Vol 68, No 12 (2013)

ONCOLOGY: CURRENT ISSUES
ONCOLYTIC PROPERTIES OF SOME ORTHOPOXVIRUSES, ADENOVIRUSES AND PARVOVIRUSES IN HUMAN GLIOMA CELLS
Razumov I.A., Svyatchenko V.A., Protopopova E.V., Kochneva G.V., Kiselev N.N., Gubanova N.V., Shilov A.G., Mordvinov V.A., Netesov S.V., Chumakov P.M., Loktev V.B.
Abstract
Currently one of the most promising approaches in development of cancer virotherapy is based on the ability of oncolytic viruses to selective infection and lysis of tumor cells. Aim.The goal of the study was to identify and evaluate perspective oncolytic viruses capable of selectively destroying human glioma cells. Patients and methods. Original GB2m, GA14m and GB22m glioma cell cultures derived from patients were used for evaluating in vitro oncolytic activity of some typical orthopoxviruses, adenoviruses and parvoviruses. Results. The oncolytic activity in the human glioma cell models was confirmed for LIVP and WR strains of vaccinia virus,  Adel2 and Ad2del strains with deletions within E1B/55K gene and derived from human adenoviruses type 2 and 5, respectively. Conclusions. We consider these oncolytic viruses as promising agents for the treatment of human malignant glioma.

 

Annals of the Russian academy of medical sciences. 2013;68(12):4-8
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COMPARATIVE ANALYSIS OF VASCULARIZATION DEGREE OF HEPATOCELLULAR CARCINOMA AND FOCAL NODULAR HYPERPLASIA OF THE LIVER ACCORDING TO COMPUTED TOMOGRAPHY AND MORPHOLOGICAL STUDIES
Tumanova U.N., Karmazanovskii G.G., Dubova E.A., Shchegolev A.I.
Abstract

A comparative analysis of vascularization degree of hepatocellular carcinoma and focal nodular hyperplasia of the liver according to the multislice computed tomography and histological study of tissue is presented. It was established that computed tomography with bolus contrast enhancement allows to study the characteristics of blood supply of the liver and focal formations. Frequently only the use of this method helps to evaluate specific morphological structure of tumors - hepatocellular carcinoma or focal nodular hyperplasia. As an additional differential diagnostic feature is recommended to increase the density determination of tissue formation in the arterial phase computed tomography study. The maximum of vascularization by computed tomography and immunohistochemistry (with antibodies CD34) are installed in a tissue of highly differentiated hepatocellular carcinoma.

Annals of the Russian academy of medical sciences. 2013;68(12):9-15
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РATHOPHYSIOLOGY: CURRENT ISSUES
HYPOXIC PRECONDITIONING OF STEM CELLS AS A NEW APPROACH TO INCREASE THE EFFICACY OF CELL THERAPY FOR MYOCARDIAL INFARCTION
Maslov L.N., Podoksenov Y.K., Portnichenko A.G., Naumova A.V.
Abstract

During the last decade, stem cell research has developed at an accelerated pace. Various types of stem cells have been tested for myocardial infarction therapy. Despite the preclinical benefits of cell therapy success in clinical trials remains modest. The main obstacles to regeneration of the infarcted heart using stem cells are: 1) not every stem cell type can differentiate into cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been shown to improve transplantation efficacy of mesenchymal stem cells and cardiac progenitor cells in animal models of myocardial infarction. It has also been shown that transplantation of preconditioned cells decreases infarct size, prevents postinfarction remodeling of the heart, and positively modulates development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents extensive death of transplanted cells due to necrosis and apoptosis during long-term hypoxia or oxidative stress. The protective effect of HP is based on three main processes: (1) modification of cell phenotypes to help survival during hypoxia (enhancement of HIF-1α expression, ERK1/2 and Akt activation, enhancement of erythropoietin receptor expression and erythropoietin production, and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2) upregulation of various secretable factors including the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2 and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors, which play an important role in mobilization and homing of stem cells in the ischemic region.

