Vol 69, No 9-10 (2014)

РATHOPHYSIOLOGY: CURRENT ISSUES
AUTONOMIC NERVOUS STATUS AND BIOELECTRIC BRAIN ACTIVITY IN ADOLESCENTS-INHABITANTS OF THE POLAR NORTH
Demin D.B., Poskotinova L.V., Krivonogova E.A.
Abstract

Background: Northern European areas are differing in degree of extreme climatic conditions in the Polar and Subpolar latitudes. Formation of the nervous system in adolescents most of all is affected by these adverse climatic factors. Objective: The aim was to study of the autonomic regulation of cardiac activity and brain bioelectric activity in adolescents-inhabitants of the North depending on these autonomic nervous tones. Methods: 300 adolescents (male and female) aged 15–16 years living in the Polar (67°40' N) and Subpolar (64°30' N) northern regions of Russia are examined. Assessment of autonomic nervous tone was determined by the heart rate variability (HRV) and blood pressure parameters. After the initial analysis of these indicators, all subjects in both areas were further divided into groups with vagotonic, normotonic and sympathotonic types. Electroencephalogram (EEG) was recorded in the state of quiet wakefulness with closed eyes (16 standard monopolar leads). EEG characteristic were performed on the values of the amplitude and the index in each frequency band. All described changes were statistically significant at p <0,05–0,001. Results: According HRV and central hemodynamics among adolescents of the Polar North revealed an increase the proportion of individuals with a predominance of sympathetic influences on cardiac activity (37,3%) and significant decrease the proportion of persons with a predominance of vagal influences (10%). A high activity of diencephalic subcortical brain structures in groups of normotonic and sympathotinic persons in the Polar region was revealed, which manifests itself in the form of increased levels of theta and alpha EEG-activity, as well as increased occurrence hypersynchronous EEG-types (50%). In adolescents-inhabitants of the Subpolar region occurs more intensive age optimization of neural processes then in adolescents-inhabitants of the Polar region. Conclusion: The predominance of sympathetic effects on the cardiac activity and higher activity of diencephalic subcortical brain structures in adolescents of the Polar region were revealed.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):5-9
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CALF BLOOD GEMODIALIZAT REDUCES NEUROTOXIC EFFECT OF HYDROGEN PEROXIDE ON HUMAN NEUROBLASTOMA CELLS
Yurinskaya M.M., Vinokurov M.G., Astashkin E.I., Grachev S.V., Orekhova N.S., Novikova A.N., Sokolova I.N.
Abstract

Objective: Our aim was to study the effect of calf blood gemodializat  on apoptosis and intracellular signaling pathways of neuroblastoma cells SK-N-SH human. Methods: Apoptosis was recorded by fluorescent microscopy using Hoechst 33342. Necrosis cells was monitored by propidium iodide. The fluorescence of the cells was recorded on a fluorescence inverted microscope Keyence BZ8100 (Japan). Formation of reactive oxygen species (ROS) in the cells of SK-N-SH was determined using nitroblue tetrazolium by absorbance at 620 nm on a plate reader «Uniplan». Results: When adding hydrogen peroxide to the background of the calf blood gemodializat been decreasing apoptosis of these cells with 43 to 17% relative to apoptosis in the presence of a hydrogen peroxide. Under these conditions, the calf blood gemodializat  significantly reduced ROS formation in human neuroblastoma cells SK-N-SH by the action of hydrogen peroxide. In these cells, we investigated the influence of calf blood gemodializat  on apoptosis and intracellular signaling pathway involving mitogen-activated protein kinase (p38MAPK), extracellular regulatory kinase (ERK), phosphatidylinositol 3-kinase (PI-3K) and-Jun-N-terminal kinase (JNK) using their selective inhibitors. Conclusion: It was shown that the mechanism of the protective effect of calf blood gemodializat   against peroxide-induced apoptosis in SK-N-SH dominant role is played by p38 MAPK and PI-3K.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):10-14
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CARDIOLOGY: CURRENT ISSUES
DIASTOLIC DYSFUNCTION IN HYPERTROPHIC NONOBSTRUCTIVE CARDIOMYOPATHY
Bogdanov D.V.
Abstract

