Vol 71, No 1 (2016)

INFECTIOUS DISEASES: CURRENT ISSUES

Assessment of Protective Properties of the Recombinant Complex of the Outer Membrane Protein F and the Toxoid of Pseudomonas aeruginosa

Kaloshin A.A., Leonova E.I., Soldatenkova A.V., Mikhaylova N.A.

Abstract

Pseudomonas aeruginosa induces the complications after burns, injuries, surgical interventions and appears to be one of the main causative agents of nosocomial infections. This pathogen has the high resistance to the antibacterial preparations, therefore the immunoprophylaxis is considered as one of the major approaches to reduce Pseudomonas infection. Objective: The aim of our investigation is to study the protective properties of the recombinant complex of the outer membrane protein F (OprF) and a non-toxic variant of the exotoxin A (toxoid) against Pseudomonas infection. Methods: The recombinant proteins which contained the additional histidine residues were synthesized into Escherichia coli with isopropyl-βD-thyogalactopyranoside (IPTG). The recombinant proteins were purified by affinity chromatography on Ni-Sepharose. The preparations of recombinant proteins were injected intraperitoneally into the mice. Aluminum hydroxide was used as an adjuvant. For an experimental infection in mice, animals were challenged intraperitoneally by a live virulent culture of P. aeruginosa (PA-103 strain). Results: The best protective effect for the complex containing 25 μg OprF and 50 μg toxoid was identified when we used the double immunization of mice (Index of efficiency of the protective properties in this case was 4.0). Indexes of efficiency of separated recombinant proteins which were injected twice in the same doses were 2.0 for OprF и 2.3 for toxoid. The triple immunization of animals was inefficient for separated recombinant proteins in the same doses. The injection of doses which were lowered twice (12.5 μg for OprF and 25 μg for toxoid) resulted in increased survival of mice immunized by individual proteins (indexes of efficiency: 3 for OprF and и 3,5 for toxoid). However when we administered to the complex of proteins with the same doses Index of efficiency was 2.8. Conclusion: It was shown that the maximum protective effect in a short time is achieved by the combination of double immunization and the mixture of the recombinant proteins OprF and the 25 and 50 μg doses of recombinant toxoid . 

Annals of the Russian academy of medical sciences. 2016;71(1):5-10
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Lipid Peroxidation State in Women of Reproductive Age with Acute Form of Viral Hepatitis

Kolesnikova L.I., Darenskaya M.A., Rashidova M.A., Sholokhov L.F., Grebenkina L.A., Vanteeva O.A.

Abstract

Objective: The objective of this study was to identify features of the lipid status and lipid peroxidation-antioxidant defense system in women of reproductive age with acute form of hepatitis. Methods: The study involved 36 women with acute viral hepatitis and 28 healthy women of the same age. Spectrophotometric and fluorometric methods were used. Results: In patients with acute viral hepatitis we detected an increase in triglycerides levels by 21% and very low density lipoprotein values — by 17% in relative to control group, high-density lipoprotein cholesterol content reduced by 38%. In group with acute viral hepatitis the TBA-reactive products level increased by 2.21 times and superoxide dismutase activity decreased by 1.43 times in comparison with control group. Conclusion: The acute form of hepatitis is characterized by series of metabolic disorders that require a more careful approach in therapeutic and diagnostic administration. 

Annals of the Russian academy of medical sciences. 2016;71(1):11-15
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CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUES

Possibilities of Pharmacological Preconditioning

Levchenkova O.S., Novikov V.E.

Abstract

The review is devoted to the experimental and clinical data analysis about the effectiveness of preconditioning as a method of organism’s tolerance development to ischemia/hypoxia. Characteristics of the trigger, signaling and effector stages of the preconditioning mechanism are described. Medicinal agents which can stimulate processes of endogenous metabolic adaptation are discussed. As is shown in the review the role of inducers of preconditioning can play drugs from different pharmacological groups: adenosine receptor agonists, some agents for inhalation anesthesia, potassium channel activators, opioid analgesics, antagonists of excitatory amino acids, inducers of transcription factors, drugs of erythropoietin, inhibitors of the mitochondrial pore, bioflavonoids, drugs with antihypoxic action. Examples of successful preconditioning with help of pharmacological agents are presented. The prospects of pharmacological preconditioning usage in cerebral ischemia and myocardial infarction are discussed in the article.

