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Vol 77, No 5 (2022)

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Influence of Collagen Production, Collagenase Activity and Amino Acids Level on Formation of Fetal Growth Restriction in Women with Placental Insufficiency

Krukier I.I., Avrutskaya V.V., Levkovich M.A., Galusyak A.V., Grigoriants A.A., Nikashina A.A.


Rationale. According to WHO, about 21 million children are born annually in the world with low body weight. Currently, the problems of etiology, diagnosis and treatment of fetal growth retardation (FGR) are very relevant for obstetrics and perinatology. Purpose — to study the level of collagen (COL1) collagenase activity (MMP1), and content of proline, ornithine in the maternal blood serum, amniotic fluid, placenta and cord blood of patients with placental insufficiency, and to identify their role in the formation of fetal growth restriction (FGR) during early pregnancy. Methods. 150 women were examined, which made up 2 groups — control (with uncomplicated pregnancy, n = 105) and main (with IUGR, n = 45). All measurements were performed in maternal blood serum, amniotic fluid, placenta and cord blood of women of both groups. Collagen content and collagenase activity are determined by ELISA kits, USA. Determination of amino acids (proline, ornithine) was carried out by capillary electrophoresis on the device “Capel-105” (St. Petersburg). Results. As a result of the correlation analysis in the study of all biofluids by the Spearman method with the calculation of the rank correlation coefficient (r) in the group of women with FGR, significant correlations between collagen production and collagenase activity were revealed. The most pronounced interdependence (r = 0.85; p < 0.05) was found in the maternal blood serum. Conclusions. A relationship was found between the studied parameters (collagen, collagenase, proline, ornithine) in blood serum, amniotic fluid, cord blood and placenta of women with placental insufficiency and their role in the formation of fetal growth retardation was established.

Annals of the Russian academy of medical sciences. 2022;77(5):313-319
pages 313-319 views


Diagnostic Possibilities of Magnetic Resonance Cholangiography with Intravenous Contrast in Diseases of the Bile Ducts

Karmazanovsky G.G., Chzhao A.V., Ayvazyan K.A., Goncharov A.B., Saraeva V.A., Trifonov S.A.


Every year the number of operations on the hepatobiliary zone is steadily increasing due to diseases of the bile ducts. Against this background, there is a need for an accurate diagnosis of complications of these interventions; classical magnetic resonance cholangiopancreatography (MRCP) is of limited use. With the introduction of a liver-specific contrast agent (Gd-EOB-DTPA), the possibility of diagnosing diseases of the bile ducts has expanded. In this clinical review, we review the technical aspects and benefits of Gd-EOB-DTPA-enhanced MR cholangiography. Various types of contrast agents, methods of their use in MRI, the dependence of the signal intensity in the bile ducts on the time of administration of the substance, the presence of chronic liver diseases are covered in detail. Separately, studies are given on the diagnosis of diseases of the bile ducts with altered biliary anatomy, biliary fistulas after surgical interventions. In conclusion, data are presented on promising studies of the functional state of the liver based on the use of MRI with hepatotropic contrast enhancement.

Annals of the Russian academy of medical sciences. 2022;77(5):320-325
pages 320-325 views


The Relationship of Changes in Oral Microbiocenosis and Mucosal Immunity in the Conditions of 14-Day Isolation of a Person in a Hermetic Object with an Artificial Habitat

Ilyin V.K., Solovieva Z.O., Rykova M.P., Skedina M.A., Kovaleva A.A., Nosovskiy A.M., Sheblaeva A.S., Tsarev V.N., Podporin M.S., Bystrova O.V., Gizinger O.A., Lovtsevich S.M., Komissarova D.V.


Background. Changes in the human oral microbiota is an adaptive process. Infections will be particularly manifest in extreme conditions, especially during a long stay in space flight, where the astronaut is exposed to various nonspecific stresses. Aim — the aim of the work is to estimate the complex influence of 14-day isolation conditions of human being in sealed environment on the state of natural barriers of periodontal colonization. Methods. During the experiment 6 volunteer subjects (4 men and 2 women) aged 24 to 45 years old were confined for 14 days to an air-tight space simulating a spaceship capsule. Then from 6 to 18 days after leaving the experiment the experimental group (4 people) received Lactobacillus spp. autoprobiotics once a day on an empty stomach in the morning. During this period the control group (2 persons) took Linex (Lebenin®: Lactobacillus acidophilus (species L. gasseri) — 300 mg, Bifidobacterium infantis — 300 mg, Enterococcus faecium — 300 mg, lactose — 50 mg). Qualitative and quantitative changes of oral microbiota, concentration of immunoglobulins (sIgA, IgA, IgM) and cytokines (IL-6, IL-8, IL-1β, IL-4, INFγ, TNFα) in periodontal samples were recorded. The number of periodontopathogens and regional blood flow in the periodontium under conditions of prolonged confinement and hypokinesia were studied. Results. In comparison with the background period during the time of isolation, a quantitative growth of obligate periodontopathogens was observed in the subjects. This was accompanied by increased levels of immunoglobulins (IgM, IgA, sIgA) and pro-inflammatory cytokines (IL-1, IL-6, IL-8). There was an increase in blood flow in the arteriolo- venular part of the microcirculatory channel of periodontal tissues after leaving isolation. Subsequently, there was a tendency to optimize microbiocenosis through the use of probiotic and autoprobiotic agents. Along with this, there was a decrease of anti-inflammatory interleukin IL-4 practically to the initial values on the 18th day.

