Vol 72, No 1 (2017)

BIOCHEMISTRY: CURRENT ISSUES

Paraoxonase: The Universal Factor of Antioxidant Defense in Human Body

Borovkova E.I., Antipova N.V., Korneenko T.V., Shakhparonov M.I., Borovkov I.M.

Abstract

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.
Annals of the Russian academy of medical sciences. 2017;72(1):5-10
pages 5-10 views

The Role of Reactive Oxygen Species in the Pathogenesis of Adipocyte Dysfunction in Metabolic Syndrome. Prospects of Pharmacological Correction

Prokudina E.S., Maslov L.N., Ivanov V.V., Bespalova I.D., Pismennyi D.S., Voronkov N.S.

Abstract

It is established that oxidative stress induces insulin resistance of adipocytes, increases secretion leptin, IL-6, TNF-α by adipocytes. Adiponectin secretion by adipocytes is reduced after the action of reactive oxygen species. Metabolic syndrome contributes to oxidative stress in adipose tissue, on the one hand due to the activation of production of reactive oxygen species by adipocyte NADPH-oxidase, and on the other hand by reducing the antioxidant defense adipocytes. It is found that obesity itself can induce oxidative stress. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α play an important role in the pathogenesis of oxidative stress of adipocytes. Metformin remains the cure for the treatment of insulin resistance. The positive results in the treatment of metabolic syndrome by losartan were obtained. Antioxidants and flavonoids exhibit a positive impact on the course of the experimental metabolic syndrome.
Annals of the Russian academy of medical sciences. 2017;72(1):11-16
pages 11-16 views

CELL TRANSPLANTOLOGY AND TISSUE ENGINEERING: CURRENT ISSUES

Urethra Reconstruction with Tissue-Engineering Technology

Vasyutin I.A., Lyundup A.V., Vinarov A.Z., Butnaru D.V., Kuznetsov S.L.

Abstract

Urethral stricture is a disease characterized by a pathological narrowing of the urethra. Treatment for this condition often requires surgery using autologous grafts (urethroplasty). It is common practice to use patient’s own tissue like genital and extragenital skin, tunica vaginalis, buccal mucosa as a source of the graft. Alternative and safer approach is to use tissue-engineered graft created in a laboratory using patient’s autologous cells and biocompatible matrix (scaffold). The article presents the up-to-date achievements in lab-created tissue-engineered graft, describes all components needed to build a tissue-engineered structure of the graft for urethroplasty, and summarizes authors’ thoughts on advantages and disadvantages of various approaches to choose both cellular component and the matrix of future construction. The article reviews clinical studies conducted in the field of tissue engineering of the graft material for urethraplasty.
Annals of the Russian academy of medical sciences. 2017;72(1):17-25
pages 17-25 views

HEALTH CARE MANAGEMENT: CURRENT ISSUES

Efficacy of Management for Rational Use of Antibiotics in Surgical Departments at a Multi-Disciplinary Hospital: Results of a 7-year Pharmacoepidemiological Research

Korableva A.A., Yudina E.V., Ziganshina L.E.

Abstract

Background. Irrational medicine use including excessive use and abuse of antibiotics remains a crucial problem for the healthcare systems. In this regard, studies examining approaches to improving the clinical use of medicines are highly important. 

Aim: to assess the efficacy rate of management for the rational use of antibiotics in surgical departments of a multi-disciplinary hospital. 

Material and methods. The intervention complex combined the research, educational, and methodological activities: local protocols for perioperative antibiotic prophylaxis (PABP) for various surgical departments were developed; local PABP protocols were discussed with the physicians of specialized surgical departments; official order on implementation of PABP was issued; the list of drug prescriptions for registration of the first pre-operative antibiotic dose was changed; audit and feedback processes were introduced as well as consultations of a clinical pharmacologist were implemented. We assessed the efficacy rate of the interventions basing on the changes in consumption of antibiotics (both quantitatively and qualitatively) at surgical departments of a hospital using ATC/DDD methodology. Comparison of the studied outcomes was performed before and after the intervention implementation and between the departments (vascular and abdominal surgery). The consumption of antibacterial agents (ATCJ01) was measured as a number of defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days, indicator recommended by the World Health Organization, WHO) and DDD per 100 treated patients (DDD/100 treated patients). 

