Vol 70, No 4 (2015)

Parametabolism as Non-Specific Modifier of Supramolecular Interactions in Living Systems
Kozlov V.A., Sapozhnikov S.P., Sheptuhina A.I., Golenkov A.V.
As it became known recently, in addition to the enzyme (enzymes and/or ribozymes) in living organisms occur a large number of ordinary chemical reactions without the participation of biological catalysts. These reactions are distinguished by low speed and, as a rule, the irreversibility. For example, along with diabetes mellitus, glycation and fructosilation of proteins are observed resulted in posttranslational modification with the low- or nonfunctioning protein formation which is poorly exposed to enzymatic proteolysis and therefore accumulates in the body. In addition, the known processes such as the nonenzymatic carbomoylation, pyridoxylation and thiamiation proteins. There is a reasonable basis to believe that alcoholic injury also realized through parametabolic secondary metabolites synthesis such as acetaldehyde. At the same time, the progress in supramolecular chemistry proves that in biological objects there is another large group of parametabolic reactions caused by the formation of supramolecular complexes. Obviously, known parameterizes interactions can modify the formation of supramolecular complexes in living objects. These processes are of considerable interest for fundamental biology and fundamental and practical medicine, but they remain unexplored due to a lack of awareness of a wide range of researchers.
Annals of the Russian academy of medical sciences. 2015;70(4):397-402
Features of Urine Biomineralization in Long-Livers
Shabalin V.N., Uvarova D.S., Shatokhina I.S.

The increasing number of long-livers in the developed countries indicates the demand for clarification of the body vital systems’ functioning features which allow the long-livers to prolong their active involvement in social life.

Objective: Aim of our study/research was to define a functional condition of urinary system in long-livers using the new diagnostic technology which analyses the structures of biological liquid at its phase transition in a solid state.

Methods: A case series study was held. All long-livers suffered from atherosclerosis and its complications as well as from associated diseases. An exclusion criterion was acute conditions. The creatinine level in blood serum, indicators of common urine analysis and features of urine facies (using cuneiform dehydration) were defined.

Results: Participants included 60 long-livers (mean age 87.34±4.17 years) who were passing clinical laboratory tests at in-patient department of gerontological hospital. In urine facies of 41 (68.3%) long-livers a phenomenon of salt crystals distribution was identified. It presents the concentration of anisotropic salt crystals in the form of a ring in a regional facies zone. The tenfold increase in concentration of calcium and double increase in concentration of phosphorus in comparison with the central zone was detected in long-livers with a higher percent sulphur in the regional zone of urine facies.

Conclusion: The urine facies of the majority of long-livers have signs of age structure formation associated with a specific distribution of anisotropic salt crystals which fix detritus in its inert form to block the autointoxication.

Annals of the Russian academy of medical sciences. 2015;70(4):403-407
The Effect of the Antioxidant Drug U-74389G on Magnesium Levels During Hypoxia–Reoxygenation Injury in Rats
Τsompos C., Panoulis C., Τοutouzas K., Ζografos G., Papalois A.

Objective: The aim of this experimental study was to examine the effect of the antioxidant drug U-74389G in a rat model of hypoxia – reoxygenation using the previously established protocol. Effects of treatments were evaluated by magnesium (Mg2+) levels in blood.

Methods: Nonrandomized controlled study was performed. Mg2+ levels were determined in 60 min (groups A and C) and 120 min (groups B and D) after starting the reoxygenation. Groups A and B received no drugs, whereas rats from groups C and D were administered with U-74389G.

Results: 40 rats 16–18 weeks old of a mean weight of 2312 g were employed in the study. It is demonstrated that U-74389G administration did not alter the Mg2+ levels (decrease in Mg2+ concentration was 0.28±2.75%; p =0.917). Reoxygenation non-significantly increased the Mg2+ levels by 4.27±2.66% (p =0.107). Together, the U-74389G administration and reoxygenation non-significantly increased the Mg2+ levels by 0.36±1.64% (p =0.823).

Conclusion: U-74389G administration, alone or in concert with reoxygenation did not significantly affect Mg2+ level in blood after experimental hypoxia in rats.