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Annals of the Russian academy of medical sciences. 2013;68(12):16-25
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CURRENT CONCEPTS OF PERINATAL ISCHEMIC INJURY IN THE BRAIN NEUROVASCULAR UNIT: MOLECULAR TARGETS FOR NEUROPROTECTION
Morgun A.V., Kuvacheva N.V., Taranushenko T.E., Khilazhieva E.D., Malinovskaya N.A., Gorina Y.V., Pozhilenkova E.A., Frolova O.V., Salmina A.B.
Abstract

Perinatal hypoxic-ischemic brain injury is a relevant medical and social problem. Among many pathological processes in the neonatal period perinatal hypoxic-ischemic injury is a major cause of further hemorrhage, necrotic and atrophic changes in the brain.  This review presents recent data on the basic mechanisms of the hypoxic-ischemic brain injury along the concept of neurovascular unit (neurons, astrocytes, endothelial cells, pericytes) with the focus on alterations in cell-to-cell communication. Pathological changes caused by ischemia-hypoxia are considered within two phases of injury (ischemic phase and reperfusion phase). The review highlights changes in each individual component of the neurovascular unit and their interactions. Molecular targets for pharmacological improvement of intercellular communication within neurovascular unit as a therapeutic strategy in perinatal brain injury are discussed.

 

Annals of the Russian academy of medical sciences. 2013;68(12):26-35
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PEDIATRICS: CURRENT ISSUES
CHANGES OF EPIDERMAL GROWTH FACTOR LEVEL IN BLOOD SERUM, SALIVA AND GASTRIC JUICE IN CHILDREN WITH DUODENAL ULCER
Zhukova E.A., Vidmanova T.A., Viskova I.N., Kolesov S.A., Korkotashvili L.V., Shirokova N.Y., Kan'kova N.Y.
Abstract

92 children, age 8-17 years, with duodenum ulcer were under observation. The peculiarities of EGF level changes in human biological mediums, depending on phase of the disease. The highest EGF level was detected with acute peptic ulcer in the presence of ulcerous defects. EGF level increasing was marked out in the remission phases ulcerous defects healing, and it didn`t reach normal values in gastric juice. EGF content changes in biological mediums were revealed with different variants of duodenum ulcer clinical course in children. The lowest EGF level was marked out in blood, saliva and gastric juice with unfavorable course of the disease (frequent relapses, cicatricial-ulcerous strains formation), which can serve as a prognostic factor.

Annals of the Russian academy of medical sciences. 2013;68(12):36-40
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CORTISOL LEVELS IN CORD BLOOD WITH VARIOUS VIOLATIONS OF NEONATAL ADAPTATION
Kolesnikova N.I., Popova A.S., Sinitskii A.I., Kozochkin D.A., Gornostaeva A.B.
Abstract

Shifting extra uterine existence is a serious test of maturity of all functional systems of the newborn , so in recent years, the more attention is payed for the adaptation of the newborn. It is known that the pathological course of pregnancy is a violation of the functional state of the adrenal cortex, and prolonged exposure of the pathological factor leads to the inhibition of adrenocortical function and a decrease of the adaptive capabilities of a newborn. Therefore, serum cortisol levels could be a predictor of complications in preterm infants. Based on this, it seems appropriate to study changes in the content of serum cortisol cord blood prior to the development of various syndromes neonatal maladjustment. The clinical and laboratory examination of term infants with various disorders of adaptation: regurgitation, pain, hyperexcitability , depression , cardio - respiratory depression, bleeding in the skin , toxic erythema. It is shown that the most prominent violations maladjustment processes occur on the background of decreased cortisol. Border states, which are formed on the background of normal or elevated cortisol, are not accompanied by significant impairments of adaptation processes . On the basis of the data was drawn a conclusion about the possibility of using changes of cortisol in cord blood as a reliable indicator of neonatal adaptation processes, pointing to the possibility of the development of pathological conditions.

 

Annals of the Russian academy of medical sciences. 2013;68(12):41-43
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USE OF MATHEMATICAL MODELS INFRARED SPECTROSCOPY SERUM IN THE DIFFERENTIAL DIAGNOSIS OF ULCERATIVE COLITIS AND CROHN'S DISEASE IN CHILDREN
Fedulova E.N., Gordetsov A.S., Fedorova O.V., Korkotashvili L.V., Tutina O.A.
Abstract

Relevance of research. Inflammatory bowel diseases are among the most severe pathologies in pediatric gastroenterology, often lead to disability. Despite the similarity of the clinic, pathogenetic mechanisms, the question of the differential diagnosis of ulcerative colitis and Crohn's disease is relevant in view of their different prognosis and treatment strategy. In recent years, in medical uses infrared spectroscopy of blood serum for the differential diagnosis of various inflammatory diseases, benign and malignant tumors. Besides finding increasing application of mathematical methods for data processing, the so-called mathematical modeling of pathological processes, allowing objectify the survey results for a more accurate diagnosis and prognosis of pathological processes. Objective: improving the differential diagnosis of ulcerative colitis and Crohn's disease in children. Patients: 21 children with ulcerative colitis, 56 children with Crohn's disease and 34 healthy children. The method of infrared spectroscopy of serum and mathematical modeling results through multivariate entropy analysis. Results: the obtained spectral characteristics of blood serum in children with ulcerative colitis and Crohn's disease and in healthy children, as well as "images of disease" in these pathologies. Conclusion: The use of this medical technology reduced the time of diagnosis, which contributes to the timely choice of rational treatment strategies and provides an opportunity to avoid the development of complications, worsening of the disease.