Results. From 2006 to 2012, a decrease in antibacterial consumption in surgical departments by 188 DDD/100 treated patients was observed. We obtained the opposite results when using an indicator of DDD/100 bed-days (increase by 2.5 DDD/100 bed-days) which could be explained by the dependence on indices of overall hospital work and its changes during the examined period. Observed changes in antibacterial consumption varied in different surgical departments. The most pronounced positive changes were noted in the department of vascular surgery: decrease in total antibacterial consumption by 298 DDD/100 treated patients, decrease in the use of cephalosporins of the III generation from 141 to 38 DDD/100 treated patients. These positive changes were accompanied by the same (low) level of consumption/use of reserve antibiotics. In the department of abdominal surgery, there was no decrease in total antibiotic consumption, as well as in consumption of broad-spectrum cephalosporins of the III generation and fluoroquinolones, and we observed an increase in the use of reserve antibiotics (carbapenems) during the study period. Positive changes in antibiotic consumption were associated with the positive attitude of the manager/head of the department towards interventions: we observed the most pronounced decrease in antibiotic consumption straight after the publication of the administrative order on perioperative antibacterial prophylaxis. 

Conclusion. The combination of scientific, educational, and methodological interventions is effective for improving antibiotic application. The study results provide the rationale for analyzing the drug consumption using the DDD/100 treated patients measure in addition to the WHO-recommended indicator of DDD/100 bed-days which depends on overall hospital performance.

Annals of the Russian academy of medical sciences. 2017;72(1):26-32
pages 26-32 views

PEDIATRICS: CURRENT ISSUES

Peculiarities of Allergy Diagnosis in Children

Namazova-Baranova L.S., Snovskaya M.A., Mitushin I.L., Kozhevnikova O.V., Batyrova A.S.

Abstract

Allergic disease is a serious problem in practical healthcare. Over the last 40 years there has been exponential growth in the prevalence. According to the world health organization information, allergic diseases are at the 2nd place in prevalence the children, behind the viral infections. Their frequency and severity are increasing. In this regard, the relevance of timely and skilled diagnostic allergopathology is most important. In this study the current state of the question of allergy diagnostics is considered, the international experience is summarized and the approach to the allergy diagnosis based on use of step-by-step identification of a causal and significant factor of allergic reactions is offered. On the basis of the analysis of relevance and the importance for patients of one or the other allergens (taking into account a source of allergens and age of patients) use of a step-by-step allergy diagnostics algorithm is offered. The first step is definition of clinical implications of an allergy. It means direct contact of the phisition with the patient, clarification of its complaints, clinical symptoms, medical history disease. The second step is the confirmation of IgE-dependent mechanism. It involves the using of screening tests that are selected depending on the clinical symptoms and seasonality manifestations (the screening module). The third step is to identify the source of the allergens that are most meaningful for the patient with using test panels (modules). The panels include the most common and clinically relevant triggers of allergic reactions. The fourth step is the search for an individual significant allergens, which were not included in the diagnostic modules. On the fifth step, we plan to conduct component-divided diagnostics and detect the antibodies to unique components of significant allergens. The developed diagnostics algorithm, corresponds to needs of both the adult, and children’s population and provides the personalized approach to the patients.
Annals of the Russian academy of medical sciences. 2017;72(1):33-41
pages 33-41 views

RHEUMATOLOGY: CURRENT ISSUES

Complement System Abnormalities in Patients with Atypical Hemolytic Uremic Syndrome and Catastrophic Antiphospholipid Syndrome

Demyanova K.A., Kozlovskaya N.L., Bobrova L.A., Kozlov L.V., Andina S.S., Yurova V.A., Kuchieva A.M., Roshchupkina S.V., Shilov E.M.

