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Vol 17, No 6 (2019)

Articles

Mikhail Alexandrovich Paltsev. To the 70th birthday

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Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):3-4
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Gene polymorphism in TOLL-like receptor and associated diseases

Dvornikova K.A., Bystrova E.Y., Platonova O.N., Nozdrachev A.D.

Abstract

Introduction. In recent years, there have been aroused and actively studied mutations associated with Toll-like receptor genes (TLRs). The emerging interest is related to the identification of many associations between the TLRs polymorphism and the development of pathological conditions. Single nucleotide polymorphism (SNP) is a variant of point mutation. If two sequences in DNA differ by one nucleotide, then two alleles appear. As a result of single nucleotide polymorphisms in TLRs, the functioning of some key signaling pathways is impaired which in turn increases the risk of developing autoimmune, oncological and cardiovascular diseases. The aim of the study. The present study is devoted both to examining the current state of the problem, and, in particular, summarizing the information presented in the literature about the role of TLRs polymorphism in the occurrence of a number of diseases of the digestive system. Results. The analysis of studies on the nature of SNPs and their role in the body allowed establishing some functional consequences of polymorphisms in TLRs. The relationship of SNPs with susceptibility to infectious and inflammatory diseases of the gastrointestinal tract in some cases has been established clinically. A significant number of studies are devoted to identifying associations of SNPs of Toll-like receptors with the occurrence of malignant tumors. Conclusion. At present, it has not yet been possible to determine the exact mechanism of the inflammatory response leading to cancer, however, the data indicate the involvement of TLRs in the inflammatory response and the possibility of its modification through SNPs, which, in turn, may alter the course of the tumor process. One can hope further research in this area to provide more information about the effects of SNPs on genes in order to predict and prevent diseases based on genomic risk markers, as well as to help to identify new ways in the diagnosis and treatment of cancer using gene therapy
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):5-12
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Relevant aspects of the activation of mast cells mechanisms in ischemic and reperfusion injury

Yagudin T.A., Ishmetov V.S., Plechev V.V., Pavlov V.N., Hong-Yu L.

Abstract

This article provides a modern analysis of the literature on the mechanisms of activation of mast cells (MC) because they are regulatory cells that make up an important part of the immune system and are part of the first line of defense against various pathological agents. The important role of MC in anaphylactic response and allergy was proved, but there was evidence that mast cells participate in a wider range of pathologies. Ischemic/reperfusion(I/R) injury triggers an inflammatory response and triggers a tissue damage/repair program known as immune control. The unique location of MC around the microcirculatory vessels makes them potentially the first link in response to early and specific I/R injury by releasing MC mediators. Multifunctionality and heterogeneity are the distinctive features of MC acquired as a result of different adaptations during phylogenesis. Thus, these important functions of MC, which may differ depending on the tissues in which they are located, and the various effects inherent in them during I/R are a topical issue today. This review provides a literature analysis on the role of MCs in I/R injury of myocardium, brain, kidneys, and internal organs or systems. The understanding of the mechanisms and the role of the MCs in I/R injury can help in the development of therapeutic strategies aimed at protection against specific damage.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):13-20
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The possibilities of anomalous viscosity time dependence method for determination of cell radiosensitivity

Ivanov K.Y., Patochka G.L., Varganova I.A., Medvedev Y.I., Nagiba V.I., Nikanorova E.A.

Abstract

The initial state of an organism and its initial reactivity are the main prognostic criteria for the individual radiosensitivity evaluation. Particulars of the DNA structure and chromatin conformation determine in many respects the cell radiosensitivity. The method of the anomalous viscosity time dependence (AVTD) allows to research the chromatin conformational state, as well as to evaluate its reactivity based on the response to hyperthermia (heat shock). The DNA damage degree after irradiation under the test dose is a general criterion for the cell radiosensitivity evaluation. The goal of research. The work is aimed to analyse the radiation-induced DNA damage dependence on the initial chromatin conformational state and reactivity. Material and methods. The radiobiological studies were performed using the cells of white outbred male rats in vitro. Using the AVTD method, with respect to each animal, it was determined the initial chromatin conformational state and reactivity. After gamma radiation exposure of 60Со at the dose of 3,0 Gy it was determined the DNA damage degree using DNA-comet assay. Results. In a group of animals in general, the irradiation led to a considerable increase of the DNA damage degree relative to the spontaneous level (р0,001). It was found the meaningful positive correlative dependence (r=0,37; p0,05) of the individual radiationinduced DNA damage degree on the initial chromatin reactivity to heat shock.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):21-25
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Bioimpendancemetria as a method for diagnosis of visceral obesity in pediatric practice