Annals of the Russian academy of medical sciences. 2015;70(4):408-412
Hyposlenism After Splenectomy
Morozov D.A., Klyuev S.A.
Splenectomy is a serious operation, which includes the removal of the largest peripheral immune organ. Vast array of different pools of immunocompetent cells and immune-factors eliminate from the body as a result of this operation. Occurrence of hyposplenism in our country pediatric service is not determined — there are neither clear criteria for its diagnosis, nor approved algorithms for prevention. Data of postsplenectomy sepsis incidence in Russia are unknown. In this review article authors give contemporary literature data relating to the issue of developing hyposplenism and changes in the body after removal of spleen. Systemic effect of organ-resecting operation and the basic directions of overwhelming post-splenectomy infection and sepsis prevention are discussed.
Annals of the Russian academy of medical sciences. 2015;70(4):413-418
Sanfilippo Syndrome
Osipova L.A., Kuzenkova L.M., Namazova-Baranova L.S., Gevorkyan A.K., Podkletnova T.V., Vashakmadze N.D.
Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system. Progressive cognitive decline resulting in dementia and behavioural abnormalities are the main clinical characteristics of Sanfilippo syndrome. Mucopolysaccharidosis type III may be misdiagnosed as other forms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders because of lack of somatic symptoms, presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low urinary glycosaminoglycans levels resulting in false negative urinary assay. Definitive diagnosis is made by enzyme assay on leucocytes and cultured fibroblasts. There is currently no effective treatment of mucopolysaccharidosis type III, though ongoing researches of gene, substrate reduction and intrathecal enzyme replacement therapies expect getting curative method to alter devasting damage of central nervous system in near future.
Annals of the Russian academy of medical sciences. 2015;70(4):419-427
Development of Specific Therapy to Category A ToxicInfections
Kolesnikov A.V., Ryabko A.K., Shemyakin I.G., Kozyr A.V.
Category A select agents continue to be major threat to human population both as naturally occurring diseases and as potential weapon of bioterrorists. Anthrax and botulism are probably the most threatening agents as both have virtually uncontrolled natural reservoirs from which they can be isolated and propagated. Available specific antitoxin therapy of both diseases is outdated; its efficiency is questionable as well as safety of reactogenic or human-derived components used in treatment. Highly sensitive toxin detection techniques are still not as widespread as it needed for timely alerting medical services. There is urgent need of pre-exposure prophylaxis and postexposure specific antitoxin therapy for anthrax and botulism. Analysis of modern studies in the field suggests oligoclonal antibodies acting against receptor-binding toxin subunits and nucleic acid aptamers as allosteric inhibitors of metlloproteolytic toxin components as the most promising candidates for development of efficient antitoxin therapy
Annals of the Russian academy of medical sciences. 2015;70(4):428-434
Species Diversity of Bifidobacteria in the Intestinal Microbiota Studied Using MALDI-TOF Mass-Spectrometry
Chaplin A.V., Brzhozovskii A.G., Parfenova T.V., Kafarskaia L.I., Volodin N.N., Shkoporov A.N., Ilina E.N., Efimov B.A.

Background: The members of genus Bifidobacterium represent a significant part of intestinal microbiota in adults and predominate in infants. Species repertoire of the intestinal bifidobacteria is known to be subjected to major changes with age; however, many details of this process are still to be elucidated.

Objective: Our aim was to study the diversity of intestinal bifidobacteria and changes of their qualitative and quantitative composition characteristics during the process of growing up using MALDI-TOF mass-spectrometric analysis of pure bacterial cultures.

Methods: A cross-sectional study of bifidobacteria in the intestinal microbiota was performed in 93 healthy people of the ages from 1 month to 57 years. Strains were identified using Microflex LT MALDI-TOF MS, the confirmation was performed by 16S rRNA gene fragment sequencing.

Results: 93% of isolated bifidobacterial strains were successfully identified using MALDI-TOF mass-spectrometry. At least two of the strains from each species were additionally identified by 16S rRNA gene fragment sequencing, in all of the cases the results were the same. It was shown that the total concentration of bifidobacteria decreases with age (p <0.001) as well as the frequency of isolation of Bifidobacterium bifidum (p =0.020) and Bifidobacterium breve (p <0.001), and the frequency of isolation of Bifidobacterium adolescentis, increases (p <0.001), representing the continuous process of transformation of microbiota.

Conclusion: The method of MALDI-TOF mass spectrometry demonstrated the ability to perform rapid and reliable identification of bifidobacteria that allowed the study of changes in the quantitative and qualitative characteristics of human microbiota in the process of growing up.