Annals of the Russian academy of medical sciences. 2022;77(5):326-335
pages 326-335 views


Composition and Possibility of Application in Practical Medicine of Exosom/Extracellular Vesicles from Multipotent Stromal Cells

Maiborodin I.V., Maslov R.V., Ryaguzov M.E., Maiborodina V.I., Voevoda M.I.


The therapeutic effect of multipotent stem cells (MSCs) is largely mediated by the secretion of exosomes/extracellular vesicles (EMSCs), which reflect the biophysical characteristics of MSC-producers and are considered more effective. The use of EMSCs can help overcome practical and ethical issues that limit cell therapy. The importance of EMSCs is also recognized because of their ability to transfer various proteins, DNA and RNA to target cells and change the behavior of them and neighboring cells. EMSCs contribute to cellular processes such as transcription, proliferation, adhesion, migration and differentiation. EMSCs are involved in the induction of angiogenesis, inhibition of fibrosis, stimulation of extracellular matrix remodeling, abolition of the local inflammatory response, and also in the regulation of immune cell activity. A deeper understanding of the content of EMSC and its dynamics may affect the study and treatment of various diseases. However, EMSCs, even obtained from MSCs of the same origin and cultivated under the same conditions, can differ significantly in their components and, accordingly, in efficiency. Modification, including genetic modification, of the initial cellular elements is of certain importance for purposeful and, therefore, predictable changes in the content of EMSCs, but this approach also does not solve the problem of sufficient standardization of their components. Perhaps more promising is the artificial creation of exosome-like structures with a predetermined composition and, as a result, an accurate and predictable effect.

Annals of the Russian academy of medical sciences. 2022;77(5):336-344
pages 336-344 views


Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part I. Tumor-Promoting Inflammation. Serum Inflammatory Markers

Sergeeva N.S., Karmakova T.A., Polyak M.A., Alentov I.I., Kaprin A.D.


Chronic inflammation caused by exposure to external or internal factors increases the risk of developing malignancies and promotes tumor progression due to the influence on the key elements of carcinogenic mechanisms. At the system level signs of a chronic inflammation are manifested by an increase of inflammatory mediators and acute phase proteins levels in the blood, a change in the ratio of circulating leukocyte populations, and disturbances in the hemostasis system. This review is devoted to serum and hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The first part of the review outlines general concept about the role of inflammatory factors in the development of malignant tumors. It provides information on the most well studied serum inflammatory markers in breast cancer: cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), as well as C-reactive protein (CRP). The main properties of these polypeptides, which link them with tumor-promoting inflammation, are considered. An analysis of the data on the clinical significance of the serum level of cytokines and CRP in breast cancer accumulated to date is presented. Correlations of the elevated levels of the serum inflammatory markers with clinical and morphological characteristics of the disease, tumor response to chemotherapy, overall and relapse-free survival of patients indicate the feasibility of in-depth investigation of the issue for the purpose of the practical application of the systemic inflammatory markers as predictive and prognostic indicators in BC.

Annals of the Russian academy of medical sciences. 2022;77(5):345-353
pages 345-353 views


Omics technologies in screening for kidney disease in children with congenital uropathy

Bukharina A.B., Fedulkina A.O., Demidova K.N., Pento A.V., Maltseva L.D., Simanovsky Y.O., Nikiforov S.M., Morozova O.L.


Background: Primary vesicoureteral reflux (VUR) is the most common congenital uropathy (CU) in children, leading to the development of reflux nephropathy and chronic kidney disease, reaching the terminal stage in 25-60% of patients. The insufficient sensitivity of modern methods of instrumental and laboratory diagnostics of the initial stages of renal parenchyma damage dictates the need to develop new non-invasive technologies for screening and monitoring kidney conditions in patients with CU.

Aims: To evaluate the possibility of separating groups of healthy children and children with kidney damage with CU using the analysis of the mass spectra of volatile organic compounds (VOCs) in urine samples.

