Vol 72, No 4 (2017)

MOLECULAR MEDICINE AND GENETICS: CURRENT ISSUES

GENETIC APPROACHES TO DIFFERENTIAL DIAGNOSIS OF HEREDITARY FORMS OF CONGENITAL ANIRIDIA

Vasilyeva T.A., Voskresenskaya A.A., Khlebnikova O.V., Pozdeyeva N.A., Marakhonov A.V., Zinchenko R.A.

Abstract

Congenital aniridia (AN) is a hereditary autosomal dominant developmental disorder of the eye. Heterozygous mutations in the PAX6 gene and chromosomal rearrangements involving the 11p13 locus lie behind the pathogenesis of the AN. The key role of the PAX6 gene in the regulation of embryogenesis and the pleiotropic effect of this transcription factor explain the damage of several tissues of the anterior and posterior segments of the eye, brain structures, and the disturbance of morphogenesis and endocrine function of the pancreas observed in AN. Recently AN has been considered a syndromic pathology by several researchers. The review suggests classification and summarizes information on the clinical characteristics and genetic basis of various forms of AN. The problem of discrimination of clinical-genetic variants of the dysgenesis of the anterior segment of the eye and the differential diagnosis of PAX6-associated AN with WAGR syndrome, anterior dysgenesis, other rare monogenic and chromosomal syndromes is discussed, and the role of molecular diagnostics is emphasized.

Annals of the Russian academy of medical sciences. 2017;72(4):233-241
pages 233-241 views

THE NEW GENOME VARIANTS IN RUSSIAN CHILDREN WITH GENETICALLY DETERMINED CARDIOMYOPATHIES REVEALED WITH MASSIVE PARALLEL SEQUENCING

Savostyanov K.V., Namazova-Baranova L.S., Basargina E.N., Vashakmadze N.D., Zhurkova N.V., Pushkov A.A., Zhanin I.S., Sdvigova N.А., Lukanina V.Y., Nikitin A.

Abstract

Background: Cardiomyopathies in children are serious, continuously progressing myocardium diseases which are characterized by a variety of the causes, symptoms, implications, and high lethality. More than 400 genes that can cause hereditary heart and vessels diseases are described in scientific literature. The application of a high-performance method of massive parallel sequencing allows to conduct the investigation of genome extended targeted areas revealing the variants and analyzing them (bioinformatics) for pathogenicity.

Aims: Identification of a genetic etiology of hereditary cardiomyopathies development in children’s population of the Russian Federation.

Materials and methods: The research included 103 patients with various phenotypes of cardiomyopathies aged from 3 months up to 17 years 9 months who at the moment of examination were observed in the cardiology department and the department of recovery treatment with cardiovascular diseases in the NMRCCH. All patients were performed massive parallel sequencing analyzing the targeted areas of 404 genes which mutations lead to the development of heart and vessels hereditary diseases.

Results: The diagnostic algorithm based on the method of a massive parallel sequencing was developed. 176 258 minor options were identified in the explored target areas of genome of 103 patients. An average number of the revealed nucleotide replacements different from the reference sequence was 1711. We observed that about 40% of all variants founded by our means were found in MYH7, MYBPC3, TTN, MYH6, SCN5A, DSC2 and TPM1 genes. Bioinformatics analysis allowed revealing 68 novel genome variants associated with cardiomyopathy development. The reliable association of carriage of pathogenic option in MYBPC3 gene with development of hypertrophic cardiomyopathy in the Russian children was found.

Conclusions: The application of the offered algorithm allowed establishing laboratory diagnoses to 99 (96.1%) patients out from 103 investigated subjects including the syndromal and non-syndromal forms of heart and vessels hereditary diseases which showed a cardiomyopathy phenotype.