Annals of the Russian academy of medical sciences. 2015;70(4):435-440
Intramedullary Elastic Transphyseal Tibial Osteosynthesis and Its Effect on Segmental Growth
Popkov D.A., Kononovich N.A., Mingazov E.R., Shutov R.B., Barbier D.

Background: Intramedullary transphyseal elastic osteosynthesis is used in children for the diseases accompanied by the reduced strength properties of bone tissue, and primarily for osteogenesis imperfecta.

Objective: The purpose of the experimental study was to investigate tibial growth under the conditions of transphyseal counter-directed insertion of elastic rods without bone integrity breaking, under transverse fracture modeling, as well as under combining transphyseal reinforcement and subperiosteal positioning the titanium mesh with the elastic rods intervolved in it.

Methods: Non-randomized controlled trial was performed. Three series of experiments performed in 18 puppies. Counter-directed transphyseal reinforcement of tibia performed in Series I,, transphyseal reinforcement combined with transverse osteotomy of leg bones — in Series II, transphyseal elastic osteosynthesis and subperiosteal positioning the titanium nickelide mesh with intervolved in it elastic rods during transverse leg bone osteotomy performed in Series III.

Results: Transphyseal reinforcement resulted in growth retardation of the operated tibia. The loss of residual growth was 3.8 mm (p =0.078) in series I; 7.8 mm (p =0.032) — in series II; 7.7 mm (p =0.042) — in series III. Eccentric insertion of transphyseal rods formed an angular deformity (mean value 7°; p =0.023) of the distal tibial epiphysis in the process of residual growth. Periosteal and endosteal reactions contributed to enlargement of diaphyseal diameter of 3.9 mm (series II; p =0.037) and 3.8 mm (series III; p =0.041). Any difference of diameter between operated and intact tibia was not observed in series I.

Conclusion: Intramedullary transphyseal reinforcement retards longitudinal bone growth. The positioning of the telescopic systems should be as close as possible to the center of growth plates in order to prevent angular deformities. Subperiosteal reinforcement doesn’t retard consolidation of fragments, and it can be combined with intramedullary transphyseal osteosynthesis

Annals of the Russian academy of medical sciences. 2015;70(4):441-449
Disorder of the Longitudinal Limb Growth and Muscular Contractility
Schurov V.A.

Background: The reduction of the muscular contractility in the patients after operative lengthening of the limb with delayed growth is the main factor limiting the volume of orthopaedic treatment.

Objective: Our aim was to study the dependence of the muscular contractility of the femur and tibia on their longitudinal sizes in healthy individuals and patients of various age and in the patients with different variants of natural growth disorders of one of the lower limb before and after its operative lengthening according to Ilizarov.

Methods: Maximal torque of various groups of the femoral and tibial muscles was evaluated in 78 patients aged from 4 to 40 years with delayed longitudinal growth from 3 to 12 cm of one of the lower limbs using original dynamometers. Control group included 424 healthy children aged from 7 to 15 years and 36 persons aged from 18 to 35 years.

Results: The dependence of maximal torque of various groups of the femoral and tibial muscles on their longitudinal sizes in healthy individuals and patients of various ages and gender as well as in the patients with growth disorders before and after their operative lengthening was presented. The affected limb muscular strength and the same of the intact one reduced every cm of the longitudinal growth delay (for instance, the posterior tibial muscle for 3.2 and 1.7 Nm correspondingly).

Conclusion: Compensatory increase of the muscular strength in the contralateral femur was found only in significant reduction of the muscular contractility of the affected tibia. In equal amount of the tibial shortening its muscular strength reduced relatively more in the patients with congenital disease and consequences of the osteomyelitis and less in trauma cases.

Annals of the Russian academy of medical sciences. 2015;70(4):450-455
Years of Life Lost Due to Premature Death and Their Relationship with Climate and Socio-Economic Performance of Regions
Boytsov S.A., Samorodskaya I.V., Tret’jakov V.V., Vatolina M.A.

Background: The «years of potential life lost» (YPLL) indicator is widely used in international studies. Still YPLL's variety in the Russian regions is poorly investigated.

Objective: Our aim was to study the performance of YPLL in the regions of Russia in 2013 and their relationship with the regional socio-economic indicators.

