Yakut Medical Journal

ISSN 1813-1905 (print) ISSN 2312-1017 (online) 4(64) `2018 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

The founder The Yakut Science Centre of Complex Medical Problems YAKUT Editor- in- chief Romanova A.N., MD Editorial Board: MEDICAL Deputy Chief Editor and Executive secretary Nikolaev V.P., MD Scientific editor Platonov F.A. MD JOURNAL

Editorial Council: SCIENTIFIC - PRACTICAL JOURNAL Aftanas L.I., MD, Professor, OF THE YAKUT SCIENCE CENTRE OF COMPLEX acad. RAMS (Novosibirsk) MEDICAL PROBLEMS Voevoda M.I., MD, Professor, Corresponding Member RAMS (Novosibirsk) Ivanov P.M., MD, Professor (Yakutsk) Kryubezi Eric, MD, Professor (France) Quarterly Maksimova N.R., MD (Yakutsk) Mironova G.E., Doctor of Biology, Registered by the Office of the Federal Service on Professor (Yakutsk) supervision in the field of communications, information Mikhailova E.I., Doctor of Pedagogics, Professor (Yakutsk) technologies and mass communications in the Republic Nikitin Yu.P., MD, Professor, Sakha (Yakutia) December 13/2016 Acad. RAMS (Novosibirsk) Odland John, MD, Professor (Norway) Registration number PI No.ТU 14-00475 Puzyrev V.P., MD, Professor, Acad. RAMS (Tomsk) Subscription index: 78781 Reutio Arya, MD, PhD, Professor (Finland) Fedorova S.A., Doctor of Biology (Yakutsk) Free price Husebek Anne, MD, Professor (Norway) Khusnutdinova E.K., Doctor of Biology, Professor (Ufa) «Yakut Medical Journal» is included in the approved by Editors: the Higher Attestation Commission of the Russian Chuvashova I.I., Federation List of leading peer-reviewed scientific Kononova S.l. journals and publications, in which the main scientific Semenova T.F. (English) results of dissertations for the acquisition of scientific degrees of Doctor and Candidate of science on Computer design biological sciences and medicine should be published. Nikolashkina A.A. Chekurova S.M. (English) The journal is included in the international directory system under periodic and proceeding editions “Ulrich’s Address: International Periodicals Directory” Sergelyakhskoe Highway, 4, Yakutsk Republic Sakha (Yakutia) Russian Federation 677019 Fax: +7 (4112) 32-19-81; Phone: +7 (4112) 39-55-52 [email protected] e-mail: [email protected] http: // www.ymj.mednauka.com

The articles are given in the authors’ translation

CONTENTS

5 Editor’s Column

Original researches

Diakonova A.T., Pavlova N.I., Solovyeva N.A., Varlamova M.A., Alexandrova T.N., Kurtanov Kh.A. Molecular-genetic analysis of the connection of the SLC6A3 gene 6 with nicotine addiction in Yakutia Sidorova N.S., Sotskaya Ya.A. Evaluation of sub-population composition 9 of lymphocytes in chronic toxic liver disease and anemia of chronic disease on the background of transmitted infiltrate pulmonary tuberculosis Kirillina M.P., Ivanova A.K., Lushnikova E.L. Cytological analysis of cervix inflammatory diseases in different age 12 groups on the example of the Sakha (Yakutia) Republic Nikolaev V.M., Tsypandina E.V., Rumyantsev E.K., Sofronova S.I., Vinokurova F.V., Efremova S.D., Aleksandrova E.N., Ivanova F.G., Ivanov P.M., Fedorova S.A. Evaluation of glutathione system indicators 16 in the body of patients with lung cancer Alekseev R.Z., Golderova A.S., Mamayeva S.N., Nikolaeva N.A., Buzinayeva M.T. Assessment of change of erythrocytes by method of raster 18 electronic microscopy at the persons who died of fatal hypothermia Usenko G.A., Vasendin D.V., Usenko A.G. Gamma background environment during magnetic storms 21 and the contents of sodium and potassium in erythrocytes in patients with arterial hypertension depending on the temperament and antihypertensive therapy Alekseeva Z.N., Egorova A.G., Arhipova N.S., Okhlopkova E.D., Nikolaev V.M. Gender features of psychoemotional status 27 in cardiovascular pathology Poroyskiy S. V., Firsova I. V., Mikhalchenko D.V., Makedonova Yu.А., Fomichev E.B. Comparative study of reparative regeneration 30 of the oral mucosa in experiment Ubeeva E.A., Razuvayeva Ya.G., Olennikov D.N., Ubeeva I.P., Nicolaev S.M., Dymsheeva L.D. Experimental phytocorrection of acute 33 D-galactosamine hepatitis Gatilova M.I., Chibiyeva L.G. 37 Clinical characteristics of alcoholic liver disease Garmaeva D.K., Buzinaeva M.T., Pavlova A.I. Morphology of mucosa-associated lymphoid tissue 39 (MALT) of larynx in general hypothermia

Methods of diagnosis and treatment

Antonov A.V., Volovik V.E., Palshin G.A. The role and the place of arthroscopy of the hip joint 42 in treatment of aseptic necrosis of the femoral head Koval A.N., Tashkinov N.V., Melkonyan G.G., Marochko A.Y., Kogut B.M., Boiarintsev N.I., Yanovoi V.V., Kosenko P.M. Basic principles of surgical treatment of artificial 44 pyoinflammatory diseases of soft tissues Pshennikova V.G., Teryutin F.M., Barashkov N.A., Gotovtsev N.N., Nikanorova A.A., Solovyev A.V., Romanov G.P., Posukh O.L., Dzhemileva L.U., Khusnutdinova E.K., Fedorova S.A. 47 Postlingual deafness in Eveno-Bytantaysky National District of the Sakha Republic (Yakutia): audiological and clinical-genealogical analysis 4’ 2018 3

Arkhipova N.S., Popova E.K. Estimation of body mass index in patients with coronary heart disease 53 aged over 60 in the case of Yakutian citizens Semenov S.I., Stepanov K.M., Platonov F.A., Shadrina S.S., Pisareva M.M., Komissarov A.B., Fadeev A.V., Egorova A.A., Kuzin S.N. Serological and molecular-biological verification of viral hepatitis 55 B, C, D and E in various populations of the Republic Sakha (Yakutia)

Healthy lifestyle. Prevention

Avdeeva M.S. Physical development and physical fitness of 7-8-year-old girls 60 with peculiarities of perinatal development period Cherdonova A.M., Pshennikova V.G., Solovyev A.V., Barashkov N.A., Rafailov A.M., Romanov G.P., Kononova S.K., Fedorova S.A. Opinion of young people on the potential risk 62 of the birth of deaf child

Organization of Health, Medical Science and Education

Sleptsova S.S., Gogolev N.M., Zamorshchikova O.M. 65 Analysis of the infectious service in the Republic of Sakha (Yakutia) Rykov M.Yu. Medical care for children with cancer 68 in the Far Eastern Federal District

Actual topic

Sosina S.S., Vinokurova J.V., Yakovleva E.P., Nikolayeva I.N., Sleptsov A.P. The detectability of Helicobacter pylori CAGA 71 strain in adults and children according to the data of RH№1-NCM Evdokimov G.E., Egorova V.N., Vinokurova S.P. Medical and social assistance 73 to HIV-infected patients Sizykh E.Yu., Solovyova N.A., Varlamova M.A., Dyakonova A.T., Kurtanov Kh.A., Pavlova N.I. Molecular genetic studies as an auxiliary method 75 for determining risk factors in the clinical examination of the adult population Egorova A.G., Burtseva T.E., Evseeva S.A. Total dynamics of child mortality rates 78 in the Republic of Sakha (Yakutia) for the period 2006-2015 Zasimova E.Z., Golderova A.S., Krivoshapkina Z.N., Olesova L.D., Efremova S.D., Okhlopkova E.D., Sivtseva A.I. Risk factors for the development of metabolic syndrome 80 among employees of river transport of Yakutia Arctic medicine Kodochigova A.I., Parshina S.S., Samsonov S.N., Petrova P.G., Strekalovskaya A.A., Olenko E.S., Magomedova A.R., Gadzhieva Z.T., Belousova K.O., Afanas`eva T.N. Space weather effects on the features of personal response 85 of volunteers in a multiple-latitude monitoring Averyanova I.V., Vdovenko S.I. Indicators of the cardiovascular system in the Caucasian residents of Magadan region depending on the term of residing 89 under conditions of Russia’ northeast 4 YAKUT MEDICAL JOURNAL

Soboleva M.S., Zhmerenetsky K.V., Voronina N.V., Loskutova E.E., Dobryh V.A. Usage of the fixed-doses combinations for drug therapy 92 of arterial hypertension in northern regions of the Far Eastern Federal district Sofronova S.I., Romanova A.N., Nikolaev V.M. Association of ACE gene polymorphism with hypertension 96 and risk factors among indigenous people of the northern territory of Yakutia

Scientific reviews and lectures

Kononova I.V., Zakharova F.A., Kirillina M.P., Nikiforov P.V., Mamaeva S.N., Antonov S.R., Pavlov A.N., Nikolaeva N.A. Diagnostic significance of the human papilloma virus 100 detection in blood Terentiev I.T., Varlamova M.A., Pavlova N.I., Dyakonova A.T., Solov’eva N.A., Kononova S.K., Kurtanov Kh.A. Necessity of screening patients 102 with stenting for acute coronary syndrome by CYP2C19 polymorphism

Experience exchange

Mikhailova U.N., Solovyova N.A., Varlamova M.A., Kurtanov Kh.A., Pavlova N.I. Hospital morbidity rates as a factor in the selection 106 of pathology to develop personalized prevention and treatment methods Shadrina S.S., Zakharova R.N., Donskaya А.А., Sergeeva A.N. The most frequent symptoms of joints damage 108 among the residents of Yakutia

Methods of diagnosis and treatment

Davydova T.K., Nikolaeva T.Ya., Okoneshnikova L.T. Comparative analysis of sporadic cases and family form 110 of progressive muscular atrophy over a 30-year period (1986-2016) in the Republic Sakha (Yakutia) Douglas N.I, Ignateva N.N., Baisheva N.S., Rad Ya.G., Bourtseva T.E. Pharmacological and surgical termination 113 of missed abortion in the first trimester at the department of gynecology №1of the SBI RS (Ya) Yakutsk city clinical hospital 4’ 2018 5 EDITOR’S COLUMN

We are representatives of the most with authors, etc.). The main headings of humane profession - the profession of a the journal will remain the same. At the doctor. And our activity is entirely focused same time, the priorities are “Original on improving and preserving the health research”, “Methods of diagnosis and of people, increasing the lifespan and treatment”, “Arctic medicine”, “Scientific improving the quality of their life. Many reviews and lectures”, “Hot topic”, etc. scientific developments of the YSC CMP Special attention will be paid to headings have global and practical significance. that publish practical medicine materials. This is what stimulates us to work, to We will continue work on improving overcome, and sometimes to exploits the site of our journal. The editorial board that are not always noticeable to the will contribute to a steady feedback from others, but this does not diminish their the users of the Yakut Medical Journal significance. in order to improve the quality of the A strong fundamental and applied journal in every way, increase of its science, combined with practical competitiveness, informativeness and developments, new technologies, quick accessibility. The editorial board works response to innovation is the visiting card with authors with great inspiration and Dear Colleagues! of the YSC CMP. On the pages of our does everything so that readers can get Journal you will find a confirmation of this acquainted with the interesting results We are summing up the outgoing statement. of scientific research in the pages of our 2018 on the threshold of the upcoming Thanks to sustainable financing journal. We are ready to listen to your 2019. For the Yakut Medical Journal, and professional work of the editorial opinion about the magazine and take the year was prosperous and fruitful: we board, the Yakut Medical Journal good suggestions for its improvement. have celebrated the 15th anniversary has successfully passed the stage of On the eve of the New Year, I wish our of the journal; the journal is included in formation and has sufficient potential for dear authors and readers good health the international citation database Web further sustainable development. Work and high spirit, new great ideas and of Science in test mode; the journal’s on improving the quality of published achievements! May the New Year be demand for authors and readers from materials will continue, which implies an successful and productive for all of us! different regions of Russia, including improvement in the pre-production work Well-being and happiness! Yakutia, has significantly increased. (collection, review of the material, work

Director of the YSC CMP, MD A.N. Romanova 6 YAKUT MEDICAL JOURNAL

ORIGINAL RESEARCHES

A.T. Diakonova, N.I. Pavlova, N.A. Solovyeva, M.A. Varlamova, T.N. Alexandrova, Kh.A. Kurtanov MOLECULAR-GENETIC ANALYSIS OF THE CONNECTION OF THE SLC6A3 GENE DOI 10.25789/YMJ.2018.64.01 WITH NICOTINE ADDICTION IN YAKUTIA

ABSTRACT The purpose of this work is to study the relationship of the gene SLC6A3 rs27072 with nicotine addiction in the smoking population living in Ya- kutia. In total, we examined 100 people (men and women aged 20 to 70 years). The status of smoking was revealed at the questionnaire. Smoking cigarettes, like many other addictives, has a genetic component. The SLC6A3 gene is an important candidate for predisposition to nicotine addiction. Analysis of the polymorphism association of SLC6A3 rs27072 with nicotine addiction testified the absence of statistically significant differences between carriers of different genotypes, not only in the study group as a whole, but also separately in men and women. Probably, this is due to the small sampling and difficulties in determining the status of smoking using only questionnaires. Keywords: smoking, nicotine addiction, SLC6A3 gene, Yakutia, polymorphism.