Annals of the Russian academy of medical sciences. 2017;72(4):242-253
pages 242-253 views

CELL TRANSPLANTOLOGY AND TISSUE ENGINEERING: CURRENT ISSUES

ACELLULAR TRACHEAL CARTILAGINOUS SCAFFOLD PRODUCING FOR TISSUE-ENGINEERED CONSTRUCTS

Baranovsky D.S., Demchenko A.G., Oganesyan R.V., Lebedev G.V., Berseneva D.A., Balyasin M.V., Parshin V.D., Lyundup A.V.

Abstract

Background: Tissue-engineered trachea transplantation remains the last chance for a variety of patients suffering from severe cicatricial tracheal stenosis. Despite the series of carried studies, the final solution hasn’t been found. Creating a functionally complete hyaline cartilage graft in vitro still presents a fundamental problem, and a number of researchers consider it as the key to a successful tracheal tissue-engineering.

Aims: The study aimed to investigate the capability of detergent complex and DNAse I for human tracheal cartilage decellularization in short-time exposition for acellular scaffold obtaining.

Materials and methods: Isolated from cadaveric trachea human native cartilage was used for decellularization by ensimatic-detergent complex including Triton X-100, DMSO, and DNAse I. The scaffold was characterised by histological examinations, analysis of the residual DNA content, and cell metabolic activity colorimetric test with culture in the scaffold fragments.

Results: The obtained scaffolds presented highly porous structure mostly composed of collagen and glycosaminoglycans with an insignificant residual DNA level, absence of citotoxicity, and capability for cell proliferative activity stimulation.

Conclusions: Thus, the study provides a new short-time technology for hyaline cartilage decellularization in order to achieve acellular scaffolds in step with the tissue engineering requirements.

Annals of the Russian academy of medical sciences. 2017;72(4):254-260
pages 254-260 views

ONCOLOGY: CURRENT ISSUES

GLUTATHIONE AND GLUTAREDOXIN IN ROSCOVITINE-MEDIATED INHIBITION OF BREAST CANCER CELL PROLIFERATION

Shakhristova E.V., Stepovaya E.A., Nosareva O.L., Rudikov E.V., Novitsky V.V.

Abstract

Background: Breast tumors are number one cause of cancer morbidity and mortality among women around the world, and Russia is not an exception. Many proteins that control proliferation of immortalized cells are redox-regulated, which is essential for modulating cellular proliferative activity, especially during tumor growth. Studying the role of glutaredoxin and glutathione in cell cycle phase distribution will allow not only to identify the molecular targets regulating cell proliferation, but also to develop methods of diagnosis and targeted therapy of socially sensitive diseases, including breast cancer, in the future.

Aims: To evaluate the role of glutathione and glutaredoxin in the molecular mechanisms regulating MCF-7 breast cancer cell proliferation under the effects of roscovitine, a cyclin-dependent protein kinase inhibitor.

Materials and methods: The MCF-7 cell line (human breast adenocarcinoma) was used in the study. The cell culture was incubated in the presence and absence of roscovitine in the final concentration of 20 µmol for 18 h. The production of reactive oxygen species, the distribution of cells between cell cycle phases and the amount of Annexin V positive cells were determined using flow cytometry. The concentrations of total, reduced and oxidized glutathione, protein SH groups and protein-bound glutathione were measured by spectrophotometry. The levels of glutaredoxin, cyclin E and cyclin-dependent protein kinases were estimated by Western blotting with monoclonal antibodies.

Results: The effects of roscovitine in the MCF-7 cells resulted in cell cycle arrest in G2/М phases with the decreased levels of cyclin E and cyclin-dependent protein kinase 2. It was accompanied by activation of programmed cell death. In tumor cells incubated in the presence of roscovitine, oxidative stress was triggered, which was accompanied by the elevated generation of reactive oxygen species, the decrease in the concentration of reduced glutathione, and the rise in the level of glutaredoxin. It contributed to the increase in protein glutathionylation against the backdrop of the decreased SH group concentration.

