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Vol 11, No 1 (2024)
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ALLERGY AND IMMUNOLOGY

6-18 586
Abstract

   Sarcoidosis is a systemic inflammatory disease of unknown etiology with a wide range of clinical manifestations. The annual incidence ranges from 1 to 15 per 100,000 population. Due to the lack of specific clinical features, the diagnosis of this disease is still challenging. The significant variability in clinical presentations and target organs, as well as concomitant diseases, greatly complicate the diagnostic search and make sarcoidosis a diagnosis of exclusion. This article discusses a clinical case of a patient with generalized chronic sarcoidosis and provides a review and analysis of the current literature on this issue. At the moment, there is no biomarker or combination of biomarkers that would reliably predict the development and spread of the pathological process.

MEDICINAL CHEMISTRY

19-27 446
Abstract

   Introduction. According to WHO, acute disorders of cerebral circulation are anticipated to become a predominant contributor to the global disease burden by 2030. The comprehensive management of vascular depression entails not only the use of antidepressants but also fundamental interventions. The development of a novel molecule based on thietane-containing heterocycles, merging the attributes of an antidepressant and an antiplatelet agent, holds promise for enhancing therapeutic efficacy in patients with acute cerebrovascular accidents through multimodal action.

   Objective is to conduct a preclinical assessment of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide concerning model thrombosis in rats.

   Materials and Methods. The investigation involved the evaluation of thrombosis processes and the haemostasis system in rats subjected to complete occlusion of the inferior vena cava within 24 hours post-thrombosis induction. Techniques employed included thromboelastography, Born aggregometry, standard clotting assays to appraise the coagulation facet of haemostasis, and morphological examinations.

   Results. The results demonstrate that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide mitigates thrombosis mass, restores platelet hyper aggregation, and counters hypercoagulation observed in acute inferior vena cava thrombosis in rats. Comparative analysis with reference drugs substantiates the superior effectiveness of the chosen compound in thrombosis prevention.

   Conclusion. The preclinical investigation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide unveils a fusion of established antidepressant and antithrombotic activities, laying groundwork for further drug development endeavours.

NANOTECHNOLOGY

28-44 541
Abstract

   Background. Despite the ongoing mutations of the SARS-CoV-2 virus, the causative agent of the COVID-19 disease, its mechanism of entry into the cell remains unchanged, which can be used to create virus “traps”. Intravenous medications aggravate the symptoms of the disease. An alternative means of combating the virus could be enterosorbents synthesized on nanosized carriers that intercept SARS-CoV-2 directly at the site of its introduction into the body, namely in the gastrointestinal tract.

   Objective. To study and refine the methods of synthesis of different spacer types on the surface of aerosil nanoparticles, immobilization of model protein with the possibility of using the compounds as enterosorbents of SARS-CoV-2 virus.

   Design and method. Aerosil A-200 grade was used as carrier nanoparticles. The chemical composition of the obtained compounds was studied by FTIR spectroscopy. The absorption spectra of the samples were studied using a spectrophotometer. The dimensions of nano-objects were determined by dynamic light scattering. Qualitative and quantitative determination of protein chemisorption on the synthesized particles was carried out.

   Results. Prototypes of SARS-CoV-2 enterosorbents on aerosil particles were developed. The efficacy of the spacers was tested on the model protein, albumin.

   Conclusion. Further research may be directed to the development of an oral drug that reduces the viral load of SARS-CoV-2.

МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА

45-54 445
Abstract

   Background. We used the “Mitochondrial Membrane Potential Kit” (Sigma-Aldrich) to detected MMP but encountered difficulties by applied this kit because in manual there not JC-10 concentration and it not allowing for account cell type, size, density, differences in incubation time for different cell cultures.

   Objective. Adaptation of the method for determining MMP (mitochondrial membrane potential) in C2C12 cells using in microplate reader and electron microscope.