Introduction. Cigarette smoking re- and causes neurochemical changes in porter gene of dopamine and the age of mains widespread, a risk factor for more the future patient even before the meet- onset with regard to the use of tobacco than two dozen diseases and is the big- ing with psychoactive substances, and and alcohol. Studies conducted predomi- gest cause of death all over the world. this includes nicotine addiction. Which nantly in the European population have Smoking damages virtually all systems determines the biological basis of the revealed that the allele of this polymor- of the human body and is a habit that can predisposition proper. However, the phism increases the risk of smoking, be got rid of. Smoking of tobacco causes conclusions between previous studies while studies in the Japanese population psychological and physiological addiction are difficult to explain because smoking have shown a link between this genotype and, in addition, is closely related to so- cigarettes is a very complex process, in- and smoking. Previously, the influence of cial and cultural factors. Despite widely fluenced by various factors such as age, polymorphisms on ethnicity was also con- recognized risks, about one third of the sex, environment [1]. sidered. In association studies between world’s adult population continues to The dopamine transporter gene the variant ANKK1 / DRD2 and SLC6A3 smoke tobacco [1]. (SLC6A3) localized in the short arm of alleles and smoking, it was suggested According to the World Health Organi- chromosome 5 (5p15.3) participates in that the presence of the ANKK1 / DRD2 zation (WHO), smoking causes nearly 6 the control of dopaminergic transmis- Taq I allele along with the A SLC6A3 al- million deaths each year, of which more sion. The rs27072 polymorphism of the lele increases the craving for cigarettes, than five million occur among - smok SLC6A3 gene is associated with more causing addiction. In addition, several ers. The Fig. 1 shows the prevalence of severe symptoms with an alcohol with- studies have suggested that, compared smoking in the world. Smoking preva- drawal syndrome, such as convulsions. to non-carriers, carriers of the A SLC6A3 lence is prevalent in Asian countries [2]. Many authors report that the gene of the allele have a lower risk with early onset of Also among non-smoking people, dopamine transporter (SLC6A3) is asso- smoking [3, 4, 6]. more than 600,000 are exposed to sec- ciated with the syndrome of hyperactivity The results of population studies in ond-hand tobacco smoke. WHO esti- and attention deficit disorder (ADHD). A different countries are presented in Table mates that tobacco contains more than link was also found between the trans- 1. In the world, the frequency of allele A 7,000 chemical compounds, 60 of which are known or suspected carcinogens, i.e. cause changes in the cells of the body leading to the development of cancer, and 250 have a proven cytotoxic effect. Eleven substances contained in tobacco smoke (2-naphthylamine, 4-aminobiphe- nyl, benzene, vinyl chloride, ethylene oxide, arsenic, beryllium, nickel compounds, chromium, cadmium and polo- nium-210), the International Agency for Research on Cancer refers to the first group of carcinogens ie with a proven carcinogenic effect) [2]. It is assumed that there is a central pathophysiological mechanism for maintaining addiction on psychoactive substances, under genetic control. This mechanism is independent of the spe- Fig.1. Prevalence of tobacco smoking in the world: light to dark shows the increase in the cific type of psychoactive substance percentage of smoking population by country (WHO data on trends in tobacco prevalence, 2015) 4’ 2018 7

was 21%. Studies were conducted in the Table 1 Chinese population of Han (South China) in which the percentage of allele A was Frequency distribution of alley polymorphism rs27072 gene SLC6A3 31%. Also in the Chinese population of Population Dai (China) was A - 31%, which is the Allele highest rate in the world. In the population All Southern Han Chinese Dai, African in Yorubain of African descent (South-West USA), the Chinese, China China Southwest, US Ibadan, lowest A is 10%. In the Yoruba population Allele А (%) Nigeria 31 31 10 13 (Nigeria), the percentage of allele A was Allele G (%) 79 69 69 90 87 13%, which is also one of the least. The authors who studied the SLC6A3 Table 2 gene relationship with the nicotinic addic- PCR conditions tion insisted that it had an effect on smoking cessation [4, 8]. Gene Amplificate PCR conditions The purpose of this work was to study 1. 95°С – 5 min the relationship of the gene SLC6A3 SLC6A3 217 п.н. 2. (94°С – 30 sec; 62°С – 30 sec; 72°С – 1 min)-35 cycles rs27072 with nicotine addiction in the 3. 72°С – 7 min smoking population living in Yakutia. Materials and methods of the re- carried out by horizontal electrophoresis ants / genotypes was carried out using search. The experimental part of the in a 2% agarose gel plate with the addi- the Pearson method for the 2x2 conju- genotyping of polymorphism rs27072 tion of ethidium bromide-a specific inter- gacy tables, OR, 95% confidence interval of the SLC6A3 gene was carried out in calating fluorescent DNA (RNA) dye-us- (95% CI) . Differences were considered the laboratory of hereditary pathology ing a standard tris-acetate buffer at a field reliable at P <0.05. of the department of molecular genetics strength of ~ 20 V / cm for 30 minutes. Results and discussion. As a result of the Yakutsk Scientific Center of Com- After PCR amplification was subjected of genotyping polymorphism rs27072 plex Medical Problems. DNA samples to restriction with the use of endonucle- of the SLC6A3 gene, it was established from the YMC KMB biomaterial collec- ase Msp I (OOO SibEnzim, Novosibirsk) that the incidence rate of the GG geno- tion were used for the study using the for 3 hours at 37 ° C. The detection of type among all the examined individuals UMU “Genome of Yakutia” (registration RFLP products was carried out by hori- is 69.1%. The allele frequency G was #USU_507512). The study involved resi- zontal electrophoresis in a plate of 4% 80.9% (Table 3). dents of the Republic of Sakha (Yakutia). agarose gel with the addition of ethidium In our sample, smoking frequency of The study was conducted with the written bromide using standard tris-acetate buf- allele A was 17, 34%, in the non-smoking consent of the participants. A total of 97 fer at a field strength of ~ 20 V / cm for 45 sample- 20, 83%. Also, with the gender DNA samples, 45 males and 52 females, minutes (Figure 2) division in the groups of smokers (wom- were examined. Interpretation of genotyping results en) and non-smokers (men), the frequen- Genomic DNA was extracted from the was performed on the basis of different cy of allele A was 8.7%, and in the groups peripheral blood of each participant using band patterns: GG genotype 137, 80 bp, not smoking (women) and smoking (men) the Excell Biotech DNA Excellence Kit AG genotype 217, 137 and 80 bp, AA - 22.4%. The results of the association (Russia) in accordance with the manu- genotype 217 bp. evaluation of rs27072 polymorphism of facturer’s instructions. The DNA concen- Statistical analysis of the results of the the SLC6A3 gene showed that the in- tration in each sample was determined research was carried out using the pro- cidence of the A allele in the sample of on an Implen Nano Photometer (Ger- gram: “Office Microsoft Excel 2010”. The smokers and non-smokers is not signifi- many) spectrophotometer for measure- correlation of the genotype distributions cantly different. However, in the sample ment in microvolumes. Single nucleotide with the expected values at the Hardy- of smokers, the number of carriers of the polymorphisms (SNP) were determined Weinberg equilibrium and the compari- homozygous AA genotype exceeded the by polymerase chain reaction (PCR- son of the frequencies of the allelic vari- number with such a genotype in the non- RFLP). Amplification of the region of a gene containing a polymorphic variant was carried out by standard pairs of primers produced by Biotech-Industriya LLC, Moscow. Reaction mixture primer direct and reverse 1 μl; Dream Taq PCR master mix -12.5 μL; 9.5 μl of desionized water and 1 μl of DNA. The total volume of the reaction mixture for amplification was 25 μl. The restriction mixture was 20 μl, 7 μl of amplification, 10.9μ l of desionized water, 2 μl of restriction buffer, and 0.1 μl of restriction endonuclease MspI. The temperature-time mode for conducting PCR is optimized to amplify this nucleotide sequence and is presented in Table 2. Fig.2. The electrophoregram of the amplification product of the region of the SLC6A3 gene in The detection of PCR products was a 4% agarose gel: tracks number 1, 5, 7, 8, 10, - genotype AA; № 2, 3,4, 6 and 9 - genotype of GG; M - marker PUC19 / + Msp I, Bp - base pairs. 8 YAKUT MEDICAL JOURNAL

smoking sample by a factor of two. Allele Table 3 in smokers A allele reaches 17.3%, which is almost the same as the percentage of Frequency distribution of alleles and genotypes of rs27072 polymorphism of the SLC6A3 gene allele A in the sample of non-smokers. The analysis of statistical data between Frequency of occurrence of Frequency of OR (95% CI), samples of men and women showed occurrence of Comparable genotypes, abs. (%) alleles,% Р similar results in the two groups. This is groups р most likely due to the fact that at a small АА АG GG А G Allele of risk А sample it is necessary carefully refine the Smoking 5 (10.2) 7 (14.28) 37 (75.51) 17 (17.34) 81 (82.65) unreliability of the detection of smoking 1.247 0.537 Do not smoke 2 (4.16) 16 30 (62.5) 20 (20.83) 76 (79.16) (0.389-1.636) in the survey, adding aspects such as (33.33) length, the number of cigarettes smoked. Smoking 1 (4.4) 2 (8.7) 20 (86.9) 4 (8.7) 42 (91.3) Analysis of the association of SLC6A3 Women 0.991 (0.100-1.091) 0.061 rs27072 polymorphism with nicotine ad- Do not smoke 1 (3.5) 11 (37.9) 17 (58.6) 13 (22.4) 45 (77.6) diction indicated that there was no sta- Women tistically significant difference between Smoking Men 4 (13.8) 5 (17.3) 20 (68.9) 13 (22.42) 45 (77.58) 9.125 carriers of different genotypes, not only 0.061 Do not smoke (0.916-10.041 in the study group as a whole, but also Men 1 (4.34) 2 (8.69) 20 (86.95) 4 (8.7) 42 (91.3) separately in men and women (Table 3). The conclusion. The results of a htm Res – 2002 - № 4 – Р.333–340. DOI: study of polymorphism in the smok- 2. Tabak VOZ. Informacionnyj 10.1080/14622200210142689 ing population among residents of the byulleten’ [News bulletin]. 2013, №339, 8. The dopamine transporter gene Republic of Sakha (Yakutia) found that https://tobaccoatlas.org/topic/prevalence (SLC6A3) variable number of tandem among the surveyed persons prevalence 3. Allelic association of a dopamine repeats domain enhances transcription was 81% among smokers and in non- transporter gene polymorphism in alcohol in dopamine neurons / S. Michelaugh, C. smoking 76% of the G. allele, which is not addiction with withdrawal seizures Fiskerstrand, E. Lovejoy, M. Bannon or delirium / T. Sander, H. Harms, J. [et al.] // Neurochem.- 2001. - №79. – associated with nicotine addiction. In the Podschus, U. Finckh [et al.] // Biol Р.1033–1038. https://doi.org/10.1046/ sample of smokers, the number of carri- Psychiatry. – 1997 - № 41. – P. 299–304. j.1471-4159.2001.00647.x ers of the homozygous AA genotype ex- doi:10.1111/j.1530-0277.2011.01509.x ceeded the number with such a genotype 4. Association of smoking and The authors in the non-smoking sample by a factor of personality with a polymorphism of YSC CMP, Yakutsk, Russia: two. But on the whole, according to the the dopamine transporter gene./ A. 1. D’yakonova Aleksandra statistical data, it turned out that the reli- Jorm, A. Henderson, P. Jacomb, H. Timofeevna – junior researcher of the ability of the samples was not found. Christensen, A. Korten, B. Rodgers [et laboratory of heritable pathology Tel.: 8 Thus, as a result of this study, we al.] // Am J Med Genet. – 2000.-№96.- (914) 238 68 93. E-mail: dyakonovaa@ found that polymorphism rs27072 of the P. 331–334. doi.org/10.1002/1096- bk.ru; SLC6A3 gene did not reveal a connec- 8628(20000612)96:3<331::AID- 2. Pavlova Nadezhda Ivanovna tion with nicotinic addiction in the studied AJMG19>3.0.CO;2-0 – PhD, temporary acting chief scientific sample. This probably depends on the 5. Genetic influence of dopamine officer - head of the laboratory of heritable small sample size and the difficulty in de- receptor, dopamine transporter, and pathology. Tel.: +7 (914) 289 39 36. termining smoking using questionnaires. nicotine metabolism on smoking E-mail: [email protected]; Since we were based only on the honesty cessation and nicotine addiction in a 3. Solov’eva Natal’ya Alekseevna of our respondents, in the future, when Japanese population / M. Ohmoto, T. – PhD, temporary acting chief scientific composing samples, it is necessary to Takahashi, Y. Kubota, S. Kobayashi [et officer - head of the Laboratory of group them according to the age and age al.] //BMC genetics. – 2014. – V. 15. – №. Population Genetics. Tel.: 8 (924) 171 34 of the beginning of smoking. 1. – С. 151. doi.org/10.1186/s12863-014- 89. E-mail: [email protected]; The research was carried out within 0151-2 4. Varlamova Marina Alekseevna the framework of the R & D study of the 6. Lerman C. Non-replication of –researcher of the laboratory of heritable genetic structure and cargo of the heredi- genetic association studies: is DAT all pathology Tel.: 8 (914) 298 87 60. E-mail: tary pathology of populations of the Re- folks? / C. Lerman, G. Swan //Nicotine [email protected]. public of Sakha (Yakutia). Tobacco Res. - -2002; - № 4 - Р. 247–249. 5. Аleksandrova Tujara Nikonovna doi.org/10.1080/14622200210141220 - Junior researcher of the laboratory of References 7. Smoking status and the heritable pathology E-mail: alexandrova_ 1. Аleksandrov А. А. Аleksandrova human dopamine transporter variable [email protected] V. Yu. Profilaktika kureniya: rol’ i mesto number of tandem repeats (VNTR) 6. Kurtanov Khariton Alekseevich psihologa [Prevention of smoking: the polymorphism: failure to replicate and – PhD, Chief Scientific Officer - Head of role and place of a psychologist] Voprosy finding that never smokers may be the Department of Molecular Genetics. psikhologii [Psychology issues]. 1999, different / D. Vandenbergh, C. Bennet, Tel.: +7 (914) 106 00 30. E-mail: hariton_ №4, p. 35-42. http://www.voppsy.ru/ M. Grant, A. Strasser, R. O’Connor, [email protected]. journals_all/issues/1999/994/994035. R. Stauffer [et al.] // Nicotine Tobacco 4’ 2018 9