Conclusions: Breast cancer cell proliferation under the effects of roscovitine is reduced following not only the decrease in the cyclin level and cyclin-dependent protein kinase activity, but also the shift in the intracellular oxidant/antioxidant ratio. Roscovitine-induced oxidative stress in the MCF-7 cells contributed to protein glutathionylation with the changes in the protein structure and functions. It results in impaired cell cycle progression, indicating a possibility to regulate cellular proliferation through modulating functional properties of redox-dependent proteins using the glutathione/glutaredoxin system.

Annals of the Russian academy of medical sciences. 2017;72(4):261-267
pages 261-267 views

OPHTHALMOLOGY: CURRENT ISSUES

MODERN ASPECTS OF MULTIFOCAL INTRAOCULAR CORRECTION: A REVIEW

Morozova T.A., Pokrovskiy D.F., Medvedev I.B., Kerimov T.Z.

Abstract

During the last decade multifocal intraocular lenses (IOL) became widely used in cataract surgery and proved to be effective in recovery of visual functions. Lots of clinical studies with different multifocal IOL models showed high effectiveness of multifocal correction to achieve good visual quality for far, intermediate, and near distances. Uncorrected visual acuity at a distance is equal to multifocal and monofocal correction, while uncorrected near vision is significantly better with multifocal IOLs. Additional segment position in asymmetric multifocal IOL models did not significantly influence on visual acuity. Multiple multifocal IOL designs (bifocal, trifocal) and ADD power level provide different functional results for near and intermediate distances which allows to select the specific IOL model depending on the patient`s needs. The review covers the following aspects of multifocal intraocular correction: update for classification of multifocal IOLs, visual acuity (functional results) at different distances after multifocal IOL implantation, comparison of clinical results with different multifocal IOL designs and add power levels, influence of add segment position in asymmetric multifocal IOLs on visual quality, comparison between multifocal and monofocal correction.

Annals of the Russian academy of medical sciences. 2017;72(4):268-275
pages 268-275 views

РATHOPHYSIOLOGY: CURRENT ISSUES

SOLUBLE CD25 AND CD95 MOLECULES LEVEL AT BURNS

Lebedev M.J., Sholkina M.N., Novikov D.V., Shumilova S.V., Novikov V.V., Karaulov A.V.

Abstract

Background: Burn injury is accompanied by modulation of the many components of immunity, including the system regulation, which includes soluble forms of leukocyte differentiation molecules. Earlier in burn patients, we detected changes in serum levels of soluble differentiation molecules CD25 (sCD25) and CD95 (sCD25). Despite the existence of data on change of serum level of the soluble molecules CD25 and CD95 in the blood of patients with a burn trauma, there are no data on particular cell producers.

Aims: To conduct the analysis of serum level of the molecules sCD25 and sCD95 in the blood of patients with acute burn trauma in comparison with peripheral blood cells composition to obtain data on the types of cells that produce the molecules sCD25 and sCD95.

Materials and methods: Blood samples from 24 heavily burnt patients aged 16 to 77 years were studied. Determination of sCD25 and sCD95 molecules serum levels was performed by ELISA. Number of CD45+CD25+ lymphocytes, CD45+CD95+ cells, CD14+CD95+ monocytes, CD16b+CD95+ neutrophils, and RFMI (relative mean fluorescence intensity) was evaluated by flow cytometry.

Results: In the first five days of the date of burn sCD25 and sCD95 serum levels tended to increase. sCD25 molecules contents in the blood of surviving and dead patients did not depend on the relative content of CD45+CD25+ lymphocytes, RFMI index, but correlated with the absolute level of lymphocytes and leukocytes. Serum levels of sCD95 molecules showed the dependence on the absolute neutrophil count and leukocytes in the survivors and on the absolute content of lymphocytes, neutrophils, and leukocytes in patients who died.

Conclusions: The findings suggest that the lymphocytes in the early period of burn disease are the main cells-producers of sCD25 and affect the increase of its content in the blood serum not due to changes in the density of CD25 molecules expression on their membrane followed by increased shedding but by increasing the number of CD25 positive cells. The main cells-producers of sCD95 molecules for survivors in the early period of burn disease are likely to be the neutrophils and lymphocytes; in the dead patients, the main producers are neutrophils.