Samoilova Y.G., Kudlay D.A., Podchinenova D.V., Kobyakova O.S., Koshmeleva M.V., Oleynik O.A.

Abstract

Introduction. Visceral obesity is a key factor in the development of metabolic syndrome, which can lead to early disability and lower quality of life. The body mass index, which is widely used as a method of diagnosing obesity, does not allow for the differentiation of visceral fatty tissue. Radiation-based visceral obesity diagnostic methods, which are the gold standard, cannot be used as a screening method due to radiation exposure and high costs. Therefore, there is a need for early diagnosis of visceral obesity, which can be used in outpatient care. Objective. To develop a non-invasive method of early diagnosis of visceral obesity in children and adolescents. Methods. The study was conducted among children and adolescents aged 3 to 18 years (n=1914). A complex examination was carried out on everyone, including anthropometry and analysis of body composition by Inbody 770. A group of patients with and without visceral obesity (n=227) was identified among those studied (n=210). From both groups, the examined patients (n=88) were randomly selected for a CT scan to determine the visceral fat area. The data obtained were used by the IBM Watson cognitive system to build a multivariate statistical model of the decision support system. Results. A model for screening visceral obesity among children and adolescents was obtained, comparable in accuracy to CT (Sensitivity 91%, specificity 80%.).Conclusion. The obtained model for screening visceral obesity among children and adolescents can be used for the annual medical examination, as it is easy to use, has an accuracy comparable to CT, but lacks its drawbacks, such as radiation exposure, high cost, inability to use outpatient.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):26-31
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Alleles and genotypes distribution of xenobiotic biotransformation genes in mothers of children with congenital heart diseases

Tsepokina A.V., Shabaldin A.V., Ponasenko A.V., Shmulevich S.A.

Abstract

Introduction. In this research the frequency of variant alleles of genes for xenobiotic biotransformation in women living in a highly urbanized region of Western Siberia and having children with congenital heart diseases was studied. Materials and methods. Women having children with congenital heart diseases (n=101) and the comparison group included mothers who have more than one child without this pathology, birth defects and developmental abnormalities (n=103) were examined in the present study. The genotyping was performed by PCR in 10 polymorphic variants of four xenobiotics biotransformation genes. Results. We found no statistically significant differences in the distribution of alleles and genotypes of polymorphic variants of xenobiotics biotransformation genes in Russian women residing in the highly urbanized region and having both healthy children and children with congenital heart defects.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):32-37
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Determination of the diffusion coefficient for the drug Rivanol in the human buccal mucosa in vitro

Selifonov A.A., Naumova G.N., Tuchin V.V.