Objective: The purpose of research was to assess the availability and prevalence of types of diastolic dysfunction of the left ventricle (LV) in hypertrophic nonobstructive cardiomyopathy (NHCM). Methods: 97 NHCM patients. Mean age 42,5±14,9 years. Diastolic dysfunction assessed by Doppler echocardiography. Results: Signs of chronic heart failure NYHA class I observed in 44 (45%) patients, class II — in 40 (41%), class III — in 13 (13%) patients. 83% patients had LV diastolic dysfunction, mainly on the hypertrophic type. One third of the patients had pseudonormal type with uncertain interpretation. Diastolic dysfunction in terms of clinical manifestations determined mainly NYHA class III and syncope. Severity of LV diastolic dysfunction in NHCM depended on the severity of hypertrophy not only left, but the right ventricle too. In 94% of cases we observed not only diastolic dysfunction, but also reduction of secondary fibers shortening fraction — as sign of contractile dysfunction. Conclusion: Thus, in NHCM dominated diastolic dysfunction of hypertrophic type. Such dysfunction defining a clinic cardiac deficiency or syncope. One third of the patients had pseudonormal transmitral flow type, difficult to assess diastolic function. Diastolic dysfunction in NHCM was combined with impaired contractility of the walls of ventricle.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):15-20
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DEPRESSION AND CARDIOVASCULAR DISEASES
Nuralieva N.F., Napalkov D.A.
Abstract

Depression is considered to be an independent cardiovascular risk factor and it may worsen the symptoms of already established cardiovascular pathology such as coronary heart disease, chronic heart failure, stroke and hypertension. 3 key psychobiological mechanisms by means of which depression influences cardiovascular system: disbalance in stress response of endocrine system, hyperregulation of autonomic nervous system and immune disorders leading to dysregulation of acute phase proteins and proinflammatory cytokines release. In majority of studies in patients with depression and cardiovascular diseases it was shown that antidepressants improve the symptoms. By the way, in some studies controversial results were obtained. Future studies in this direction with involvement of cardiologists and psychiatrists should be held.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):21-26
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MICROBIOLOGY: CURRENT ISSUES
RECIPROCAL FORMATION OF MUCOSAL MICROFLORA OF OPEN CAVITIES OF DIFFERENT HABITATS IN WOMEN AS AN IMPORTANT FACTOR OF THEIR REPRODUCTIVE HEALTH
Kungurtseva E.A., Popkova S.M., Leshchenko O.Y.
Abstract

This review presents the current data on the human microbiome. In recent increase of erased and primary chronic forms of inflammatory diseases of the female genital organs is observed, in which the clinical manifestations are varied, but the symptoms are not so much related with the changes in the pelvic organs, but with abnormalities in other body systems, secondarily involved in the pathological process. Recent research proved mutual influence of intestinal, vaginal and nasopharyngeal biocenosis. Women with vaginal microbiota disorders often revealed intestinal dysbiosis and chronic diseases of ENT (Ear Nose Throat) organs, which in turn contributes to chronic inflammatory process of pelvic organs, failure of therapeutic interventions, reduced quality of life and increased risk of adverse pregnancy outcomes.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):27-32
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MOLECULAR GENETIC IDENTIFICATION OF STAPHYLOCOCCUS AUREUS STRAIN, CAUSED A FOODBORNE ILLNESS OUTBREAK IN ST. PETERSBURG IN 2013
Onishchenko G.G., Abaev I.V., Dyatlov I.A., Skryabin Y.P., Korobova O.V., Solov'ev P.V., Bogun A.G.
Abstract

Background: Staphylococcus aureus is one of the most important human pathogens and causes over 100 nosological forms of diseases. The lack of data on the spread of S. aureus genetic types specific for different forms of staphylococcal infections in Russia makes it difficult to timely identify and control strains of this epidemiologically dangerous bacterial pathogen. Objective: The aim of the study was to carry out a molecular genetic research of S. aureus isolates obtained during a widespread foodborne illness outbreak among builders at the Pulkovo airport in St. Petersburg in 2013. Methods: The ability of the isolates to produce staphylococcal enterotoxins was studied by immunoenzyme techniques. Gene typing was carried out by sequence-specific primer-based PCR, as well as by sequencing genomic nucleotide sequences of two independent isolates of the pathogen. Results: An enterotoxin A gene in genomes of S. aureus isolates etiologically associated with the outbreak was identified. The production of enterotoxin A by the isolates was shown. According to the complex analysis all isolates producing staphylococcal enterotoxins were identical and constituted the S. aureus strain, sequence-type ST30 and spa-type t2509. The genome of the identified S. aureus strain carried a set of various staphylococcal toxins. The full genome sequence among other techniques revealed high levels of similarity between genomes of the strain under study and well-known reference strain S aureus MRSA 252. Conclusion: The complete molecular genetic study of the S. aureus strain involved into the widespread foodborne illness outbreak was first carried out in Russia, allowing of further using the strain as a Russian reference strain to study potential epidemic outbreaks in the Russian Federation.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):33-38
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ACINETOBACTER: MICROBIOLOGICAL, PATHOGENETIC AND RESISTANT PROPERTIES
Chebotar' I.V., Lazareva A.V., Masalov Y.K., Mikhailovich V.M., Mayanskii N.A.
Abstract