 

Annals of the Russian academy of medical sciences. 2013;68(12):44-48
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PHARMACEUTICALS: CURRENT ISSUES
TECHNOLOGY TRANSFER TO THE FACILITY FOR PRODUCTION OF MEDICINES
Beregovykh V.V., Spitskii O.R.
Abstract

Innovation development of pharmaceutical industry is close connected to knowledge transfer going to each subsequent life cycle phase of medicinal product. Formal regulation of technology and knowledge transfer is essential for achievement high quality during production of medicines designed during development phase. Conceptual tools, approaches and requirements are considered that are necessary for knowledge and technology transfer across all the life cycle phases of medicines. They are based on scientific knowledge of medicinal products and take into account both international and Russian regulations in the area of development, production and distribution of medicines. Importance of taking into consideration all aspects related to quality of medicines in all steps of technology transfer is shown. An approach is described for technology transfer organization for Russian pharmaceutical manufacturers based on international guides in this area.

 

Annals of the Russian academy of medical sciences. 2013;68(12):49-57
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POTENTIAL SENSITIVITY TO METFORMIN OF THE DIABETICS SUFFERING AND NOT SUFFERING WITH CANCER: A PHARMACOGENETIC STUDY
Berstein L.M., Ievleva A.G., Vasil'ev D.A., Kovalenko I.M., Imyanitov E.N.
Abstract

The group (totally156 postmenopausal women) used for the study of ‘standard’ (S) and ‘associated’ (A) genetic markers of potential sensitivity to metformin (MF) consisted of 37 healthy females, 32 — with diabetes (DM) without cancer, 64 cancer patients with DM, and 23 cancer patients without DM. No significant difference in carrying of S-polymorphisms was found between DM patients without and with cancer. In cancer patients without DM most characteristic data regarding potential MF-response were detected with polymorphisms of STK11 gene while data on OCT1_rs622342 and OCT1_R61C variants showed opposite trends. In regard of A-markers, the tendency to the more often finding of GC genotype of OLR1_G501C in DM patients carrying ‘MF-positive’ variant of OCT1_R61C deserves to be underlined. In patients with new-onset diabetes who carried S-markers of potential response to MF higher insulin resistance (OCT1_R61C and OCT1_rs622342) as well as lower estradiolemia (STK11 and C11orf65) were discovered. Thus, according to genetic S-criteria of sensitivity to MF, DM patients with and without cancer differ in lesser degree than they differ from cancer patients without DM. It can not be excluded, that The efficiency of such criteria might be increased due to combination with A-markers and certain hormonal-metabolic indices.

 

Annals of the Russian academy of medical sciences. 2013;68(12):58-63
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SURGERY: CURRENT ISSUES
TREATMENT OF PATIENTS WITH PURULENT WOUNDS BY USING THE ORIGINAL METHOD OF HYDRODYNAMICAL DRAINAIGE
Kazaryan N.S., Kozlov K.K., Bykov A.Y., Kokorin S.V., Viktorov S.I.
Abstract

In this article the work of the Omsk State Medical Academy’s department of general surgery is presented. The aim of study was tot treat patients with purulent and necrotic wounds of soft tissue by using novel hydrodynamical drainaige. In this research 92 patients were taken part, who were inpatient treatment in the department of purulent surgery City Clinical Hospital № 1 named Kabanov A. N.  2010 – 2013 with purulent and necrotic wounds of soft tissue. Clinical, laboratory, cytological, bacteriological monitoring were conducted over the of wound process during the treatment. Assessment of the reliability of differences between the mean value of clinical indicators was with the calculation of the criterion t – Student, the method x2 and Criterion Mann – Whitney U. The proposed method of treatment of purulent wound promotes fast the removal of necrotic tissue and pus in the first phase of the wound process that led to more rapid relief of symptoms of intoxication (fever, leukocytosis and common symptoms) at the patients of the basic group. Due to faster removal of necrotic tissue, reduction of common symptoms of intoxication at the patients of the basic group the transition from degenerative and inflammatory type of cystograms to regenerative occurred one or two days before than in the comparison group.