Abstract

Introduction. Dyes have long been successfully used in medicine as exogenous chromophores to increase the effectiveness of the interaction of light with biological tissues, as contrast agents and photosensitizers in diagnosis and photodynamic therapy. At present, the current area of medicine is the development of methods for photodynamic therapy, both for the treatment of cancer pathologies and for antibacterial anti-inflammatory procedures, which can effectively influence resistant strains of microorganisms. The aim of the study. The work is devoted to the determination of the effective diffusion coefficient of the preparation Rivanol in the human buccal mucosa in vitro using the method of optical spectroscopy of diffuse reflection with the usage of the model of free diffusion. The active ingredient of the pharmaceutical preparation Rivanol is ethacridine lactate - acridine low toxic dye with antiseptic and photosensitizing properties, the solution of which has absorption bands in the UV/visible range of320-450 nm, as well as fluorescence in the green. Methods. In this work, the determination of the effective diffusivity of Rivanol in biological tissue was based on measuring the kinetics of changes in the diffuse reflectance spectrum and estimating the effective optical density when fitting experimental data using the equation obtained from the second Fick law and the Beer-Lambert-Bouguer law. Results. For the first time, an effective in vitro diffusion coefficient of Rivanol in human buccal mucous was detected, which on average (n=6) accounted for (2,36+0,73)-Ш7cm2/s. Conclusion. This value correlates with the published data for the diffusion coefficients of other dyes in the skin dermis and the pathologically changed mucosa of the maxillary sinus of a volunteer. The results can be used for the development of modern methods in medicine, combining diagnostic and therapeutic technologies, which are now known under the general name - theranostics, as well as clinicians to develop sound protocols for photodynamic therapy, eliminating the trauma due to laser effects.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):38-43
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The role of transcription and growth factors in the development of the tumor pathology of the prostate gland

Spirina L.V., Kovaleva I.V., Fedotov D.A., Gorbunov A.K., Usynin E.A., Slonimskaya E.M., Kondakova I.V., Dyakov D.A.

Abstract

Introduction. The molecular mechanisms of the development of the prostate tumor pathology are associated with the activation of both androgen-dependent and androgen-independent signaling pathways, accompanied by the development of chronic inflammation and hypoxia. However, the role of transcription and growth factors in the initiation of prostate tumor changes is not investigated The aim of the study was to investigate the expression of transcription and growth factors in the tissue of prostate cancer (PCa) cases and patients with benign hyperplasia (BH). Material and methods. 97 patients with prostate pathology were included in the study. They received treatment in the Department of General Oncology of the Cancer Research Institute of the Tomsk National Research Medical Center. 42 patients had BH, in 55 patients T2-3N0M0 was verified due to locally advanced PCa. The PSA level and the amount of testosterone in the serum were determined by ELISA. The expression of nuclear factors NF-κBp65, NF-κBp50, HIF-1, HIF-2, growth factors VEGF, VEGFR2, CAIX was investigated by PCR in real-time.Results. In PCa patients PSA and testosterone levels in with prostate cancer were revealed to be declined if compared with BH cases. The growth of the nuclear factor NF-κBp65 with a decrease in nuclear factors activated by hypoxia (HIF-1, HIF-2) was observed in PCa tissues, compared with BH patients. At the same time, an increase in VEGFR2 expression with a decrease in the level of CAIX mRNA in the transformed tissues was detected. Conclusion. The study shows the multidirectional nature of changes in the level of PSA and testosterone with the severity of the prostate tumor pathology. The formation of inflammatory responses with an increase in the NF-κBp65 expression and the VEGFR2 growth is significant for the malignant transformation of prostate cells. At the same time, the development of hypoxia and the increase in the expression of factors HIF-1, HIF-2 were recorded in BH patients.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):44-48
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Expression of p-defensin-1 in rat colon tissue

Bystrova E.Y., Platonova O.N., Shpanskaya A.A., Dvornikova K.A., Nozdrachev A.D.

Abstract

Introduction. At present, signaling pathways involved in the development of innate and adaptive immune responses and comprising, inter alia, the interaction of pattern-recognizing receptors, such as TLR, with antimicrobial peptides associated with inflammation, proliferation, production of cytokines and chemokines, are actively studied. Among them, there is f-defensin, the localization of which in rat colon tissue and expression changes under bacterial endotoxemia are still poorly understood. At the same time, an important problem in the study of neuroimmune interactions is to reveal potential relationships between the production of endogenous defensins and TLR expression, in particular, by enteric neurons. The aim of the study. In the present study, we investigated the localization of f-defensin-1 (rBD1) in rat colon tissue under normal conditions and on the model of bacterial endotoxemia induced by Escherichia coli lipopolysaccharide (LPS). Results. By means of immunohistochemistry, we have shown rBD1 to be mainly localized in the submucous layer of the rat colon and characterized by constitutive and inducible expression. Bacterial endotoxemia provides a statistically significant increase in rBD1 expression after 6 hours and 24 hours following LPS administration. Conclusion. Despite the lack of convincing data verifying the expression of f-defensin-1 by enteric neurons, we cannot exclude endogenous inducible defensins upregulation following LPS administration through signaling pathways associated with TLR4, which is expressed by rat colon sensory neurons.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):49-54
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Changes in the quantitative composition of neuroglia in the prefrontal cortex of rats with modeled post-traumatic stress disorder