Annals of the Russian academy of medical sciences. 2017;72(4):276-281
pages 276-281 views

PEDIATRICS: CURRENT ISSUES

EFFECTIVENESS OF PALIVIZUMAB IN PREVENTING RSV HOSPITALIZATION IN HIGH-RISK CHILDREN: A PROSPECTIVE OBSERVATIONAL MULTICENTER STUDY

Chubarova A.I., Davydova I.V., Vinogradova I.V., Degtiareva E.A., Keshishyan E.S., Safina A.I., Nesterenko E.V.

Abstract

Background: Palivizumab is indicated for the prevention of serious respiratory syncytial virus (RSV) disease in high-risk infants.

Aims: The purpose of the study was to assess the real-world effectiveness and safety of palivizumab in children at high risk for serious RSV disease during the 2014−2015 RSV season in the Russian Federation.

Methods: A prospective, observational, multicentre, cohort study was conducted in a population of infants at high-risk for serious RSV illness: infants born ≤35 weeks of gestation and infants ≤24 months with bronchopulmonary dysplasia (BDP) or congenital heart disease (CHD), who were administered palivizumab immunoprophylaxis in routine clinical settings. The study was conducted at 16 investigational sites of European Russia and Western Siberia.

Results: A total of 359 infants were enrolled (180 boys and 179 girls). Of them, 148 (41.2%) infants had BDP, 45 (12.5%) infants had hemodynamically significant CHD, and 166 (46.2%) children of prematurity were at the risk of RSV. The majority of infants (86.9%) received three or more injections during the course of study. Of the 359 participants enrolled, 11 (3.1%; 95% CI 1.5−5.4) patients were hospitalized for lower respiratory tract infection. A RSV diagnostic test was performed in 9 infants, and RSV was detected in one patient giving an overall incidence of RSV hospitalization as 0.3% (95% CI 0.0−1.5).

Conclusions: This study showed that immunoprophylaxis with palivizumab was associated with a low rate of RSV hospitalization. Overall, therapy with palivizumab was well-tolerated and showed a favourable benefit-risk profile.

Annals of the Russian academy of medical sciences. 2017;72(4):282-289
pages 282-289 views

ENDOCRINOLOGY: CURRENT ISSUES

MICRORNA: ROLE IN GH-SECRETING PITUITARY ADENOMA PATHOGENESIS

Lutsenko A.S., Belaya Z.E., Przhiyalkovskaya E.G., Mel'nichenko G.A.

Abstract

MicroRNA presents small (19–25 nucleotides long) non-coding RNA molecules which regulate gene expression on post-transcriptional level. Numerous studies revealed microRNA’s important role in physiological processes. Moreover, its aberrant expression has been described in many pathological conditions including pituitary tumors. Pituitary adenomas are benign intracranial tumors with various clinical presentations depending on the type of hormone secretion. Prediction of the pituitary adenoma aggressive level and treatment response is challenging due to the lack of reliable clinical predictors or non-invasive biomarkers. MicroRNAs in body fluids could potentially be a minimally invasive biomarker for tumor diagnosis and a predictor of treatment response and prognosis. Some studies reveal that microRNA is specific for a different pituitary adenoma subtypes. In the article, we review existing evidence on microRNA expression in GH-secreting tumors and its possible involvement in pathogenesis of somatotroph tumors.

Annals of the Russian academy of medical sciences. 2017;72(4):290-298
pages 290-298 views

STATE OF MEDICAL SCIENCES

PLAGIARISM AND ACADEMIC INTEGRITY IN SCIENCE

Byvaltsev V.A., Stepanov I.A., Belykh E.G., Kalinin A.A., Bardonova L.A.