N.S. Sidorova, Ya. A. Sotskaya EVALUATION OF SUB-POPULATION COMPOSITION OF LYMPHOCYTES IN CHRONIC TOXIC LIVER DISEASE AND ANEMIA OF CHRONIC DISEASE ON THE BACKGROUND OF TRANSMITTED DOI 10.25789/YMJ.2018.64.02 INFILTRATE PULMONARY TUBERCULOSIS

ABSTRACT The article presents the results of the estimation of the subpopulation composition of lymphocytes in 66 patients with chronic toxic liver damage and anemia of a chronic disease on the background of the transferred infiltrative pulmonary tuberculosis. The use of a combination of sirepar and sodium nucleate in the treatment of such patients contributes to the elimination of the clinical phenomena of the combined pathology, and along with the improvement or complete normalization of the clinical indices in the patients examined, normalization of the cellular immunity parameters was noted, which gives grounds for recommendations on the use of the proposed combination of drugs in the complex treatment. Keywords: lymphocytes, cellular immunity, tuberculosis infection, chronic hepatitis, anemia.

Introduction. Among infectious dis- ern ideas, anemia arising in similar situ- consent, positive ELISA test for the pres- eases, tuberculosis continues to be one ations is conventionally designated as ence of certain markers of viral hepatitis. of the leading causes of morbidity and anemia in chronic diseases (ACH). The All observed patients were divided into mortality among adults throughout the frequency of ACH in acute and chronic two groups: the main group (34 patients) world. Approximately 2 billion people of infections varies from 18 to 95% [13]. and the comparison group (32 patients), the world’s population are infected with AChs with long-term preservation of the randomized by sex, age, and course of M. Tuberculosis [12]. Every year, almost inflammatory process, which is typical for the disease. All patients received stand- 10 million people become infected with tuberculosis infection, may present dif- ard therapy of hepatitis, including hepa- an active form of tuberculosis and 2 mil- ficulties in terms of differential diagnosis totropic therapy, drugs ursodeoxycholic lion people die from it [14]. Every 10 sec- with iron deficiency anemia and further acid, essential phospholipids, a mixture onds from tuberculosis in the world one treatment. of amino acids. Patients from the main person dies. So, in the territory of Lugan- One of the pathogenetic links of the group were additionally received in a sk region in recent years, due to a num- studied comorbid pathology is the bind- combination of sireppar therapy of 3 ml ber of problems: forced migration, the for- ing of metabolites to hepatocyte proteins IV drip in 100 ml of 0.9% fiz. solution and mation of post-traumatic stress disorder with the appearance of autoantigens cir- sodium nucleate for 2 capsules (200 mg) and a decrease in the standard of living culating and fixed on the membranes of 4 times a day for 2 weeks. of the population, there is an increase in hepatocytes, the formation of immune The diagnosis of toxic hepatitis was the incidence of tuberculosis. According complexes of autoantigen-autoantibod- established expertly, taking into account to statistical data in 2015, the incidence ies, and the development of T cell-medi- the history, the results of clinical and was 58.9 per 100 thousand people, the ated immunological reactions. laboratory (biochemical) research, char- mortality rate is 12.3 per 100 thousand Purpose of the study: evaluation of acterizing the functional state of the liver population, in 2016 these figures were the subpopulation composition of lym- and gallbladder, as well as data from so- 68.2 and 15.3, in 2017 70.4 and 15.8 per phocytes in chronic toxic liver damage nographic examination of the abdominal 100.000 of the population, respectively, (CTLD) and anemia of a chronic disease cavity. To confirm anemia of a chronic which exceeds the epidemic threshold. against a background of transferred infil- disease, hemoglobin (Hb), hematocrit The need for continued use of an- trative pulmonary tuberculosis. (Ht), reticulocyte count, serum iron level tituberculosis drugs led to an increase in Materials and methods of research. (Fe), total iron binding capacity of serum the proportion of adverse reactions [11]. Under our supervision, there were 66 pa- (TICS) were evaluated. The development of adverse reactions tients with CTLD, with AChs on the back- To achieve the goal of the study, an to antituberculosis drugs poses a threat ground of tuberculosis of the lungs, age additional immunological study was per- to a full-fledged chicken chemotherapy from 18 to 50 years. The criteria for inclu- formed to analyze the state of the cellular [2, 10]. Interruptions in taking antituber- sion in the study were: age from 18 to 50 immune system. At the same time, the culosis drugs lead to a decrease in the years, hospital treatment, history of first content of T- (CD3 +) and B-lymphocyte effectiveness of treatment, the formation diagnosed infiltrative pulmonary tubercu- (CD22 +) populations, T helper / induc- of tuberculosis with drug resistance, and losis, chemotherapy under standard regi- tor subsets (CD4 +) and T-suppressor / to an increase in the reservoir of tubercu- mens using 4 drugs or more, informed killer (CD8 +) populations was studied losis infection [1, 3, 8]. consent for participation in the study, the in the peripheral blood using a cyto- One of the most common hemato- presence of toxic liver damage caused by toxic test using monoclonal antibodies logical disorders in patients with acute or reception of antituberculous drugs. The (MBAT). Commercial MCAT classes CD3 chronic activation of the immune system criteria for exclusion were: age younger +, CD4 +, CD8 +, CD22 + NIC of “Med- due to various infectious diseases is ane- than 18 years and over 50 years, refusal BioSpectr” (RF - Moscow) were used in mic syndrome [4, 5]. According to mod- from inpatient treatment, lack of informed the work. The immunoregulatory index 10 YAKUT MEDICAL JOURNAL

CD4 / CD8, which was treated as the ra- CD4 / CD8 index relative to the norm that the cellular response of the immune re- tio of lymphocytes with helper and sup- speaks about the formation in patients sponse after completion of the treatment, pressor activity (Th / Ts), was taken into with CKTP and AChs on the background we found that in the main group of pa- account. Evaluation of immunological of the transferred pulmonary tuberculosis tients (who received a combination of shifts of T-cell regulatory subpopulations more often with respect to the suppres- sirep and sodium nucleate), the amount was performed using the “immunological sor variant of immunodeficiency (with the of CD3 + cells (total population of T-lym- compass” method, taking into account predominant decrease in the number of phocytes) and T-helper / inducers CD4 the relationship between subpopulations cells with helper activity Yu). In connec- +) almost completely normalized, in con- of T-helpers and T-suppressors. Func- tion with general T-lymphopenia, the ab- nection with which the immunoregulatory tional activity of T-lymphocytes was stud- solute number of lymphocytes with the index CD4 / CD8 rose to normal. It is sig- ied by the reaction of blast transformation CD8 + phenotype also moderately de- nificant that along with the normalization of lymphocytes (RTBL) when it was for- creased, however, to a slightly lesser ex- of the quantitative indices of the T-cell link mulated with a micromethod using phy- tent than the number of lymphocytes with of immunity, the restoration of the func- tohemagglutinin (PHA) as a nonspecific the CD4 + phenotype (table). tional activity of T-lymphocytes was also mitogen. Thus, the immunoregulatory index noted in the examined patients, which is Statistical processing of the results of CD4 / CD8 in all of the examined pa- confirmed by the dynamics of RBTL with was carried out according to methods tients with CTLD and AChs was signifi- PHA. Indeed, in the patients of the main common in experimental medicine using cantly lower than the norm (P <0.001) in group (who received the combination of the package of licensed programs Micro- the presence of pulmonary tuberculosis. sirepah and sodium nucleate), the indi- soft Exel. The reliability of the differences The number of B cells (CD22 +) in most cator of RBTL with PHA increased from in the groups was determined by the Stu- cases did not change significantly in rela- 38.6 ± 3.0% to 68.2 ± 2.4%, that is, 1.76 dent’s t-criterion using the Microsoft Exel tive value, whereas the absolute number times the baseline and reaches lower 5.0 and MedStat software packages [7]. of B-lymphocytes in patients was signifi- limit of the norm (table). Thus, under the Results and discussion. The clinical cantly reduced (Table). At the same time, influence of a combination of sirepar and picture of CTLD and AChs on the back- the functional activity of T-lymphocytes in sodium nucleate preparations in patients ground of the transferred infiltrative pul- the examined patients for this combined with CTLD and AChs on the background monary tuberculosis is characterized by diagnosis was significantly Dynamics of cellular immunity indices in patients with the presence of varying degrees of as- reduced: in the main group, CKTP and AChs on the background of the transferred thenic, astheno-neurotic, moderate cyto- an average of 1.82 times pulmonary tuberculosis during treatmen(М±m) lytic syndromes, anemia, hepatomegaly, the norm (P0.01) and in in some patients – cholestatic syndrome, the comparison group 1.74 Group of patients and characteristic changes on the chest times (P 0.01). Immunological Norm radiograph (resorption of infiltrative -fo Thus, before the begin- parameter the main comparison cal changes in the affected lobes of the ning of the treatment, the (n=34) (n=32) lungs, scarring of cavities of decay and examined patients of both 51.3±2.0** 50.9±1.8** compaction of foci). groups had quite significant CD3+. % 69.8±2.1 67.9±0.2 56.3±0.9* In the ultrasound study, signs of mod- disorders from the cell link erate increase in the liver and an in- of immunity. They consisted г/л 1.32±0.04 0.87±0.01*** 0.85±0.03*** crease in its echogenicity were found in in the presence of T-lym- 1.25±0.04 0.95±0.04** all patients, no signs of obstruction of the phopenia, an imbalance in 30.3±1.9** 30.9±1.8** biliary tract. In laboratory studies, a ten- the subpopulation composi- CD4+. % 45.6±1.5 43.6±2.0 35.8±2.1* dency to anemia was found in the blood tion of T lymphocytes with (a decrease in the level of red blood cells a predominant decrease г/л 0.87±0.03 0.46±0.01*** 0.5±0.02*** and hemoglobin, hematocrit (Ht) was re- in the number of T helper / 0.80±1.3 0.60±1.4** duced, the number of reticulocytes in the inducers (CD4 +) circulating blood was normal or slightly elevated, the in the peripheral blood and a 18.5±0.1 19.0±0.2 CD8+. % 22.3±0.9 21.5±2.5 21.3±2.1 serum iron level was normal or moder- decrease in the immunoreg- ately lower, the OJSS was normal or de- ulatory index of CD4 / CD8. 0.29±1.1* 0.3±1.0* creased, moderate leukocytosis, moder- The number of lymphocytes г/л 0.42±0.02 0.38±0.01 0.33±0.02* ate increase in ESR, hyperbilirubinemia with the CD8 + phenotype with a predominant increase in the conju- (T suppressor / killer) and CD4/CD8 2.04±0.03 1.58±0.02*** 1.6±0.02*** gated fraction, a moderate increase in the CD22 + (B-lymphocytes) 2.1±0.03 1.81±0.03** activity of alanine aminotransferase, in did not decrease in relative 19.7±0.2 20.1±0.3 some patients - an increase in the activity amounts, however, due to CD22+. % 21.6±1.1 21.2±1.3 20.9±1.4 of alkaline phosphatase, gammaglutam- general lymphopenia, the iltranspeptidase, hypercholesterolemia. absolute number of CD8 + г/л 0.41±0.02 0.31±0.01* 0.3±0.03* Prior to the start of treatment in both and CD22 + lymphocytes 0.37±0.02 0.35±0.02 groups, we observed similar changes in decreased moderately. At RTBL clinical immunity parameters character- the same time, there was 38.6±3.0** 39.1±2.7** w i t h P H A . 69.5±2.3 68.2±2.4 50.9±2.5* ized by T-lymphopenia, a decrease in the a significant decrease in % number of T-helper / inducers circulating the functional activity of T- in the blood (CD4 +) and an imbalance in lymphocytes according to Note: in the numerator - indicators before the start of treatment, in the denominator - after its completion; the the subpopulation composition of T cells RBTL data. probability of a difference in the indicators relative to the with a decrease in the immunoregulatory In a second study of norm: * - for Р<0,05, ** - Р<0,01, *** - Р<0,001. 4’ 2018 11