Khayrullina G.M., Vacoliuk I.A.

Abstract

Introduction. Neuroglia plays an important role in maintaining the stable functioning of the CNS. Of particular importance are neuroglial cells in the organization of the immune system of the brain, activating both with physical, physiological damage, and with chronic stress or other extreme, including mental, effects. The aim of the study. Characterizing the state of neuroglia in the prefrontal cortex of rats with a simulated post-traumatic stress disorder is crucial for understanding the cellular mechanisms underlying the development of pathological behavioral disorders in PTSD. Methods. Animal model of PTSD. Immunohistochemistry. Results. Significant quantitative differences in astrocytes were detected in all three zones of the medial prefrontal cortex in experimental and control animals, namely: a decrease in the number of astrocytic cells and their density in the first group (p<0,05). Conclusion. In the animal model of PTSD, the decrease in the density of astrocytes in the medial prefrontal cortex of the rat brain, despite the heterogeneity in the quantitative changes in the astrocytic network of individual zones of brain, is a general phenomenon not specific to a specific zone.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):55-59
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Age features of the expression of signal molecules - protein p53, collagen type II, VEGF and VEGFR in bioptates of intact myometry in uterine myoma

Shapovalova A.I., Tsypurdeeva A.A., Kakhiani M.I., Popov E.N., Polyakova V.O.

Abstract

Introduction. Leiomyomas also called fibroids, is the most common benign gynecological tumor in premenopausal women. The complex pathogenesis shows multiple biogenetical and multifactorial aspects to influence the etiology and growth of leiomyomas. A clinical and morpho-immunohistochemical study of 40patients aged from 25 to 43 years with diagnosed uterine myoma was conducted. As a result, the presence of two variants of the development of myomatous nodes as simple fibroids and proliferating fibroids in the reproductive age was confirmed with the latter to be more prevailed. The myomatous node arising from progenitor muscle cells of the vascular wall is characterized by increased expression of p53 protein in women over 36 years, high expression of growth factors (VEGF and VEGFR), the formation of a capillary network and low apoptosis, which causes their rapid growth (proliferating development). The aim of the study. To study the correlation of expression of p53, type II collagen, VEGF and VEGFR in biopsy specimens of intact myometrium in women of different age groups. Methods. Immunofluorescence and morphometric analysis of p53 proteins, type II collagen, VEGF and VEGFR using Olympus FV1000. Results. The average area of p53 protein expression in the second group was higher (p>0,05) and amounted to 6,3±2,74, while in the first group it accounted of 5,0±2,14. VEGF and VEGFR levels were statistically significantly (p<0,05) higher in proliferating myomas in women from the first group (VEGF - 23,51±6,97%; VEGFR - 26,31±4,11%) if compared to the second group (VEGF - 5,75±2,39%; VEGFR - 9,29±1,85%). In the study of type II collagen, the expression area in the first group (3,23±1,83%) was twice less if compared with the second group (7,37±3,95%). The expression of the investigated marker in terms of optical density had a similar tendency. Conclusion. The revealed features of proliferation, apoptosis, and neoangiogenesis indicate new aspects of pathogenetically substantiated therapy for uterine fibroids. It becomes possible to develop drugs that contribute to the inhibition of the processes of proliferation, neoangiogenesis, and stimulation of apoptosis. Apparently, this group of drugs will occupy an important place in therapeutic agents for conservative treatment at the initial stage of the development of myomatous nodes in young women.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(6):60-64
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