I.P. Pavlov Russian Medical Biological Herald
ISSN (print): 0204-3475, ISSN (online): 2500-2546 Founders: Ryazan State Medical University, Eco-Vector Editor-in-cheif: Roman E. Kalinin, Doctor of Sc., Full Professor Frequency / Access: 4 issues per year / Hybrid Included in: White List (2nd level), RISC, Scopus
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The relationship between ADD1 (Gly460Trp) rs4961 polymorphism and the main physiological parameters of the cardiovascular system in pregnant women
INTRODUCTION: Physiological development of pregnancy is possible only with the proper functioning of the cardiovascular system (CVS) of mother in general and of the placental vascular system in particular. Research continues into the factors and genetic polymorphisms that influence the development of cardiovascular diseases in women during pregnancy. AIM: To evaluate the relationship between the ADD1 (Gly460Trp) rs4961 polymorphism and CVS parameters in women during pregnancy. METHODS: The study included 170 pregnant women aged 20 to 38 years in the third trimester of pregnancy. Of these 76 women with normotensive pregnancy (control group) and 94 women with gestational arterial hypertension. Echocardiography, cardiotocography, assessment of uteroplacental and fetoplacental blood flow with determination of the resistance indices (RI) of the uterine arteries and umbilical artery were performed. Genotyping of the ADD1 (Gly460Trp) rs4961 polymorphism was performed using the TagMan probe detection method based on the relative fluorescence units of each probe on a CFX96 amplifier with a detection system in Real-time mode. Bio-Rad IQ5-Standart Edition software was used for allele discrimination. RERSULTS: In the control group, Gly/Trp and Trp/Trp genotype carriers had a higher cross-sectional area of the left ventricle (LV) in diastole and increased end-diastolic and stroke volumes of the LV compared with similar parameters in women with Gly/Gly genotype (р <0.05). Women with Trp/Trp genotype were found to have elevated levels of systolic, diastolic and pulse blood pressure compared with Gly/Gly and Gly/Trp genotype carriers (р <0.05). In women with normotensive pregnancy with Gly/Trp genotype, higher levels of RI of the umbilical artery (by 9.3%), right uterine artery (by 10.6%), and left uterine artery (by 10.4%) were observed compared with Gly/Gly genotype carriers (р <0.05). CONCLUSION: The ADD1 (Gly460Trp) rs4961 polymorphism is most significant in the Gly/Trp and Trp/Trp genotypes, which are associated with a larger LV diastolic volume in women with normotensive pregnancy. The pregnant women with Trp/Trp genetic variants were found to have the highest systolic, diastolic, and pulsed pressure levels. In women with normotensive pregnancy, an informative parameter of the functional condition of the umbilical and left uterine arteries is Gly/Trp of ADD1 (Gly460Trp) rs4961 polymorphic variant.
Copyright (c) 2025 Eco-Vector https://creativecommons.org/licenses/by-nc-nd/4.0/
VEGF-dependent angiogenesis in therapeutic pathomorphosis of breast cancer
INTRODUCTION: The involvement of angiogenic factors in the tumor progression and invasion processes, in escape from immunological surveillance and alterations in the signal sensitivity implicates the perspectiveness of investigating VEGF-dependent angiogenesis in the context of therapeutic regression of breast cancer (BC). AIM: To study the immunohistochemical features of angiogenesis markers: vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang2) and its receptor tyrosine kinase (Tie2), depending on the degree of breast carcinoma regression with the underlying neoadjuvant chemotherapy (NACT). METHODS: The study included 65 patients with verified locally advanced breast cancer and 10 patients with proliferative fibrocystic disease. Breast cancer patients underwent NACT according to the following regimen: 5-fluorouracil 500 mg/m2, adriamycin (=doxorubicin) 50 mg/m2, cyclophosphamide (FAC) 500 mg/m2. At the screening stage, a core needle biopsy of the breast tumor was performed, and an examination of the surgical material upon completion of NACT. The key marker for breast cancer, the human epidermal growth factor receptor-2 (Her2/neu), and angiogenesis markers (VEGF-A, Ang2, Tie2) were assessed using the immunohistochemical method, and morphological regression of the tumor was determined using the residual cancer burden (RCB) system. RESULTS: The most common type of breast carcinoma is invasive ductal breast carcinoma, luminal A, Her2/neu-negative subtype. Immunohistochemical characteristics of breast carcinoma angiogenesis are independent of the morphological and surrogate molecular subtype of tumor. Parameters of angiogenesis activity (VEGF-A, Ang2, Tie2) are maximally expressed in patients with the proliferative fibrocystic disease and BC before the start of NACT. NACT produces a weak suppressive effect on the parameters of angiogenesis activity irrespective of tumor type. CONCLUSION: Objectification of the obtained results and clarification of the specific angiogenesis features in BC patients undergoing neoadjuvant chemotherapy requires further investigation of this matter using additional molecular genetic methods. We believe it would be appropriate to conduct experimental studies of the effects of cytostatic agents in various regimens (including ultra-low doses), as well as to conduct additional studies on the role of integrins and Notch receptors.
