Vol 71, No 3 (2016)

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BIOCHEMISTRY: CURRENT ISSUES

Energy Metabolism in the Placenta and the Role of Disturbances in the Development of Placental Insufficiency at an Exacerbation of Cytomegalovirus Infection

Lucenko M.T., Andrievskaya I.A., Dovzhikova I.V.

Abstract

Objective. Determine the characteristics of placental energy metabolism and to establish its role in the development of placental insufficiency at an exacerbation of cytomegalovirus (CMV) infection in 25–28 weeks of gestation.

Methods. In a prospective study of the case-control type included pregnant, delivery on term of 37–38 weeks. The sample of 50 pregnant women, including 25 CMV-seropositive with exacerbation of CMV infection at 25–28 weeks of gestation and with the titer of IgG antibodies to CMV 1: 1600 at the time of the study and 25 CMV-seronegative women the same pregnancy. The study was conducted at the obstetric department of pathology of pregnancy and laboratory «Etiopathogenesis mechanisms and recovery processes with non-specific lung diseases» Far Eastern Scientific Center of Physiology and Pathology of Respiration together with the urban maternity ward at City Hospital in the period from 2014 to 2015. The activity of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and a dehydrogenase lipoic acid was determined by histochemical methods on cryostat sections of fresh frozen tissue placenta by the method of R. Lilly. Evaluation of the intensity of histochemical reactions carried out by the program cytophotometry Scion. The morphology of the placenta was studied in paraffin sections stained with hematoxylin Böhmer-eosin, van Gieson’s picrofuchsin and alcian blue by Steedman. 

Results. Exacerbation of CMV infection at 25–28 weeks of gestation leads to a decrease in the intensity of the histochemical reaction of pyruvate dehydrogenase in 2.4 times, lipoic acid dehydrogenase — in 2.9 times, and α-ketoglutarate dehydrogenase — in 1.5 times in the syncytiotrophoblast villous placenta. The placental morphological structure study showed villi in a state of death or necrotic changes, as well as increasing the number of avascular immature villi. In the maternal part of the placenta were marked constriction clearances, hypertrophy of muscle and connective tissue layers blood vessels. 

The conclusion. The findings suggest that the exacerbation of CMV infection at 25–28 weeks of pregnancy causes a decrease in the intensity of energy metabolism in the placenta by suppressing the activity of the enzymes α-ketoglutarate dehydrogenase and pyruvate dehydrogenase complex, which is accompanied by disturbances of the morphological structure of the placental barrier, the development of placental insufficiency.

 

Annals of the Russian academy of medical sciences. 2016;71(3):
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INFECTIOUS DISEASES: CURRENT ISSUES

Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections

Tutelyan A.V., Pisarev V.M., Minaeva N.Z., Gaponov A.M., Gracheva A.N., Solopova G.G.

Abstract

Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. 

Aims:Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. 

Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. 

Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. 

Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.

Annals of the Russian academy of medical sciences. 2016;71(3):
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CELL TRANSPLANTOLOGY AND TISSUE ENGINEERING: CURRENT ISSUES

The Possibilities of Cell Technologies in the Treatment of Cicatricial Lesions of the Vocal Folds

Svistushkin V.M., Starostina S.V., Lyundup A.V., Dedova M.G., Budeikina L.S., Svistushkin M.V., Krasheninnikov M.E., Baranovskiy D.S.

Abstract

The article is a brief review of publications devoted to the problem of persistent dysphonia. The main cause of voice disorders is the scarring of the vocal folds resulting from trauma, surgical manipulation, inflammatory process. Treatment of cicatricial lesions of the vocal folds remains a challenge, as far as existing methods do not ensure the recovery of the ultrastructure of the vocal folds. The authors present modern data on the structure of the vocal folds at the cellular level. Considered pathologic processes occur in different stages of scarring. Applied technologies of phonosurgery and conservative treatment, their effectiveness and shortcomings are covered. Analysis of experimental research conducted in the world demonstrates the promise of using the methods of tissue engineering to treat scarring of the vocal folds and to restore the microstructure of the latter. Identified current issues remain unresolved, which leads to the need for further experimental and clinical studies in the treatment of this pathology.

Annals of the Russian academy of medical sciences. 2016;71(3):
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HEALTH CARE MANAGEMENT: CURRENT ISSUES

Digital Revolution and Innovative Business Models in Healthcare: Global Trends and Russian Realities

Bereznoy A.V., Saygitov R.T.