Annals of the Russian academy of medical sciences. 2016;71(1):16-24
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Postconditioning the Heart: Analysis of Experimental and Clinical Data

Maslov L.N., Tsibul'nikov S.Y., Mukhomedzyanov A.V., Semenotsov A.S., Tsepokina A.V., Khutornaya M.V., Kutikhin A.G., Nam I.F.

Abstract

Experimental atherosclerosis and hypercholesterolemia may reduce or eliminate the infarct-limiting and anti-apoptotic effect of postconditioning (PC). Experiments in rats and mice indicate that the PC may be quite effective in patients with diabetes type 2 or metabolic syndrome. Experimental data suggest that hypertension or the past myocardial infarction is not an obstacle for the implementation of cardioprotective effect of PC. It was established that that aging does not preclude the implementation of PC cardioprotective effect. Inotropic effect of IP can simulate on isolated human atrial trabeculae. The clinical observations suggest that the PC in patients with tetralogy of Fallot and patients with operations on the valves improves the outcome of cardiac surgery. It was established that PC in these patients reduces the intensity of reperfusion necrosis of cardiomyocytes, improves the pumping function of the heart, reduces the inotropic support, shorten the extubation time.

Annals of the Russian academy of medical sciences. 2016;71(1):25-30
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The Choice of the Treatment Method for Cerebral Aneurysms of Different Locations in the Era of Advanced Endovascular Technologies: A Meta-Analysis

Byval’tsev V.A., Belykh E.G., Stepanov I.A.

Abstract

Relevance: Until recently, microsurgical clipping was the main method to eliminate cerebral aneurysms (CA) from the circulation. The rate of endovascular versus microsurgical treatment for CA of different locations in the era of rapidly emerging endovascular medicine is unknown. Aim: To study the frequency of microsurgical or endovascular techniques for the treatment of CA of different locations. Methods: Methods of treatment and localization of CA were studied in meta-analysis of clinical series published from 2003 to 2014. Case-control studies, studies with externally balanced number of patients in the groups, and the series in which a large number of patients were treated out the study were excluded. Results: 1 international, 2 American, 2 Japanese and 3 Russian clinical series (n=5254 CA) were included in the meta-analysis. The pooled rate of microsurgical treatment used for the CA of the internal carotid artery was 65% (95% CI 55−75), the anterior cerebral artery 65% (95% CI 46−84), the middle cerebral artery 90% (95% CI 82−98), and vertebrobasilar basin 39% (95% CI 41−64). Conclusions: In clinical series both methods of CA treatment were available but endovascular closure was used for the majority of vertebrobasilar basin aneurysms, and for more than a third of anterior cerebral artery or internal carotid artery aneurysms. Middle cerebral artery aneurysms, as opposed to CA of other locations, were subjected to microsurgical treatment in the most cases (90%). In some cases CA are not suitable for endovascular closure, or require microvascular reconstructive operations. In competition with less invasive but more expensive option of endovascular treatment, and under the conditions of decreasing volume and experience of open CA surgery, microsurgical techniques should be mastered to a high level which requires centralization of the patients in the specialized centers and microneurosurgical training. 

Annals of the Russian academy of medical sciences. 2016;71(1):31-40
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NEUROLOGY AND NEUROSURGERY: CURRENT ISSUES

The Predictability of Motor and Cognitive Impairment According to Brain Asymmetry of Cognitive Evoked Potentials P300 and Features of Symptom Complex in Patients with Parkinson’s Disease

Poskotinova L.V., Krivonogova E.V., Khasanova N.M., Krasnikova M.N.