Copyright (c) 2025 Eco-Vector https://eco-vector.com/for_authors.php#07
Rationale for moderately radical preparation of mouth cavity of elderly patients for implant prosthetics
INTRODUCTION: When preparing the oral cavity for implant prosthetics, a conservative, sparing method is traditionally used. This practice (‘preserve what remained’), on the one hand, seems logical, on the other hand, more radical methods exist. The duality of approaches creates difficulties in selection of the optimal treatment strategy. AIM: To substantiate the reasonability of a radical approach to oral cavity sanation in elderly and senile individuals before implant prosthetics. METHODS: The study involved 109 elderly and senile individuals. Two groups were formed: group 1 (the study group) included patients with partial tooth loss, a ‘decompensated dentition’, and conservative, sparing preparation for prosthetics (n=49), group 2 included patients with complete tooth loss and radical oral cavity sanation (n=57). Clinical and paraclinical (cone-beam computed tomography, orthopantomography, implant mobility testing, and clinical and sociological) research methods were used. RESULTS: The results confirmed the superiority of reported anatomical, physiological and statistical parameters in patients of group 2. In addition, the prevention of complications, long-term longevity of implants and implant prostheses, fulfillment of guaranteed long-term treatment periods, significant reduction of financial and time expenditures were substantiated. Furthermore, the importance of improving the oral health of elderly and senile already comorbid and polymorbid patients by eliminating foci of periodontal and anaerobic microflora should be added. CONCLUSION: The conducted study made it possible to substantiate the rationality of radical approach to preparing the oral cavity of elderly and senile patients for implant prosthetics.
Experimental and clinical substantiation of adaptation of patents with multiple adentia to orthopedic dental structures through correction of volume and velocity of airflows in mouth cavity
INTRODUCTION: Modern dental equipment and diversity of materials and technologies ensure manufacture of highly precise and aesthetic orthopedic structures. However, these structures do not take into account the position of natural teeth and the anatomical peculiarities of the hard palate, which impairs pronunciation, fixation and stabilization of dentures in the mouth cavity, and stimulates non-physiological ‘expulsion’ of the fluid-air-food emulsion during eating, speaking and breathing. The aspect of Modernization of removable denture manufacture is critical both in terms of gaining fundamental knowledge and optimizing the quality of dental care in practical healthcare. AIM: To conduct a comparative evaluation of architecture of the hard palate, the speed of phonetic adaptation, and also the velocity and direction of airflows in patents with partial and complete absence of teeth. METHODS: The study included 220 people, of them 130 were with intact dentitions (aged 20–25 years) and 90 patients with partial loss of teeth (aged 40–60). RESULTS: It has been demonstrated that the velocity and direction of the airflows in the mouth, and also the morphometric parameters of the palatal vault should be taken into account in modeling the palatal surface of removable dentures. Analysis, recording, and accounting for these parameters accelerate patient adaptation to the manufactured structures, which effects the quality of orthopedic rehabilitation. CONCLUSION: Replacement of defects in the dental arches in patients using the developed rehabilitation concept leads to faster speech adaptation to removable dentures, without increasing the time required to manufacture orthopedic structures.