 

Annals of the Russian academy of medical sciences. 2013;68(12):64-68
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SHORT MESSAGES
INDIVIDUAL ALPHA FREQUENCY EEG AS NEUROPHYSIOLOGICAL ENDOPHENOTYPE OF AFFECTIVE PREDISPOSITIONS
Aftanas L.I., Tumyalis A.V.
Abstract

Individual alpha frequency (IAF) of electroencephalogram (EEG) is regarded as a neurophysiological endophenotypic indicator of cognitive activity featuring individual propensity to efficient cognitive performance and creativity. Considering that cognitive coping style is intrinsic part of emotional regulation, defining medical aspects of individual health as well as risks of psychosomatic diseases, we intended to assess IAF contribution into mechanisms of individual emotional reactivity. Participants and methods. As participants was healthy man subjects (n=62). Three models of laboratory induced emotions were used: emotional perception (1); anxious apprehension (awaiting of inescapable aversive punishment) (2); experience of discrete emotions of anger and joy (3). Results. It was revealed that high IAF individuals exhibit predisposition to prevalence of parasympathetic activity in the global circuit of autonomous regulation, proactive-like coping with inescapable threat, prevailing contribution of the positive emotional stance and better accessibility of recent positive memories. By contrast, low IAF subjects manifested predisposition to prevalence of sympathetic activity in the global circuit of autonomous regulation, maladaptive avoidance-like coping with inescapable threat, insufficiency positive emotional arousal mechanisms. Conclusions. It is suggested that IAF creates a «hardware» construct featuring individual emotional space and adaptability of coping styles to emotional challenges.

 

Annals of the Russian academy of medical sciences. 2013;68(12):69-79
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Estimation of the Functional Condition of a Fetus of Pregnancy in Chronic Pyelonephritis
Kadimova S.
Abstract

Aim of this study was to investigate the condition of the fetus and feto placental system in chronic pyelonephritis by identifying features in the feto- placental blood flow and middle cerebral artery system. Patients and methods.  We examined 68 pregnant women with chronic pyelonephritis and 50 healthy pregnant women as a control group . The study conducted a qualitative assessment of fetus and placental blood flow and blood flow in the middle cerebral artery of the fetus . The data on the condition of  feto- placental blood flow and blood flow in the middle cerebral artery in the examined pregnant and control group show a higher incidence of elevated systolic and diastolic performance ratio in the umbilical artery in patients with chronic pyelonephritis than somatically healthy women. Results. Studies have shown that the most accurate and informative indicator of violations feto- placental circulation is an increase in the umbilical artery  whose value ( 2.9 and above) reflects the high degree of suffering of the fetus on a background of chronic pyelonephritis. Conclusions. Diagnostically significant is the indicator of the middle cerebral artery blood flow, which reflects the mechanism of enhancement of cerebral circulation in chronic hypoxia due to violation of feto- placental circulation in patients with renal disease.

Key words: placentary insufficiency, nephritic pathology, pregnancy.

Annals of the Russian academy of medical sciences. 2013;68(12):80-82
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GENES OF ANTIOXIDANT ENZYMES
Kolesnikova L.I., Bairova T.A., Pervushina O.A.
Abstract

Oxidative stress plays an important role in the pathogenesis the most of diseases. Important components of protecting cells from oxidative stress are antioxidant enzymes. Antioxidant enzymes are characterized by population differences in enzyme activity. The purpose of the study to summarize and discuss information on genetic polymorphisms of antioxidant enzymes in the most pathology. The development plays of the role of oxidative stress.

 

Annals of the Russian academy of medical sciences. 2013;68(12):83-88
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THE CONCEPT OF INFECTIOUS DISEASES PATHOGENESIS
Uchaikin V.F., Shamsheva O.V.
Abstract

In this article a concept of infectious disease pathogenesis as consisted with clinical symptoms is provided. The course of disease, immediate and long term consequences depend on the mode of entry. If the infection comes via oropharynx, airway, gastrointestinal tract or via skin, the immune system provides adequate immune response. This leads to typical symptoms, cyclical clinic progression and usually to the recovery with the formation of full sterile immunity. In case of parenteral way of infection, which includes perinatal way, there is no full mode of entry, the disease takes chronic course involving visceral organs because of different mechanisms of affinity and new tropic organ involving. For the full sanogenesis germ or its mediators should persist in the primary focus of infection. It is suggested, that HIV, HCV, hepatitis B virus, tetanus, rabies and other infectious diseases with inner organs involvement, as well as all slow infections, should be treated as infectious diseases with the parental way of infection, proceeding with affinity changings, which lead to the appearance of new tropic sites in visceral organs. The theory of the mode of entry, affinity, appearance of tropic sites in visceral organs should form the basis of modern infectology.

Annals of the Russian academy of medical sciences. 2013;68(12):89-92
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