Abstract

Background: The role of the alternative complement pathway (AP) abnormalities in the pathogenesis of aHUS is well studied. Clinical and morphological manifestations of atypical HUS and catastrophic APS are often similar. However, studies on the state of AP in patients with CAPS are virtually absent. 

Aims: The aim of our study was to assess the state of AP in patients with CAPS and aHUS. Patients and methods: The study enrolled 67 patients (pts) with a diagnosis of CAPS (28 pts) and aHUS (39 pts). Studies of the complement system are made of 10 pts with CAPS and 20 aHUS. Factor H, I, B, D content, functional activity of factor H, and complement components C3, C4 was determined in serum by ELISA kit. 

Results: Patients with CAPS and aHUS showed similar changes in complement biomarkers. The factor H level in the serum was significantly higher than the standard value. However, the specific activity of factor H reduced, mean rate 59% for aHUS and 26% for CAPS. The median value of factor D was twice higher than the normal range in both groups, indicating the activation of the AP. 

Conclusions: There are indications of an AP activation not only in pts with aHUS but in CAPS pts too. We suppose that the activity of factor H is a more sensitive indicator of complement system changes than factor H level. Patients with CAPS and aHUS have similar clinical and laboratory characteristics. However, CAPS is more severe, with the involvement of a larger number of vascular beds. Perhaps this is due to the double damaging effects on the endothelium ― of antiphospholipid antibodies (aPL) and activated complement. So we hypothesize that CAPS can be called aPL-mediated TMA in pts with a complement system defect.

Annals of the Russian academy of medical sciences. 2017;72(1):42-52
pages 42-52 views

TRAUMATOLOGY: CURRENT ISSUES

The Primary Metatarsalgia: Pathogenesis, Biomechanics and Surgical Treatment

Bobrov D.S., Slinjakov L.J., Rigin N.V.

Abstract

This paper presents a comprehensive review on the current concept of the diagnosis and treatment of central metatarsalgia on the basis of medical literature analyses. Metatarsalgia is the term for pain in the forefoot. This is a set of symptoms corresponding to a wide range of diseases. Central metatarsalgia is a kind of metatarsalgia which arises from structural-functional changes that lead to excessive pressure in the area of metatarsal heads. The data analysis demonstrated that presently various types of osteotomies of metatarsal bones are the main surgical treatment options with the chance of complication ranging from 6 to 50%. Weil-osteotomy is known to be the most popular type of osteotomy for treatment of central metatarsalgia. The most common complication of Weil-osteotomy is floating toe, the one that doesn’t contact with the supporting surface. In case Weil-osteotomy and intraphalangeal arthrodesis with trans acticular fixation are both performed, the complication of floating toe increases up to 50%. When Weil osteotomy, plantar plate repair, extensor digitorum longum tendon lengthening and triple Weil-osteotomy are performed simultaneously, the complication rate is 15% approximately which is much lower. Using combined osteotomy techniques as well as taking into account structural-functional pathologic changes of the forefoot and ligaments repair of metatarsalphalangeal joint will ensure the most successful development of surgical treatment techniques for central metatarsalgia.
Annals of the Russian academy of medical sciences. 2017;72(1):53-58
pages 53-58 views

ENDOCRINOLOGY: CURRENT ISSUES

Prospects for the Use of Cannabinoid Receptor Ligands for the Treatment of Metabolic Syndrome and Atherosclerosis: Analysis of Experimental and Clinical Data

Maslov L.N., Karpov R.S.