Evaluation of the efficacy of modern endoscopic powdered hemostatic agents using piezoelectric thromboelastography: a pilot experimental non-randomized study
INTRODUCTION: The treatment of gastrointestinal bleeding and the choice of method of endoscopic hemostasis remain urgent issues in surgery. Application of insufflation endohemostasis methods with use of powdered hemostatic systems is currently a promising approach in therapeutic endoscopy. AIM: To conduct a comparative analysis of the effect of powdered hemostatic agents EndoClot®, Aseptisorb® and alginate polymer polysaccharide hemostatic hydrogel (APPHH) on the dynamics of parameters of the blood aggregate condition regulation system using piezoelectric thromboelastography method. METHODS: The object of the study was citrated venous blood from 14 healthy male volunteers aged 20 to 30 years, with mean age (23.70±2.86) years. With each blood sample, several analyses were conducted: without the test material (control group) and with the addition of EndoClot® (group 2), Aseptisorb® (group 3) and APPHH (group 4). The effect on the aggregate condition of blood in vitro was evaluated by thromboelastography (АRP-01М Mednord piezoelectric thromboelastograph (Mednord-Tekhnika, Russia)). The following chronometric parameters were analyzed: time of the contact phase of coagulation, time to reach thrombin constant, blood clotting time, clot polymerization time, fibrin-platelet clot formation time, fibrinolysis onset time, and also qualitative parameters: intensity of the contact phase of coagulation, thrombin activity constant, coagulation drive intensity, clot polymerization intensity and maximal clot density. RESULTS: It was found that the studied samples are not effective in the initial clot formation process (platelet adhesion and aggregation), they realize the main hemostatic effect through the influence on coagulation processes: EndoClot® reduces blood clotting time from 9.90 (8.90–11.30) minutes to 7.25 (5.50–7.80) minutes (p <0.0001), Aseptisorb® — to 5.40 (3.40–7.50) minutes (p <0.0001), and APPHH — to 3.20 (2.40–3.90) minutes (p <0.0001). However, EndoClot® does not affect the first stage of the coagulation cascade — the process of reaching the thrombin constant, which reduces its hemostatic activity. Hemostatic agents Aseptisorb® and APPHH initiate hemostatic activity at the stage of reaching the thrombin constant and then increase it at the stages of clot polymerization. CONCLUSION: Powdered hemostatic agents EndoClot®, Aseptisorb® and APPHH possess pronounced hemostatic activity affecting coagulation processes. The domestic hemostatic agents Aseptisorb® and APPHH demonstrated the best hemostatic properties a significant effect has been recorded already at the initial stages of the coagulation cascade with subsequent increase in the hemostatic activity and reduction of blood coagulation time.
Pulmonary embolism in women of reproductive and menopausal periods
INTRODUCTION: High morbidity and mortality from pulmonary embolism (PE) make it relevant to search for predisposing factors specific of different categories of patients. AIM: To establish the frequency of verification of PE diagnosis, peculiarities of its course and predictors of development in women of reproductive and menopausal age. METHODS: The study involved 238 women suspected of PE. The diagnosis was confirmed in 125 of them: 39 patients aged 23 to 43 years (Group 1), 86 patients aged 60 to 94 years (Group 2). In the remaining 113 women, PE was excluded: 41 women aged 29 to 43 (Group 3) and 72 women aged 60 to 92 years (Group 4). The identification rate and disease course were compared across the groups, and significant surgical, gynecological and therapeutic risk factors for PE were established for each life period with determination of their relationships with each other and with clinical, laboratory and instrumental factors. RESULTS: Significant factors for PE development in women include: estrogen background (a tendency for this hormone to increase endogenously due to physiological and pathological gynecological conditions, or exogenously due to intake of hormonal drugs); the presence of thrombophilic conditions; obesity (body mass index ≥30 kg/m2); limited physical activity. The combination of these risk factors increases the likelihood of developing the disease, especially in the 23–43 age groups, which accounts for almost 30% of PE cases in women, often with thrombosis originating from the superior vena cava system. CONCLUSION: Women at different ages have different risk factors for developing PE, primarily related to estrogen status. Absolute and relative hyperestrogenism can create predisposition to hypercoagulability and thromboembolic complications.
