respective arterial region. In the territory of the Russian Federation, the most common manifestation of Takayasu nonspecific aortoarteritis is lesion of the branches of the aortic arch, which in rare cases leads to development of the so called “bald arch” syndrome. In response to hypoxia, intersystemic collaterals are formed through the neoangiogenesis or redirection of the blood flow from the occluded vessels to small-diameter vessels. In patients with “bald arch” syndrome, the key role in blood supply to the brain is played by the vertebral arteries. Here, collateral blood supply is realized through the intersystemic anastomoses, most often through the anastomotic leaks between the intercostal and internal thoracic arteries. In the literature, single cases of formation of collaterals between coronary and bronchial arteries are reported. The article presents a clinical case of coronary-vertebral anastomoses in a patient with extremely severe course of Takayasu arteritis with occlusion of the brachiocephalic trunk, right common carotid artery (CA), left common CA, right internal CA, left internal CA (“bald arch” syndrome). The probable cause of such course of the disease was late referral for medical help by the patient and lack of adequate basic therapy.

CONCLUSION: The demonstrated case is the fourth case in the world literature describing the existence of collaterals between the coronary arteries and cerebral arteries, and the first case in the world describing the existence of collaterals from the right and left coronary arteries to the vertebral artery. Such unusual pathway of collateral blood supply in the patient is explained by the absence of the possibility for collateral compensation from the systems of subclavian and intercostal arteries, severe chronic cerebral ischemia. Usually, the causes of angina pectoris in patients with nonspecific aortoarteritis are spread of arteritis to the coronary arteries, insufficiency of the aortic valve, hypertrophy of the left ventricle. In the described case, none of these conditions was present, and angina can only be attributed to the existence of unusual collaterals and the development of a transient steal syndrome.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):387-396
pages 387-396 views

Reviews

Analysis and Evaluation of Modern Approaches to Development of Medical Drugs Using Micro- and Nanotechnologies

Raguzin E.V., Yudin M.A., Glushenko D.D., Vengerovich N.G., Raguzina O.G., Pechurina T.B., Shefer T.V., Ivanov I.M.

Abstract

INTRODUCTION: TDespite the achievements of the modern medicine, use of some medical drugs (MDs) is associated with both the absence of a significant therapeutic effect due to peculiarities of the physico-chemical interaction in the internal environment of an organism, and with the adverse effect on organs and tissues. The advanced technologies of creation of micro- and nanoparticles will permit to improve pharmacokinetics and pharmacodynamics of the drug, its bioavailability and solubility, the ability of crossing blood-brain barriers, and to reduce undesirable systemic effects. MDs using micro- and nanoparticles, have a targeted effect on the focus of pathological lesion. An important additional advantage is a possibility of using micro- and nanoparticles in development of long-acting MDs. The main active substances immobilized to micro- and nanoparticles, open up new prospects for effective treatment of different pathological conditions (neoplasms, diseases of cardiovascular and central nervous system, inflammatory processes, wounds), and for realization of new imaging capabilities in foci of a pathological process, which is especially important in diagnostic procedures.

CONCLUSION: The article presents a summary of the ideas of methods of micro- and nanoencapsulation, and assessments of the prospects for the development of drugs for the correction of pathological conditions using innovative technologies.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):397-410
pages 397-410 views

Actualization of Positions of Gliflozins in Treatment Algorithms for Patients with Heart Failure: Chronology of Success

Nikulina N.N.

Abstract

INTRODUCTION: Despite the efforts of the cardiologic communities to introduce approaches to treatment of heart failure (HF) based on the highest level of evidence, HF remains one of the “least satisfied demands in the therapy of cardiovascular diseases” due to high prevalence, poor prognosis and insufficient use of treatment methods with clinically proven effectiveness. The article considers chronology of study and introduction of sodium-glucose cotransporter 2 inhibitors (syn.: gliflozins; SGLT2is) in clinical practice from the moment of creation of the first drug of this group ― florizin ― and further, stepwise with the change of the therapeutic paradigm as the result of performed clinical trials. Thus, EMPAREG OUTCOME, CANVAS, DECLARE-TIMI 58 studies demonstrated that SGLT2is not only produce a glucosuric effect, but also reduce the development and progression of HF and increase the life expectancy of patients with type 2 diabetes mellitus (DM2) and with reduced left ventricular ejection fraction (LFEF). DAPA-HF, EMPEROR-Reduced studies proved a possibility of improving the outcomes for patients with HF with reduced LVEF irrespective of the presence or absence of DM2, thereby significantly expanding the potential target group for SGLT2is. EMPEROR-Preserved study is the only study of SGLT2is to date (the study drug ― empagliflozin) that has demonstrated high effectiveness of the drug in prevention of cardiovascular mortality and hospitalizations for HF, probably irrespective of LVEF and the existence of DM2. In result, on September 9, 2021, FDA (Food and Drug Administration, USА) assigned the “breakthrough therapy” status to Jardiance® (empagliflozin) drug for treatment of HF with preserved LFEF. EMPA-REG OUTCOME, DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, DAPA-CKD studies have shown SGLT2is to slow down the development of the terminal stage of chronic kidney disease. Finally, the main result of EMPULSE study completed in 2022, was the proven clinical benefit of empagliflozin in hospitalized and stabilized patients with acute HF decompensation irrespective of HF status and existence of DM2.

CONCLUSION: From the moment SGLT2is have been introduced in the clinical practice, they rapidly and successfully passed the way from the second-line antidiabetic drugs for which it was just enough not to worsen the prognosis for serious cardiovascular complications, to independent and effective class of drugs for treatment of HF (with class I and IIa recommendations). The totality of clinical trials of empagliflozin showed that empaflorizin is so far the only drug of the SGLT2is group with the proven safety and clinical effectiveness including the influence on the prognosis, in patients with HF irrespective of the LVEF status, presence or absence of DM2, for use in outpatient treatment and in stabilized patients in hospital.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):411-421
pages 411-421 views

Discussion

Changes in the Procedure of Issuing and Circulation of Prescriptions in the Russian Federation

Titov D.S., Yakusheva E.N., Novikova Y.E., Maystrenko M.A., Uliteonok E.E.

Abstract

INTRODUCTION: The regulatory and legal framework controlling the procedure for registration and circulation of prescriptions in the Russian Federation is dynamic and changes with the level of development of digital technologies. The Ministry of Health of the Russian Federation is continuously working on improvement of the existing regulatory documents with the aim to optimize the activities of medical and pharmaceutical workers in the field of issuing prescriptions and sale of prescription drugs. The article presents an analysis of the regulatory and legal framework regulating the procedure for registration and circulation of prescriptions for medical drugs.

CONCLUSIONS: On March 1, 2022, Order No. 1094n came into force, that regulates the new procedure for registration and circulation of prescriptions. The changes made to the rules are aimed at optimizing the procedure for issuing prescriptions and simplifying it for doctors. However, for a number of formulations used in the current version of the order, explanations from the Ministry of Health of the Russian Federation are desirable, or it is necessary to form a unified opinion of the professional community.

I.P. Pavlov Russian Medical Biological Herald. 2022;30(3):423-430
pages 423-430 views


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