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Vol 18, No 1 (2020)

Articles

Role of autoantibodies to GAD65 protein in neurological patients

Khodova A.E., Polyakov D.S.

Abstract

Anti-glutamate decarboxylase (GAD65 isoform) autoantibodies are present in the blood of patients with such various autoimmune disorders, as diabetes type I, as well as relatively rare neurological diseases, such as StiffPerson syndrome and cerebellar ataxia. This review reports the published literature data on the presence of autoantibodies against the GAD65 protein in a variety of neurological diseases. The possible role of autoantibodies in the pathological process is discussed. The potential use of autoantibodies against GAD65 as a marker of neurological diseases is considered
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):3-10
pages 3-10 views

Molecular mechanisms of the functioning system mother-placenta-fetus in women with obesity and gestational diabetes mellitus

Evsyukova I.I.

Abstract

The review summarizes a number of published reports about the influence of total hormonal and metabolic disturbances on the functioning system mother - placenta - fetus in the organism of the women with obesity and gestational diabetes mellitus. The circadian disruption of maternal melatonin production is demonstrated to cause the asynchronous metabolic process, hyperglycemia hyperinsulinemia, increased insulin resistance, hyperleptinemia, activated oxidative stress, development mitochondrial and endothelium dysfunction. Molecular mechanisms of the damage of placental structure and function changes, affecting on the supply of nutrients, oxygen, and methyl donors and alter the secretion of hormones and other signaling molecules into the fetal circulation, are examined. The results of experimental and clinical investigations testify of placental trophic, metabolic, endocrine and transport functions, which determine the pathophysiological mechanisms of development fetus overweight, hyperinsulinemia, changes of qualitative composition of serum density lipoproteins, high content in free fatty serum acids, insulin-like growth factor (IGF-1), markers of endothelium dysfunction and inflammation. Epigenetic modifications of the fetal genome determine the disorders in the morphological-functional development of brain structures, cardio-vascular, and other infant functional systems in early ontogenesis and programming obesity and risk metabolic alterations during adulthood. Hence, the preconception and perinatal period offer a unique opportunity to modify both short and long term risks for both the woman and her offspring.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):11-15
pages 11-15 views

Neuroimmunoendocrine profile of sarcoid granulema: expression of signal molecules

Yablonsky P.K., Polyakova V.O., Krylova Y.S., Drobintseva A.O., Leonteva D.O., Sokolovich E.G., Kvetnoy I.M.

Abstract

Introduction. Sarcoidosis is a systemic granulomatous disease of unknown etiology, which leads to disruption of the human respiratory system and can lead to damage to other systems. In clinical practice, doctors often run into difficulties in differentiating sarcoidosis from tuberculosis - another granulomatous disease, because of their similar clinical and radiological pictures. None of the existing methods for diagnosing sarcoidosis or tuberculosis is absolute. However, the correct and timely diagnosis plays an important role in the successful treatment of these pulmonary pathologies. The aim of the study. Determination of the neuro-immuno-endocrine profile of sarcoid granuloma. Methods. Namely, proteins were studied: interleukin-8 (IL8), Protein gene product 9.5 (PGP9.5), tissue inhibitor of metalloproteinases (TIMP1), melatonin receptor 1A (RM-1A), melatonin receptor 1B (RM-1B). Results. Studies have shown sarcoid granulomas to express IL-8 with the presence of nerve - PGP9.5 positive terminals in peri-granuloma tissue, thus labeling granuloma, we suggest IL-8 be able to become a diagnostic marker of lung sarcoidosis. The data on the expression of TIMP1, RM-1A, and RM-2B are ambiguous and require further study. Conclusion. Thus, the neuro-immuno-endocrine aspects of granulomatous inflammation are interesting for further research at various stages of sarcoidosis, as well as for tuberculosis.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):16-20
pages 16-20 views

Effect of 2-ethyl-6-methyl-3-hydroxypyridine derivative on the course of nonalcoholic fatty liver disease in the experiment

Sukhanov D.S., Ivkin D.Y., Plisko G.A., Karavaeva A.V., Krasnova M.V., Poveryaeva M.A., Karev V.E., Bunyat A.V., Stepanova I.L., Okovityj S.V.