Abstract

Link the degree of progression of motor and cognitive impairment in Parkinson’s disease and parameters of cognitive evoked potentials brain activity recognized not always unambiguous. This is due to the wide range of differences in amplitude and latency time of evoked potentials in the different leads of electroencephalogram caused functional reorganization of neuronal activity in brain structures in the early stages of the disease. Objective. The aim is to determine the correlation of the cognitive auditory evoked potentials P300 characteristics and symptom features in patients with Parkinson’s disease. Methods. The study involved 60 people, right-handers: 34 people (24 women and 10 men) with a verified diagnosis of Parkinson’s disease and the control group — 26 people (20 women and 6 men). The disease duration, severity of symptoms (Unified Parkinson’s Disease Rating Scale), and stage of the disease (Hoehn, Yahr) were determined, the 15-item Geriatric Depression Scale was used to indicate the depression symptoms. Assessment of the electroencephalogram and auditory evoked potentials P300 was performed by an electroencephalograph «Encephalan» (Medicom, Taganrog, Russia). The minimum amplitude and the maximum latency of P300 in electroencephalogram-leads (F3, F4, C3, C4, P3, P4, F7, F8, T3, T4, T5 and T6) on the right and left sides were determined. Results. A significant positive correlation between the amplitude of evoked potential P300 on the left and duration of Parkinson’s disease was revealed, moreover the severity of disease symptoms such as left-side resting tremors of the hand, left-side muscle tension of the hand and/or foot, rising from a chair without using their hands, posture disorder were established. Conclusion. Marked brain asymmetry in the form of increase of the P300 amplitude on the left side combined with a significant reduction in the P300 amplitude on the right side in contra lateral electroencephalogram-lead indicates unfavorable prognosis in relation to cognitive dysfunction and motor disorders identified with left-sided Parkinson’s disease onset.

Annals of the Russian academy of medical sciences. 2016;71(1):41-45
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РATHOPHYSIOLOGY: CURRENT ISSUES

Disorders of Protein Conformation as a Typical Component of Various Human Disease Pathogenesis

Sakharov V.N., Litvitskiy P.F.

Abstract

The review is aimed to analyze the data of the recent studies and to describe all the disorders of protein conformation as a typical pathogenic process of protein structure and metabolism involved in various human disease pathogenesis. The existing group of the disorders of protein metabolism doesn’t clearly reflect the involvement of misfolding in the pathogenesis of many human diseases (as a significant factor) and the term disproteinosis is being broadly used only in the context of some «typical» protein misfolding diseases or conformational diseases (for example, amyloidosis and sickle cell anemia). However, protein conformational stability disorders are well-described as physico-chemical processes; there are diseases, in which the manifestations of protein disorders reach their maximum. The revealing of universal form of conformational stability pathology may eliminate the gaps in the understanding of many human diseases, including some diseases with high social significance. 

Annals of the Russian academy of medical sciences. 2016;71(1):46-51
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PEDIATRICS: CURRENT ISSUES

Sex Differences of Spectral Characteristics of Baseline EEG in Primary School-Aged Children

Gribanov A.V., Dzhos Y.S.

Abstract

The formation of brain bioelectrical activity occurs differently in girls and boys. The results of primary investigations show gender differences of functional brain organization in adolescents and adults. However, there is an opinion on the lack of gender distinctions in children before puberty. Objective: to define features of brain bioelectrical activity in primary school-aged children depending on a gender. Methods: on the basis of parental consent 200 7−9 aged right-handed schoolchildren took part in research (2012−2014). All children were divided into groups depending on biological age and gender. The monopolar electroencephalogram was registered according to 16 standard leads. Changes of the maximal amplitude, full power, the dominant frequency and the index of the main rhythms power of the electroencephalogram were assessed. Results: Prevalence of slow wave delta and theta activity in boys of 7 and 10 years, and also activities of theta range in 9-aged girls were revealed. The increase of the dominant alpha range frequency in 7-aged girls in occipital (p≤0,016) and temporal (p≤0,045) brain regions, and rising of full power of this rhythm in 8 aged girls in the left hemisphere (p≤0,023) while in 9-year aged girls in the right hemisphere (p≤0,040) were proved. At the age of 10 years full power of alpha range has the largest values in boys (p≤0,038). Among high-frequency components the predominance of the index beta-ranges in girls of 7 and 10 years were revealed. The increase in amplitude fluctuations in beta1-range mainly in the sensorimotor brain areas was typical for 7 aged boys. Conclusion: The revealed gender distinctions of the electroencephalogram testify to a larger maturity of the central nervous system in girls comparing with boys. It is shown that the age of 9 years is the active period of the cerebral cortex frontal lobes formation in girls.

 

Annals of the Russian academy of medical sciences. 2016;71(1):52-60
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Jeune Syndrome: Case Series Report

Ovsyannikov D.Y., Stepanova E.V., Belyashova M.A., Degtyareva E.A.

Abstract

Jeune syndrome (synonym: asphyxiating thoracic dystrophy) is a rare genetically heterogeneous autosomal recessive disease, characterized by the development of generalized osteochondrodysplasia, anomalies of skeletal system with multi-organ involvement. This syndrome is based on mutations of the IFT80, DYNC2H1, WDR19, TTC21B genes localized in the locus of chromosomes 3q25.33, 11q22.3, 4p14, 2q24.3 respectively and mutation in the locus of chromosome 15q13 too. These genes play an important role in functioning of cilia in the mammalian body. These organelles participate in the development of the skeletal and hepatobiliary system, nephrons, retina, and other structures of the body. Thurs Jeune syndrome belongs to the ciliopathies. The article presents modern literature findings on genetics, pathogenesis, its clinical, X-ray presentations and CT patterns, diagnosis and treatment of this rare disease. The article also presents the first Russian case series including 7 patients with this disease. Combinations of such symptoms as narrow bell-shaped thorax, variable limb shortness, respiratory failure, including oxygen dependence, recurrent respiratory infections, and motor development delay in observed patients helped to diagnose Jeune syndrome in all cases. 

Annals of the Russian academy of medical sciences. 2016;71(1):61-67
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Age-specific Epidemiology of the Antibody Response Prevalence in Children with Food Allergy

Snovskaya M.A., Namazova-Baranova L.S., Semikina E.L., Makarova S.G., Kozhevnikova O.V., Batyrova A.S., Marushina A.A.

Abstract

Food allergy (FA) is an important health problem which determines lower life quality of a patient and his family. Egg proteins, milk, soy, wheat, and nuts provoke FA more often but any food product may potentially cause allergic reactions. So the aim was to study the age-specific dynamics of antibody response and select the most meaningful IgE production triggers in children with PA. Materials and Methods. The study included 682 children with FA divided into groups according to age: 2−5 months, 6−18 months, 1.5−4 years, 4−10 years, older than 10 years. The IgE levels to cereals, vegetables, bananas, meat, and poultry allergens were measured in blood samples. Results. The age dynamic of IgE-positive responses was detected. The frequency of positive responses was higher in older children. The most significant IgE production triggers for 2−5 months children were allergens of potatoes, pork and cereals (8−14%); for 6−18 month children potatoes (22.7%), buckwheat (19,3%), cereals (10−15%); for 1.5−4 years children bananas (29.5%), cereals, carrots and potatoes (19,5−24%); for 4−10 years children bananas, carrots and cereals (20−28%); for the senior children carrots (47.5%), bananas, cereals and tomatoes (30−36%). Chicken-specific IgE-positive response was minimal for all ages, and meat or poultry specific IgE were observed in 8−15% of patients. Conclusion. Different groups of food allergens provoke sensitization in children during their life. The range of food products with low allergenic activity remains constant in various ages. Age characteristics of IgE production requires differentiated diagnosis approach. 

Annals of the Russian academy of medical sciences. 2016;71(1):68-76
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STATE OF MEDICAL SCIENCES

Fundamental Sciences and Fundamental Medicine

Zueva M.V.

Abstract

An analytic paper discusses current understanding of the status and the role of fundamental and applied research and specifically of medical science for the socio-economic development of society. The related concept of scientific development is presented; classification and definitions used by UNESCO and other international and national organizations of different countries including the Russian Federation are given. The unique role of medicine science that is mostly related to the category of strategic basic research and is aimed at understanding the fundamental basis of applied ultimate goal is debated. Research is now recognized as a major component of innovation and the key to the development of modern society. Attention is drawn to the fact that future breakthrough technologies grow from today’s innovative ideas and achievements of fundamental and applied sciences. The fact that the funding of applied research provides tangible benefits in the short term is determined to be significant. At the same time sustainable public investment in basic research (seemed to be unprofitable) is a crucial factor for the socio-economic development of any country and a reasonable measure in the long term.

Annals of the Russian academy of medical sciences. 2016;71(1):77-83
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