of transferred infiltrative pulmonary tuber- Thus, the obtained data testify that the Medicinskij sovet [Medical advice], 2013, culosis, normalization of both quantitative use of a combination of sirepar and sodi- №6, p. 45-51. DOI: 10.21518/2079- and functional indices of the T-cell link um nucleate preparations in the complex 701x-2017-0-33-37. of the immune response is noted. Con- of treatment of patients with CTLD and 2. Drel’ V. F., Vinogradov A. A. Poka- cerning the number of CD8 + and CD22 AChs with pathology of lung tuberculosis zateli pechenochnyh markerov syvorotki + lymphocytes in patients of the main is pathogenetically sound and clinically krovi pri toksicheskom porazhenii peche- group, these indicators also normalized effective, since this combination of drugs ni do i posle fizicheskoj nagruzki [Param- (table). contributes to both elimination of clini- eters of hepatic markers of blood serum In the comparison group, we also cal and biochemical manifestations of with toxic damage of the liver before and noted a positive dynamics of the studied the disease and normalization of indices after physical exertion] Nauchnye vedo- indices of the cellular immunity, but it is of immunological homeostasis, namely mosti [Scientific statements], 2013, №25 much less pronounced. Therefore, after the state of the cellular link of immunity. (168), Vyp. 24/1. p. 179- 182. the completion of treatment in the com- There were no any side effects from 3. Il’chenko L. YU., Korovich T. I. Le- parison group patients, there are shifts the use of the proposed combination of karstvennaya bolezn’ pecheni [Medicinal between the majority of the immunologi- drugs, including allergic reactions. disease of the liver] Rol’ gepatoprotekto- cal parameters studied, both in relation Conclusions. 1. The clinical picture rov v ee terapii. Medicinskij sovet [medi- to the main group and the corresponding of CTLD and AChP in the presence of cal advice], 2013, №10, p. 32-37. norm indicators (table). Thus, a signifi- infiltrative pulmonary tuberculosis is 4. Inyakova N.V. Rasprostranennost’ cant difference in the number of T-cells characterized by the presence of varying i metody korrekcii narushenij obmena (CD3 +) was established between the degrees of asthenic, asthenic-neurotic, zheleza pri tuberkuleznoj infekcii: avtoref. groups of patients both in relative terms mild cytolytic syndromes, anemia, hepa- diss. … kand. med. Nauk [Prevalence (an average of 11.6 ± 0.7%, P <0.05), and tomegaly, in some patients - cholestatic, and methods of correction of iron metab- in calculating the absolute number (in 1.3 as well as characteristic changes in the olism disorders in tuberculosis infection: times, P <0.05). The relative number of chest radiograph author’s abstract. diss. ... cand. med. sci- CD4 + lymphocytes in the comparison 2. Immunological examination re- ences] Federal’nyj nauchno-klinicheskij group after completion of treatment was vealed violations of the cellular immunity, centr detskoj gematologii, onkologii i im- 7.2 ± 0.5% lower than in the main group characterized by T-lymphopenia, an im- munologii Roszdrava [Federal Scientific (P <0.05), and the absolute number of balance in the subpopulation composition and Clinical Center for Pediatric Hema- CD4 + cells was 1.3 times (P < 0.05). The of T-lymphocytes, mainly by reducing the tology, Oncology and Immunology of the immunoregulatory index of CD4 / CD8 af- number of circulating lymphocytes circu- Federal Healthcare Service]. Ryazan’, ter the completion of the course of treat- lating in the peripheral blood, having a 2011, 26 p. ment in the main group was 1.16 times CD4 + (T helper / inducer) phenotype and 5. Knyaz’kova I.I. Anemiya higher than in the comparison group (P an immunoregulatory CD4 index / CD8, hronicheskih zabolevanij [Anemia of <0.05), the indicator of RBTL with PHA a significant decrease in the functional chronic diseases] Zdorov’ya Ukraїni [The was 1.33 times higher (P <0.05) . activity of T cells according to the data of health of Ukraine], 2016, №5, p. 48-49. Thus, the obtained data indicate that RBTL with PHA. In general, the obtained 6. Kovtun A.V., YAkovenko A.V., Iva- the use of a combination of sireppara data indicate the formation of a second- nov A.N. Lekarstvenno-inducirovannye and sodium nucleate helps to restore the ary immunodeficiency state, mainly on a porazheniya pecheni. Diagnostika i lech- indices of immunological homeostasis relatively suppressor version. enie [Drug-induced liver damage. Diag- in patients with CKTP and AChs on the 3. The use in the treatment of patients nostics and treatment] Gastroehnter- background of the transferred pulmonary with CTLD and AChs on the background ologiya [Gastroenterology], 2011, №2, p. tuberculosis, namely, it ensures the elimi- of the transferred pulmonary tuberculosis, 35-41. nation of T-lymphopenia, the normaliza- a combination of preparations of sirepar 7. Kozlov A.P., Popov N. N. Medi- tion of the relation between the helper and sodium nucleate contributes to the cinskaya statistika: uchebnoe posobie and suppressor subpopulations of T elimination of the clinical phenomena of [Modern estimation of the features of the cells, an increase in the indicator of RBLT the combined pathology, and along with medicinal liver damage in patients with from the PHA. the improvement or complete normaliza- pulmonary tuberculosis receiving spe- It is significant that in the clinical plan, tion of clinical parameters in the patients cific therapy]. Har’kov, izdat. centr HNU, the use of sirepar and sodium nucleate examined, there was an improvement in 2006, 88 p. in the treatment of drugs, accompanied biochemical parameters characterizing 8. Bereznikov A. V., Mordyk A. V., by an improvement in the well-being and the functional state liver. Konev V. P., Pis’mennyj I. V., Berezniko- general condition of the patients, primar- 4. In patients who received a combi- va T. N. Lekarstvennye porazheniya ily a reduction in general weakness, ma- nation of sirepar and sodium nucleate, pecheni s upornym techeniem u bol’nyh laise, increased capacity for work and ap- the normalization of the cellular immu- tuberkulyozom [Medicinal lesions of petite, and improved mood, disappeared nity parameters was noted, which gives the liver with persistent flow in patients in the right hypochondrium, the sub-skin grounds for recommendations on the use with tuberculosis]. Tuberkulyoz i bolezni and sclera. In the comparison group, we of the proposed combination of drugs in lyogkih [Tuberculosis and lung disease], also noted a positive dynamics of clinical complex treatment. 2010, №4. p. 43–46. indicators, but less pronounced. When 9. Mordyk A. V., Ivanova O. G., analyzing biochemical parameters, it References Nagibina L. A., Sitnikova S. V. Lekarst- was found that the activity of serum ami- 1. Antonenko O. M. Toksicheskie vennye porazheniya pecheni i ih lechenie notransferases practically normalized in porazheniya pecheni: puti farmako- v klinike tuberkuleza [Medicinal lesions of patients of the main group (96% of pa- logicheskoj korrekcii [Toxic liver damage: the liver and their treatment in the tuber- tients). ways of pharmacological correction]. culosis clinic] Tuberkulez i bolezni legkih 12 YAKUT MEDICAL JOURNAL

[Tuberculosis and lung disease], 2015, «Chelovek i lekarstvo» [Proceedings of №9, p. 47-52. DOI: 10.21145/2499-9954- the jubilee XX National Congress “Man The authors 2017-4-128-131. and Medicine”]. M., 2014, p. 386-408. 1. Nataliya Sidorova, Assistant of 10. Merkulov S. A., Koroleva M. V. 12. Petrenko V.І., Procyuk R.G. the Department of Phthisiology, Clinical Sovremennaya ocenka osobennostej Problema tuberkul’ozu v Ukraїnі [The Immunology and Medical Genetics of the lekarstvennogo porazheniya pecheni u problem of tuberculosis in Ukraine] State establishment of Lugansk people`s bol’nyh tuberkulezom legkih, poluchay- Tuberkul’oz. Legenevі hvorobi. VІL- republic Saint Luka state medical ushchih specificheskuyu terapiyu [Mod- іnfekcіya [Tuberculosis. Pulmonary dis- university, e-mail: 75natalyasidorova@ ern estimation of the features of the ease. HIV-infection], 2015, №2 (21), p. gmail.com, Lugansk, Street Ostraya medicinal liver damage in patients with 16-29. Mogila, 156/18; pulmonary tuberculosis receiving specific 13. Bogun L. V. Anemia of chronic 2. Sotskaya Yana, Doctor of therapy] Vestnik VolgGMU [Bulletin of disease [Anemia of chronic disease] Medical Sciences, Professor, Head of the VolgSMU], 2012, №2 (42), p. 19-22. Journal of V. N. Karazin` KhNU [Journal Department of Infectious Diseases and 11. Okovityj S.V. Aktual’nye voprosy of V. N. Karazin KhNU], 2015, 1154, p. Epidemiology named after V. M. Frolov primeneniya gepatotropnyh sredstv: lek- 81-87. of the State establishment of Lugansk cii dlya praktikuyushchih vrachej [Topical 14. Global TB report 2013 [ehl. people`s republic Saint Luka state issues of the use of hepatotropic drugs: resurs] //http: //apps.who.int /iris /bit- medical university, e-mail: Sotckaya@ lectures for practicing doctors] Trudy yu- stream /10665 /91355/1/9789241564656 mail.ru, Lugansk, Quarter Jugnii, 6. bilejnogo HKH Hacional’nogo kongressa eng.pdf.

M.P. Kirillina, A.K. Ivanova, E. L. Lushnikova CYTOLOGICAL ANALYSIS OF CERVIX INFLAMMATORY DISEASES IN DIFFERENT AGE GROUPS ON THE EXAMPLE DOI 10.25789/YMJ.2018.64.03 OF THE SAKHA (YAKUTIA) REPUBLIC

ABSTRACT Cytological analysis of cervix inflammatory diseases was conducted on women aged 18 to 88. The results of the analysis showed a high incidence of disease in the age groups 18-29. In the middle age group (30-44 and 45-59 years), balancing of genital infections is noted and the first effects of infection with viral infections appear (dysplasias of varying severity and background changes in the epithelium). In women in the older age group, mainly inflammatory processes (atrophic colpitis) were observed, which is associated with the intense influence of sex hormones. Generally, long-term preservation of viral HPV is associated with high-oncogenic risk types of HPV infection (mainly HPV 16). Remote causes of viral infection were found rarely (2.9%) on menopause, but it has the important prognostic value, which can predict the risk of cervical pathology development. Inflammation processes (senile vaginitis) are found in the old age group of women (20,9%), which is due to the intensive influence of sex hormones (estrogens). At this period the lack of estrogen harms the main protective properties of the stratified squamous epithelium. As a result, the number of lactobacilli is decreased or completely disappeared by the cause of conditionally pathogenic and pathogenic flora overgrowth. Thus, infectious-inflammatory diseases of the female genital organs caused by various pathogens, sexually transmitted diseases, or nonspecific microflora, represent a serious medical and social problem. Keywords: oncocytology, diagnostics, inflammation.

Relevance. Pelvic inflammatory transmitted infections [8, 12]. The (senile vaginitis); various physical and diseases (PID) establish itself as a immune system takes an important part chemical effects; earlier diseases that leading position in the structure of in the pathogenesis of female genital harm the immunity system; infections [1]. gynecological disorders, also become organs inflammation. Inflammation Modern PID is a problem of the most common cause of women’s and immune process are inextricably sexually active women. Recently most reproductive system disability. Thereby, linked, and currently, inflammatory and researchers find out that social factors it creates a major health, social and immune responses are considered as take the main part in the genesis of the economic problems worldwide [2, 7, 10, a complete whole [9]. Notice that at the PID progression, such as early sexual 11, 13, 15]. beginning of the pathological process debut, high sex frequency, high number The starting moment for the progression only one infectious agent activates the of sexual partners, sexual activity during of acute inflammatory diseases is the inflammatory response, changes local menstruation, using of drugs [6, 16]. invasion of microorganisms. Cervix is an immune system functioning. Thereby Many scientists consider that genital important protective barrier on the way it prepares the breeding ground for inflammatory process is the onset for plaque formation in the internal genital further contamination with opportunistic of majority gynecological diseases. organs. Almost all microorganisms pathogens [8, 14]. According to V. N. Serov et al, chronic those present in the vagina, except for There are different factors in cervix inflammatory process in the genital lactobacillus and bifidobacteria, can inflammatory process: bacterial organs responsible for the formation of be involved in the development of the imbalance; thinning of stratified such pathology as endometriosis, uterine inflammatory process [4]. However, in squamous epithelium in postmenopausal fibroid, hyperplastic processes, infertility most cases, PID is caused by sexually years along with the inflammatory process of various origins, neoplastic diseases 4’ 2018 13

of the cervix, as well as Note: in the numerator - indicators before the start of treatment, in the denominator - after its comple- functional disorders that tion; the probability of a difference in the indicators relative to the norm: * - for Р<0,05, ** - Р<0,01, violate the normal course *** - Р<0,001. of pregnancy [5]. Age Chlamydia and 18-29 30-44 45-59 60 years and Total trichomonas viruses have older the most severe course Inflammatory process 540 (29.8%) 348 (19.2%) 542 (29.9%) 379 (20.9%) 1809 (39%) and complications for Flora dysbiosis 740 (40.7%) 693 (38.2%) 337 (18.5%) 45 (2.5%) 1815 (39.2%) women’s health. Candidal colpitis 57 (49.5%) 38 (33%) 17 (14.8%) 3 (2.6%) 115 (2.5%) The importance of Trichomonas colpitis 29 (49.1%) 16 (27.1%) 13 (22%) 1 (1.7%) 59 (1.3%) inflammatory infection of Follicular cervicitis 47 (49.5%) 25 (26.3%) 13 (13.7%) 10 (10.5%) 95 (2%) the female genital system Remote causes of chlamydia 14 (29.7%) 18 (38.3%) 12 (25.5%) 3 (6.4%) 47 (1%) primarily determined by the fact that this disease Remote causes of viral infection 269 (39%) 269 (39%) 131 (19%) 20 (2.9%) 689 (14.9%) affects organs and tissues Total 1696 (36.6%) 1407 (30.4%) 1065 (23%) 461 (9.9%) 4629 (61%) of reproductive function. The Imbalance of bacteria Cytogram of the inflammatory process noted in age groups of 18-29 years, 47 in the vagina can be asymptomatic in marked by the presence of so-called cases (49.5 %) and 30-44 years, 25 almost half of affected women. Usually, it mixed bacterial flora, leukocytosis and cases (26.3%). Cytological results of has no any signs of disease, and remains reactive changes of the epithelium. this pathology are characterized by the without medical treatment [9]. Maximum incidence observed in the presence of lymphoid elements (fig.5). The aim of the study: to determine age group of 18-29 years - 740 cases In most cases, trichomonas vaginitis the incidence of cervix inflammatory (40.7 %) and 30-44 years 693 cases (1.3% of cases from total number of PID) diseases among women of different age (38.2 %). Next by incidence of occurrence were found in age group of 18 -29 years, groups. was inflammatory processes in 1809 49.1% (fig.6). Materials and methods. Cytological cases (39%). The highest incidence was Urogenital chlamydiosis is one of material of cervix has been analyzed recorded in the age groups of 45-59 the most common sexually transmitted in M.K. Ammosov NEFU Medical clinic years – 542 cases (29.9%) and 18-29 – infections. According to our data, 47 cases laboratory of pathomorphology, histology, 540 cases (29.8%). (1%) were diagnosed with remote causes and cytology. Material was taken from Currently, the greatest interest among of chlamydial infection (fig.7). The highest 7600 women aged 18 to 88, who appealed sexually transmitted infections represents incidence was registered in the age group to various medical centers of the Sakha the human papillomavirus (HPV). The of 30-44 years (38.3 %). The data of (Yakutia) Republic for prophylactic and main cytological feature is the presence cytological examination in the detection diagnostic purposes during 2017. of the so-called koilocytes, cells of layered of chlamydial infection are indicative Material for the cytological study was epithelium with an extensive perinuclear and should be supplemented by other smears taken from the cervical mucosa region of enlightenment of cytoplasm, research methods (immunofluorescence and cervical canal. Eliseev (2007) age and with a characteristic arrangement of analysis, polymerase chain reaction, classification was applied to identify nuclei («kissing») in smears (fig.2). etc.). trends of the epidemic process in different The study of remote causes of viral Conclusion: Hereby, the results of age groups. According to it, persons from infection were determined in 689 cases, cytological examination (fig.8) revealed 18-29 are young age, from 30-44 are which composed 14.9% of the total that inflammatory diseases of sexually mature age, from 45-59 are middle age, number of inflammatory diseases. In transmitted infections dominate among from 60-74 are old age [3]. general, the maximum incidence of women aged 18-29 years (49.5%). The diagnosis was conducted by this pathology registered on women of The main reason is the increased Romanovsky-Gimza staining method active reproductive age from 18 to 44 sexual behavior of young people, which Cytological diagnosis was determined years, 269 cases (39%) (fig.3). These registered at this age period. Frequent according to the clinical and morphological women are recommended to test HPV. sexual partners changes are causes classification of Bohman (1976). The highest response has a method dysbiosis of the vaginal flora. Usually, Results and discussion. The age of polymerase chain reaction (PCR), chronic inflammation occurs on young composition of the studied was as follows: unfortunately, there is no data on post- from 18 - 29 years - 2645 women (34,8%), process treatment, including PCR. The 30-44 years – 2315 women (30,4%), 45- complete virus-eliminating occurs in a 59 years – 1840 women (24.2%) and 60 carrier with a good immunological status. years and over - 800 women (10.5 %). This explains the disappearance of the Results of the cytological examination cytopathic effect of viral infection in the (table 1) diagnosed cervix inflammatory additional smear of HPV carrier. disease in 4629 cases; it is about 61% Candidal colpitis was registered of the total investigated women. In the among 115 (2.5 %) women: budding different age groups we registered the yeast cells, spores and pseudomycelium highest rate in the 18-29 years – 1696 in smears (fig.4). cases (36.6%), and 30-44years – 1407 Much less follicular cervicitis cases (30,4%). In women aged 45-59 (postmenopausal) and chronic years 1065 PID cases were noted (23%). inflammation (of childbearing age)is In most cases 1815 (39.2%) studied diagnosed and detected in 2% of cases Fig.1. The abundance of small bacteria, «clue women had flora dysbiosis (bacterial from the total number of inflammatory cell» in their smear ectocervix with bacterial vaginosis (BV) and Lactobacillus). diseases. The maximum incidence is vaginosis, x200 14 YAKUT MEDICAL JOURNAL

Fig.2. Binuclear or «kissing» nuclei in cervix smear for papillomavirus infection (conventional smear) and koilocyte for liquid-based cytology Fig.3. The frequency occurrence of remote causes of (staining method by Romanovsky-Gimza), x400 viral infection in different age groups women, who take oral contraceptives References and using the intrauterine device. In 1. Аnkirskaya А.S. the middle age group (30-44 and 45- Bakterial’nyj vaginoz: osobennosti 59), genital infections and dysbiosis klinicheskogo techeniya, are balanced, which associated with a diagnostika i lechenie / А.S. stabilization of family relations. Аnkirskaya [i dr.] [Bacterial The maximum frequency of remote vaginosis: features of the clinical causes of viral infection depends on age course, diagnosis and treatment] that shows the peak detection in the age Rus. med. zhurn. [Rus. honey. groups of 18-29 years and 30-44 years. Journal]. Moscow, 1998, V.6, №5, HPV infection disappears by itself within p. 276-282. 12 months after diagnosis date in about 2. Krasnopol’skiy 70% of young women cases. Generally, V.I. Vliyaniye infektsiy na long-term preservation of viral HPV is reproduktivnuyu sistemu associated with high-oncogenic risk zhenshchin [Influence of infections Fig.4. Thrush. Pseudomycelium and fungal spores in types of HPV infection (mainly HPV 16) on the reproductive system of the smear from the cervix, x400 [2]. Remote causes of viral infection were found rarely (2.9%) on menopause, but it has the important prognostic value, which can predict the risk of cervical pathology development. Inflammation processes (senile vaginitis) are found in the old age group of women (20,9%), which is due to the intensive influence of sex hormones (estrogens). At this period the lack of estrogen harms the main protective properties of the stratified squamous epithelium. As a result, the number of lactobacilli is decreased or completely Fig.6. Trichomonas and leucocytes in a disappeared by the cause of conditionally smear from the ectocervix with trichomonas Fig.5. Follicular cervicitis. x200 pathogenic and pathogenic flora colpitis. X400 overgrowth. Thus, infectious-inflammatory diseases of the female genital organs caused by various pathogens, sexually transmitted diseases, or nonspecific microflora, represent a serious medical and social problem. This work is based on R&D ”Epidemiology aspects of cancer on the Far North living environment, development of methods for the prevention, diagnosis, treatment using the high-informative basic research methods (М06;01;01)» (№ 0556-2014- Fig.7. Layers of metaproterenol epithelium cells with vacuoles of various size, which contain fills 0006). associated with different stages of the chlamydial infection development. x400 4’ 2018 15

– Vol. 30, N 4. – P. 777-793. 12. Mardh P.A. Tubal factor infertility, with special regards to chlamydial salpingitis /P.A. Mardh //Curr. Opin. Infect. Dis. – 2004. – Vol. 17, N 1. – P. 45-52. 13. Pelvic Inflammatory Disease / Edited by R.L. Sweet, H.C. Wiesenfeld. – London and New York: Taylor & Francis, 2006. – 173 p. 14. Price B. Outpatient management of pelvic inflammatory disease / B. Price, M. Martens // Curr. Womens Health Rep. – 2001. – Vol. 1, N 1. – P. 36-40 15. Quentin R. Pelvic inflammatory disease: medical treatment /R. Quentin, J. Lansac //Eur. J. Obstet. Gynecol. Reprod. Biol. – 2000. – Vol. 92, N 2. – P. 189-192. 16. Viberga I. Characteristics of Fig.8. The rate of incidence of cervix inflammatory diseases among women of different age women at low risk of STI presenting with groups pelvic inflammatory disease / I. Viberga, V. women] Rossiyskiy vestnik akushera diseases of the uterus and appendages: Odlind, G. Lazdane // Eur.J. Contracept. ginekologa [Russian bulletin of pathogenesis, clinical and morphological Reprod. Health Care. – 2006. – Vol. 11, N obstetrician of gynecologist]. Moscow, characteristics, treatment]. Chelyabinsk, 2. – P. 6068. 2004, V. 4, № 5, p.26-29. 2001, р.280. 3. Vozrastnye bolezni: poln. 8. Serov V.N. Sovremennyye The authors sprav. [Age diseases] Pod.red. YU. YU. printsipy terapii vospalitel’nykh 1. Kirillina Maria - candidate of Eliseev [edition Y.Y. Yeliseyev]. Moscow, zabolevaniy zhenskikh polovykh Biological Sciences, Senior Research EHksmo, 2007, 736p. organov [Modern principles of therapy of Scientist, Head of Yakut Science Centre 4. Gazazyan M.G. Optimizaciya inflammatory diseases of female genital of complex medical problems laboratory, diagnostiki i lecheniya hronicheskih organs] Metod. posobiye dlya vrachey Head of M.K. Ammosov North Eastern sal’pingooforitov [Optimization of [Method. manual for doctors]. Moscow, Federal University Medical Institute Clinic diagnosis and treatment of chronic 2003, p.23. laboratory, [email protected], Yakutsk, salpingo-oophoritis] Rossiyskiy vestnik 9. Serov V.N. Immunomodulyatory Russia; akushera-ginekologa [Russian bulletin v kompleksnoy terapii vospalitel’nykh 2. Ivanova Anna - clinical of the obstetrician-gynecologist]. 2009, zabolevaniy organov malogo pathologist of M.K. Ammosov North Moscow, V. 9, №3, p. 67-71. [Immunomodulators in the complex Eastern Federal University Medical 5. Serov V.N. Ginekologiya: therapy of inflammatory diseases of the Institute Clinic, ivanova.ak11@gmail. Rukovodstvo dlya vrachey [Gynecology: pelvic organs]. RMZh [RMZH]. Moscow, com, Yakutsk, Russia. A Guide for Physicians]. Moscow: Litterra 2011, №20, p.20-21. 3. Lushnikova Elena Leonidovna: [Litterra]. 2008, p.840. 10. Barrett S. A review on pelvic Doctor of Biological Sciences, Professorб 6. Krasnopol’skij V.I. Gnojnaya inflammatory disease /S. Barrett, C. Head of Institute of Molecular Pathology ginekologiya [Purulent gynecology]. Taylor // Int. J. STD AIDS. – 2005. – Vol. and Pathomorphology Federal State Moscow, MEDpress, 2001, p.288. 16, N 11. – P. 715-720. Budget Scientific Institution «Federal 7. Medvedev B.I. Vospalitel’nyye 11. Beigi R.H. Pelvic inflammatory Research Center of Fundamental zabolevaniya matki i pridatkov: disease: new diagnostic criteria and and Translational Medicine» 630117, patogenez, kliniko-morfologicheskaya treatment /R.H. Beigi, H.C. Wiesenfeld // Novosibirsk, Timakov’s Str., 2; tel.: +7 kharakteristika, lecheniye [Inflammatory Obstet. Gynecol. Clin. North Am. – 2003. (383)334-80-03; [email protected].

V.M. Nikolaev, E.V. Tsypandina, E.V. Rumyantsev E.K., S.I. Sofronova, F.V. Vinokurova, S.D Efremova., E.N. Aleksandrova, F.G. Ivanova, P.M. Ivanov, S.A. Fedorova EVALUATION OF GLUTATHIONE SYSTEM INDICATORS IN THE BODY OF PATIENTS DOI 10.25789/YMJ.2018.64.04 WITH LUNG CANCER

ABSTRACT Glutathione is very important in cells protecting, however, its high concentration in tumor cells can increase their survival by raising resistance to chemotherapeutic drugs and free radical oxidation. The effectiveness of chemotherapy treatment often depends on the individual genetic characteristics of the patient, his sensitivity to pharmaceutical drugs. According to scarce existing research it is indicated that tolerability of chemotherapy among Asians is lower compared to Caucasians. In this regard, we decided to evaluate the influence of ethnicity on the indicators of the glutathione system in patients with lung cancer and persons not suffering from oncopathology. 16 YAKUT MEDICAL JOURNAL

We examined 50 people with lung cancer, admitted to the Yakut Republican Oncology Center. The control group was selected based on age, gender and ethnicity and included 50 people. The main criterion for selection in the control group was the absence of cancer. The concentration of reduced glutathione, TBA-active products, activity of glutathione reductase, glutathione-S-transferase, glutathione peroxidase were determined by the spectrophotometric method. The results of our study showed that the concentration of reduced glutathione (Yakuts by 70.7, Russians by 52.4%), the activity of glutathione peroxidase (Yakuts by 34.4, Russians by 18.6%) in the body of patients had been decreasing. The activity of glutathione reductase in the body of patients with lung cancer decreased in Yakuts by 10.5%, while in Russians it increased by 13.0%. The results of our research testify to the depletion of the glutathione system in the group of cancer patients of the Yakut ethnicity, which is probably the reason for the severe tolerance of chemotherapy. Keywords: glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, TBA-active products, glutathione system. Introduction. Glutathione is an in- based on age, gender and ethnicity and it was 2.50 ± 0.05 μM / gHb, in the sec- tracellular tripeptide consisting of the included 50 people. The main criterion for ond - 2.04 ± 0.06 μM / gHb, that is, in the amino acids: L-glutamate, L-cysteine and selection in the control group was the ab- Yakuts it was higher by 18.4%, compared L-glycine, it is present in the cells of all sence of cancer. The study material was to the Russians. eukaryotes, including tumor cells. The venous blood, which was taken on an Glutathione reductase activity was 6.8 concentration of glutathione in the cells is empty stomach from the ulnar vein. ± 0.30 μM GSSG / min * g Hb. The level very high, reaching from 1 to 10 mM [15]. The concentration of indicators of the of the average activity of glutathione re- The main reservoirs of this tripeptide in glutathione system was determined in ductase in the first group (7.5 ± 0.10 the cell are: cytosol (90%), mitochondria erythrocytes, and the level of TBA-AP in µMGSSG / min * gHb) was 20% higher (10%) and a small percentage falls to the blood serum using SF-2000 spectropho- (p <0.05) than in the second (6.01 ± 0.30 share of the endoplasmic reticulum [13]. tometer. The content of reduced glutathi- µMGSSG / min * hb). The glutathione metabolism proceeds one was determined by the reaction with Glutathione-S-transferase activity was fairly quickly, for example, in the liver of 5.5-dithiobis (2-nitrobenzoic acid) at 412 2.44 ± 0.07 µMGSH / min * gHb. We ob- rats, the period of its half-life is only 2-3 nm and was expressed in μM/gHb [2]. served a decrease in the activity of glu- hours [4]. Glutathione reductase activity was deter- tathione-S-transferase in the first group Glutathione readily reacts with electro- mined by the oxidation rate of NADPH + (2.20 ± 0.06 μM GSH / min * gHb) by 9% philic compounds (carcinogens, drugs), in the presence of oxidized glutathione at compared with the second group (2.42 ± reducing their toxicity [14]; in the nucle- 340 nm and expressed in μMGSSG/min 0.03 μM GSH / min * gHb). us, it promotes the repair of damaged * gHb. Glutathione-S-transferase activity The level of glutathione peroxidase DNA [3]; neutralizes free radicals and was determined at 340 nm by the rate was 6.10 ± 0.005 μM GGSH / min * peroxides [11]; provides active transport of formation of conjugates with 1-chlo- gHb. Depending on the ethnicity, differ- of amino acids [6]; participates in the ro-2.4-dinitrobenzene in the presence ences in enzyme activity were noted: in modulation of the immune response [8], of reduced glutathione and expressed in the first group (6.50 ± 0.009 μM GGSH / regulates the redox state of the thiol pro- μM GSH / min * g Hb [10]. Glutathione min*gHb), it was significantly higher (by teins NFkB, caspase, which are involved peroxidase activity was determined at 35.4%) than in the second (4.20 ± 0.002 in apoptosis [12]. It should be noted that 412 nm in the tertiary butyl hydroperoxide μM GH /min* ghb). glutathione is very important in cells pro- cleavage reaction using reduced glutathi- The concentration of the lipid peroxi- tecting, however, a high concentration of one as a substrate. The enzyme activity dation index - TBK-AP was equal to 1.61 glutathione in tumor cells can increase was expressed in μM GSH / min * gHb ± 0.10 μM / l and depended on ethnicity. their survival by increasing their resis- [1]. The level of TBA-AP was determined So, in the first group this indicator cor- tance to chemotherapeutic drugs and by the reaction of the end products of responded to 1.71 ± 0.16 μM / l, in the free radical oxidation [5]. free radical oxidation of lipids with thio- second - 1.38 ± 0.28 μM/l, i.e. in the first The effectiveness of chemotherapy barbituric acid to form a colored trime- group, the level of TBA-AP was higher by treatment often depends on the individ- thine complex, which was measured at a 19.3% (p <0.05). ual genetic characteristics of the patient, wavelength of 532 nm and expressed in Depending on the ethnicity of rela- his sensitivity to pharmaceutical drugs μM / L [17]. tively healthy individuals, the indicators [9, 16]. According to scarce existing re- Statistical processing of the data was of the glutathione system change. In the search it is indicated that tolerability of performed using the SPSS for Windows Yakut group higher concentrations of chemotherapy among Asians is lower 10.0 application statistical software reduced glutathione (18%), glutathione compared to Caucasians [7]. In this re- package. Standard methods of variation reductase activity (20%) and glutathione gard, we decided to evaluate the influ- statistics were used: calculation of aver- peroxidase (35.4%) are noted. We also ence of ethnicity on the indicators of the ages, standard errors, 95% confidence noted the intensification of free radical glutathione system in patients with lung interval. The significance of differences oxidation of lipids in the body of Yakuts, cancer and persons not suffering from between averages was evaluated using as evidenced by an increase in the con- oncopathology. Student’s t test for independent samples. centration of TBA-AP by 19.3%. The objective of this study is to as- The data in the tables are presented as In the body of patients with cancer, the sess the level of glutathione levels in the M ± m, where M is the average, m is the concentration of reduced glutathione was body of patients with lung cancer. average error. The probability of the va- significantly lower (by 28.8%) compared Research materials and methods. lidity of the null hypothesis was taken at with those not suffering from oncopathol- 50 people with lung cancer, admitted to p <0.05. ogy and was equal to 1.65 ± 0.01 µM / the Yakut Republican Oncology Center Results and discussion. According gHb. This can probably be caused by a were under study. The diagnosis of lung to our data, the content of reduced glu- high rate of consumption and a low rate cancer was confirmed histologically. The tathione in the group of relatively healthy of its recovery. Maintaining a sufficiently patients were divided into two groups people not suffering from oncopathology high level of reduced glutathione by re- according to ethnicity: the first group is was 2.32 ± 0.09 μM / gHb. The concen- storing its disulfide form is provided by the Yakuts, the second group is the Rus- tration of reduced glutathione changed glutathione reductase. Glutathione re- sians. The control group was selected depending on ethnicity: in the first group ductase activity in the group of patients 4’ 2018 17