Abstract

The review presents an analysis of contemporary literary data on the problem of plagiarism and violations of the standard codes of scholarly conduct and ethical principles, as well as methods to combat them. Academic integrity includes a set of spiritual values such as honesty, justice, trust, respect, and responsibility, as well as ideal samples which all the participants of the scientific and educational processes should follow. Violations of the principles of academic integrity are a number of incorrect actions performed by any participant of scientific or educational process. Plagiarism is an element of misconduct in academic sphere. The category of scientific plagiarism includes obvious and unobvious scientific plagiarism. The specific aspects of the problem are self-plagiarism and mosaic plagiarism. The developed anti-violation strategies and recommendations should provide guidelines and instructions for improving the level of academic knowledge of all the participants of scientific and educational processes. A modern and effective method for combating plagiarism is online text detection for originality, although this technique is not free from shortcomings. The fight against academic misconduct should be carried out on the national level: including but not limited with gaining new knowledge, training skills, and formation of professional and general cultural values at all the levels of scientific and educational processes. Further development of universal training modules which provide information on the goals of academic integrity, the most frequent reasons that lead to its violation, types of violations, how to deal with them, and possible consequences is requested. Such reference data should be widely available; introduction of new knowledge and control on implementation of its key provisions should be an integral part of modern Russian academic education.

Annals of the Russian academy of medical sciences. 2017;72(4):299-304
pages 299-304 views

HEALTH CARE MANAGEMENT

PROBLEMS OF CHILDREN'S DISABILITY IN MODERN RUSSIA

Baranov A.A., Namazova- Baranova L.S., Terletskaya R.N., Antonova E.V.

Abstract

 

Creation of system of early prophylaxis of children disability and support of the families bringing up disabled children and children with limited opportunities are among the main priorities of the Russian Federation state social policy. There are a number of problems requiring immediate solutions. Dynamics of children’s disability in our country is characterized by process stagnation. The age and gender structure of children’s disability practically doesn’t change. The analysis of its nosological structure shows that alienations and disorders of behavior, illness of a nervous system and congenital anomalies of development steadily occupy more than 60% among the illnesses which caused disability of children of all age groups. There was a decrease in the prevalence of total disability in most classes of diseases, such as injuries, diseases of the genitourinary system, respiratory system, musculoskeletal system, digestive system and growth of disability caused by neoplasms and diseases of the endocrine system. The underestimation of children’s disability bound to various reasons is supposed: social motivation of a family, complexity of legal veneering, strict requirements of service of medico-social examination, insufficient medical experts awareness on criteria of disability. Among disability formations risk factors the most discussed are the achievements of perinatology leading to improvement of nursing of prematurely born and small newborns, and wide uses of auxiliary genesial technologies. An important part of all preventive measures aimed at reducing the genetic load of population is prenatal and preimplantation diagnosis. It seems appropriate to extend the screening to congenital and hereditary metabolic diseases in neonatal period, including the most common nosological forms of infrequent illnesses. In solving problems of childhood disability prevention a priority should be given to development of services of family planning; improving antenatal and perinatal care; preventive work with healthy but having deviations in development children; development of medical genetic services; implementation of programs of different types of pathology screening.

Annals of the Russian academy of medical sciences. 2017;72(4):305-312
pages 305-312 views

ЮБИЛЕИ

IGOR' VALENTINOVICH BUKHTIYAROV

vestnik rams e.

Abstract

.

Annals of the Russian academy of medical sciences. 2017;72(4):313-314
pages 313-314 views

VLADIMIR IOSIFOVICH KONENKOV

vestnik rams e.

Abstract

.

Annals of the Russian academy of medical sciences. 2017;72(4):315-316
pages 315-316 views

VLADIMIR VIKTOROVICH KUTYREV

vestnik rams e.

Abstract

.

Annals of the Russian academy of medical sciences. 2017;72(4):317-318
pages 317-318 views

VALERII PAVLOVICH PUZYREV

vestnik rams e.

Abstract

.

Annals of the Russian academy of medical sciences. 2017;72(4):319-320
pages 319-320 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies