Vol 28, No 1 (2020)

Original researches
Comparative analysis of the change of bone tissue metabolism condition and cytokine profiles in patients with endoprosthesis instability after primary knee arthroplasty
Galashina E.A., Ulyanov V.Y., Gladkova E.V., Shpinyak S.P., Bondarenko A.S.

Aim. To define relations between serum concentrations of sRANKL and BMP-2, IL-1β, TNFα, IL-4 as well as their role in endoprosthesis instability pathogenesis in patients following primary knee arthroplasties.

Materials and Methods. 80 patients were retrospectively divided into 2 groups: there were 40 patients with osteolysis and aseptic instabilities of knee endoprosthesises that had developed before 12 months after the surgery in the 1st group; the 2nd group was made up of 40 patients with implantat-associated inflammations that had developed in 4 weeks to 12 months after primary knee arthroplasties. 20 volunteer donors made up the control group. The enzyme-linked assay was used to define serum content of sRANKL (pg/ml, Biomedica, Austria), BMP-2 (pg/ml, Ray Bio, USA), cytokines TNFα (pg/ml), IL-1β (pg/ml) and IL-4 (pg/ml) (Vector-Best, CJSC, Novosibirsk, Russian Federation). The comparative analysis of statistically significant indicants was performed defining Spearman rank correlation coefficient.

Results. Positive statistically valid relations of average force between concentrations of sRANKL and BMP-2, TNFα, IL-4 were found in patients of the first group in 1 month after surgeries. In 12 months positive relations of the parameters under study subsisted although the relation with IL-4 absented. The emerging of moderate negative statistically significant relations of sRANKL with BMP-2 and TNFα was observed in patients of the 2nd group in 1 month after surgeries. In 12 months negative relations of average force between sRANKL and BMP-2 subsisted, also new moderate relations emerged: negative relation of BMP-2 with IL-1β as well as positive of sRANKL with IL-1β and TNFα, IL-1β with IL-4.

Conclusion. We found that the disorder of metabolic processes in bone tissue surrounding the implantat with the predominance of osteoclastogenesis activating pro-inflammatory cytokines might be the pathogenic factors of endoprosthesis instability development in patients following primary knee arthroplasty.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):5-12
Succinate and succinate dehydrogenase of mononuclear blood leukocytes as markers of adaptation of mitochondria to hypoxia in patients with exacerbation of chronic obstructive pulmonary disease
Belskikh E.S., Uryasiev O.M., Zvyagina V.I., Faletrova S.V.

Aim. To study the concentration of succinate and the activity of succinate dehydrogenase (SDH) of mononuclear blood leukocytes as markers of rapid adaptation of mitochondria to hypoxia in patients with exacerbation of chronic obstructive pulmonary disease (COPD).

Materials and Methods. The study involved 58 patients with COPD and 13 conventionally healthy volunteers of 40-75 years of age. In accordance with GOLD 2018 principles of complex assessment, the patients were divided to groups B (n=18), C (n=20), D (n=20) comparable in age, FEV1 and in pack-of-cigarettes/year index. Patients of D group were characterized by more pronounced hypoxemia. Activity of SDH and concentration of succinate were determined in mononuclear leukocytes isolated from blood.

Results. Patients with exacerbation of COPD divided to groups on the basis of the frequency of exacerbations and evidence of symptoms, were characterized by different severity of disorders of mitochondrial functions of mononuclear leukocytes. Patients of C group had the highest succinate concentration (428 [357;545] nmol/106 cells in I ml of suspension) and SDH activity (64[56;73] nmol of succinate/min * 106 cells of 1 ml of suspension) in mononuclear leukocytes as compared to groups B (1.43-times reduction of succinate, p<0.002; 1.88-times reduction of SDH, p=0.0015) and D (2.06-times reduction of succinate, p<0.0001; 4.26-times reduction of SDH, p<0.0001). Patients of D group demonstrated the most pronounced reduction of markers of adaptation to hypoxia.

Conclusions. A small amount of symptoms in exacerbation of COPD is associated with the highest parameters of the mechanism of rapid adaptation of mitochondria of mononuclear leukocytes to hypoxia. Existence of evident symptoms and frequent exacerbations in patents is associated with a severe frustration of mechanisms of adaptation of mitochondria to hypoxia.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):13-20
A study of the main parameters of immunogenicity of Ultrix vaccine
Evdokimova O.V., Afanasiev S.V., Antonova O.A., Konopleva V.I., Gorelov I.S., Kruglova A.P., Biryukov V.V.

Aim. Clinical trial of Ultrix vaccine of OOO FORT manufacture containing different serotypes of influenza virus: H1N1 A/California/7/2009 (H1N1) pdm 09, H3N2 A/HongKong/ 4801/2014, NYMCX-263B(15/184) and B/Brisbane/60/2008 NYMCBX-35 (15/300) Victo-rialineage strains (epidemiological season of 2016) and H1N1 A/Michigan/45/2015 NYMCX-275 (16/248), H3N2 A/HongKong/4801/2014, NYMCX-263B(15/184) иB/Brisbane/60/2008 NYMCBX-35 (15/300) Victorialineage strains (epidemiological season of 2017).

Materials and Methods. A study of the basic parameters of immunogenicity included determination of the geometric mean value of the antibody titer, of seroprotection and seroconversion and of relative number of individuals with 4-fold increase in the antibody titer after vaccination. Immunogenicity was determined by a micromethod in hemagglutination inhibition reaction. Sera were tested with diagnosticums obtained from serotypes of influenza virus identical to vaccinal strains.

Results. The level of seroprotection with Ultrix made 91.7-95.8% (2016) and 93.8-97.9% (2017). The maximal level of seroprotection was achieved in 6 months after vaccination with Ultrix containing H1N1A/California serotype. 2.55-4.36-Fold increase in the geometric mean value of anti-HA to all vaccinal strains was found in vaccination in 2016 and 2017, and 4-fold increase in antibody titer in more than 70% of volunteers on the 21st day after the first immunization in 2016.

Conclusion. The obtained results of clinical trials of Ultrix vaccine with different antigenic composition confirms the correspondence of the immunogenicity parameters of the drug to the requirements of the Committee for Proprietary Medical Products (CPMPEMEA, CPMP/ EWP/1045/01) and of State Pharmacopoeia of RF of XIII edition (SP SP XIII).

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):21-29
Physical development of primary school-age orphan boys with mental retardation
Ovcharenko E.S., Fefelova V.V., Kasparov E.V., Koloskova T.P., Smirnova O.V., Ignatova I.A.

Mental retardation is considered one of the most common pathologies of children's mental development. Parameters of physical development are actively used as informative markers of health status, social and hygienic well-being both in norm and in various pathologies. At the same time, not enough attention is given to orphans with intellectual disabilities in this context.

Aim. To study the parameters of physical development in primary school-age boys with mental retardation brought up in a specialized orphanage.

Materials and Methods. 34 Boys (7-11 years old) were examined. Of these, 20 children with a diagnosis of moderate mental retardation (F71) were brought up in a specialized children's home for mentally retarded children (without parental care). The control group included 14 intellectually healthy boys of the same age who were brought up in an orphanage of a physiological type. Anthropometric parameters (body length, body weight, chest and head circumference, cross-section diameter of the chest), ‘sthenia’ index, level of physical development, and Quetelet II index were studied.

Results. The data obtained indicate a sharp decrease in parameters that characterize physical development of orphan boys with mental retardation in comparison with intellectually healthy orphan boys. Since children were in the same social and hygienic conditions, the identified features may be due to the combined influence of the presence of deviations in the intellectual deve-lopment of children and upbringing in a residential home.

Conclusion. The results obtained determine the need for closer medical and hygienic support for orphans with mental retardation.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):30-36
Functional condition of the central nervous system of medical personnel of maternity hospitals
Kotelevets E.P., Kiryushin V.A.

Aim. Analysis of functional capacities of the central nervous system (CNS) of medical personnel of maternity hospitals in the dynamics of the work shift.

Materials and Methods. Using the WAM method, the functional condition of the central nervous system of doctors (obstetricians, gynecologists, neonatologists), nurses (midwives, anesthesiologists, ward nurses) in perinatal centers and maternity hospitals in the cities of Ryazan, Smolensk, Lipetsk, and Kolomna at the beginning and end of the work shift was studied.

Results. Analysis of parameters of operational self-assessment of the functional state of the central nervous system (well-being, activity, mood) revealed the dynamics of reducing the levels of well-being and activity of the main professional groups by the end of the work shift. Calculation of the W+A/M index in the dynamics of the working shift showed its reduction in obstetricians-gynecologists and neonatologists of perinatal centers by 5.0% (p=0.024174) and 10.6% (p=0.026637), respectively; by 10.6% in maternity hospitals in both professional groups (p=0.037452 and 0.039579). Among the nursing staff of perinatal centers, the index decreased in midwives and nurses anesthesiologists by 5.3% (p=0.000752) and 10.6% (p=0.000752), respectively. In groups of nursing staff of maternity hospitals, decrease in the index was determined in anesthesiologists, midwives and ward nurses by 16.7% (p=0.006566), 10.6% (p=0.003385) and 11.2% (p=0.001059), respectively.

Conclusion. Statistically significant differences were found in the analysis of well-being parameters of neonatologists and midwives of perinatal centers, in all the studied respondents of maternity hospitals; of activity – in obstetrician-gynecologists, neonatologists and midwives of perinatal centers, in all surveyed respondents of maternity hospitals; of W+A/N index – in obstetrician-gynecologists, neonatologists, midwives, in anesthesiologists of perinatal centers and in all studied professional groups of maternity hospitals. Reduction of the functional condition of the central nervous system by the end of the work shift may indicate developing fatigue.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):37-43
A study of prevalence of polymorphic variants of genes of blood coagulation factors in onco-logical patients
Zykova T.A., Vladimirova L.Y., Katelnitskaya O.V., Maslov A.A., Shevyakova E.A., Lysenko I.B., Abramova N.A., Storozhakova A.E., Popova I.L., Novoselova K.A., Tikhanovskaya N.M., Lyanova A.A., Ryadinskaya L.A., Tishina A.V., Tishchenko I.S., Kabanov S.N., Kalabanova E.A.

Aim. To study the prevalence of carriage of polymorphic allele variants of genes of blood coagulation factors in oncological patients.

Materials and Methods. 213 Patients with morphologically confirmed oncological diseases were examined. Samples of genomic DNA of peripheral blood of the patients were examined. Using polymerase chain reaction (PCR), polymorphic sites of genes of hemostatic system were studied in real time: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889).

Results. The prevalence of carriage of alternative allele of F2 (G20210А) polymorphic locus in the studied group was 1.6%, of F5 (G1691A) – 3.5%, of F7 (G10976A) – 13.4%, of F13 (G226A) – 28.2%, of FGB G(-455)A – 24.9%, of ITGA2-α2 (C807T) – 41.5%, of ITGB3-b (Т1565С) – 15.5%, of PAI-1 4G(-675)5G – 56.6%. A statistically significant increase in the frequency of ‘risk alleles’ of F5 G1691A (р=0.0169), F13 G226A (р=0.0007), FGB G(-455)A (р<0.0001) and ITGA2-α2 C807T (р=0.0201) polymorphic loci was found in oncological patients as compared to the general population. In the same loci, except ITGA2-α2 (C807T), statistically significant differences in the frequency of alternative alleles were found in different localizations of the oncological process. In 92.0% of patients, SNR combination was determined in different components of hemostatic system.

Conclusion. Taking into account a high frequency of identification of ‘risk alleles’ in all components of hemostatic system, it is reasonable to carry out additional research to determine the necessity of addition of antiaggregants to antithrombotic therapy in oncological patients.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):44-56
Experience of application of mechanochemical scleroobliteration in treatment for recurrence of lower extremity varicose vein disease
Gaibov A.D., Ne’matzoda O., Burieva S.M., Kalmykov E.L.

Aim. Evaluation of the effectiveness of mechanochemical scleroobliteration in treatment for recurrent lower extremity varicose veins (VVD).

Materials and Methods. A retrospective analysis of the results of examination and treatment of 19 patients (17 women and 2 men, average age 36.3±4.5 years) with recurrences of VVD, in whom mechanochemical sclerotherapy as the main method of treatment was used. In all cases, mechanochemical ablation of the superficial venous trunks was performed using Phlebogriph catheter. As a hardener, 3% sodium tetradecyl sulfate solution (fibro-vein) was used in the volume not more than 10 ml per procedure.

Results. According to the CEAP classification, 15 patients had C2 and 4 patients had C3 class. Recurrence of VVD in one lower extremity was diagnosed in 17 (89.5%) patients, and bilateral – in 2 (10.5%). In 6 (31.6%) cases, recurrence occurred in 5 or more years after the first operation, in 8 (42.1%) patients – after 3-5 years, in 5 (26.3%) – after 1-3 years. The diameter of varicose veins before treatment according to color duplex scanning (CDR) was 7.9±0.8 mm. The duration of the detected saphenofemoral reflux (n=10) with the trunk of the great saphenous vein (GSV) left on the hip was 5.7±1.4 s, with the length 31.2±31.4 mm. With the preserved зtrunk of the GSV, crossectomy was performed in combination with mechanochemical scleroobliteration. Crossectomy was also performed in two patients with repeated dilation of the trunk of the small saphenous vein (SSV) followed by mechanochemical scleroobliteration. In two cases, insufficient shin perforants were ligated from mini-incisions, and in two more cases, foam scleroobliteration of them was performed. Within 3 weeks after the procedure, a good result was recorded in 94.7% of cases in the form of complete occlusion of sclerotized veins with the absence of reflux in them. Only in one observation incomplete occlusion of the sclerotized vein on the hip was noted, which required a repeated procedure. Long-term results were studied in 19 patients, in 94.7% of who complete obliteration of sclerotized veins and improvement of the clinical course of chronic venous disease were recorded.

Conclusion. Mechanochemical scleroobliteration has proven to be an effective method of treatment for lower extremity VVD being a minimally invasive procedure.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):57-66
Clinical cases
A complex case of diagnosis of Conn’s syndrome
Ignatenko G.A., Grekov I.S., Grushina M.V., Dubovyk A.V.

The primary hyperaldosteronism also known as Conn’s syndrome, is a rarely diagnosed disease that commonly runs under a ‘mask’ of ischemic heart disease and the primary arteria hypertension (AH). Nevertheless, the incidence of the given pathology among all patients with AH makes almost 17%. On the other hand, the absence of specific clinical manifestations of the disease makes its timely and correct diagnosis difficult which is fraught with serious complications. In the article a clinical case of Conn’s syndrome and peculiarities of its diagnosis are described.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):67-72
A foreign body (a coin) of Meckel’s diverticulum in a two-year-old child
Gavrilyuk V.P., Kostin S.V., Muchkina V.A., Severinov D.A., Kosolapova N.V.

Meckel’s diverticulum is a sac-like bulge of the wall of ileum formed in result of incomplete closure of the viteline duct that participates in nutrition of the embryo.

Aim. To familiarize a wide community of colleagues with an interesting clinical case of a foreign body (a coin) in Meckel’s diverticulum. In the article, approaches to diagnostics and operative treatment of such patients are given. This clinical observation is of interest to abdominal surgeons from the point of view that Meckel’s diverticulum is most commonly identified by clinical symptoms present in diverticulitis, bleeding or perforating ulcer, in intestinal obstruction caused by formation of a node or of invagination.