Methods: Non-clinical observational study was conducted. The object of study — YPLL in the Russian regions. YPLL per 100 thousand population (non-standardized and standardized to the world standard population age structure) is based on data of Rosstat. Subject of investigation — YPLL variability in the regions, the evaluation of the correlation between YPLL, climatic effect and socio-economic indicators of the regions.

Results: The average standardized YPLL in the region was 20 185 (95% CI 19 272–21 029); non-standardized — 25 880 (95% CI 24 744–26 957). Maximum standardized YPLL above the minimum in 3.4 times. Minimum YPLL rates were recorded in the North Caucasus, Moscow and St. Petersburg; maximum — in Chukotka, Republic of Tuva and the Jewish Autonomous Region. Negative statistically significant correlation to the average power detected between YPLL and: 1) specific weight of the total space, equipped with water supply, hot water supply and sanitation; 2) share of population with tertiary education in total population; 3) road density (km of roads per 1000 sq km); 4) climatic conditions.

Conclusion: The regional YPLL indicators vary considerably and are higher than the similar indicators in developed countries. According to the findings PYLL indicator are influenced by economic factor,indicators of household living conditions of the population, the infrastructure system in the region, the level of education of the population and climatic effect. The resuts we got require further multidisciplinary study of the problem.

Annals of the Russian academy of medical sciences. 2015;70(4):456-463
Orbital Adipose Tissue: Just a Fat Pad or Terra Incognita in Ophthalmology
Borzenok S.A., Afanasyeva D.S., Gushchina M.B.
Our understanding of the role of adipose tissue has been completely changed during the past decades. The knowledge of its contribution to endocrine and immune pathways opened the new insights on the pathogenesis and therapy of many diseases and new perspectives for the regenerative medicine. The further researches should be provided to study anatomy and functions of local fat depots in more details. Of the most interest is the orbital adipose tissue due to its origin from the neural crest. This review represents the current data about anatomy, structure, cell composition and biochemistry of orbital fat. The main attention is put to such cell types as adipocytes and adipose derived mesenchymal stem cells. The foreign authors’ findings on such characteristics of stem cells from orbital adipose tissue as CD markers and differential capacity are reviewed. The found evidences of interaction between orbital adipose tissue, eyeball and associated structures allow us to hypothesize that this fat depot may contribute to various ocular pathology. In this paper, we outlined the possible directions for further investigation and clinical application of orbital fat and cells its composing in ophthalmology, reconstructive and plastic surgery and regenerative medicine.
Annals of the Russian academy of medical sciences. 2015;70(4):464-467
Influence of Adamantilbromphenylamine on Parameters of Immunity and Symptoms of Asthenia in Patients with Non-Psychotic Mental Disorders
Vetlugina T.P., Nikitina V.B., Sergeeva S.A., Axenov M.M., Lobacheva O.A., Savochkina D.N., Epanchintseva E.M., Bokhan N.A.

Objective: Our aim was to assess effect of antiasthenic drug adamantilbromphenylamine on the immune system and symptoms of asthenia in patients with non-psychotic mental disorders and to reveal possible criteria for prediction of treatment efficiency.

Methods: Uncontrolled study with interrupted time series was carried out. According to efficiency of treatment patients were divided into two groups (group 1 (n =21) — very much improved and much improved; group 2 (n =9) — minimally improved). Adamantilbromphenylamine was administered to patients as a monotherapy 100 mg a day for 28 days. Examination was conducted before and after therapy. Severity of asthenic symptoms according to MFI-20 scale was identified; cellular and humoral immunity parameters, mitogen-induced production of interleukins (IL) 1β and IL 4 by immunocompetent cells of patients were assessed.

Results: 30 patients with non-psychotic mental disorders with predominance of asthenic symptomatology in clinical picture of the disease were examined. Before therapy every proband had over 60 points across 5 items of MFI-20 scale. As compared with control decrease of number of lymphocytes of CD3+-, HLA-DR+, CD16+-phenotypes; increase in the ratio of CD4+/CD8+; concentration of serum IgМ; phagocytic activity of neutrophils were revealed. In the end of therapy in group 1, sum total of points of asthenia decreased up to 26 (23–37) (p <0.001); in group 2 — up to 57 (47–61). Only in group 1 positive dynamic of immune parameters was revealed. It was shown that baseline level of proinflammatory cytokine IL 1β in group with apparent therapeutic effect of the drug was reliably lower, than in group with minimal improvement (p =0.005). These differences remained also after course of therapy (p =0.042).