The impact of some non-drug treatments on the state of endotoxin-binding systems and level of systemic inflammation in patients with bronchial asthma in post-COVID period
INTRODUCTION: Bronchial asthma (BA) is one most common disease in the world, with complete control not exceeding 50%. A relevant research trend is the search for new methods of achieving control over BA, taking into account personalized approach. AIM: Based on laboratory markers of endotoxin-binding systems and systemic inflammation, to evaluate the effectiveness of magnetic therapy (MT) and ‘dry’ carbon dioxide baths (DCDB) in combination with grape polyphenols (GP) in spa treatment of BA patients with past coronavirus infection. METHODS: Patients (n=75) undergoing spa treatment in the Pulmonology Department of the Sechenov Academic Research Institute of Physical Treatment Methods, Medical Climatology and Rehabilitation, were divided into 3 groups: group 1 (n=25) — patients who additionally received MT and GP concentrate during treatment, group 2 (n=25) — DCDB and GP concentrate, group 3 (n=25) — only standard spa treatment. Before admission and after treatment, blood plasma was collected for analysis for the following markers: C reactive protein (CRP), bactericidal permeability increasing protein (BPI), lipopolysaccharide-binding protein (LBP), lipopolysaccharide, soluble form of CD14 protein (sCD14), zonulin. RESULTS: The CRP level decreased only in group 1 — from 2.93 to 1.93 mg/l (p=0.011). The BPI level increased in all groups: in group 1 — from 65.50 to 70.70 pg/ml (p=0.012), in group 2 — from 57.60 to 95.00 pg/ml (p <0.001), in group 3 — from 64.90 to 88.30 pg/ml (p=0.008). The level of sCD14, which was initially absent in the blood of patients, after spa treatment increased to 1.54 ng/l in group 1 (p=0.003), to 7.20 ng/l (p <0.001) in group 2 and to 6.40 ng/l (p <0.001) in group 3. The level of zonulin increased several-fold in all groups: in group 1 — from 4.94 to 275.60 ng/ml (p <0.001), in group 2 — from 0.20 to 40.70 ng/ml (p <0.001), in group 3 — from 0.90 to 127.50 ng/ml (p=0.002). CONCLUSION: Use of magnetic therapy and ‘dry’ carbon dioxide baths in combination with grape polyphenol concentrate enhances the effectiveness of classic spa treatment in patients with BA with past coronavirus infection: it activates endotoxin-binding systems and inhibits increased intestinal permeability. Magnetic therapy also reduces systemic inflammation.
Non-achievement of therapeutic range of antihypertensive drug concentration in a triple combination as a cause of ineffective control of primary arterial hypertension: ambiguous results of a cross-sectional clinical trial in routine clinical practice
INTRODUCTION: High blood pressure (BP) is one most important risk factor for coronary heart disease, stroke, chronic kidney disease, and dementia. Despite a wide range of pharmacological and non-pharmacological treatments, BP control can be achieved in less than 50% of cases, therefore, the development of new methods to improve the effectiveness of arterial hypertension (AH) treatment is urgent. One possible approach is monitoring antihypertensive drug (AHD) for their correspondence to the therapeutic range (TR). AIM: To analyze the effect of serum concentrations of lisinopril, indapamide and amlodipine on blood pressure parameters in patients with stage III essential hypertension taking these drugs in a triple combination. METHODS: A cross-sectional clinical study included 147 patients with stage III essential hypertension who were simultaneously receiving the three studied AHDs (lisinopril, amlodipine, indapamide); mean age (63.7±11.0) years; 44% were men; 54% of patients had uncontrolled hypertension. Using high-performance liquid chromatography with tandem mass spectrometry (Ultimate 3000 chromatograph and TSQ Fortis mass spectrometer (ThermoFisher, USA)) the concentrations of AHDs in blood serum were analyzed: steady-state concentration (C0h) and 2 hours after administration of AHDs (C2h). Using univariate and then multivariate regression analysis, the