Abstract

Introduction. In the treatment of non-alcoholic fatty liver disease (NAFLD), which is the main cause of chronic liver disease, a certain role is assigned to hepatoprotectors. One of the hepatoprotectors currently used to treat NAFLD is ademetionine. At the same time, a number of preclinical and clinical studies have shown hepatotropic activity of 2-ethyl-6-methyl-3-hydroxypyridine succinate (EMHPS) both in hypodynamic conditions and in NAFLD. The aim of the study. Comparative evaluation of the effectiveness of the new compound-2-ethyl-6-methyl-3-sulfopyridine (EMSP), a derivative of 2-ethyl-6-methyl-3-hydroxypyridine, in comparison with 2-ethyl-6-methyl-3-hydroxypyridine succinate (Armadin) and ademetionine (Heparetta) on the model of experimental nonalcoholic fatty liver disease. Methods. The study was conducted on 125 inbred male mice of the C57BL/6 line, weighing 18-20 g. by randomization, the animals were divided into 5groups (n=25 in each): intact animals, control without treatment, group 3-NAFLD + EMSP model, 4-NAFLD + EMGPS model, 5-NAFLD + ademetionin model. NAFLD was modeled by combining a high-fat diet and the administration of a toxicant (carbon tetrachloride). Results. It was established that against the background of the introduction of the studied compound, there was a decrease in animal mortality in combination with a positive effect on the morphological picture of the liver. By the end of the 4th month of the experiment, a decrease in the frequency of necrotic changes and liver fibrosis was observed, while fibrosis of degree F1 in one case of observation was reversible and was not determined by the end of the experiment. The indicated compound has a moderate anticytolytic effect, as well as a hypocholesterolemic effect in the early stages of application. The efficacy of 2-ethyl-6-methyl-3-sulfopyridine and comparison drugs on the NAFLD model used was comparable. Conclusion. Taking into account the positive effect of the studied compound on the survival of animals in combination with the improvement of the histological picture of the liver in NAFLD, comparable with comparison drugs, it is advisable to further study EMSP in the experiment.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):21-26
pages 21-26 views

Technology for the determination of minor fractions of modified LP lipoproteins-α in coronary atherosclerosis

Kanskaya N.V., Baikov A.N., Udut V.V., Fedorova N.A., Kudlay D.A., Pozdniakova I.A., Samoilova Y.G., Oleynik O.A., Udut E.V., Denisov N.S., Dyakov D.A., Medinceva E.Y., Skurihina V.E.

Abstract

Introduction. For the first time in clinical practice, diagnosis of different stages of lipidemia is conducted according to the level of blood lipids, lipoproteinsand catalase activity. This diagnostic approach can detect early stage of lipidemia against the progression of inflammation and pathogenesis due to the timely appoint a statin therapy, and predict the progress of lipidemia. The research of lipidemia is relevant for the differential diagnosis of coronary atherosclerosis. The aim of the study. At the same time, to study the activity of blood catalase and lipid profile of blood serum with the assessment of dyslipoproteinemia of atherogenic genesis to improve the diagnosis of coronary heart disease (CHD). Methods. Diagnosis of coronary heart disease is verified using clinical and laboratory research methods by using modern equipment. Over 40 male patients with coronary heart disease aged 40-50 years with a history of pathology more than 2 years were examined. The comparison group examined 20patients with neurocirculatory dystonia (NDC), comparable by sex and age. Statistical data processing was performed using the Statistica 13.0 application software package using student’s T criteria. Results. When analyzing the indicators, the most unfavorable prognosis of the course of coronary atherosclerosis was noted with a high level of lipoprotein-α in the blood against a background of a change in the activity of blood plasma catalase. Conclusion. Biochemical studies of blood lipids revealed a tendency to the development of the initial stage of lipidemia, combined with a slight increase in plasma catalase activity and atherogenic index. Therefore, in clinical practice, the use of kinetic determination of catalase activity is justified to clarify developing lipidemia.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):27-30
pages 27-30 views

The role of SWI/SNF chromatin remodeler composition in sensitivity to GSK126 and ABT263

Fatkhutdinov N.R., Zhang R., Kiyamova R.G.

