Vol 25, No 2 (2021): EXPERIMENTAL AND CLINICAL PHYSIOLOGY

EXPERIMENTAL PHYSIOLOGY
Association of BTNL2 gene single nucleotide polymorphism with knee osteoarthritis
Sahoo S.S., Choudhari O.K., Bhadra J., Kabi B.C.
Abstract

Relevance. Osteoarthritis (OA) is one of the chronic debilitating condition mostly seen in the aged population. The etiology behind the OA is multifactorial and the exact cause of the disease often remains uncertain. Apart from the conventional risk factors, there are the speculations of role of genetics playing a pivotal role in the causation of OA. The available literature showed BTNL2 gene polymorphism association with risk of Osteoarthritis whether the same relation is present in north Indian population needs to be elucidated. Objective. To find the association between single nucleotide polymorphism (SNP) (rs10947262) in BTNL2 gene and the susceptibility in knee Osteoarthritis (OA) subjects from northern Indian population. Materials and Methods. Blood samples of 100 patients of knee osteoarthritis and 100 healthy subjects were collected after institutional ethical clearance and participants consent. The BTNL2 gene fragment was amplified using Amplification Refractory Mutation System (ARMS-PCR) with predesigned primers after DNA extraction. The corresponding product bands were identified on the gel electrophoresis for 200 samples and the results were statistically analyzed. Results and Discussion. The genotypic distribution of the SNP followed Hardy-Weinberg Equilibrium. The genotype frequency analysis of the polymorphism was statistically significant (χ2=7.788; P=0.005) with Odd’s Ratio of CT+TT/CC: OR=2.303; P=0.008 revealing association of BTNL2 polymorphism with risk of Knee Osteoarthritis. Conclusion. The SNP (rs10947262) in the BTNL2 gene region is associated with risk of knee osteoarthritis.

RUDN Journal of Medicine. 2021;25(2):89-95
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Estimation of corneal thickness ex vivo and in vivo at instillation of photosensitizer solutions in different modifications of UV corneal crosslinking
Bikbov M.M., Khalimov A.R., Surkova V.K., Kazakbaeva G.M.
Abstract

Objectives: to evaluate the effectiveness of photosensitizer solutions in the experiment in different modifications of standard UV corneal crosslinking. Materials and Methods. Experiments were performed on 32 enucleated porcine eyes ex vivo and 12 rabbits (24 eyes) in vivo, divided into 4 groups depending on instillations of the photosensitizer solutions: «Dextralink», «Ribolink», «Hypolink» and «Riboflavin». Evaluation of corneal saturation was performed using two modifications of standard UV CXL: in the first case, instillation of the photosensitizer solution was performed during the entire crosslinking procedure (30 min - saturation and 30 min - ultraviolet irradiation); in the second case, instillations lasted only for the first 30 minutes, the precorneal riboflavin film was removed, and instillation of solution was not performed. Results and Discussion. Instillation of photosensitizer solutions within 60 minutes showed that Dextralink significantly reduced the thickness of the cornea by about 24 % ex vivo and 21 % in vivo, while Hypolink, on the contrary, caused its increase by 9 % ex vivo and 23 % in vivo, respectively. The use of Ribolink and Riboflavin did not change the linear parameters of the cornea during the entire follow-up period. The results of the 2nd series of studies showed that effects of solutions on the cornea during their instillation for 30 minutes were generally preserved during the entire observation period up to 60 minutes. In the group where Dextralink and Hypolink solutions were used, there was a slight tendency to normalization of the initial parameters of the cornea. Conclusion. Safe and effective implementation of UV crosslinking of the cornea is possible on the basis of a rational approach to the performing the stages of stroma saturation with photosensitizer solutions, depending on the initial state of the cornea: Dextralink is recommended for a thickness of more than 450 µm, Ribolink - at 400-450 µm, Hypolink - from 350 to 400 µm. Halting of instillations on the saturated stroma during UV irradiation is advisable to be accompanied by intraoperative control of its thickness. When performing a standard crosslinking technique, where instillations of photosensitizer accompany the stage of UV irradiation of the cornea, it is necessary to take into account the presence of a precorneal film that can absorb some of the radiation energy. The peculiarity of this crosslinking technique can be considered as a potential way to protect intraocular tissues from excessive exposure to UV radiation.

