CLINICAL AND EXPERIMENTAL MEDICINE
An analysis of historical documents and facts, scientific publications and information materials on the creation of the Department of Medical Sciences within the structure of the National Academy of Science of Belarus, the main stages of the development of fundamental and applied research in scientific organizations, the achievements of domestic medical scientists and the results of activities in the field of medicine was carried out. Promising directions for improvement and innovative development of academic medical science with the formation of integration platforms for interdisciplinary and interdepartmental interaction have been identified.
The molecular genetic basis for pathogenesis of leukoplakia and squamous cell carcinoma of the oral mucosa (OM) is not well understood. Few studies are devoted to this problem and their results are incomplete and contradictory. At the same time, the early diagnosis of OM cancer and the prediction of its development are important public health problems.
The aim of the study was to analyze the relationship of somatic mutations with the formation of leukoplakia and squamous cell carcinoma of the oral mucosa.
48 altered OM epithelium samples of patients with OM leukoplakia (OML) (24 samples) and OM squamous cell carcinoma (OMSCC) (24 samples) were taken as material for research.
The pathogenic and probably pathogenic variants of the TP53, NRAS, and BRAF genes identified in this study, both as one by one and in combination, are associated with high probability (RR 3000‒11 000) with OML with grade 1 epithelial squamous intraepithelial neoplasia. Identified pathogenic and probably pathogenic variants of the ERCC3, HOXB13, KRAS, MSH3, MSH6, PIK3CA, and TP53 genes are associated with a high probability (RR 90‒22 000) with the OMSCC development. The observed pathogenic variants of the KRAS and TP53 genes are highly likely to lead to the formation of OML with grade 1 squamous intraepithelial neoplasia of the epithelium; a subsequent formation of pathogenic variants of the PIC3CA and/or HOXB13 and MSH3 genes leads to malignant transformation of altered OM epithelial cells ( p = 0.0000048). This information allows designing PCR-and NGS-test systems for predicting the development and early diagnosis of OMSCC.
The aim of the study was to develop a virtual software package that, when it is based on personalized indicators, allows planning surgical tactics and performing differentiated treatment of patients with degenerative lumbar spondylolisthesis.
The results of surgical treatment of retrospective group patients were the basis for creation of a virtual complex.
A virtual software package has been developed. It is an expert system for making decisions about surgical tactics for patients with lumbar degenerative spondylolisthesis. The operation of the program is based on the automated analysis of a given list of input parameters. The core of the virtual complex is represented by two configurations, one of which contains an artificial neural network. As a result of virtual processing of the patient’s individual parameters, the program gives an answer in the form of two color scales with numerical labels: a scale of differentiated choice between isolated decompression and decompression supplemented with posterior fusion; scales for a differentiated choice between laminectomy supplemented with medial facetectomy and bilateral decompression of the spinal canal from a unilateral approach. Using the developed software package, surgical treatment of 26 patients with lumbar degenerative spondylolisthesis was performed.
The Scales virtual complex, based on key general somatic and clinical and radiological parameters of a patient, creates an opportunity for a surgeon to make the most balanced and informed decision on the tactics of surgical treatment of lumbar degenerative spondylolisthesis. A personalized approach, accompanied by artificial intelligence technology, is aimed at reducing the likelihood of tactical errors and long-term complications of surgical interventions. The use of color scales with digital labels makes it possible to simplify the process of preoperative planning and to create conditions for achieving a balance between the decision of the program and the individual opinion of a specialist surgeon. The result of differentiated treatment of a group of patients using a virtual system was a significant and statistically significant ( p < 0.001) improvement in the life quality of operated patients in the long-term period.
Multiple sclerosis (MS) is a multifactorial, autoimmune, chronic disease of the nervous system, manifested by multifocal neurological symptoms and occurring in typical cases in the presence of symptoms of a relapsing course. MS is one of the problems of modern neurology, which is characterized by the prevalence of diseases, the prevalence of patients in the age group from 20 to 40 years, as well as high disability. The main target of therapeutic options in MS is the appearance on the immune system in order to suppress the inflammatory process leading to demyelination. With a set of drugs that allow clinically modifying the course of MS (beta-interferon, glatiramer acetate, fingolimod, etc.), 40 % of patients have a good effect, 40 % have a questionable result, and 20 % of patients with MS do not detect treatment. Lack of treatment protocols aimed at selective stimulatory suppression of autoreactive T-lymphocyte clones and restoration of affected areas of the CNS, weakening of the ever-increasing interest in identifying the immunomodulatory and neuroprotective properties of mesenchymal stem cells (MSCs). From carriers, the benefits of allogeneic versus autologous MSC implantation are widely discussed without the presence of objective evidence of the superiority of one type of cell therapy over the estimated and estimated fees of autologous or allogeneic transplants in obtaining MS remains controversial.