Species of the genus Acinetobacter represent opportunistic bacteria with a growing clinical significance. In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe physiology, taxonomy, ecology, pathogenicity, and antibiotic resistance of these bacteria. Molecular pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial infections are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance as well as identification of Acinetobacter. In addition, treatment and prophylaxis of acinetobacterial infections are discussed.

Annals of the Russian academy of medical sciences. 2014;69(9-10):39-50
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PEDIATRICS: CURRENT ISSUES
FEATURES OF MUCOSAL LESIONS OF STOMACH AND DUODENUM IN CHILDREN WITH CHRONIC GASTRODUODENITIS WITH DIFFERENT MICROFLORA CONTENT
Kan'kova N.Y., Zhukova E.A., Shirokova N.Y., Vidmanova T.A.
Abstract

Objective: Our aim was to reveal the features of histological mucosa with different composition of the microflora of stomach and duodenum in children with chronic gastroduodenitis. Methods: The study included 122 children with chronic gastroduodenitis from 5 to 17 years old. All patients underwent endoscopy with histology of biopsy specimens of gastric and duodenal mucosa in 94 patients and in 48 patients among them with morphometry of biological material. Identification of herpes simplex virus 1, 2 types, cytomegalovirus, human papilloma virus 16, 18 types, Helicobacter pylori was carried out using polymerase chain reaction in biopsies of gastroduodenal mucosa and gastric juice. Results: Children with chronic gastroduodenitis depending on the identified microorganisms were divided into groups: 1st (n =51) — without detectable microorganisms, 2nd (n =28) — with associations of H. pylori and viruses, 3rd (n =15) — only with viruses, 4th (n =28) — with H. pylori. Thus, in patients with H. pylori  inflammation was noted mainly in the antral mucosa and dystrophic changes - in the duodenal mucosa. In the presence of viruses the inflammation was expressed more in the fundal stomach and duodenum. When viral-bacterial associations were observed most pronounced inflammatory-dystrophic process was localized throughout the gastroduodenal mucosa. Conclusion: In children with chronic gastroduodenitis in the presence of bacterial, viral and mixed microflora in the stomach and duodenum identified characteristic histological features of the mucosa, manifested in a different localization and severity of inflammatory and dystrophic changes.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):51-56
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CLINICAL EXPERIENCE OF THE REPEATED MULTILEVEL INJECTIONS OF THE BOTULINUM TOXIN TYPE A (ABOBOTULINUM TOXIN A) IN THE SPASTIC FORMS OF CEREBRAL PALSY
Klochkova O.A., Kurenkov A.L., Karimova K.M., Namazova-Baranova L.S., Mamed"yarov A.M., Kuzenkova L.M., Bursagova B.I.
Abstract

Objective: Our aim was to analyze the dosages of Abobotulinum toxin A used for each muscle in the clinically effective and safe repeated multilevel injections in CP children, and the intervals between injections. Methods: Retrospective analysis of 229 injection sessions into 359 muscles of the upper and 361 muscles of the lower extremities in 133 children (2–18 years) with spastic CP. Analysis included only patients who were injected for the first time and demonstrated decrease of spasticity in injected muscles according to modified Ashworth and/or Tardieu scales without significant side effects 2–4 weeks after injections. Motor deficit according to GMFCS was: GMFCS I — 16 (12%) children, GMFCS II — 26 (19.6%), GMFCS III — 43 (32.3%), GMFCS IV — 30 (22.6%), GMFCS V — 18 (13.5%). Repeated injections (up to 5 sessions) were done in 59 children. Maximum follow-up perion was 22 months. 40 patients (30.1%) had one-sided injections, 93 (69.9%) — two-sided, 125 (94%) — multilevel injections. Results: We presented minimal and maximal dosages, interquartile ranges for each injected muscle, also «off-label» and our proposition of per-segment calculation of dosages in multilevel injections in CP. We also demonstrated the stability of intervals between repeated injections and dosages per kg in a patient. These results are compared with the official Russian and international recommendations of BTX-A treatment for children. Conclusion: We presented our experience of BTX-A dosages calculation for the spastic CP treatment which could be used as a recommendation and guide for the multilevel injections treatment according to the aims of rehabilitation, spasticity level, muscle size and motor deficit of a concrete patient.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):57-63
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CASE OF COMBINATION OF BECKWITH-WIEDEMANN SYNDROME WITH WEST SYNDROME
Kuzenkova L.M., Kremenchugskaya M.R., Globa O.V., Podkletnova T.V.
Abstract

