Preview

Translational Medicine

Advanced search
Vol 11, No 5 (2024)
View or download the full issue PDF (Russian)

CARDIOVASCULAR MEDICINE

378-387 403
Abstract

Background. The choice of an antiarrhythmic drug, proof of its effectiveness and safety in a short period of time in patients with non-coronary ventricular arrhythmia are the most pressing problems of practical arrhythmology. Objective. To resolve the issue of choosing an antiarrhythmic drug in patients with a mixed nature of ventricular arrhythmia, several ectopic foci, and to optimize further tactics for their management. Design and methods. Of 167 patients with ventricular arrhythmia distribution during periods of wakefulness who performed a stress test, 32 individuals with non-coronary arrhythmias of a mixed nature (by the participation of the autonomic nervous system) were selected. All patients underwent an acute pharmacological stress test with a beta-blocker. Antiarrhythmic therapy was selected under the control of multi-day ECG telemonitoring. Results. In the pretest of exercise tests, single ventricular parasystole was recorded in all 32 patients. In 3 patients, the arrhythmia persisted throughout the entire load, in 4 patients it progressed, in 25 patients the parasystole of the initial morphology disappeared, and at the peak of the load/early recovery period, arrhythmia of a different morphology appeared. Indications for drug treatment were determined for all patients with the choice of the drug after acute pharmacological tests. Then, therapy with two antiarrhythmic drugs was initiated using multi-day ECG telemonitoring, the purpose of which was to control the efficacy, safety, choice of doses and time of drug administration. On days 5–6, combination therapy was effective in 25 patients (78 %). Conclusion. With the help of stress tests, it is possible to accelerate not only the search for the cause of ventricular arrhythmia, but also the choice of a personalized method of treatment. Supplementing the examination with pharmacological tests allows predicting the result of combined antiarrhythmic therapy with a beta-blocker and a class IС drug with an anticholinergic effect.

388-397 315
Abstract

Background. A promising method of surgical treatment of aneurysms of the root and ascending aorta (AA) with unchanged aortic valve (AV) cusps is aortic valve-sparing root replacement (VSRR) with AV reimplantation (David procedure). To date, there are no clear indications to make a choice in favor of valve-replacing or valve-sparing intervention. The result of visual evaluation and the choice of treatment method based on the surgeon’s experience remains the main criteria. Objective. In the experiment to develop a prototype and method of application of the device for positioning of AV cusps, which will simplify and standardize aortic valve-sparing root replacement, improve the results and increase the reproducibility of these operations. Design and methods. Three-dimensional (3D) modeling of the device components was performed in the parametric open-source computer-aided design environment FreeCAD 0.20.1. Two-dimensional sketches were converted into three-dimensional models and exported as stl files for 3D printing. Solid components of the model were made of polylactic acid (PLA-plastic), elastic components were made of rubber-like photopolymer (Dropstil F556 10 shore A) also by 3D printing using SLA technology. Results. The device consists of 2 similar ring-sizers of variable diameter connected by three struts of variable length. In the upper part of each of the struts fastenings to the distal ring represents T-shaped cutouts for temporary locking of the suture-holders passed through the commissures of the AV cusps. For proximal locking of the aortic graft and the proximal ring-sizer, 3 U-shaped sutures are used, passed from inside to outside through the AV ring, the proximal part of the graft and taken in the tourniquets. The diameters of the ring-sizers can be varied between 25–40 mm by rotating a worm drive. A graft is placed on the inner side of the device, the suture-holders attached to the tops of the commissures are locked in the T-shaped notches in the upper parts of the struts. The device will allow changing the position of the coaptation point, coaptation square and performing hydraulic tests in different positions of the cusps, as well as variable diameters at the level of the AV ring and sinotubular junction (25–40 mm). When the target position of the coaptation point, coaptation area and satisfactory hydraulic test result are achieved, the cusps with commissures are locked inside the graft and the device is removed. Conclusion. A new device has been developed to facilitate, reproduce, and standardize VSRR. The results obtained will facilitate and accelerate the performance of VSRR, increase the reproducibility of the technique, and reduce the risks of complications.

INFECTIOUS DISEASES

398-406 277
Abstract

According to the World Health Organization (WHO), nearly 10.6 million new cases of tuberculosis were detected in 2022, indicating an increase of 3.5 % from the reported 10.3 million in 2021. After the COVID-19 pandemic, the incidence of tuberculosis increased by 3.9 % from 2020 to 2022. According to the latest regulatory documents, multidrug-resistant pathogen is diagnosed when any bacteriologic or molecular genetic methods reveal drug resistance of M. Tuberculosis complex at least to isoniazid and rifampicin regardless of resistance to other antituberculosis drugs.