was less by 36.7% than in the control, our research have shown that in patients 420117-0.00002-5 and was 4.30 ± 0.05 μM GSSG / min * with lung cancer, indicators of the gluta- 7. Ethnic Difference in Hemato- g Hb. Consequently, the regeneration of thione system vary depending on ethnic- logical Toxicity in Patients with Non-small glutathione in the blood erythrocytes of ity. Among patients the concentration of Cell Lung Cancer Treated with Chemo- patients with lung cancer at the proper reduced glutathione in the Yakuts de- therapy A Pooled Analysis on Asian ver- level does not occur. We consider the creased by 34.4%, Russians - by 18.6%, sus Non-Asian in Phase II and III Clinical most likely cause of this phenomenon an glutathione peroxidase activity - by 70.7 Trials / Y. Hasegawa, T. Kawaguchi, A. insufficient regeneration of NADPH+H+ and 52.4%, respectively. The activity of Kubo [et.al] // Journal of Thoracic Oncol- in the pentose phosphate pathway. The glutathione reductase in the body of pa- ogy. – 2011. - №11 (6). P. 1881-1888. activity of glutathione-S-transferase did tients with lung cancer decreased in the ISSN: 1556-0864/11/0611-1881 not actually differ from the control, it was Yakuts by 10.5%, while in the Russians 8. Glutathione fine-tunes the in- equal to 2.42 ± 0.01 µM GSH / min * it increased by 13.0%. The results of our nate immune response toward antiviral gHb. Glutathione peroxidase activity de- research testify to the depletion of the pathways in a macrophage cell line increased by 68.8% (1.9 ± 0.001 μM GSH glutathione system in the group of cancer dependently of its antioxidant properties / min * gHb) than in the control group. In patients of the Yakut ethnicity, which is / M. Diotallevi, P. Checconi, A. T. Pala- patients with lung cancer, a significant probably the reason for the severe toler- mara [et al.] // Frontiers in Immunology. increase in free radical oxidation of lip- ance of chemotherapy. – 2017. – №8. – P.1239. DOI: 10.3389/ ids was noted. The average content of This study was conducted in the fimmu.2017.01239 TBA-AP in the blood of patients with lung framework of the research work “Epide- 9. Hollman A. L. The Association cancer was 32.6% higher than the control miological aspects of malignant tumors in between gene-environment interactions value and was 2.39 ± 0.32 μM/L. the conditions of the Far North, the de- and diseases involving the human GST In the group of patients, the concentra- velopment of modern methods for early superfamily with SNP variants / A. L. Hol- tion of the reduced form of glutathione, as diagnosis, prevention using highly infor- lman, P. B. Tchounwou, H. C. Huang // well as the activity of glutathione reduc- mative fundamental research methods” International Journal of Environmental tase, did not have significant differences in the department of studying the adap- Research and Public Health. – 2016. depending on ethnicity. In the first group tation mechanisms of the Yakut Science – №13 (4). – P.1–14. DOI: 10.3390/ of patients, the content of reduced glu- Center of Complex Medical Problems. ijerph13040379 tathione was 34.4% less (P <0.05) com- 10. Increase in blood glutathione pared with the control group (1.64 ± 0.01 References and erythrocyte proteins related to gluta- µM / gHb), in the second group of pa- 1. Alwaleedi S. A. Alterations in thione generation, reduction and utiliza- tients it was 18.6% lower (P <0.05) (1.66 antioxidant defense system in hepatic tion in african-american old women with ± 0.009 μM / gHb). Glutathione reductase and renal tissues of rats following aspar- diabetes / G. Shan, F. Yang, L. C. Zhou activity in the first group of patients was tame intake / S. A. Alwaleedi // Journal [et al.] // Journal of Science, Technology 10.5% lower (6.71 ± 0.09 μM GSSG / of Applied Biology and Biotechnology. – and Environment Informatics. – 2015. – min * gHb), and in the second group of 2016. – №4(2). – P.46–52. DOI: 10.7324/ №5 (1). – P.1-15. PMID: 26770888 patients it was 13.0% higher than control JABB.2016.40207 11. Kurutas E. B. The importance of (6.9 ± 0.15 μM GSSG / min * hb). 2. Analysis of GSH and GSSG af- antioxidants which play the role in cellu- Significant differences in the activity ter derivatization with N-ethylmaleimide lar response against oxidative/nitrosative of the enzyme performing the detoxifica- / D. Giustarini, I. Dalle-Donne, A. Mil- stress: current state / E. B. Kurutas // Nu- tion function in patients with lung cancer, zani [et al.] // Nature Protocols. – 2013. trition Journal. – 2016. – №15. – P.1–22. depending on ethnicity, were not found. – №8 (9). – P.1660-1669. DOI: 10.1038/ DOI: 10.1186/s12937-016-0186-5 Glutathione-S-transferase activity in the nprot.2013.095. 12. L-Cysteine protects intestinal first group of patients was 7.1% (2.37 ± 3. Bansal A. Glutathione metabo- integrity, attenuates intestinal inflamma- 0.15 μM GSH / min * gHb), in the second lism in cancer progression and treatment tion and oxidant stress, and modulates group 3.0% (2.49 ± 0.25 μM GSH / min * resistance / A. Bansal, M. C. Simon // NF-iB and Nrf2 pathways in weaned gHb) above the control value. Journal of cell biology. – 2018. – №217 piglets after LPS challenge / Z. Song, G. An assessment of the enzymatic sta- (7). – P.2291–2298. DOI: 10.1083/ Tong, K. Xiao [et.al] // Innate Immunity. tus of antioxidant protection in the blood jcb.201804161 – 2016. – №22 (3). – P.152–161. DOI: of patients with lung cancer showed that 4. Bilinsky. L. M. The role of skel- 10.1177/1753425916632303 glutathione peroxidase activity in both etal muscle in liver glutathione metabo- 13. Lu S. C. Glutathione synthesis / groups of patients was significantly -re lism during acetaminophen overdose / L. S. C. Lu // Biochimica et Biophysica Acta. duced. In the first group, the glutathione M. Bilinsky, M. C. Reed, H. F. Nijhout // – 2013. – №1830 (5). – P.3143–3153. peroxidase activity was 70.7% less than Journal of Theoretical Biology. – 2015. DOI: 10.1016/j.bbagen.2012.09.008. the control (1.90 ± 0.005 μM GSH / min * – №376. – P.118–133. DOI: 10.1016/j. 14. Ramsay E. E. Glutathione S- gHb); and in the second group - by 52.4% jtbi.2015.04.006. conjugates as prodrugs to target drug- (2.00 ± 0.012 μm GSH / min * gHb). 5. Corso C. R. Glutathione system resistant tumors / E. E. Ramsay, P. At the same time, the intensity of free in animal model of solid tumors: from reg- J. Dilda // Frontiers in Pharmacology. radical oxidation in the body of cancer ulation to therapeutic target / C. R. Corso, – 2014. – №5. – P.1-16. DOI: 10.3389/ patients increased, as evidenced by the A. Acco // Critical Reviews in Oncology / fphar.2014.00181 increase in the content of TBA-AP in Hematology. – 2018. – №128. – P.43–57. 15. Real-Time monitoring of glu- patients of the first group to 2.35 ± 0.12 DOI: https://doi.org/10.1016/j.critrev- tathione in living cells reveals that high μmM / l, which was 27.2% higher than onc.2018.05.014 glutathione levels are required to main- the control (P <0.01), the second group 6. Emerging regulatory paradigms tain stem cell function / E. M. Jeong, J. H. was equal to 2.45 ± 0.25 μM / L, which in glutathione metabolism / Y. Liu, A. S. Yoon, J. Lim [et.al] // Stem Cell Reports. exceeds the control indicators by 43.6% Hyde, M. A. Simpson [et.al] // Advances 2018. – №10 (2). – P.600–614. DOI: (P <0.05). in Cancer Research. – 2014. – №112. 10.1016/j.stemcr.2017.12.007 Conclusions. Thus, the results of – P.69–101. DOI: 10.1016/B978-0-12- 16. Significance of polymorphisms 18 YAKUT MEDICAL JOURNAL

and expression of enzyme-encoding Studying the Mechanisms of Adaptation Yakutsk, ul. Sergelyahskoe highway, 4, genes related to glutathione in hema- of the Yakut Science Center of Complex tel.: (4112) 39-55-48, e-mail: sara2208@ topoietic cancers and solid tumors / S. Medical Problems, 677010, Yakutsk, ul. mail.ru. Zmorzynski, G. Uwiderska-Kobacz, D. Sergelyahskoe highway, 4, tel .: (4112) 7. Ivanov Pyotr Mikhailovich - Koczkodaj [et.al] // BioMed Research In- 32-19-81, e-mail: [email protected]. Ph.D., Leading Researcher, Department ternational. – 2015. – P.1-6. DOI: http:// 3. Vinokurova Fekla Vasilyevna - of Epidemiology of Chronic Noncommu- dx.doi.org/10.1155/2015/853573 Researcher of the Department of Study- nicable Diseases, Yakut Science Center 17. The concentration of thiobarbi- ing the Mechanisms of Adaptation of of Complex Medical Problems, 677010, turic acid reactive substances (TBARS) the Yakut Science Center of Complex Yakutsk, ul. Sergelyahskoe highway, 4, and paraoxonase activity in blood of pa- Medical Problems, 677010, Yakutsk, ul. tel.: (4112) 45-04-02, e-mail: ynckmp@ tients with osteoarthrosis after endopros- Sergelyahskoe highway, 4, tel .: (4112) yandex.ru. thesis implantation / D. M. Olszewska- 32-19-81, e-mail: [email protected]. 8. Aleksandrova Elena Nikolaevna Słonina, D. Mątewski, R. Czajkowski [et. 4. Tsipandina Evgenia Viktorovna - - head of the outpatient department of the al] // Medical Science Monitor. – 2011. Junior Researcher of the Department of Yakut Republican Oncologic Dispensary, – №17(9). – P.498–504. DOI: 10.12659/ Studying the Mechanisms of Adaptation 677005, ul. Sverdlov, 3/1, (4112) 50-76- MSM.881936. of the Yakut Science Center of Complex 53, e-mail: [email protected]. Medical Problems, 677010, Yakutsk, ul. 9. Ivanova Feodosia Gavrilievna The authors Sergelyahskoe highway, 4, tel.: (4112) - PhD, Head of the Department of 1. Nikolaev Vyacheslav Mikhailov- 32-19-81, e-mail: [email protected]. Antitumor Drug Therapy of the Yakut ich - Ph.D., Head of the Department of 5. Rumyantsev Egor Konstanti- Republican Oncology Center, 677005, Studying the Mechanisms of Adaptation novich - Junior Researcher of the Depart- ul. Sverdlov, 3/2, tel.: (4112) 50-76-50, of the Yakut Science Center of Com- ment of Studying the Mechanisms of Ad- e-mail: [email protected]. plex Medical Problems, 677010, Ya- aptation of the Yakut Science Center of 10. Fedorova Sardana Arkadyevna kutsk, ul. Sergelyahskoe highway, 4, tel Complex Medical Problems, 677010, Ya- - Doctor of Biological Sciences, Head of .: (4112) 32-19-81; Associate Professor, kutsk, ul. Sergelyahskoe highway, 4, tel .: the Research Laboratory of Molecular Department of Agronomy and Chem- (4112) 32-19-81, e-mail: tzeentch1993@ Biology at the M.K. Ammosov North- istry, Yakutsk State Agricultural Acad- mail.ru. Eastern Federal University, 677000, emy 677010, Yakutsk, ul. Sergelyahskoe 6. Sofronova Sargylana Ivanovna highway, 3, tel .: (4112) 507-971, e-mail: - PhD, Head of the Scientific-Organiza- Yakutsk, ul. Kulakovskogo 46, room [email protected]. tional and Information and Publishing 504, tel.: (4112) 49-68-42, e-mail: 2. Efremova Svetlana Dmitrievna - Department of the Yakut Science Center [email protected]. Junior Researcher of the Department of of Complex Medical Problems, 677010,

R.Z. Alekseev, A.S. Golderova, S.N. Mamayeva, N.A. Nikolaeva, M.T. Buzinayeva ASSESSMENT OF CHANGE OF ERYTHROCYTES BY METHOD OF RASTER ELECTRONIC MICROSCOPY AT THE PERSONS WHO DIED OF FATAL DOI 10.25789/YMJ.2018.64.05 HYPOTHERMIA

ABSTRACT Red blood cells (RBC) morphology of deceased from various causes (injury, hypothermia) was examined in this study by using scanning electron microscopy. The obtained data shows that the appearance of certain forms of cadaveric erythrocytes depends on the causes of death. Therefore, when death is caused by stabbing and gunshots RBC take acanthocyte forms and in cases of fatal hypothermia RBC take echinocyte forms. The results of an experiment carried out in vitro, at small negative temperatures,show the appearance of acanthocytes in observed blood samples. Based on theobtained data and on the ability of echinocyte to return to normal form, it can be concluded that the probability of restoring the vital activity of the frozen organismsare possible. Keywords: red blood cells, erythrocytes,hypothermia, scanningelectron microscopy.

Introduction. Frostbite and is that during the first 2 days when the available to the public, there are no data hypothermiaare the most severe types of victims are in a state of cold anabiosis on the SEM study of the RBCs of people cold trauma, often leading to a high level (a very rare pulse, low blood pressure) who diedfrom the cold temperatures. of disability and death of the affected [1]. it is may be possible to restore the vital Revealing the features of the Till present time, the questions of death activity of the organism(there are cases morphology of the blood cells of the from freezing in conditions of extremely of preservation of the vital functions deceased from hypothermia may possibly low temperatures (below -40°C) have of the heart and other organs in frozen supplement the idea of the cellular- not been fully examined in the world. In animals).The results of our work suggest molecular mechanisms of the process real conditions, people who died from a theoretical probability of the restoration of general cooling of the organism and hypothermia (by external signs) without of frozen tissues, organs, and also the confirm the possibility of restoring the carrying out resuscitation measures are revitalization of the frozen organisms. vital activity of the organism. delivered to the morgue. The key-point At present time, in the literature The purpose of this article is toexamine 4’ 2018 19