RUDN Journal of Medicine. 2021;25(2):96-105
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CLINICAL PHYSIOLOGHY
Features of angiogenesis in eye diseases
Khalimov T.A.
Abstract

Based on the analysis of published data, the review provides information on the role and mechanisms of angiogenesis in the development of eye diseases. It has been shown that the developing inflammatory process associated with infections or damage to the organ of vision almost always leads to the appearance of newly formed vessels in the avascular cornea. The progression, in particular, of age-related macular degeneration is associated with the immune-mediated development of angiogenesis processes. A key inducer of angiogenesis is vascular endothelial growth factor (VEGF), whose activity can be enhanced by a number of pro-inflammatory cytokines (tumor necrosis factor alpha, TNF-α), growth (fibroblast growth factor, FGF) and transforming factors (transforming growth factor beta, TGF- β). In addition, VEGF overproduction is mediated by an imbalance of pro-angiogenic (angiogenin) and anti-angiogenic (angiostatin, vasostatin, endostatin; tissue inhibitors of matrix metalloproteinases) factors. Antiangiogenic activity based on inhibition of vascular endothelial growth factor (VEGF) has been successfully used in the treatment of a number of eye diseases, such as exudative age-related macular degeneration and diabetic macular edema, the pathogenesis of which is based on the growth of newly formed vessels. The review presents information on the main anti-angiogenic drugs for intravitreal administration, used in ophthalmology.

RUDN Journal of Medicine. 2021;25(2):106-113
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Regulation of neurogenesis and cerebral angiogenesis by cell protein proteolysis products
Teplyashina E.A., Komleva Y.K., Lychkovskaya E.V., Deikhina A.S., Salmina A.B.
Abstract

Brain development is a unique process characterized by mechanisms defined as neuroplasticity (synaptogenesis, synapse elimination, neurogenesis, and cerebral angiogenesis). Numerous neurodevelopmental disorders brain damage, and aging are manifested by neurological deficits that are caused by aberrant neuroplasticity. The presence of stem and progenitor cells in neurogenic niches of the brain is responsible for the formation of new neurons capable of integrating into preexisting synaptic assemblies. The determining factors for the cells within the neurogenic niche are the activity of the vascular scaffold and the availability of active regulatory molecules that establish the optimal microenvironment. It has been found that regulated intramembrane proteolysis plays an important role in the control of neurogenesis in brain neurogenic niches. Molecules generated by the activity of specific proteases can stimulate or suppress the activity of neural stem and progenitor cells, their proliferation and differentiation, migration and integration of newly formed neurons into synaptic networks. Local neoangiogenesis supports the processes of neurogenesis in neurogenic niches, which is guaranteed by the multivalent action of peptides formed from transmembrane proteins. Identification of new molecules regulating the neuroplasticity (neurogenesis and angiogenesis). i. e. enzymes, substrates, and products of intramembrane proteolysis, will ensure the development of protocols for detecting the neuroplasticity markers and targets for efficient pharmacological modulation.

RUDN Journal of Medicine. 2021;25(2):114-126
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Heart rate variability analysis of students with different motor activity levels
Emelyanova A.S., Simonyan L.A., Stepura E.E.
Abstract

Relevance. Assessment of the functional state of the body is one of the leading tasks of physiology. The article deals with the analysis of the initial vegetative status of students with different levels of motor activity. Materials and Methods. Registration and analysis of the heart rate variability was carried out with the help of a modern complex electrophysiological laboratory «CONAN - 4.5». The heart activity of students engaged in physical culture within the educational process was evaluated on the basis of heart rate variability analysis. Results and Discussion. It was revealed that among the entire studied array of students (with the differentiation of the initial vegetative status calculated according to muscle tension index), «normotonics» are characterized by an optimal ratio between the parasympathetic and sympathetic divisions of the autonomic nervous system. At the same time, the value of the coefficient of physical activity in the studied group was determined at the level of 1.73±0.1. Conclusion. For vagotonics, the value of the triangular index was 2.5±0.2 conventional units (CU), which confirms the idea of an increase in the influence on the autonomic nervous system. The value for normotonics is 2.2±0.1 CU. This group was characterized by the balance between the sympathetic and parasympathetic parts of the autonomic nervous system. In sympathicotonics - 1.9±0.5 CU, which confirms the idea of increasing the influence of the sympathetic division of the autonomic nervous system. In hypersympathicotonics-1.1±0.4 CU. To ensure adequate functioning of the cardiovascular system and for normal adaptation to physical exertion in students, it is necessary to form a level of motor activity that quantitatively corresponds to a coefficient of physical activity of at least 1.75.