Beckwith–Wiedemann syndrome (BWS) is etiologically connected with genetic / epigenetic growth dysregulation. The supposed localization of this disorder is a short arm of chromosome 11 (11p 15.5). Its prevalence is 1:13 per 700 newborns. West syndrome is an age-dependent epileptic syndrome related to a group of infantile epileptic encephalopathies and characterized by a triad of basic symptoms: series of infantile spasms, psychomotor retardation and severe paroxysmal EEG changes. The incidence of West syndrome is estimated at 1 case per 2,000–4,000 newborns. The article describes a rare clinical case: a combination of BWS with one of the types of infantile epileptic encephalopathies — West syndrome. A detailed analysis of the West syndrome progression in a female patient with BWS is given, the tactics of antiepileptic therapy is analyzed, and its complexity in terms of metabolic disorders caused by the presence of a genetic syndrome in a patient is shown. The results of a long catamnesis are described. The figures are the fragments of native electroencephalograms at the eruptive phase of West syndrome and against the background of a long-term remission. When describing the clinical case in detail, the authors actively discuss the obtained information and available literature data. The article also presents practical guidelines for the early detection of metabolic disorders in patients with infantile epileptic encephalopathies. In addition to anti-epileptic drugs, the authors propose to include a mandatory metabolic correction in the therapy complex for these patients.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):64-69
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ASSESSMENT OF MOTOR AND SENSORY PATHWAYS OF THE BRAIN USING DIFFUSION-TENSOR TRACTOGRAPHY IN CHILDREN WITH CEREBRAL PALSY
Mamed"yarov A.M., Namazova-Baranova L.S., Ermolina Y.V., Anikin A.V., Maslova O.I., Kashkaradze M.Z., Klochkova O.A.
Abstract

Background: Diffusion tensor tractography — a new method of magnetic resonance imaging, that allows to visualize the pathways of the brain and to study their structural-functional state. Objective: The authors investigated the changes in motor and sensory pathways of brain in children with cerebral palsy using routine magnetic resonance imaging and diffusion-tensor tractography. Methods: The main group consisted of 26 patients with various forms of cerebral palsy and the comparison group was 25 people with normal psychomotor development (aged 2 to 6 years) and MR-picture of the brain. Magnetic resonance imaging was performed on the scanner with the induction of a magnetic field of 1.5 Tesla. Coefficients of fractional anisotropy and average diffusion coefficient estimated in regions of the brain containing the motor and sensory pathways: precentral gyrus, posterior limb of the internal capsule, thalamus, posterior thalamic radiation and corpus callosum. Results: Statistically significant differences (p <0.05) values of fractional anisotropy and average diffusion coefficient in patients with cerebral palsy in relation to the comparison group. All investigated regions, the coefficients of fractional anisotropy in children with cerebral palsy were significantly lower, and the average diffusion coefficient, respectively, higher. Conclusion: These changes indicate a lower degree of ordering of the white matter tracts associated with damage and subsequent development of gliosis of varying severity in children with cerebral palsy. It is shown that microstructural damage localized in both motor and sensory tracts that plays a leading role in the development of the clinical picture of cerebral palsy.

Annals of the Russian academy of medical sciences. 2014;69(9-10):70-76
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PECULIARITIES OF FUNCTIONAL HEMISPHERIC ASYMMETRY FORMATION IN CHILDREN AND ADOLESCENTS WITH HYPERTENSION
Polyakov V.M., Kolesnikova L.I., Kolesnikov S.I., Dolgikh V.V., Kosovtseva A.S., Rychkova L.V., Prokhorova Z.V.
Abstract

Objective: Peculiarities and age dynamics of hemispheric asymmetry investigation in children and adolescents with hypertension. Methods: 196 children and adolescents aged 10 to 17 years (15.0±1.4), including 98 patients with arterial hypertension (AH) (15.1±1.5) and 98 healthy children of the control group (14.9±1.3). The number of boys in the comparison group and the main group of patients with AH was 60 (61.2%) and 59 (60.2%), girls 37 (37.8%) and 39 (39.8%), respectively. Results: The majority of children and adolescents with hypertension sensorimotor asymmetry differed by low intensity, indicating a decline in the dominance of the left hemisphere. Accumulation of ambi- and left lateral features traced mainly in motor (53.6%) and auditory (60.2%) system, while asymmetry in the visual analyzer did not differ from the control group. Differences in the degree of hemispheric asymmetry increases in the ontogeny compared to control group. Conclusion: Identification of specificity hemispheric interaction in patients with hypertension (low asymmetry and its weak performance in ontogeny) can be considered not only as a pathological consequence of hypertension, but also as a compensatory mechanism for the redistribution of loads to the right hemisphere in terms of the functional deficit of the left hemisphere. It can be assumed that the rear parts of the brain may play a significant role in the processes of adaptation and compensation of occurring disorders in hypertension.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):77-82
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CONTRIBUTION OF NON-HLA GENES TO JUVENILE IDIOPATHIC ARTHRITIS SUSCEPTIBILITY
Savost'yanov K.V., Alexeeva E.I., Chistiakov D.A.
Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease in children. JIA is a group of disorders that share the clinical manifestation of chronic joint inflammation. The Human Leukocyte Antigen region (HLA) seems to be a major susceptibility locus for JIA that is estimated to account for 17% of familial segregation of the disease. Genome-wide association studies (GWAS), case-control studies and meta-analyses of the post-GWAS era revealed over 20 non-HLA loci conferring susceptibility to JIA. At least a half of those are shared between JIA and rheumatoid arthritis, an adult rheumatic disease, thereby suggesting for similarity of pathogenic mechanisms of both diseases. New findings also suggest for a likely role of epigenetic alterations in the pathogenesis of JIA that should be investigated in the future.

Annals of the Russian academy of medical sciences. 2014;69(9-10):83-94
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SHORT MESSAGES
THE MORPHOFUNCTIONAL CONDITION OF STRUCTURES OF THE HIP IN EXPERIMENTAL TREATMENT OF ITS DYSPLASIA
Kirsanova A.Y.
Abstract

Objective: Our aim was to determine the dynamics of reparative tissue changes in the surgical treatment of hip dysplasia it using autograft in conditions of use external fixation. Methods: The experiment was performed on 12 mongrel dogs of both sexes between the ages of 7 to 15 months. Preliminary data of the animals (before the closure of the growth zones of the acetabulum) was performed surgery to obtain acetabular dysplasia. After the formation of the standard pattern of dysplastic 2 degree (subluxation) was performed according to the animal treatment, which combined the use of a semicircular incomplete osteotomy in the supra-acetabular area, an autologous bone graft and the Ilizarov external fixation. The conditions of external fixation provided autograft stability, simultaneous unloading of the articular surfaces and allowed for dosed joint motion during the treatment by releasing the hinge units thus contributing to the prevention of cartilage degeneration. The external apparatuses were dismounted on day 21 after the operation. The animals for histological study were euthanized on day 14, 21, 51 and 111 after the operation. We used clinical and experimental, radiographic and histological methods. Results: It is found that after 90 days after the frame removal there is a complete replacement of the newly formed bone graft. This maintains a full cartilaginous acetabular coverage presented hyaline cartilage, which revealed minor structural and functional changes in reactive and reparative nature. Conclusion: The hip joint has a high adaptive potential. There is a strong trend towards the restoration of hip joint in new conditions created by an external fixation device. Nevertheless, given the suppression of its own regenerative capabilities of the articular cartilage at the dysplastic process, its maximum possible recovery in the treatment is impossible without the participation of external stimulants chondrogenesis.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):95-101
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HORMONAL CHANGES IN RESPONSE TO EXTREME ENVIRONMENT FACTORS
Kubasov R.V.
Abstract

In this paper presented current state about hormonal changes in sympathetic-adrenal, hypophysis-adrenal, hypophysis-gonads and thyroid levels from extreme environment factors. It’s shown that hypophysis gonads and thyroid endocrine links along with sympathetic adrenal, hypophysis adrenal axes are very important relevance in response to extreme environment factors and organism adaptation. In this time a hormonal secretion changes corresponds as interrelated reactions cascade in mechanisms of homeostasis maintenance. A studying of this mechanisms and revealing of its role in stress pathogenesis is fundamental biomedical investigation task. A problem solving allow to perfect prophylactic and treatment methods against stress diseases.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):102-109
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MECHANISMS OF IMMUNE AND CYTOKINE REGULATION IN PATHOGENESIS OF IXODES TICK-BORNE BORRELIOSIS
Minoranskaya N.S., Sarap P.V., Minoranskaya E.I.
Abstract

Background: Our aim was to identify the mechanisms of immune and cytokine regulation in different clinical forms of Ixodes tick-borne borreliosis. Methods: The clinical observations performed on 581 patients with erythemic (113 patients), non-eritemic (242 patients) forms of Ixodes tick-borne borreliosis and Borrelia co-infection tick-borne encephalitis (226 patients) in the manifestation of the disease. The examination included the determination of the levels of cytokines (interleukin 1β, 4, 8, and tumor necrosis factor α), indicators of cell immunity (CD3+, CD4+, CD8+) and phagocytosis (phagocytic index, the number of phagocytic neutrophils) during the height of the disease and during convalescence. Results: We established the correlations of cytokine production, lymphocyte subpopulations and phagocytosis. Revealed divergent immune-mediated mechanisms of pathogenesis, depending on the clinical forms of Ixodes tick-borne borreliosis and period of the disease, indicating the complexity and diversity of the immune system rearrangements. Cytokine regulation of immune response, mainly consists in the synthesis of the chemoattractant interleukin 8 production which is inversely correlated with the number of phagocytic neutrophils (r = -0,440, p <0,001) with erythemic form of the disease, is directly correlated with the level of interleukin 4 (r =0,313, p <0,001) at non-eritemic form borreliosis, with the production of interleukin 1β (r =0,367, p <0,001) and interleukin 4 (r =0,348, p <0,001) in Borrelia co-infection tick-borne encephalitis. Conclusion:In the manifestation of acute Borrelia infection, regardless of the clinical form was typical Th1/Th2 type of immune response and then switches to the period of convalescence for Th1 (cellular) immune response in the form of erythemic Ixodes tick-borne borreliosis and Borrelia co-encephalitic tick-borne infection, and Th2 (humoral) immune response when non-eritemic form of the disease.

Annals of the Russian academy of medical sciences. 2014;69(9-10):110-116
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APPLICATION OF RISK-BASED APPROACH FOR DETERMINATION OF CRITICAL FACTORS IN TECHNOLOGY TRANSFER OF PRODUCTION OF MEDICINAL PRODUCTS
Beregovykh V.V., Spitskii O.R.
Abstract

Risk-based approach is used for examination of impact of different factors on quality of medicinal products in technology transfer. A general diagram is offered for risk analysis execution in technology transfer from pharmaceutical development to production. When transferring technology to full-scale commercial production it is necessary to investigate and simulate production process application beforehand in new real conditions. The manufacturing process is the core factor for risk analysis having the most impact on quality attributes of a medicinal product. Further important factors are linked to materials and products to be handled and manufacturing environmental conditions such as premises, equipment and personnel. Usage of risk-based approach in designing of multipurpose production facility of medicinal products is shown where quantitative risk analysis tool RAMM (Risk Analysis and Mitigation Matrix) was applied.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):117-122
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COMPARATIVE STUDY OF THE EFFECTS OF NEW NEUROACTIVE AMINO ACID DERIVATIVES ON THE POSTNATAL DEVELOPMENT OF THE RAT'S OFFSPRING WITH EXPERIMENTAL PREECLAMPSIA
Turenkov I.N., Perfilova V.N., Mikhailova L.I., Zhakupova G.A., Lebedeva S.A.
Abstract