Abstract

Digital revolution is one of the major global trends resulting in the unprecedented scale and depth of penetration of information and communication technologies into all sectors of national economy, including healthcare. The development of this trend brought about high expectations related to the improvement of quality of medical assistance, accessibility and economic efficiency of healthcare services. However, euphoria of the first steps of digital revolution is passing now, opening doors to more realistic analysis of opportunities and conditions of realization of the true potential hidden in the digital transformation of healthcare. More balanced perception of the peculiarities of innovation processes in the sector is coming together with understanding of the serious barriers, hampering implementation of the new ideas and practices due to complicated interweaving of social, economic, ethical and psychological factors. When taking into account the industry specifics it becomes evident that digital revolution cannot be a quick turnaround but rather would pass a number of phases and is likely to last more than one decade. In this context the article focuses on the prospects of the new business models, capable of making significant changes in today’s economic landscape of the sector (including uber-medicine, retail clinics, retainer medicine, network models of medical services). The authors also provide assessment of the current situation and perspectives of digital healthcare development in Russia.

Annals of the Russian academy of medical sciences. 2016;71(3):
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Pediatric Health Quality Assessment in Different Regions of Russian Federation

Baybarina E.N., Baranov A.A., Namazova-Baranova L.S., Piskunova S.G., Besedina E.A., Sadovshikova A.N., Yuldashev O.R., Mukhortova S.A., Artemova I.А., Chernikov V.V., Kharkin A.V., Chistyakova E.G., Vologdina E.L., Kaputskaya T.N., Kiripova R.F.

Abstract

Background: The quality of pediatric healthcare is a cornerstone for good maternal and infant health. 

Aims: To evaluate the quality of healthcare in secondary and tertiary regional pediatric hospitals in the Russian Federation.

Methods: Healthcare quality assessment was performed in 21 pediatric hospitals (tertiary, n=5; secondary, n=16) of four regions. The WHO recommendations were used. 

Results: In all regions, similar traits of inpatient pediatric healthcare determining a poor quality were observed. These included low preparedness for emergent care at admission departments; a high rate of unjustified hospitalization due to lack of clear indications for inpatient care; a widespread polypharmacy and unnecessary painful procedures and treatment; inadequate unjustified antimicrobial and parenteral therapy. 

Conclusions: The revealed identity of problems in different regions of the country allows to consider a common strategy to overcome them, which, obviously, should primarily involve education of medical personnel, restructuring of hospital beds to increase day care beds, increasing the clinical expert work in hospitals.

Annals of the Russian academy of medical sciences. 2016;71(3):
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OPHTHALMOLOGY: CURRENT ISSUES

Ultraviolet Corneal Crosslinking

Bikbov M.M., Khalimov A.R., Usubov E.L.

Abstract

This review presents basic information on UV corneal crosslinking. The method is widely used in ophthalmology to treat various types of ectasia, which are characterized by progressive degenerative changes in the cornea, associated with its thinning , hazing and scarring, which leads to a significant reduction in visual acuity. Crosslinking is based on ultraviolet (UV) irradiation of the cornea wavelength 370 nm in the presence of riboflavin, leading to photochemical intracorneal interactions. As a result of crosslinking of collagen treatments, an increase of strength and mechanical properties of the cornea, stops the progression of the disease. The article displays the steps of the method development and the ways of its implementation are described especially occurring biomechanical, biochemical, morphological and ultrastructural changes, as well as the main areas of clinical application of riboflavin-UV-A-induced crosslinking of cornea.
Annals of the Russian academy of medical sciences. 2016;71(3):
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PULMONOLOGY: CURRENT ISSUES

Effects of the Airway Obstruction on the Skin Microcirculation in Patients with Bronchial Asthma

Tikhonova I.V., Kosyakova N.I., Tankanag A.V., Chemeris N.K.

Abstract

BackgroundPulmonary hemodynamic disorders depend on the inflammatory phases and severity of the obstructive syndrome. However, the effect of asthma bronchial obstruction on the state of peripheral hemodynamics remains insufficiently known. 

Aims: To study the effects of airway obstruction on skin blood flow parameters and its regulatory systems in patients with persistent atopic bronchial asthma in the remission state.

Materials and methods: A comparative study of the skin peripheral blood flow in patients with bronchial asthma with severe airway obstruction (1st group) and without obstruction (2nd group) was conducted. 20 patients with confirmed diagnosis of atopic asthma of 50–74 years old participated in the study. All patients received basic therapy in a constant dosing of high doses of inhaled glucocorticosteroids/long-acting beta-2-agonists. The control group included 20 healthy volunteers without evidence of bronchial obstruction. The study lasted for 3 months. The forced expiratory volume in 1 s (FEV1) was used to evaluate the bronchial obstruction by spirometry technique. Skin blood perfusion changes were recorded by laser Doppler flowmetry at rest and in response to short-term local ischemia. Registered peripheral blood flow signals were examined using the amplitude temporal filtering in five frequency intervals to identify the functional features of the peripheral blood flow regulation systems. 