existence of a relationship between the mean level of daytime and nighttime blood pressure, pharmacokinetic parameters (C0h, C2h, achievement of TR) and general clinical criteria (age, gender, body weight, creatinine clearance) was determined. RESULTS: The proportion of patients with C0h below TR was: 8.2% for lisinopril, 27.9% for amlodipine, 69.4% for indapamide, 8.8% for simultaneous indapamide and amlodipine, and 0.7% for the three simultaneous AHDs. The proportion of patients with non-achievement of the target BP level was the following: with C0h of lisinopril within the TR (n=135) — 56.0%, with C0h of lisinopril below the TR (n=12) — 33.0%, with C0h of amlodipine within the TR (n=106) — 57.0%, with C0h of amlodipine below the TR (n=41) — 49.0%, with C0h of indapamide within the TR (n=45) — 44.0%, with C0h of indapamide below the TR (n=102) — 59.0%, with C0h of indapamide and amlodipine simultaneously below the TR (n=13) — 85.0%, with C0h of the three drugs simultaneously below the TR (n=1) — 1 out of 1. According to the results of multiple regression analysis, a significant factor influencing the level of daytime SBP was age, daytime DBP — age and non-achievement of the TR of amlodipine and indapamide C0h; of nighttime SBP — body weight, of nighttime DBP — age and non-achievement of the TR of amlodipine and indapamide C0h. CONCLUSION: A high prevalence of subtherapeutic serum concentrations of indapamide and amlodipine has been recorded. Non-achievement of the TR level of both amlodipine and indapamide is associated with higher diastolic blood pressure with no significant effect on systolic blood pressure. The problem of poor hypertension control cannot be explained solely by serum antihypertensive drug concentrations — no convincing, unambiguous correlation has been established.
Endovascular treatment of acute symptomatic infrarenal aortic aneurysm in a patient with bilateral atherosclerotic renal artery disease and chronic kidney disease: a case report
INTRODUCTION: Currently, X-ray endovascular technologies in the amount of endovascular aneurysm repair (EVAR) are widely used not only in the treatment of scheduled patients with abdominal aortic aneurysm, but also in emergency situations, such as acute symptomatic aneurysm or its rupture, as an alternative to an open surgery. Endovascular treatment is characterized by minimal trauma, low mortality and a short hospital stay. However, for some patients, EVAR poses significant challenges and risks. One such group is patients with chronic kidney disease due to atherosclerotic lesions of the renal arteries. The article discusses a clinical case of a 67-year-old patient with an acute symptomatic abdominal aortic aneurysm, 5 cm in diameter, with a prominent concomitant cardiac pathology and stage IV chronic kidney disease (glomerular filtration rate 25 ml/min/1.73 m2) with the underlying critical stenosis of both renal arteries (subocclusion on the left and 85% stenosis on the right). The patient underwent emergency surgery in the amount of infrarenal aortic grafting and stenting of both renal arteries using gadodiamide. A reduction in the volume of contrast agent administered was achieved by stenting the renal arteries before EVAR. As a result, the stents, due to their radiopaque properties, were used as a guide for localizing the renal arteries during endograft placement. The postoperative period was uneventful, except for an early postoperative increase in blood creatinine up to 344 µmol/l and stabilization at this level. The patient was transferred to the vascular surgery department for symptomatic treatment. With infusion therapy, the blood creatinine level decreased to 270 µmol/l. On day 5, the patient was discharged for outpatient follow-up at the place of residence. CONCLUSION: This clinical case demonstrates a possibility of performing endovascular intervention in patients with stage IIIb–IV chronic kidney disease, due to, on the one hand, improvement of endovascular technologies, and, on the other, reduction of the volume of contrast agent used during surgery.