Abstract

Introduction. Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer characterized by frequent mutations in the ARID1A gene and low sensitivity to standard-of-care chemotherapeutic agents. The aim of the study. To determine the role of ARID1A in sensitivity of OCCCs to GSK126 and ABT263 Methods. ARID1A-mutant OCCC cell lines were used as study models. The effects of EZH2 andBCL2 inhibition on cellular proliferation were determined by 3D-colony formation assay using Matrigel. Lentiviral particles carryingpLX304-ARID1A vector were used for ARID1A restoration. Results. ARID1A-mutant OCCC cells are susceptible to EZH2 and BCL2 inhibition. Combination of ABT263 and GSK126 further decreases cellular proliferation. Sensitivity to aforementioned targeted therapies is dependent on ARID1A expression: restoration of wild type ARID1A in ARID1A-mutant OCCCs leads to the decrease in efficacy of EZH2 and BCL2 inhibitors. Conclusion. ARID1A is a key factor determining sensitivity of OCCCs to GSK126 and ABT263.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):31-35
pages 31-35 views

Immunohistochemical study of NeuroD1, Nkx2.2, Isl1 transcription factors, somatostatin and chromogranin a in different forms of congenital hyperinsulinism

Mitrofanova L.B., Hazratov A.O., Galkovsky B.E., Sukhotskaya A.A., Bairov V.G., Ryzhkova D.V., Poyda M.D., Nikitina I.L.

Abstract

Objective: a morphological study of the transcription factors NeuroD1, Nkx2.2, Isl1; somatostatin and chromogranin A in various forms of CH The methods included immunohistochemistry examination with antibodies to NeuroD1, insulin, somatostatin, ChrA, Nkx2.2, Isl1, and morphometric analysis of pancreas fragments from 18 CH children and 9 pancreases of children, who died of heart failure. Results. Somatostatin was expressed in 26,3+3,3% of endocrine cells (EC) in diffuse CH (DCH), and in 41,1+6,8% of EC in focal CH (FCH). Isl1 was expressed in 59,8+7,1% of EC in DCH and in 87,3+3,2% of EC in FCH. Nkx2.2 was expressed by 55,9+7,9% and 69,3+10,4% of EC in DCH and in FCH respectively. Its expression level was comparable to Isl1 in adenomatous structures and in true adenomas. NeuroD1 was expressed in 58,4+9,7% and 83+4,7% of EC in DCH and in FCH respectively. This transcription factor was expressed by 65,5+7,4% and 77,3+9,4% of exocrine cells in DCH and in FCH respectively. The number of cells with the expression of chromogranin A, Isl1, Nkx2.2 and NeuroD1 in the endocrine part, and NeuroD1 - and in the exocrine part with DCH and FCH was significantly higher than in the normal pancreas. Conclusion. Immunohistochemical analysis established the number of cells expressing chromogranin A, Isl1, Nkx2.2 and NeuroD1 in the endocrine portion to be significantly higher than in the normal pancreas in any form of CH. The most demonstrative marker of CH is NeuroD1.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):36-47
pages 36-47 views

Effect of small intestine bacterial overgrowth syndrome on the course of bronchial asthma

Zolnikova O.Y., Potskherashvili N.D., Kokina N.I., Trukhmanov A.S., Ivashkin V.T.

Abstract

Aim. The work was carried out to study the role and features of small intestine bacterial overgrowth (SIBO) in the pathogenesis of bronchial asthma (BA). Material and methods. 80 BA patients were included in the study. SIBO was detected by the hydrogen breath test with lactulose. The patients were treated by conventional basic therapy with combined drugs (long-acting β2-adrenomimetics, and inhaled glucocorticoids). Rifaximinum or Rifaximinum followed by probiotic feeding was administered for the SIBO treatment. Results. 30 (67%) and 15 (43%) of the patients with the allergic form and non-allergic asthma form suffered from SIBO respectively, p=0,028. Patients with SIBO and allergic asthma had higher levels of IgE in blood, eosinophils in sputum, impaired of the respiratory function (p<0,01). Gut microbiota modification by Rifaximinum and or probiotic feeding resulted in a decreased immune response (IgE) and improved in the function of respiration (p<0,001) and reduced levels of patient hospitalization (р<0,05). At the non-atopic asthma phenotype case, the microbiota correction contributed to an increase in the disease remission also.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):48-52
pages 48-52 views

Liver alveococcosis: ultrasound and morphological comparisons

Stepanova Y.A., Ashivkina O.I., Ionkin D.A., Glotov A.V., Vishnevsky V.A.

Abstract

Introduction. Alveococcosis is a parasitic disease associated with the formation of the liver tumor-like lesion. This parasitic tumor has infiltrative growth and the ability to metastasize, that is, it exhibits the properties of malignant tumors. The disease is asymptomatic for a long time, as a result of which the lesion is often revealed with a significant spread of the pathological process. All this requires a high-quality pre-operative diagnosis. Therefore, the assessment of the possibilities of constantly updated diagnostic imaging methods is relevant at the present time. The studies in which researchers estimate an insignificant number of clinical observations (from 5 to 17), using various echo-contrast substances (of both the last and previous generations) on the use of echo contrast ultrasound in the treatment of alveococcal lesions are currently rare. It should be noted that in the presented study, the data obtained with ultrasound echo contrasting are compared with the data of other radiological methods of research. Comparison of the echo contrasting data of alveococcal liver damage with morphological data is not noted in the literature. Objective to determine the possibilities of ultrasound with echo contrast enhancement in the assessment of alveococcal liver damage. Materials and methods. The study included 15 patients aged from 36 to 54 years (men - 6, women - 9), who were in A.V. Vishnevsky National Medical Research Center of Surgery with a diagnosis of liver alveococcosis. Ultrasound examination was performed for all patients (B-mode, duplex scanning, echocontrast enhancement). All patients were operated on, the lesions were morphologically verified as alveococcosis. Results. The analysis of the data obtained during echo contrasting of liver alveococcal lesions showed that additional information in comparison with ultrasound in B-mode and duplex scanning can be obtained by two parameters: evaluation of the lesion structure; the prevalence of the pathological process. At the same time, the characteristics of the echo contrast of the parasitic node during ultrasound investigation allow us to speak about the activity of the pathological process and the prognosis of the development of the disease. Conclusion. Our experience of using ultrasound echo contrast to assess the structure and prevalence of alveococcal liver damage has shown the effectiveness of this technique. It is advisable to accumulate experience of such studies in order to evaluate the data obtained on a more representative sample.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):53-60
pages 53-60 views

The level of expression of progesterone, estradiol and Vitamin D receptors in mononuclear cells of the peripheral blood of patients with surgical menopause

Kruchinina E.V., Gorenkova O.S., Kochina N.A., Krasnoshchok E.V., Glazkova A.V., Polyakova E.Y., Zaydieva Y.Z., Kareva E.N., Serebrova S.Y.

Abstract

Introduction. Patients with surgical menopause are at risk for an osteopenic syndrome. For adequate medical correction of osteoporosis, it is necessary to clarify the mechanisms of the pathogenesis of this condition. It is known that osteoclasts, the activation of which is a recognized component of bone tissue destruction, are formed from circulating monocytes, and recently an active search is considered for ways to regulate this process. However, among monocytic marker molecules (the level of which varies in women with and without osteoporosis), there are no receptors or enzymes for steroid hormone metabolism. At the same time, the link between the level of sex steroids in women and the development ofpostmenopausal osteoporosis is obvious. The aim of the study. The level of transcription of possible target genes (estradiol and progesterone receptors, as well as vitamin D) was studied in peripheral blood mononuclear cells (PBMC). Methods. Densitometry, RT PCR. Results. It turned out that surgical menopause is characterized by manifestation of the osteopenic syndrome of the varying severity - from osteopenia to osteoporosis. At the same time, in patients with severe osteopenic syndrome (osteoporosis), there was a decrease in the expression of receptors for VDR, ER-alpha, andPR-A in PBMC by ll, 30and 7times, respectively (p<0.05). Conclusion. Decrease in the expression of receptors for VDR, ER-alpha, and PR-A in PBMC can be regarded as one of the early pathogenesis of disorders of bone tissue metabolism caused by a deficiency of sex steroids.
Molekulyarnaya Meditsina (Molecular medicine). 2020;18(1):61-64
pages 61-64 views

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