Conclusion: Interrelationship of clinical-immunological effect of adamantilbromphenylamine has been revealed; intensity of production of IL 1β may be considered as a criterion of prognosis of efficiency of treatment with adamantilbromphenylamine in patients with non-psychotic mental disorders

Annals of the Russian academy of medical sciences. 2015;70(4):468-474
β-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells
Isaeva A.V., Zima A.P., Shabalova I.P., Ryazantseva N.V., Vasil’eva O.A., Kasoayn K.T., Saprina T.V., Latypova V.N., Berezkina I.S., Novitskii V.V.
The article presents the data on the structure and mechanisms of β-сatenin functioning. The basic aspects of the role of β-сatenin in malignant transformation have been studied at various tumors. Primary structure of β-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al. This interaction is the base for β-catenin's intracellular multifunctioning. The review presents data on the participation of β-catenin in the mechanisms of adhesion, regulation of RNA metabolism, formation contacts with the cytoskeleton and its role in the canonical Wnt signaling pathway, marked examples pro-inflammatory and anti-inflammatory effects of β-catenin. The β-catenin involvement in malignant transformation and progression of certain tumors is not in doubt. The data on the changes in β-catenin expression in the given examples of colon cancer, prostate cancer, different forms of thyroid cancer and hepatocellular carcinoma are presented with the prospects of its use as a marker and a predictor of malignant transformation. Continued research in this area will not only make use of β-catenin as a potential predictor of malignant tumors, but also to develop approaches to targeted therapy.
Annals of the Russian academy of medical sciences. 2015;70(4):475-483
MicroRNAs As An Important Precursors of Diagnostic Obstetric Pathology
Nizyaeva N.V., Kan N.E., Tyutyunnik V.L., Lomova N.A., Nagovitsyna M.N., Prozorovskaya K.N., Shchyogolev A.I.
MicroRNAs (miRs) are the class of short nucleotide sequences (21–27 nucleotides) RNA, non-coding protein synthesis. miRs are known as effective posttranscriptional negative regulators of gene expression with specific binding sites of targeted messenger RNA (mRNA) in the cytoplasm, providing translational repression or degradation of the target miR transcript. In this review we studied the role of miRNAs in the development of a physiological pregnancy and obstetric complications. The placenta is a unique organ which provides modulation of the immune system of the maternal organism during pregnancy including miRs which determine immunological tolerance of the body to the tissues of the fetus. Thus the «placental» miRs in maternal circulation may be the potential biomarker revealed at various obstetric pathology on the early stages before clinical manifestation of the diseases.
Annals of the Russian academy of medical sciences. 2015;70(4):484-492
Algorithm of Macrophage Activation Assessment for Forecasting and Evaluation of Treatment Effectiveness of Human Diseases
Sakharov V.N., Litvitskiy P.F.
Despite the high complexity of macrophage activation and subsequent polarization, determination of the key dynamic features of these processes provides the basis for both assessment of macrophage activation current state and for disease prognosis. To sum it up either macrophage phenotype ratio or polarizing stimulus ratio may be the most important indicators.
Annals of the Russian academy of medical sciences. 2015;70(4):493-498
Vasilii Gennad'evich Akimkin


Annals of the Russian academy of medical sciences. 2015;70(4):499-500
Oleg Ivanovich Kiselev

5 сентября 2015 г. исполнилось 70 лет директору Научно-исследовательского института гриппа, известному ученому-вирусологу, внесшему существенный вклад в решение широкого спектра фундаментальных и прикладных задач в области молекулярной вирусологии, биохимии, генной инженерии, диагностики, химиотерапии и профилактики гриппа и других вирусных инфекций, академику РАН, доктору биологических наук, профессору Олегу Ивановичу Киселёву.

Annals of the Russian academy of medical sciences. 2015;70(4):501
XIX Russian pediatrician congress


Annals of the Russian academy of medical sciences. 2015;70(4):503
Anastasiya Pavlovna Shitskova

Секция профилактической медицины Отделения медицинских наук РАН с прискорбием сообщает, что 20 августа 2015 г. на 96-м году жизни скончалась выдающийся ученый-гигиенист, профессор, доктор медицинских наук, академик РАН Шицкова Анастасия Павловна.

Annals of the Russian academy of medical sciences. 2015;70(4):504

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