X-ray endovascular surgery in treatment of locally advanced bladder cancer and its complications: history of development and study of surgical tactics, modern capabilities, limitations and development prospects
INTRODUCTION: Over the past decade, the number of patients with bladder cancer (BC) has been growing worldwide. In Europe and North America, BC is the fourth most common cause of cancer in men and the second most common malignant tumor of the genitourinary system. In Russia, BC ranks 7th among cancers in men and 17th in women. It is important to note that these patients, with the mean age ≥70 years, often have a severe concomitant pathology. The predominant histological form of BC is transitional cell carcinoma accounting for 90% of cases. AIM: Based on the literature data analysis, to determine the prospects of intra-arterial embolization and chemoembolization of tumor-supplying vessels for the treatment of bladder cancer. The information search was conducted in eLibrary, PubMed, Scopus, Google Patent, Google Scholar, ResearchGate databases from May to June 2024 without restrictions on the type and time of publication. The following keywords were used: muscle-invasive bladder cancer, hematuria, bladder malignancy, interventional oncology, embolization, and vesical artery chemoembolization. The primary treatment for BC is surgical intervention, however, recently, of special attention have been interventional methods of local treatment. Chemoembolization is an innovative approach combining local therapy and embolization of the tumor-supplying vessels. This allows for the delivery of high concentrations of chemotherapeutic drugs directly to the tumor, minimizing systemic side effects. This is especially relevant when radical tumor resection is not possible, or as a variant of emergency intervention to stop bleeding. CONCLUSION: Having reviewed the works, it can be concluded that intra-arterial embolization holds promise for the treatment of such a threatening BC complication as hematuria. In addition, the interventional tactics has shown encouraging results in the treatment of locally advanced BC, as well as the potential for palliative treatment of tumors of this location. However, due to the paucity of data, this approach requires further clinical investigation.
The role of mitochondria in the development of cardiovascular diseases
INTRODUCTION: A large amount of experimental and clinical data has been accumulated that evidence the involvement of cardiomyocyte mitochondria in the pathogenesis of heart failure, cardiomyopathies and ischemic-reperfusion myocardial injury. Morphological changes of cardiomyocyte mitochondria include hyperplasia, decreased organelle size and broken structural integrity. Overexpression of various microRNAs suppresses mRNA transcription and the activity of enzymes and proteins involved in β-oxidation of fatty acids, Krebs cycle functioning, ATP production. It also inhibits the expression of genes regulating adaptive and maladaptive cardiac remodeling in heart failure. All the above events are accompanied by decreased ATP synthesis, release of pro-apoptotic proteins, fibrosis and cardiac hypertrophy. AIM: To analyze and systematize modern data on the role of mitochondrial dysfunction in the pathogenesis of cardiovascular diseases, and potential ways of its correction. To find material for this review article, we used the abstracting databases PubMed, Google Scholar, and eLibrary. The search included publications from 2013 to 2023. Analysis of literature sources showed that mitochondrial dysfunction has recently been considered an important factor in the development of heart failure. It also revealed the relationship between cardiomyopathies and mitochondrial failure as well as its role as a critical pathophysiological factor of myocardial destruction in ischemia/reperfusion. Additionally, data were obtained about an ambiguous role of microRNA-dependent regulation of the mitochondrial genes and their involvement in the development of cardiovascular diseases. Of importance is search for mitochondria-targeted medical drugs for the treatment of cardiovascular diseases. The promising drug targets are reactive oxygen species, factors controlling mitochondrial fission and fusion, biogenesis and autophagy, modulators of mitochondrial microRNA expression, and mitochondrial permeability pores. CONCLUSION: Cardiovascular diseases induced by mitochondrial dysfunction, can be associated with different organelle damages. New technologies of investigating molecular mechanisms underlying mitochondrial dysfunction and precise understanding of these disorders open up opportunities to more clearly define pathophysiological aspects and develop new therapeutic approaches for the treatment of circulatory diseases.
Evolution of surgical treatment methods for patients with varicose veins
INTRODUCTION: Treatment of varicose veins (VV) and their complications has history of several centuries. Throughout the 20th century, the surgery of choice was phlebectomy in different modifications. In recent decades, minimally invasive techniques have become the priority, which has been facilitated by technological advances and the advent of high-precision equipment minimizing surgical trauma. AIM: To conduct a comparative analysis of existing surgical treatment methods for varicose veins of the lower extremities based on literature data in terms of recurrence rates, complications, morbidity, and cost-effectiveness. An analysis of Russian and foreign publications (n=163) devoted to the surgical treatment of VV has been conducted. The search was conducted in the eLibrary and PubMed databases of biomedical publications for the past 8 years using the following keywords: varicose veins of the lower extremities, varicose vein surgery, phlebectomy, laser vein removal, endovenous laser obliteration, radiofrequency ablation, miniphlebectomy, endovenous laser ablation, mechanochemical endovenous ablation, surgery for treatment, cyanoacrylate embolization, radiofrequency ablation. From the results of the primary search, 86 articles were excluded as non-corresponding to the aim of the study. In addition, 17 articles from the period 2004–2017 were used to highlight less-used but still relevant methods. The analysis showed that the number of open interventions on the venous system has significantly decreased in recent years. Modern innovative treatment methods for patients with VV to a more extent take into account the pathogenesis of their development and physiology of venous outflow. Innovative technologies have been demonstrated to improve the quality of patients’ life both in the early and late postoperative periods, and also to reduce the incidence and severity of complications. Various novel, minimally invasive surgical treatment methods for VV are being introduced in the clinical practice of hospitals, outpatient clinics and are included in the clinical guidelines. An individual approach is important in choosing the optimal variant from the wide range of modern surgical treatments for VV. CONCLUSION: Minimally invasive treatment methods for VV are comparable in effectiveness with open phlebectomy, but have fewer complications. They are less traumatic, but more cost-effective, and thus can be referred to hospital-substituting technologies with transfer of surgical treatment for VV to an outpatient setting.