   Design and methods. MMP in C2C12 cells was measured by two way, using fluorescence microscopy (Zeiss, Zen program) and using a plate fluorimeter (CLARIOstar (BMG LABTECH). JC-10 and TMRE dyes (Sigma-Aldrich) were used as fluorescent probes.

   Results. Optimal conditions for detection changes in mitochondrial membrane potential in C2C12 cells were selected. 100- fold dilution of the dye JC-10 (Dye Loading Solution) and replacement of the manufactured buffer to PBS led to repeatability and reproducibility results.

   Conclusion. When using ready-made kits for measuring MMP, the method proposed by the manufacturer may not be suitable for the selected cell line. In our study to mouse myoblasts of the C2C12 line, a dilution of the dye for loading was required 100 times compared to that recommended by the manufacturer.

55-64 617
Abstract

   Background. Histological and genetic methods are often used in the study of pathologies. To prevent contamination of histological preparations with blood, the microvasculature is perfused with a heparin, which leads to its accumulation in the tissue. Heparin is an inhibitor of the polymerase chain reaction (PCR).

   Objective. To study the possibility of preventing the influence of unfractionated heparin (UFH), used in perfusion, on the result of gene expression in rat lung samples using RT-PCR by pretreatment RNA with heparinase.

   Design and methods. Perfusion of the rats’ vasculature was performed with UFH at concentrations of 50 IU/mL (n = 3) and 500 IU/mL (n = 3), or with a sodium chloride (n = 3) as a control. RNA was isolated from left lung samples and treated with heparinase. The relative expression of five genes (s18, HPRT, Actinβ, GAPDH, Vim) before and after heparinase treatment of isolated RNA preparations was assessed based on the absolute value of the threshold cycle (Ct) obtained by RT-PCR.

   Results. UFH increases the threshold cycle level. Treatment of samples with heparinase does not affect the quantity and quality of RNA, but reduce the Ct compared to samples not treated with heparinase.

   Conclusion. While planning a study, it is necessary to consider alterations in the results of genetic research that arise due to organ perfusion with a heparin solution. The use of heparinase effectively eliminates heparin-associated RT-PCR inhibition.

CANCER

65-76 413
Abstract

   Brain tumors are the most common group of neoplasms in children, which is in the top-3 causes of infant mortality from oncopathology.

   The aim of the study is to make a literature review of modern approaches to the personalization of treatment of CNS tumors in children based on the study of molecular genetics, immunohistochemical and imagingт characteristics.

   The article provides a description of the most common types of neoplasms of the nervous system — low grade gliomas (LGG), high grade gliomas (HGG), mixed glioneural tumors, etc. The molecular genetics, immunohistochemical, visualization characteristics of each type of gliomas are described. Modern information on prognosis and treatment of tumors is also given in the publication. The prognosis of the course of LGG/GNT in children depends more often on the patient’s age, histology, and location of the tumor, as well as its molecular profile. Older patients have a more favorable prognosis than younger children. Well-visualized tumors located superficially have a better outcome than diffuse gliomas, as well as deeply located tumors. Detection of BRAF mutations and FGFR rearrangements may indicate a better prognosis than in the presence of SNV. Local mutations of BRAF with concomitant deletion of CDKN2A, as well as mutations with H3.3 pK27 are the most dangerous.

CARDIOVASCULAR MEDICINE

77-86 406
Abstract

   Background. Complications after revascularization in individuals with peripheral atherosclerosis and diabetes mellitus can lead to negative results of surgical interventions against the background of critical ischemia.

   Objective. The aim of the study was to identify predisposing circumstances for the development of certain complications after reconstruction in patients with critical ischemia and diabetes mellitus.

   Materials and methods. A prospective study of the results of reconstructive interventions was carried out in 78 patients with trophic disorders on the background of peripheral atherosclerosis and diabetes mellitus. Complications were detected in 25 cases (the main group), 53 patients had uncomplicated course of the postoperative period. The influence of concomitant diseases, peculiarities of surgical treatment on the occurrence of adverse outcomes was analyzed.