Objective ‒ to study the effect of modifying therapy using allogeneic mesenchymal stromal stem cells on the immunological parameters of patients with multiple sclerosis.
The results of assessing the dynamics of a number of immunological biomarkers in 4 patients with relapsing-remitting MS. All patients are men. The median age is 35.0 + 11.4 years. At the screening period, the Expanded Disability Status Scale (EDSS) score was 3.6 [2.5; 6.0]. immunological and cellular-morphological parameters of MSC cultures were revealed, enhanced due to adipose tissue (AT) of 7 donors. Of the 7 samples of AT MSCs, 2 samples were selected with the highest coefficients of suppression of T-lymphocyte proliferation, of which 4 biomedical cell products should be taken for therapy.
In patients with MS, the most significant changes were observed by 6 months of the post-transplantation period and were characterized by a decrease in γIFN production, the number of functions of immature “double positive” and “double negative” T-lymphocytes, and a decrease in the cytotoxic orientation of T-lymphocytes with a γδ T-cell receptor characterized by characteristics of an increase in the number of cells expressing CD45RO+ (memory cell marker) in an increase with a decrease in the number of γδTCR CD314+ lymphocytes (expressive key activator of killer receptors).
Preliminary results from a study of transplantation of alloMSCs to the immunological status of MS patients suggest that they accept disease-modifying therapy in this application as pathogenetic, disease-modifying therapy.
Among the conservative methods of treatment of osteoarthritis the use of plasma enriched with soluble platelet factors /platelet-rich plasma (PORFT/PRP) is becoming increasingly attractive.
The aim of the study was to determine the tolerability and effect of intra-articular administration of standardized autologous PRP on patients with knee osteoarthritis status based on the survey results. Patients with knee osteoarthritis (OA) received standard drug therapy (n = 19) or additionally standardized autologous platelet-rich plasma (PRP) (n = 21). Intraarticular injection of 6 ml of PRP was carried out three times every two weeks. The administration safety was assessed. Patients were questioned with an assessment of VAS and WOMAC scales in 2 weeks, 1 month and 3 months after starting the treatment. It was shown that three-time intra-articular administration of standardized autologous PRP was safe for a patient. At the same time, the pain syndrome decreased (VAS score) and the knee joint function improved (WOMAC score) after 1 and 3 months. All indicators were significantly better compared to the control group. We concluded that standardized autologous PORFT with three intra-articular injections is safe and has an analgesic effect and preserves the function of the knee joint already within 1–3 months of observation.
The results of a comprehensive (clinical-radiological and neurophysiological) study performed in two clinical groups of patients (n = 64) with kyphotic spinal deformity of II–IV degree of severity of the thoracic and lumbar spine of various etiologies were analysed. With the progression of kyphotic spine deformity, the spinal cord (SC) located inside the spinal canal becomes involved in the pathological process. This period of dysfunction is preceded by a state of latent SM changes that are not detected clinically (prodromal period). The presence of neurological disorders is considered as a factor of increased risk of intra- and postoperative complications in the surgical treatment of kyphosis. Based on the registration and analysis of the parameters of somatosensory evoked potentials and motor responses during transcranial magnetic stimulation, electrophysiological signs of sensorimotor insufficiency of the SС nerve tracts were revealed, which correlate with the kyphotic arch value. The established electrophysiological criteria allow to verify the level of conductive lesion at the level of thoracic and lumbar SC segments, to determine its severity, to monitor recovery processes and to predict the functional outcome.
The chronic wounds (CW) bed preparation requires an integrated approach using wound assessment, microbiological and histological analysis, which will avoid skin graft failure.
The aim was to evaluate the possibility of using microbiological and morphological parameters of CW assessment to substantiate the choice of tactics of wound bed preparation to skin grafting (SG).
Morphological and microbiological indicators of CW (n = 229) at various stages of the infectious process were analyzed. To prepare CW to SG, the following treatment methods were used: dressings, vacuum therapy (VT), mechanical debridement (MD), and ultrasound debridement (UD).