Conclusion. A situation in which a blunt-ended foreign body permitted to identify Meckel’s diverticulum, is described as casuistically rare.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):73-78
Apoptosis in vascular pathology: present and future
Kalinin R.E., Suchkov I.A., Klimentova Е.A., Egorov A.A., Povarov V.O.

Apoptosis is recognized as a programmed cell death controlled by genetic mechanisms and required for normal existence of an organism. Its main task is elimination of defective or mutant cells. The particles of dead cells are engulfed by macrophages with no development of inflammatory reaction. Apoptosis actively participates in embryogenesis, cellular homeostasis, elimination of tumor cells, and may be divided to three phases: signal, effector, and degradation. Its main components are cytoplasmic proteases – caspases. Caspases exist in the cytoplasm in inactive condition – in the form pf procaspases. Being activated, they break down to subunits. Proteins of Bcl-2 family are active participants of the mitochondrial pathway of apoptosis. They influence permeability of the outer membrane of mitochondria. Disorders in the mechanisms of apoptosis underlie many diseases including ischemic lesions, autoimmune disorders, malignant neoplasms. The ability to influence survival or death of cell is known to possess enormous therapeutic potential. At present, active research is under way to study signal pathways that control cell cycle and apoptosis. The article discusses the mechanisms participating in death of vascular endothelium and smooth muscle cells, potential role of apoptosis in atherosclerosis is also described.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):79-87
Physiological correlates of neuro- and magnetic stimulation in therapy of epilepsy
Sorokina N.D., Pertsov S.S., Selitskiy G.V.

In the literature survey, non-pharmaceutical methods of therapy of epilepsy are considered including electrostimulation of vagus nerve, exposure to magnetic field and transcranial magnetic stimulation (TMS). Correlates of the effectiveness of electro- and magnetic stimulation are electrophysiological parameters, clinical data and influence on the mental and cognitive functions. Use of repetitive transcranial magnetic stimulation in addition to antiepileptic drugs has a certain ground. According to modern understanding and the results of experimental studies, the mechanism of modulator inhibitory alterations is associated with a potential of TMS to cause long-term synaptic depression or long-term potentiation. These long-lasting phenomena probably underlie anticonvulsant effects of low frequency magnetic stimulation. Inclusion of physiologists and neurophysiologists into the research will permit to solve such an important problem as a study of physiological mechanisms of the effectiveness of non-pharmacological electro- and magnetic action in epilepsy.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):88-98
Cardiomyopathy in children – clinical, genetic and morphological aspects
Saryeva O.P., Kulida L.V., Protsenko E.V., Malysheva M.V.

Cardiomyopathy is one of serious and complex problems of pediatric cardiology. Many of them are the cause of sudden death and are familial in character. Disappointing statistics increases the relevance of the problem of cardiomyopathy and dictates the need for in-depth study of the etiology and pathogenesis, structural bases and experience in clinical and morphological diagnosis of this pathology in children. Of particular importance from a practical point of view is the development of prognostic factors in primary and secondary cardiomyopathies. This literature review provides information on the etiology, pathogenesis, clinical manifestations, pathomorphological changes and outcomes of such cardiomyopathies as hypertrophic, dilated cardiomyopathies, non-compact left ventricular myocardium and histiocytoid cardiomyopathy. Peculiarities of restructure of the myocardium in the analyzed cardiomyopathies and their relationship with systolic and diastolic myocardial dysfunction are shown. Molecular genetic aspects of diagnosis of etiology and pathogenesis of this pathology in children are given in detail. The necessity of systematic pathomorphological study of the heart with full analysis of contractile, conducting microcirculatory and neuroautonomic structures in considered variants of cardiovascular pathology is emphasized. These data will help outline future research priorities for this group of diseases to provide earlier diagnosis, improve clinical outcomes and the quality of life of these children and their families.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):99-110

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