Abstract

An antagonist of central cannabinoid CB1 receptors rimonabant causes weight loss in patients with obesity and metabolic syndrome, improves blood lipid parameters, increases the adiponectin level, decreases the rate of glucose and glycosylated hemoglobin in patients with diabetes mellitus
type-2. However, rimonabant adverse effects include depression, anxiety, nausea, and dizziness which are apparently due to the blockade of central CB1 receptors. In mice with a high-calorie diet, we defined that the blockade of peripheral CB1 receptors prevents obesity, steatosis of the liver, improves lipid and carbohydrate metabolism. Experimental studies suggest that peripheral CB2 receptor agonists have antiatherogenic effect. To validate the expediency of clinical research of CB2 receptor agonists in patients with atherosclerosis the comparative analysis of antiatherogenic properties of cannabinoids should be performed. In addition, experiments are needed on the combination use of cannabinoids with well-known antiatherogenic agents, such as statins.
Annals of the Russian academy of medical sciences. 2017;72(1):59-65
pages 59-65 views

Cardiovascular Effects of Incretin-Based Therapies and Their Therapeutic Potential

Tyurenkov I.N., Bakulin D.A., Kurkin D.V., Volotova E.V.

Abstract

Antidiabetic drugs with incretin activity in addition to pronounced hypoglycemic activity cause moderate reduction in blood pressure and fat mass as well as improve the lipid profile in patients with type 2 diabetes mellitus (T2DM). In clinical trials the addition of glucagon-like peptide-1 (GLP-1) analogues to standart T2DM therapy leads to significantly reduce the risk of fatal and nonfatal cardiovascular complications. According to the results of many experimental and clinical studies it was shown that GLP-1 analogs protect endothelium in diabetic patients and protect cardiomyocytes after ischemia-reperfusion lesion.
Pleiotropic effects of GLP-1-based therapies are realized due to the presence of GLP-1-receptor in endothelial cells, cardiomyocytes, neurons, monocytes and macrophages, as well as due to the connection of the receptor with the most important intracellular signaling cascades (through activation of protein kinase A and B). Whereby GLP-1-based therapies affect the functional condition as well as processes of regeneration and apoptosis of target cells.
This review presents the results of studies the cardiovascular effects of GLP-1-based therapies of diabetes. Described proposed nowadays mechanisms of endothelium protective and cardioprotective action of GLP-1 analogs that associated with the action on endothelial function, vascular wall inflammation (the expression of adhesion molecules and inflammatory cytokines), and apoptosis of endothelial cells and cardiomyocytes.

Annals of the Russian academy of medical sciences. 2017;72(1):66-75
pages 66-75 views

ORIGINAL STUDIES

Morphological Features of Mesenhymal Stroma Cells of Chorionic Villi

Nizyaeva N.V., Sukhacheva Т.V., Kulikova G.V., Nagovitsyna M.N., Kan N.E., Baev O.R., Pavlovich S.V., Serov R.A., Shchegolev A.I., Poltavtseva R.А.

Abstract

Background: Nowadays autologous mesenchymal placental stromal cells (MSCs) may use to treat for various diseases both of the mother and the child. Stroma of the placenta villi is appropriated origin for cell culture isolation

Aim of the study was to evaluate the possibility for selection and use of placental tissue for mesenchymal stromal cells. Materials and methods: The present study was based on 45 placental samples of women aged 27−38 yy. who underwent surgical delivery at 36−40 weeks of gestation. 30 of these women have been enrolled in the basic group including children with congenital abnormalities (CA). The comparison group consisted of 15 patients with physiological pregnancy. We performed histological examination (with hematoxylin and eosin staining), immunohistochemical examination (with use monoclonal antibodies CD90 (1:25; Abcam, UK), СD105 (1:500; Abcam, UK), CD44 (1:25; Dako), СD73 (1:200, Abcam, UK), and electron microscopy (by microscope Philips/FEI Corporation, Eindhoven, Holland). Eclipse 80i microscope (Nikon Corporation, Japan) was used to examine the immunohistochemical reactions as a brown staining. The evaluation of the intensity of reaction was conducted by NIS-Elements Advanced Research 3.2 program (Czech Republic). Student’s t-test and analysis of variance were used to compare the mean values. Differences were considered statistically significant at p<0.05. 

Results: Interstitial cells of the stroma of the villi with CA had fibroblastic differentiation as revealed degenerative changes of the cells. The histologic examination with hematoxylin and eosin staining revealed significant fibrosis of the stroma of the placenta villi in CA group (p<0,01). Immunohistochemical study of stem and intermediate chorionic villi revealed no significant differences in staining of CD44+, СD90+, СD73+, and CD105+ cells if compared to the control group (p>0.05). Although CD105 expression was significantly lower in the CA group (0.058±0.0049) than in the control group (0.088±0.0039) (p<0.05). However, electron microscopy detected the villi interstitial stromal cells with fibroblastic differentiation in CA group. 

Conclusions: Thus, it is necessary to exclude placenta with obstetrical history, somatic, and congenital pathology of the mother and the child when selecting the placental cell culture. Moreover, choosing a sample the morphological structure of the placenta should be taken into consideration. However, congenital malformations of the fetus, pathology of the mother cultivate mesenchymal stromal cells of placentas is inappropriate and should be taken advantage of the donor cells.

Annals of the Russian academy of medical sciences. 2017;72(1):76-83
pages 76-83 views

ANNIVERSARIES, CONGRATULATIONS

D.I. Ivanovsky ― A Pioneer Discover of Viruses, As A New Form of Biological Life

Zhirnov O.P., Georgiev G.P.

Abstract

125 years ago, in 1992, a Russian scientist Dmitri Iosifovich Ivanovsky published first research data disclosing a unique form of filterable biological microlife. Further scientific progress in this discovery resulted in a new discipline of human knowledge, called «the Kingdom of viruses».
A fundamental understanding of viral form of biological life was established not at once and was gradually formed under the accumulation of scientific facts. Only at the beginning of 50 years of the twentieth century, a basic understanding of viral Kingdom had been formed and 1992 year was recognized as the year of the birth of Virology. Virology, which started developing by the research of D.I. Ivanovsky, gave remarkable progress and prominent results: more than 20 scientists got Nobble Prize for the outstanding works in virology. There are all arguments and grounds to nominate the international scientific award in virology named of D.I. Ivanovsky.
Annals of the Russian academy of medical sciences. 2017;72(1):84-86
pages 84-86 views

Alexandr Bogdanovich Fokht ― The Founder of Clinical-Experimental Approach in Medicine (in Honor of 170th Year Anniversary)

Maltseva L.D., Morozova O.L., Gorbachev N.A., Litvitskiy P.F.

Abstract

The review is dedicated to the investigation of the role of A.B. Fokht, who was one of the most famous scientist, teacher and doctor during the period of the development of clinical oriented approach pathophysiology. The article examines new vectors in clinical medicine development of the second half of the 19th century. It is pointed out in the article that Russian scientists of that time instead of aiming at history rewriting or repeating the traditions of the West-European science finally formed their own rational ideas and tried to provide unique scientific research. What is more, the article contains biographical information about Fokht’s family, his teachers and colleagues. The article describes the main principles of Fokht’s scientific school, which became the most remarkable in Russia in the beginning of the 20th century, and also achievements of his followers, who had been working in the largest laboratories and chairs of Great Britain, the USA, Poland etc. Moreover the article contains information about the influence which the results of Fokht’s research had on recognition of Russian independent medical science worldwide. The article emphasizes the Fokht’s political and civil position against the educational and scientific reforms, which had been conducted by the Russian government in the beginning of the 20th century. Finally, the article describes Fokht’s personality and his activities in other spheres.
Annals of the Russian academy of medical sciences. 2017;72(1):87-95
pages 87-95 views

Sergei Anatol'evich Boitsov

Abstract

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Annals of the Russian academy of medical sciences. 2017;72(1):96-97
pages 96-97 views

Viktor Aleksandrovich Tutel'yan

Abstract

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Annals of the Russian academy of medical sciences. 2017;72(1):98
pages 98 views

Aleksandr Nikolaevich Strizhakov

Abstract

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Annals of the Russian academy of medical sciences. 2017;72(1):99-100
pages 99-100 views

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