   Results. Manifestations of heart failure increase the likelihood of arterial thrombosis (p < 0.05). Signs of hepatic dysfunction increase the frequency of PE in the perioperative period (p < 0.05). Adequate correction of hypergly-
cemia reduces the risk of stroke.

   Conclusion. The data on the circumstances predisposing for the development of complications make it possible to prepare more carefully for reconstruction against the background of critical ischemia in people with peripheral atherosclerosis and diabetes mellitus and minimize the number of adverse outcomes of intervention.

NEUROLOGY

87-102 432
Abstract

   Ischemic stroke is one of the leading causes of disability and mortality. The key approaches to the treatment of this pathology are thrombolytic therapy and thromboaspiration. Despite their proven efficacy, the application of these methods is limited by a relatively narrow therapeutic window. There remains a great relevance in the further study of the molecular mechanisms of ischemic- reperfusion brain damage within the framework of the ischemic cascade concept. The impact on the mechanisms of induction and implementation of various types of programmed cell death with the help of pharmacological agents is a promising approach to reduce brain damage in ischemic stroke. This review considers the key processes leading to irreversible damage to neurons and their death. The mechanisms of formation and the role of excitotoxicity, calcium overload, oxidative and nitrosyl stress, mitochondrial dysfunction, as well as the triggering of signaling pathways of apoptosis and aseptic inflammation are considered in detail. The issue of various variants of cell death against the background of these pathological processes is discussed. Along with the consideration of signaling pathways that contribute to the progression of brain damage, special attention is paid to the activation of protective signaling mechanisms during ischemia, which provide an increase in cell resistance to death.

PAIN, CRITICAL CARE, AND ANESTHESIA

103-121 661
Abstract

   Relevance. Delirium is a severe neuropsychiatric syndrome, which is a common problem in patients in the intensive care unit (ICU). Recently published works indicate a insufficiency of awareness about the key principles of diagnosis and treatment of this condition.

   The aim of the study is to analyze and summarize data on algorithms that allow the identification and correction of delirium in patients in the intensive care unit.

   Materials and methods. A comprehensive search was conducted in the electronic databases PubMed and eLIBRARY. The review includes searchable publications for May 2023.

   Results. A literature review identified five adult delirium screening tools that have been validated against The Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for delirium. Prospects for improving clinical outcomes are multi-component programs with a large number of strategies aimed at assessing, preventing and treating delirium in the ICU.

   Conclusion. It is necessary to use validated screening tools, as well as implement preventive strategies such as ABCDEF. Prevention of delirium in the ICU by determining the level of risk, eliminating etiological development factors and early multimodal therapy should be included in the standard algorithm from the moment the patient is admitted to the hospital in order to reduce hospital mortality.

METHODICS

122-132 678
Abstract

   Background. Despite numerous measures it is still impossible to overcome translational barriers and increase the reproducibility of the results obtained. The most significant procedures that improve the reliability of in vivo studies are randomization and blinding (masking). Conducting randomization does not require significant resources. In contrast, blinding is a more labor-intensive process. Research

   Objective. To analyze the scientific literature on the use of blinding in preclinical studies to further elaborate an algorithm for this procedure in a particular testing center.

   Materials and methods. Publications were searched in PubMed and Google Scholar databases (until April 30, 2023).

   Results. A literature review of blinding in preclinical studies was conducted, methods and the stages of scientific work at which this procedure can be performed were reviewed. An algorithm for partial study blinding that does not require additional specialists has been proposed. It is shown that the application of blinding allows to increase the reliability of the obtained data. If full blinding cannot be performed, it is necessary to evaluate which stages of the preclinical study can be blinded. Appropriate procedures should be developed and implemented to perform blinding in the preclinical center.

   Conclusions. The proposed blinding algorithm can significantly reduce the influence of the specialist(s) on the experiment or interpretation of the data obtained.



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