Materials and methods: This study involved 42 patients (average age 5.4 + 2.3 years), divided into 2 groups: group 1 – 24 children with congenital uropathies (grade II-V PMR) and comparison group 2 - 18 patients with minor surgical pathology without pathology of the urinary system. Urine samples were collected  before the start of treatment.  Composition  analysis of VOCs samples was carried out through express-analysis method for biological objects at atmospheric pressure without preliminary preparation using a mass spectrometer with ionization by laser plasma radiation. Urinary levels of markers of inflammation (MCP-1, IL-8, IL-18), angiogenesis (VEGF) and fibrosis (TGF-β1) were measured by solid-phase ELISA.

Results: Composition changes in urine VOCs were detected in group 1 patients with congenital uropathies (VUR). These changes made it possible to distinguish group 1 samples from the comparison group 2. Creatinine level and glomerular filtration rate (GFR) in both groups had no statistical difference. An increase in concentration of inflammatory markers MCP-1, IL-18, IL-8, VEGF angiogenesis and TGF-β1 fibrosis was observed in the urine of children with congenital uropathies (VUR) (p<0.001). In group 1 patients the concentration of markers did not correlate with the reflux level.

Conclusions: The  performed research allowed  to find a set of peaks in the recorded mass spectra, according to which it is possible to divide groups into healthy and sick. It also demonstrated the potential of volatolom analysis to detect kidney damage in children with congenital uropathies. The use of standard methods: creatinine and GFR did not allow us to find a threshold value to divide patient into healthy and sick groups. The increase of biomarkers of inflammation, angiogenesis and fibrosis in the urine of children with congenital uropathies confirmed the presence of persistent kidney damage, parenchymal hypoxia, activation of fibrosis and inflammation in children with CU kidneys.

Annals of the Russian academy of medical sciences. 2022;77(5):354-361
pages 354-361 views


Treatment of Parathyroid Cancer: Current Status and Near-Term Prospects

Kim E.I., Krupinova J.A., Belousov P.V., Trutneva K.А., Mokrysheva N.G.


Parathyroid cancer (PС) is a rare malignant neoplasm of the endocrine system, characterized by a severe course due to the development of life-threatening hypercalcemia. Despite a relatively high survival rate, recurrence occurs about half the time. The aggressive course of PС is associated with both local spread of the process and distant metastasis. With the exception of isolated cases, cytotoxic chemo- and radiotherapy are inefficacious, and treatment protocols have not been developed. Therefore the only effective way is the surgical removal of secondary lesions, which is not always technically feasible and is associated with a high risk of postoperative complications. The literature describes individual cases of successful use of targeted therapy, as well as immunotherapy in the form of therapeutic vaccination to induce an immune response against parathyroid hormone (PTH) and block immune checkpoint. A promising direction of study is the tumor immunoenvironment, which has both diagnostic and prognostic value in relation to the likelihood of the spread of the tumor process. In this review, we describe the main directions in the treatment of PC, including disseminated forms, the possibilities of immunotherapy will be considered in details.

Annals of the Russian academy of medical sciences. 2022;77(5):362-370
pages 362-370 views


To the 85th Anniversary of Academician of the Russian Academy of Sciences Viktor Kuzmich Gostischev

Reshetov I.V., Sergeeva N.V., Serikov A.A.


November 21 marks the 85th anniversary of Viktor Kuzmich Gostischev, Professor, Honored Scientist of the Russian Federation, Laureate of the State Prize of the Russian Federation and twice the Prize of the Government of the Russian Federation (1995, 2002), Academician of the Russian Academy of Sciences, Professor of the Department of General Surgery of the Faculty of Medicine of the First Moscow State Medical University. I.M. Sechenova, Chairman of the Problem Commission of the Russian Academy of Medical Sciences and the Ministry of Health of the Russian Federation “Infection in Surgery”, President of the Association of General Surgeons of the Russian Federation, member of the Board of the Russian Society of Endoscopic Surgeons, member of the editorial boards of scientific and practical journals “Surgery. N.I. Pirogov Journal”, “Clinical and experimental surgery. Journal named after Academician B.V. Petrovsky”, “Bulletin of Experimental and Clinical Surgery”, “Wounds and wound infections. Journal named after prof. B.M. Kostyuchenka”, member of the International Society of Surgeons and the International Association of Hepato-Pancreato-Biliary Surgery.

Annals of the Russian academy of medical sciences. 2022;77(5):371-372
pages 371-372 views

To the 75th Anniversary of Academician of the Russian Academy of Sciences Alexander Ivanovich Kiriyenko

Reshetov I.V., Sergeeva N.V., Serikov A.A.


October 19, 2022 marked the 75th anniversary of the birth of Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences Alexander Ivanovich Kiriyenko — a recognized leader in the field of phlebology.

Annals of the Russian academy of medical sciences. 2022;77(5):373-374
pages 373-374 views

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