INTRODUCTION: A close functional relationship between the liver and thyroid gland suggests co-dependence of processes occurring in them not only under normal conditions, but also in pathology. The impact of thyroid dysfunction on change in the liver state has been extensively explored in the literature, while the converse — the impact of liver pathology on thyroid functional condition — requires additional analysis and study. AIM: To study changes in the functional condition of the thyroid gland in the most common liver diseases. An information search was conducted in the eLibrary, PubMed databases for the period from January 01, 2004 to April 01, 2004 with no restrictions on the type of publication. The following keywords were used: thyroid dysfunction, thyroxine, triiodothyronine, non-alcoholic fatty liver disease, chronic hepatitis, liver cirrhosis, hemochromatosis, Wilson's disease. An analysis of the literature sources demonstrates various mechanisms of thyroid dysfunction in liver diseases. Non-alcoholic fatty liver disease (NAFLD) is indirectly related to impaired thyroid function and potentiation of metabolic syndrome manifestations through insulin resistance and obesity. Data on thyroid dysfunction in a patient with NAFLD due to the development of autoimmune damage and an increased risk of thyroid cancer also deserve the attention of the clinician. A probability for autoimmune thyroid damage should necessarily be taken into account in patients with autoimmune hepatitis. The incidence of interferon-induced thyroid dysfunction is currently declining due to changes in the antiviral therapy protocols. Literature data indicate an increased risk of thyroid cancer in infection with hepatitis C virus. Data on the impact of liver cirrhosis on thyroid function are contradictory, most commonly noted are reduction of triiodothyronine and thyroxine levels due to the involvement of liver in thyroid homeostasis (liver deiodinase system, thyroxine-binding globulin). Iron overload of thyrocytes in hemochromatosis can in some cases be accompanied by changes in thyroid status. CONCLUSION: Thus, further investigation of thyroid status in liver diseases is needed, on the one hand, to elucidate mechanisms of thyroid dysfunction, and on the other, to determine a probable role of triiodothyronine and thyroxine levels as markers of severity of liver dysfunction. The data accumulated to date allow us to recommend studying thyroid hormonal status in chronic liver diseases.
Pathogenetic markers of cellular senescence
INTRODUCTION: Cellular senescence is a complex process occurring at all stages of the development and functioning of an organism. On the one hand, it is important as a mechanism protecting against cell damage, but on the other hand, it contributes to the development of age-related diseases and aging of an organism as a whole. AIM: To determine key markers of senescent cells to study pathogenetic mechanisms of aging and to search for new strategies of healthy longevity. A literature search was conducted in PubMed and eLibrary.ru databases until July 1, 2024 and included analysis of the original and review articles using the keywords: ‘senescent cells’, ‘cellular senescence’, ‘senescent cell markers’, ‘SA-β-Gal’, ‘SASP’. The best studied and widely used markers of senescent cells are cell cycle arrest factors: DNA damage response markers p53 and γH2AX, and cyclin-dependent kinase inhibitors p16 and p21. Furthermore, SA-β-Gal is a universal marker of cellular senescence, identified in both tissues and cell models of aging. SASP factors are not direct markers of aging, but an important indicator of complex interactions between senescent cells and their microenvironment. CONCLUSION: Currently, a large number of senescent cells pathogenetic markers have been identified. Their expression can vary depending on the cell type and aging context, which is important to understand for the development of senolytic therapeutic approaches and the maintenance of healthy longevity.
Stakeholders on biobanks: awareness, willingness to cooperate, challenges
INTRODUCTION: Biobanking is an important tool for the development of biomedical science that enables acquisition, storage and use of biomaterials for various studies. Key stakeholders in biobanks are their personnel, patient donors and healthcare workers providing preanalytical services. To successfully integrate biobanks into practice, it is necessary that attitudes of all stakeholders towards biobanking, especially healthcare workers be taken into account. AIM: To assess awareness, willingness to cooperate, and motivation of healthcare workers, biomedical students and the general public to participate in biobanking processes, and to identify challenges and barriers to biobank development. A manual analysis of publications in the Medline, Google Scholar, and CyberLeninka databases was conducted without publication date restrictions. The search was conducted using the following keywords: bank, biobanking, trust in biobanks (In Russ.), biobank, tissue banks, health personnel, medical students, awareness, public, biobanking knowledge, healthcare professionals, biobank participation willingness, biobank research participation, and trust (In Eng.). Studies from various regions (the Middle East, Europe, Russia, the USA, Africa, Asia, and Oceania; a total of 35 publications) were selected. The analysis included surveys, interviews, and expert opinions on awareness, willingness to donate, and ethical aspects. Awareness and willingness of healthcare workers to cooperate with biobanks depend on the sociocultural context of the country: in economically developed countries, awareness level is higher, with a positive attitude toward biobanking for precision medicine, but with barriers such as lack of knowledge and low trust. In economically developing countries awareness is low. Among students of biomedical universities awareness varies. The willingness of the population to donate also varies across the countries, but trust and education play a key role: students are more motivated by altruism. The challenges faced by biobanks in different countries are similar: ethical risks, lack of informed consent standards, infrastructural problems, and the length of the procedure. CONCLUSION: Biobanking development requires raising awareness and trust among stakeholders through educational programs. The introduction of unified standards, ethical norms and national initiatives will help overcome the barriers, integrate biobanks into practice and facilitate scientific discoveries in medicine.
Structural and functional biochemistry of OATP1B3: from polymorphisms to therapeutic targets
INTRODUCTION: Organic Anion Transporting Polypeptide 1B3 (OATP1B3) plays a key role in hepatic transport of endogenous compounds, xenobiotics and drugs. In recent years, new data have been presented on the molecular organization, mechanisms of function and regulation, genetic polymorphisms of OATP1B3, and its clinical significance in pharmacokinetics, diagnosis and treatment. Of particular interest is the extrahepatic expression of the transporter, which opens new prospects for targeted therapy. AIM: To identify the structural and functional biochemical features of OATP1B3 transporter, its genetic polymorphisms and their impact on pharmacokinetic and therapeutic properties, determine the potential of OATP1B3 for targeted and personalized medicine. Literature search was conducted using the following keywords: OATP1B3, SLCO1B3, transporter, substrate specificity, regulation, oncology, and hepatocellular carcinoma in Russian and English. Electronic databases providing access to peer-reviewed scientific articles were used: eLibrary, Medline/PubMed, and Google Scholar. The search was conducted between 2000 and 2004 to cover the current data, starting from the first publications on OATP1B3 identification, but also taking into account earlier key works on OATP1B3 identification. This review presents the biochemical features of OATP1B3 localization, structure, and transport cycle. It also systematizes literature data on substrates, inhibitors, and inducers of the transporter protein, describes regulatory mechanisms and identifies the clinical significance of this transporter protein. OATP1B3 is demonstrated to have tissue-specific localization: it is normally expressed in the liver, but in oncologic pathologies is detected in the cytosol of gastrointestinal and lung tumor cells, where it may participate in signaling pathways. Evidence of high genetic variability of the SLCO1B3 gene is presented. The clinical potential of OATP1B3 is confirmed by its role in diagnostics (liver MRI with gadoxetate) and the possibility of targeted delivery of chemotherapeutic drugs. CONCLUSION: OATP1B3 is an influx transporter protein that has an important clinical significance participating in transport of statins, cytostatics and diagnostic contrast agents, and its activity is modulated by post-translational modifications.