I.P. Pavlov Russian Medical Biological Herald

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.

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.

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.

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.

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.

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 7^th among cancers in men and 17^th 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.

INTRODUCTION: Treatment of varicose veins (VV) and their complications has history of several centuries. Throughout the 20^th 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: 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.

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.