With a wide range of virulence genes, the tuberculosis pathogen expresses genes in different phases of infection. Some genes are “switched on” in the early phases and are important for overcoming immune defenses and spreading the pathogen in the host, while others are important for survival in the latent phase. These characteristics of Mycobacterium tuberculosis determine the need for correct and adequate selection of therapy. The problem of diagnostics and treatment of drug-resistant tuberculosis remains extremely urgent. Despite the introduction of new tests for rapid determination of drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy regimen remains. When selecting therapy, the problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains. The need to assess the patient’s comorbid status, which affects the effectiveness of treatment and the occurrence of relapses, remains relevant.

Despite the introduction of new tests for rapid determination of the drug susceptibility spectrum of Mycobacterium tuberculosis, the problem of timely and adequate prescription of chemotherapy remains relevant. The problem of prescribing a combination of antituberculosis drugs with proven efficacy against M. tuberculosis remains in the selection of therapy. Currently, the introduction of bedaquiline in therapy regimens is important for improving the effectiveness of tuberculosis treatment. In addition, studies are underway to shorten the duration of therapy for MDR-TB and XDR-TB, which is particularly important for maintaining patient adherence to treatment.

МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА

407-418 217
Abstract

 

Background. Assisted reproductive technologies (ART) represent the most promising and successful methods of infertility treatment. A personalized approach may enhance its efficacy. One such approach is the development of reliable methods for assessing the quality and selection of embryos for transfer. The quality of the embryo is largely contingent upon the quality of the gametes involved in fertilization; thus, the development of non-invasive methods to assess oocyte quality represents a crucial step in the advancement of personalized ART. It is proposed that molecular and biological characterization of cumulus cells can be utilized to assess oocyte quality and predict the success of implantation of transferred embryos. The aim of the study was to evaluate the expression levels of potential oocyte quality marker genes (AREG, STAR, PTGS2, HAS2 and SCD5) in cumulus cells from healthy donors and patients with primary and secondary infertility. Materials and Methods. Nine donors and 19 patients were enrolled in the study. RNA was isolated from cumulus cells obtained during oocyte preparation for fertilization, and cDNA was synthesized. The cDNA was used as a matrix for real-time PCR with primers for the above-mentioned genes of interest. Results. Significant difference in AREG gene expression was observed between patients with successful (i.e. ended with birth) outcome and with IVF failure. No difference was found for the STAR, HAS2, PTGS2 and SCD5 genes. Conclusion. The method of assessing the expression level of marker genes in cumulus cells by real-time PCR shows considerable promise for the assessment of oocyte quality. The AREG gene is a potential candidate for use as a marker of oocyte quality.

419-427 163
Abstract

Background. In the wound process, there is a high probability of complications in the form paratraumatic eczema (РТЕ), which determines the severity the course of wound repair. Genetic factors responsible for the regulation of cytokines a leading role in the etiopathogenesis of РТЕ. Aim — determine the relationship of TNFa gene rs1800629 with the development of РТЕ and IL-1ß, TNFα, IL-6. Materials and methods. The study included 162 patients after surgical interventions. Group I — 82 people with complications in the form PTE and II — 80 people without complications. The study rs1800629 TNFα gene was carried out by the poly- merase chain reaction method. The levels TNFα, IL-1β and IL-6 in the blood was determined by the enzyme immunoassay method. Results. A connection with PTE was established with of rs1800629 gene TNFα (p = 0.033 and p = 0.005). The genotypes GA (OR = 1.64; CI 0.83–3.24) and AA (OR = 2.94; CI 0.9–9.67), allele A (OR = 2.13; CI 1.26–3.6) rs1800629 influenced the increased chances of developing PTE. In group II the IL- 1β, TNFα, IL-6 indicators were increased (p < 0.001) in carriers of the AA genotype rs1800629. Conclusion. rs1800629 TNFα gene is associated with development of PTE. An increase in the levels IL-1β, TNFα, IL-6 was associated with the presence of a pathogenetic factor — AA genotype rs1800629 TNFα gene in development of complications.

RADIOLOGY

428-444 174
Abstract

Background. In clinical practice, MRI pathophysiological and pharmacokinetic models with calculations of contrast transport indicators are unacceptably little used.