Background: Our aim was to investigate the effect of derivatives of GABA and glutamate on the postnatal development of the offspring of rats with experimental preeclampsia. Methods: The experiments were performed on 35 albino female rats aged 57 months, weighing 220240 g, and their offspring in the amount of 284 individuals. Experimental preeclampsia was modeled by replacing the drinking water by 1.8% NaCl solution to pregnant females from 7 to 21 days of gestation. Glutamic acid — compound RSPU-135 at a dose of 26 mg/kg, GABA derivative — compound RSPU-242 at a dose of 23 mg/kg and the reference drug sulodexide in a dose of 30 mg/kg administered to female orally daily, since the 7th day of gestation prior to delivery. Evaluated the physical development of offspring, sensory-motor reflexes, mental functions. Results: It was found that the experimental preeclampsia causes a delay in physical development and maturation of sensory-motor reflexes in the offspring, as indicated by the later periods of eruption of the incisors and eye opening, response to the emergence of audio and olfactory stimuli, forming vestibular stability and coordination of movements compared to pups from females with physiological pregnancy. Offspring from females with experimental preeclampsia were noted for lagging behind in mental development, as evidenced by the decline of the orienting-exploratory activity, learning and memory, increase of anxiety level. Compound RSPU-135, to a greater extent, improves physical development, increases the rate of maturation of sensory-motor reflexes, RSPU-242 — stimulation of cognitive functions, keeping the memory trace, orienting-exploratory, spontaneous locomotor activity, and reduce of anxiety level. Conclusion: The neuroactive amino acid derivatives limit the negative effects of experimental preeclampsia on the offspring.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):123-130
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MONOCLONAL ANTIBODIES IN HIGH-GRADE GLIOMAS
Chekhonin I.V., Leopol'd A.V., Gurina O.I., Semenova A.V.
Abstract

The review is devoted to a relatively young direction in therapy of malignant gliomas, which is based on applying monoclonal antibodies against tumour-associated antigens. The current data on efficacy of main therapeutic agents in clinical practice or clinical trials concerning high-grade gliomas, especially glioblastoma multiforme, is summarized. Of particular interest is bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (anti-VEGF), which is widely used in glioblastoma. Major clinical trials devoted to bevacizumab monotherapy and combinations of bevacizumab with other therapeutic modalities in primary and recurrent glioblastoma conducted since 2006 till now are reviewed. The results of experimental and clinical application of monoclonal antibodies against epidermal growth factor receptor (EGFR) and its mutant variant EGFRvIII are analyzed, showing the most significant clinical effectiveness of nimotuzumab — a humanized monoclonal antibody. Significant part of the review is devoted to discussion of experimental and clinical data concerning efficacy of antibodies against VEGF receptor 2, platelet-derived growth factor receptor α, hepatocyte growth factor and its receptor c-Met. Unbiassed analysis of clinical trials on monoclonal antibodies does not allow us to conclude that passive immunotherapy directed against antigens listed above can significantly improve the overall survival of patients suffering from glioblastoma multiforme. This finding has encouraged us to mention several alternative approaches to passive immunotherapy and to list several prospective antigens for developing monoclonal antibodies.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):131-139
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MINIMIZATION OF APPROACHES IN LAPAROSCOPIC CHOLECYSTECTOMY
Yusif-zade K.R.
Abstract

Objective: the aim of the study was to estimate the influence of a number of endoscopic approaches on the effectiveness of laparoscopic cholecystectomy. Methods: retrospective analysis of case histories of 118 patients was applied for the purpose of comparative evaluation of the results of surgical treatment using a three- and four-port laparoscopic approach. Patients were divided into two groups: patients operated using three-port laparoscopic approach (n=60 patients) and patients operated using four-port approach (n=58 patients). One of the important stages of studies was histomorphological characterization of the removed gallbladder, which was performed in all 118 patients who underwent minimally invasive operations. Conventional visual analogue scale of pain (VAS) was used for the subjective assessment of pain syndrome manifestations. Results: 60 patients underwent three-port laparoscopic cholecystectomy (LC) (main group) and 58 patients underwent four-port LC (control group). In the main group, 53 (88.3%) patients showed the absence of any pain, only 3 of them reported mild pain, and 4 – moderate pain, respectively, on the 7th day after surgical intervention. In the control group, these parameters were 50 (86.2%), 2 and 6 subjects, respectively. Terms of hospitalization and disability were relatively lower at the minimal number of ports: 3.2 and 4.4 days, respectively. Disability duration in the main group was 8.5 days versus 10.6 days in the control group. Conclusion: three-port laparoscopic approach technique allows significantly reducing the rate of pain syndrome clinical manifestations, achieving maximal cosmetic effect, and considerably shortening postoperative rehabilitation period, thus resulting in earlier activation of patients and restoration of their working capacity.

 

Annals of the Russian academy of medical sciences. 2014;69(9-10):140-144
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