ResultsConsistent two-fold decrease of the oscillation amplitudes was found in the neurogenic interval at rest (p=0.031), as well as in the myogenic (p=0.043; p=0.031) and endothelial intervals (p=0.037; p≤0.001) both at rest and during the postocclusive reactive hyperemia respectively in the 1st group of patients with bronchial obstruction (FEV1 <80%) compared with the control group. No significant changes were revealed for skin blood flow parameters in the 2nd patient group (without obstruction, FEV>80%) in comparison to control subjects.

Conclusions: The presence of bronchial obstruction has a significant impact on the changes of the amplitudes of skin blood flow oscillations in patients with bronchial asthma in the myogenic, neurogenic and endothelial intervals.

Annals of the Russian academy of medical sciences. 2016;71(3):
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ENDOCRINOLOGY: CURRENT ISSUES

Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study

Tsoriev T.T., Belaya Z.E., Rozhinskaya L.Y., Melnitchenko G.A., Grebennikova T.A., Ilyin A.V., Nikankina L.V., Dedov I.I.

Abstract

Background: Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. 

Aims: To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. 

Materials and methods: Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. 

Results: We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p<0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p<0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1.

Conclusions: Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

Annals of the Russian academy of medical sciences. 2016;71(3):
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Gender Features of Radical Oxidation of Lipids in Menopausal Women and Men in Andropause

Kolesnikova L.I., Madaeva I.M., Semenova N.V., Osipova E.V., Darenskaya M.A.

Abstract

Aims: Our aim was to assess lipid peroxidation ― antioxidant protection in menopausal women and men in andropause and to compare these processes in different gender and age groups. 

Materials and methods:74 women and 37 men were examined. This study was a prospective, randomized cohort study. Women were divided into perimenopausal group (n=22, mean age 49.03±3.13), postmenopausal group (n=15, mean age 54.43±4.54) and control (n=37, mean age 34±1.2). Men were divided into a group of andropause (n=20, mean age 50.38±2.63) and control (n=17, mean age 35.21±4.75). Body mass index in the main and control groups was comparable. Questionnaires, clinical examination, assessment of the lipid peroxidation-antioxidant defense system, and the calculation of oxidative stress ratio were conducted to all participants of the study. 

Results: In women from the reproductive phase transition to its extinction increases content of compounds with conjugated double bonds by 22% (p<0.05) in perimenopause and by 27% (p<0.05) in postmenopause, increases content of the ketodienes and coupled trienes by 21% (p<0.05) in perimenopause relative to the control group and reduced by 27% (p<0.05) in postmenopausal women relative to the group of perimenopause. The antioxidant system in women observed the following changes: decrease in the α-tocopherol levels in postmenopausal women by 37% relative to control and by 22% (p<0.05) to compare perimenopause; reduction of retinol level by 29% (p<0.05) in the perimenopause and by 39% (p<0.05) in postmenopause relative to control, increasing of the content of GSSG by 18% (p<0.05) in postmenopause to compare control. When comparing groups of men statistically significant differences were not found. When comparing the groups according to gender, we revealed in men the increased content of compounds with conjugated double bonds by 38% (p<0.05), the GSSG by 13% (p<0.05), reduced content of the ketodienes and coupled trienes by 43% (p<0,05), α-tocopherol by 24% (p<0.05), SOD activity by 9% (p<0.05).Coefficient oxidative stress in perimenopausal women was 2,5, in postmenopausal ― 3,48, in andropause ― 0,97.

Conclusions: Expressed lipid peroxidation activity is more physiological in andropause than in menopause. Men in andropause have large functional reserves and adaptive capacity than menopausal women.

Annals of the Russian academy of medical sciences. 2016;71(3):
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STATE OF MEDICAL SCIENCES

Postgenomic Medicine: Alternative to Biomarkers

Lisitsa A.V., Ponomarenko E.A., Lokhov P.G., Archakov A.I.

Abstract

In the article relevance of high-performance postgenomic technologies is tackled. The intrinsic problems of the implementation of genomics, proteomics and metabolomics in routine clinical practice are considered. Further development of postgenomic medicine requires severe change in the current research approaches. Avenue for development of such approaches are illustrated by metabolome research of human blood plasma. The postgenomic biomarkers are pictured as molecular iceberg, greater part of which is inaccessible for detection with measurement methods. Due to diversity of protein forms the spectrum of molecular markers will always evaluate in terms of incompleteness and inconsistence regardless of technological development level. These properties of «big data» are typical of data intensive domains. Special computational methods are essential for data intensive analytics and hardly suitable for the evidence-based medicine.
Annals of the Russian academy of medical sciences. 2016;71(3):
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