RUDN Journal of Medicine. 2021;25(2):127-135
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Functional interaction of chewing muscles in children with dentoalveolar system anomalies
Kosolapova I.V., Dorokhov E.V., Kovalenko M.E., Lesnikov R.V.
Abstract

Relevance. The focus of modern dental treatment not only on the elimination of aesthetic, but also functional disorders requires an understanding of the functional conjugation of the chewing muscles, the possibility of interprognosis of parameters. Objective. Assess the functional relationship between the tone of the chewing muscles proper and the bioelectric activity of the temporal and sublingual muscle groups in children with anomalies of the dentoalveolar system. Materials and Methods. The study involved 36 patients of Children’s Clinical Dental Clinic No. 2 of Voronezh, aged 6 to 12 years, who had not previously received orthodontic treatment and had distal occlusion anomalies. Evaluation of the bioelectric activity of temporal and sublingual muscles was carried out using surface electromyography on the Electromyograph Dental apparatus (Taganrog, Russia), the Chewing General sample. Evaluation of the tone of the chewing muscles proper was carried out using the Mioton-3C device in a state of physiological rest of the lower jaw. Statistical processing was carried out using Microsoft Excel, version 7.0 and the statistical programs SPSS Statistics 21 and STATISTICA 7. Results and Discussion. Correlation analysis revealed the presence of 4 weak positive, 2 weak negative, 14 moderate positive, 3 moderate negative, and 1 noticeable positive correlation between the tone of the right chewing muscle proper and the parameters of the bioelectric activity of the right and left temporal and sublingual muscles. Correlation analysis revealed the presence of 5 weak positive, 7 weak negative, 9 moderate negative correlations between the tone of the left chewing muscle proper and the parameters of bioelectric activity of the right and left temporal and sublingual muscles. Conclusion. A greater effect of the tone of the right chewing muscle on the bioelectric activity of temporal and sublingual muscles was found compared to the tone of the left chewing muscle itself. 27 equations have been derived that can be used as predictive models for calculating the tone of right and left chewing muscles proper depending on the indicators of bioelectric activity of temporal and sublingual muscles.

RUDN Journal of Medicine. 2021;25(2):136-146
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Cytogenetic effect of caffeine in the micronucleus test
Durnova N.A., Klantsataya A.R., Kurchatova M.N., Karetnikova A.Y., Sheremetyeva A.S.
Abstract

Relevance. The consumption of caffeine-containing food in the modern world must necessarily be safe for humans, including should not affect the hereditary material of the body. Objective: to determine the possible effect of caffeine at the cytogenetic level by the micronucleus method on erythrocytes. Materials and Methods. The objects for the study were non-linear mice, which were divided into 6 groups - one control group and 5 experimental groups. The first experimental group and the second in the experiment received caffeine in doses of 40 mg/kg and 100 mg/kg.The control group received saline. Caffeine was administered orally. The mutagen (dioxidine) was injected intraperitoneally. On the 5th day of the experimental study, we performed blood sampling for cytogenetic analysis. Results and Discussion. Our study of the caffeine preparation made it possible to determine the following patterns. Firstly, when administered within 5 days, caffeine at a dose of 40 and 100 mg/kg did not cause an increase in the number of micronuclei in erythrocytes in mice. Secondly, the combined use of caffeine (both at a dose of 40mg/kgand at a dose of 100 mg / kg) and dioxidine significantly increased the level of micronuclei in comparison with the control group. Thirdly, caffeine at a dose of 40mg/kgdid not increase the mutagenic activity of dioxidine, but a dose of caffeine of 100mg/kgwhen combined with a mutagen led to a significant increase in the level of cytogenetic damage. Conclusion. According to our data, caffeine in the experimental study was not a mutagen, but at a dose of 100 mg/kg it represented a comutagenic effect.

RUDN Journal of Medicine. 2021;25(2):147-153
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Use of modern forensic methods for post-mortem diagnosis of blood loss
Sundukov D.V., Putintsev V.A., Shekera V.V., Bogomolov D.V., Romanova O.L.
Abstract

In forensic medical practice, when diagnosing the cause of death from blood loss, it is often necessary to solve questions related to the etiology of loss of circulating blood volume (CBV), the degree and severity of the injury, as well as its role in thanatogenesis and the duration of the terminal (agonal) period. When investigating the cases of death from acute blood loss, the authorities often ask forensic experts to solve issues related to the possibility of performing active targeted actions by the dying person, as well as to assess the timeliness of medical care and the actions of medical personnel. The solution of these issues is often difficult for experts, and it is associated with both objective and subjective reasons. For example, in cases where the circumstances of death are unknown, or there are no medical documents, or they do not contain sufficient information, without which it is impossible to conduct a retrospective clinical and anatomical analysis for the purpose of differential diagnosis between hemolytic shock and post-hemorrhagic anemia. The article deals with the use of new methodological approaches in postmortem morphological diagnostics of blood loss by the rate of its development and its role in thanatogenesis, in forensic medical practice. For example, a particular forensic expertise (case study) shows that the application of two new methods allowed to solve the issues for the investigator related to the cause of death and duration of dying from blood loss. Experts’ knowledge of new methodological approaches to the forensic diagnosis of acute blood loss will help law enforcement authorities to counteract crimes against the life of citizens, as well as to development the measures to improve the methods for prevention and reduction of mortality from traumatic injuries with blood loss.

RUDN Journal of Medicine. 2021;25(2):154-161
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