The criteria that determine the possibility of CW preparation “under a bandage” in combination with MD are: the absence of inflammation signs and the normal state of granulations (red-pink color, firm and moist), a negative result of wound swabs, the histological result of Si 1/Si 2 and Sp 1/Sp 2. For CW performed with pathologically altered granulations colonized by potential pathogens and having Sp 3, Si 2/Si 3 criteria, the use of 2 UD procedures is indicated (1st in combination with MD, 2nd before SG), between which VT is applied. Critically colonized wounds showing the signs of Sp 3 in combination with Si 1 or Si 2, from which microorganisms are isolated in an amount of ≤105 CFU/ml and are characterized by persistent properties, are an indication for VT, which is performed between two UD procedures. Clinical infection signs, the presence of bright red friable and bulge granulations in the wound, morphological signs of Si 3/Si 2 and Sp 1/Sp 2 are indications for the use of 2 UD procedures in combination with systemic antibiotic therapy based on wound swab culture results.
Microbiological and morphological parameters characterize the CW state at various stages of the infectious process (colonization, critical colonization, infection) and are recommended as criteria for choosing tactics for wound bed prepara tion to SG.
Introducing the antibiotic therapy into clinical practice is one of the most important steps in the fight against infectious diseases. Antibacterial therapy is prescribed to more than 70 % of all patients in intensive care units. Carbapenems remain the “cornerstone” of antibiotic therapy for severe infections. The main problem on the use of antibiotics is a long-term alteration of the healthy microbiota and a horizontal transfer of resistance genes. The structure of the fund of free amino acids in biological fluids and tissues is an integral characteristic of metabolism, and the effect of antibacterial agents on their concentration in plasma has not been sufficiently studied.
The aim of this study was to conduct a comparative analysis of the effects of meropenem and imipenem/cilastatin on the bacterial flora of the intestine and the pool of free amino acids in the blood plasma of rats.
The experiments were carried out on white outbred rats kept on a standard vivarium diet and having free access to drinking water. Animals were divided into 3 groups: group 1 (n = 7) – animals were intraperitoneally injected with 0.9 % NaCl solution for 10 days; group 2 (n = 7) – animals were intraperitoneally injected with meropenem-TF (SOOO “TriplePharm”, Republic of Belarus) at a dose of 60 mg/kg body weight for 10 days, group 3 (n = 7) – animals were injected with imipenem in the same way for 10 days /cilastatin (SOOO “TriplePharm”, RB) at a dose of 120 mg/kg of body weight. Free amino acids in blood plasma were determined by chromatography.
A comparative analysis of the pool of free amino acids in the plasma of rats after the administration of antibacterial drugs of the carbapenem group revealed a number of significant confidence (p < 0.05) differences in the both study groups. Thus, in the imipenem/cilastatin group, an increase in the total amount of proteinogenic amino acids, essential amino acids, the total amount of aromatic amino acids and a decrease in the nonessential-to essential amino acid ratio were determined. In the meropenem group, these abnormalities were not identified. However, the total amount of sulfur-containing amino acids decreased.
The results obtained showed a significant change in the levels of the both individual amino acids and their total amount. A more pronounced change in the pool of free amino acids in the blood plasma after administrating imipenem/cilastatin is probably due to the presence of cilastatin (renal dehydropeptidase inhibitor) in the composition of the drug, as well as its more pronounced toxicity. When compared with meropenem, imipenem/cilastatin resulted in a greater growth of spore-forming anaerobes. In turn, meropenem more reduced the level of bifidobacteria, lactose-positive bacteria of the E. coli group than imipenem/cilastatin.
This study investigated a range of gene polymorphisms encoding IL-1, IL-6, IL-10, and TNF-α ‒308 in 100 healthy unrelated Kazakhs using real-time PCR. The findings were compared with published data on other populations. The distribution of genotypes was consistent with the Hardy-Weinberg equilibrium. However, the frequency of cytokine genotypes observed in the Kazakh population showed similarities and differences compared to neighboring ethnic groups. The most noticeable differences compared with Iranians, Turks, Russians, and Chinese were observed in the distribution of IL-1, IL-6, and IL-10 genotypes. The frequency of the TNF-α ‒308 genotype differed only with the Iranian population. Thus, our study showed a link between cytokine gene polymorphism and ethnicity. These results may be of clinical relevance in understanding the prevalence of diseases in Kazakhstan.
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