Aim of the study. To propose a pharmacokinetic technique for the quantitative assessment of primary tumors and metastases, the effectiveness of breast cancer chemotherapy (BC), from dynamic contrast enhancement MRI. Material and methods. 18 patients were included who underwent neoadjuvant chemotherapy (NACHT) in four cycles for breast cancer T1-3N0-1M0, followed by radical surgical removal of the tumor. According to the results of a three — year follow-up, patients with a relapse — free course (n = 11) formed group 1, and seven patients with detected metastatic lesions (3 in the liver, 2 in the lungs, 2 in the brain) — group 2. For the initial 120–180 s of MRI with contrast after the injection of a paramagnetic, the simplification is valid for concentrations in tumor and blood and for tranfer coefficient: d{СОПУХОЛЬ(t)} / dt = ККр-Оп * СКРОВЬ (t) , from which it is obvious: ККр-Оп = (СОПУХОЛЬ(Т)) / (∫CКРОВЬ(t) dt), which was used in all calculations of the contrast transfer constant. Gadobutrol contrast is 0.1M/10 kg of body weight, TR = 5.5–6 ms, TE = 2.5 ms. Results. If, after the first cycle of NACHT, the ККр-Оп of the primary breast cancer is < 0.22 ml/min/g of tissue, the probability of subsequent relapse-free course = 0.78. Similarly, a decrease in the KCr-Op Ккр-Оп of the sentinel lymph node after the first cycle of NAHT < 0.08 ml/min/g of tissue with a probability of 0.75 predicts a relapse-free course. Conclusion. The proposed method for calculating the ККр-Оп transfer coefficient allows obtaining additional diagnostic and prognostic information in patients with local and locally advanced forms of breast cancer.

ORIGINAL RESEARCH

445-455 250
Abstract

Objective. To evaluate the results of implantation of a new domestic self-expanding nitinol stent in experimental animals. Materials and methods. Experimental implantations of a self-expanding nitinol stent were performed in the common iliac artery of three Vietnamese Pot-bellied pigs. In the postoperative period, all animals received dual antiplatelet therapy for 3 months. Vital signs were also assessed throughout the observation period. After 3 months, the animals underwent control angiography and ultrasound examination of the iliofemoral segment, followed by withdrawal from the experiment by euthanasia. The next step was a macroscopic and histological analysis of the stented areas of the vessels. Results. The observation period of the animals was 3 months. Throughout the entire observation period, vital signs in all animals remained within normal values. The results of control angiography and ultrasound examination after 3 months demonstrated patency, as well as the absence of significant in-stent stenoses in two pigs. One animal showed signs of in-stent restenosis. The results of macroscopic and histological analysis showed signs of damage to the subendothelial layer, as well as myointimal hyperplasia. These changes were especially pronounced in the animal with restenosis. Our analysis showed that the presented results were due to excessive oversizing of the implanted stents (20–30 %). Conclusion. Our proposed self-expanding nitinol stent, in general, showed satisfactory results in the in vivo experiment. Nevertheless, it should be borne in mind that severe stent oversizing can cause excessive neointimal proliferation, which, in turn, will lead to the development of restenosis in the long-term postoperative period. In this regard, it is necessary to carry out an additional series of implantation of the presented stent to the experimental animals with less oversizing in order to determine its optimal values for this particular stent model.

456-464 172
Abstract

Background. Pulmonary hypoplasia and persistent pulmonary hypertension in congenital diaphragmatic hernia are the cause of adverse perinatal outcomes. Dissatisfaction with the outcomes of intrauterine surgical correction of CDH determines the search for alternative non-surgical prenatal methods of treating pulmonary hypoplasia in CDH. Objective. To study the effect of a reversible selective inhibitor of specific phosphodiesterase type 5 (tadalafil) on the development of fetal lungs in rats in a model of congenital diaphragmatic hernia. Design and methods. An experimental study was conducted on the possibility of correcting fetal lung hypoplasia in rats when modeling a diaphragmatic hernia with nitrophen (100 mg orally, once on the 9th day of pregnancy). Results. Congenital diaphragmatic hernia was recorded in 12.5 % of offspring. Subcutaneous administration of tadalafil to pregnant rats (0,83 mg/kg, for 10 days, from the 9th day of pregnancy) in the lungs of fetuses increases the number of alveoli (by 22 % at p ≤ 0.05), the area of microvasculature vessels and the volume of lung parenchyma increases (by 1.25 % and 1.13 % more (at p ≤ 0.05)). Conclusion. The results obtained from the first experiment conducted in the Russian Federation to study the effect of tadalafil on the lungs in congenital diaphragmatic hernia of the fetus are comparable with the data of the authors who used sildenafil, however, the use of tadalafil seems more optimal due to the ease of its administration for potential practical use.



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)