the morphological changes in RBCs temperatures of + 8.0 ° C; + 2.0 ° C; - In Fig. 3 shows the erythrocytes of a from cadaveric material (cause of death: 1.7 ° С; + 12.5 ° C and + 31.0 ° C. man who died of a gunshot wound whose hypothermia) using a scanning electron Blood sampling from deceased persons blood smear was made on the second microscopy. from hypothermia was made from the day after the onset of death. Materials and methods of research. brain region where the temperature In the case of a gunshot wound, the The study was carried out using a high- was maximum (from +6 ° C to 20 ° C) changed erythrocytes are similar in form resolution scanning electron microscope compared to other tissues and organs. to acanthocytes. The same dysmorphic (SEM) JSM-7800F («Japanese Electron The minimum temperature in the soft erythrocytes are also observed in Fig. Optics Laboratory» - «JEOL», Japan) tissues of the upper and lower extremities 1 in the case of a stab wound wound. in UNTL «Graphene nanotechnology» was -40 ° C, in the lungs +12 ° C, in the In contrast to Fig. 2 there are signs of M.K. Ammosov NEFU. The subjects liver +10 ° C. hemolysis of erythrocytes, i.e. a small of the study were blood smears from Results and discussion. There is number of fragments of erythrocytes cadaveric material of the deceased a problem of differentiation of the forms are seen, almost all cells form from various causes of death, including of acanthocytes and echonocytes, conglomerates. Unlike the first case, the hypothermiaprepared by the Bureau of therefore in this work for the evaluation amount of unchanged red blood cells is Forensic Medical Examination of the of erythrocyte species the results of significantly less, which may be due to a Ministry of Health of the Republic of other studies [3] were used, where temporary factor: in the second case, a Sakha (Yakutia). the characteristic parameters of smear was made on the second day after The device has a Schottky thermo- differentiation of different forms of the onset of death, while in the case of a field emission cathode and a superhybrid erythrocytes and their association with stab wound cut, a day later. objective lens that significantly reduces diseases based on images obtained In Fig. 4 depicts images of red blood chromatic and spherical aberration and with the scanning electron microscope cells of a 25-year-old man who died from significantly increases the resolution, SAM). Figure 1 shows the characteristic hypothermia. The blood was taken a day especially at low accelerating voltages. forms of erythrocytes - acanthocytes (A), later. The SEM used in the experiment echinocytes (E) and schizocytes (S). In this figure, all the red blood cells (enlargement range of 25 - 1 000 000) Echinocytes have small identical are changed and most likely they can be allows us to to examine the object at protuberances distributed evenly, while attributed to echinocytes, and they are an accelerating voltage of 0.1-30 kV. acanthocytes are protuberances of evenly distributed in one layer. In contrast The device is equipped with 4 types of various sizes and are unevenly distributed to the previous images in this figure, it detectors: the upper electron detector, over the surface of the cell. is observed that all red blood cells are the upper secondary electron detector, During the study of blood smears, REM interconnected very tightly and form small the backward reflected electron detector images of erythrocytes were obtained for groups. The processes of erythrocytes in and the lower secondary electron various causes of death. In Fig.2.images the frozen have a more acute form than detector. In this study a lower secondary of red blood cells of a young man whose those of the deceased from wounds, and electron detector was used. This mode blood smear was made the day after his also more evenly distributed over the allows reducing the effect of electrostatic death are presented. Death occurred entire surface of the erythrocytes. charge on the surface of the sample, within 30 minutes as a result of a stab which significantly improves the image wound. quality of the erythrocyte surface. In the field of vision with an increase in Used in the study of blood smears, 1000 times, the prevalence of dysmorphic the SEM JSM-7800F is equipped with erythrocytes is observed in comparison the «Gentle Beam» system, which with normal ones. It should be noted that allows to reduce the speed of electrons the dysmorphic erythrocytes are close in falling on the sample and accelerate shape to the acanthocytes. Unchanging the electrons emitted by them, which cells form small «coin pillars», and the significantly improves image quality at modified cells are tightly connected to low accelerating voltages. each other by processes. In this image, The «Gentle Beam» system allows for fragments of hemolyzed erythrocytes are the study of erythrocytes in blood smears not observed. Fig.1. SEM images of erythrocyte forms without the deposition of conductive coatings and without damaging the objects under investigation for a time sufficient to make the necessary photographs [2]. Investigations of blood smears were carried out at accelerating voltages of 1 and 2 kV with a voltage applied to the investigated object of 8-10 V. An experimental study of volunteer blood cells in vitro was also conducted. Blood, placed in a glass tube, was gradually cooled, and then warmed. During the cooling and heating, 6 blood smears were made alternately: immediately after venous blood sampling Fig.2. SEM images of erythrocytes died from a stab wound: a) with an increase of x1000, b) with at a temperature of + 36.6 ° C; then at an increase of x5000 20 YAKUT MEDICAL JOURNAL

In addition to studies of blood cells various temperature effects on a blood C to + 2.0 ° C), no significant changes from cadaveric material, REM studies sample. in the morphology of erythrocytes are of blood cells of a young male volunteer The blood in the test tube was observed (Fig. 5). However, at a negative were performed. cooled gradually and as the cooling temperature (-1.7 ° C), dermorphic In Fig. 5-6 presents SEM images of was carried out applying blood smears erythrocytes appear in a small amount erythrocytes of blood smears of a living to the slide. Obviously, with positive in a form close to the acanthocytes healthy person on a slide, obtained at blood temperature values (from + 36.6 ° (Figure 6), as well as a small number of schizocytes. In addition, the formation of coins and conglomerates of erythrocytes is observed. Then gradually the blood was heated. The REM images of erythrocytes obtained with the heating of blood do not differ from their images obtained after exposure to negative temperature. The results obtained by us show that the appearance of certain forms of erythrocytes of cadaveric material depends on the causes of death. So, when dying from a stab-cut and gunshot wounds, erythrocytes take acanthocyte forms, and when undercooling, they take Fig.3. SEM images of erythrocytes died of a gunshot wound: a) with an increase of x1000, b) echinocyte forms. with an increase of x5000 In the results of the experiment conducted in vitro, at small negative temperatures in SEM images, the appearance of acanthocytes is observed as in cases of death from wounds. In the deceased from hypothermia and other causes, blood samples were taken at approximately the same small positive temperatures. It should be noted that in the case of in vitro red blood cells did not change their forms up to a temperature value of + 2.0 ° C. This suggests that the appearance of acanthocytes in the blood of the deceased from hypothermia is Fig.4. SEM images of erythrocytes deceased from hypothermia: a) with an increase in x1000, possible only with prolonged stagnation b) with an increase of x5000 of the corpse in a medium with a negative temperature, i.e. Provided that the temperatures of the internal vital organs decrease to negative values. According to the results of this study, the comparison of dysmorphic erythrocytes during supercooling and cooling of blood samples in vitro shows that the mechanisms of the changes in the forms of red blood cells in these cases are different. It is known that the acanthocyte forms of erythrocytes are determined by the Fig.5. SEM images of volunteer erythrocytes at a temperature of + 2 ° C: a) with an increase of defect of the structural membrane [4, 5], x1000, b) with an increase of x5000 whereas the echinocyte forms can be induced and canceled by pH, osmolality, biochemical and even electrical changes [6-9]. Irreversibility of changes in the forms of acanthocytes is confirmed in experiments in vitro: acanthocytes, which appeared as a result of a drop in the temperature of the blood sample under study to negative values, do not disappear with and without an increase in the temperature of the blood in the field of view of SEM images. Unlike acanthocytes, erythrocytes of the echinocyte form, which are observed in Fig.6. SEM images of volunteer erythrocytes at a temperature of -1.7 ° C: a) with an increase persons who died from hypothermia, can of x1000, b) with an increase of x5000 4’ 2018 21

be restored. prilozhenie k Z. Izmeritel’naya tekhnika. pp. 281–286. Conclusion. Thus, the results of the [Metrology. Quarterlyannexto J. 9. Schwarz S, Deuticke B, Haest CW. SEM study obtained by us indicate that Measuringequipment], 2016, V.1, pp. 47- Passive Transmembrane Redistributions the forms of erythrocytes in persons who 52. of Phospholipids as a Determinant of died from various causes differ, namely, 3. Foglia A. The Acanthocyte- Erythrocyte Shape Change. Studieson during overcooling - erythrocytes take Echinocyte differential. Swiss Medical Electroporated Cells .Mol. Membr. Biol., echinocytic form, and when wounded Weekly, 2010, V.140 (03-04). pp. 1999, V.16(3), pp. 247–55. - acanthocytic. This fact gives us the 1-3; DOI:https://doi.org/10.4414/ opportunity to assume that the process smw.2010.12963 The authors of dying during hypothermia has its own 4. Bosman G.J. Erythrocyte membrane 1. Alekseev Revo Zakharovich characteristics. It is necessary to further abnormalities in neuroacanthocytosis. - MD, professor, the senior researcher in-depth study of this pathology at the Evidence for a neuron-erythrocyte axis? YSC CMP, Yakutsk, Russia; molecular-cellular level to find solutions / G.J Bosman., M.W. Horstink, W.J. De 2. Golderova Aitalina Semenovna to restore the body’s vital activity in the Grip // Neuroacanthocytosis Syndromes. – MD, professor Institute of Physics and first days after death from hypothermia. Springer Verlag, 2005, pp.153–159. Technologies, M.K. Ammosov North- 5. Acanthocyteset hypercholes Eastern Federal University, Yakutsk, References terolemia / J Perrin, A Georges, A Morali, Russia; 1. Alekseev R.Z., Tomskij M.I., [et al.] // Ann Biolo Clin., 2008, V.66 (5), 3. Mamayeva Sargylana Gol’derova A.S. [et al.] Preduprezhdenie P. 56972. Nikolaevna – candidate of f-m sciences, razvitiya nekroza pri otmorozheniyah s 6. Reinhart W.H. Red Cell Rheology in associate professor of Institute of Physics oledeneniem tkanej [Prevention of the Stomatocyte-Echinocyte Transformation: and Technologies, M.K. Ammosov North- development of necrosis during frostbite Roles of Cell Geometry and Cell Shape. Eastern Federal University Yakutsk, with icing of tissues] Mezhdunarodnyj / W.H. Reinhart, S.Chien // Blood., 1986, Russia; zhurnal prikladnyh i fundamental’nyh V.4. pp. 1110–1118. 4. Nikolaeva Nadezhda issledovanij [International Journal of 7. Wong P.A. Basis of Echinocytosis Anatalyevna - assistant of Institute Applied and Fundamental Research.], and Stomatocytosis in the Disc-sphere of Physics and Technologies, M.K. 2015, V. 8-1. pp. 35-41. Transformations of the Erythrocyte. J Ammosov North-Eastern Federal 2. Maksimov G.V., Mamaeva S.N., Theor Biol., 1999, V.196(3), pp. 343–361. University, Yakutsk, Russia; Antonov S.R. [et al.] Izmerenie morfologii DOI:10,1006 / jtbi.1998.0845 5. Buzinayeva Maria Telektesovna ehritrocitov metodom ehlektronnoj 8.Mrowietz C, Hiebl B, Franke RP, et – candidate of medical sciences, head of mikroskopii dlya diagnostiki gematurii al. Reversibility of Echinocyte Formation the laboratory bureau of forensic medical [Measurement of erythrocyte morphology after Contact of erythrocytes with various examination Ministry of Health RS (Ya), by electron microscopy for the diagnosis of Radiographic Contrast Media. Clin. Yakutsk, Russia. hematuria]. Metrologiya. Ezhekvartal’noe Hemorheol. Microcirc., 2008, V.39(1–4),

G.A. Usenko, D.V. Vasendin, A.G. Usenko GAMMA BACKGROUND ENVIRONMENT DURING MAGNETIC STORMS AND THE CONTENTS OF SODIUM AND POTASSIUM IN ERYTHROCYTES IN PATIENTS WITH ARTERIAL HYPERTENSION DEPENDING ON THE TEMPERAMENT AND DOI 10.25789/YMJ.2018.64.06 ANTIHYPERTENSIVE THERAPY

ABSTRACT Arterial hypertension is one of the major independent risk factors for complications of cardiovascular diseases, stroke, myocardial infarction, acute and chronic heart failure. In the structure of cardiovascular diseases arterial hypertension occupies the first position in disability and mortality of the working population. In recent years, this contributes to the growth of psycho-emotional stress, anxiety and depression. Periods of sharp changes heliometeofactors also combined with an increase in the proportion of individuals with complications of hypertension. Thus, in the period of magnetic storms, there was an increase in gamma radiation power (within the regional norm), an increase in the degree of psycho-emotional stress and a change in the concentration of electrolytes in the blood of both healthy and persons with cardiovascular disease. The aim of the study was to establish the relationship between the dynamics of γ-background of the environment during magnetic storms and the content of potassium and sodium in red blood cells in patients with hypertension with different temperament and anxiety, taking options for antihypertensive therapy: targeted and not targeted (empirical) on the blockade of psychosomatic characteristics of patients, as well as to determine the most effective treatment option. The prevailing temperament – choleric, sanguine, phlegmatic and melancholy – was determined using the psychological test of John Eysenck and A. Belov, the presence and severity of depression – Je. Ahmetzhanov psychological tests. Potassium and sodium content in erythrocytes was determined by ion-selective method. The gamma background of the medium was measured using the dosimeter «Master». 22 YAKUT MEDICAL JOURNAL

It was found that the decrease in the activity of the sympathetic Department of the autonomic nervous system and the hypothalamic-pituitary- adrenal system (cortisol), and the increase in the activity of the renin-angiotensin-aldosterone system (aldosterone) in the temperamental series of choleric – sanguine – phlegmatic – melancholy was combined with a decrease in the level of oxygen utilization by tissues and potassium content in erythrocytes and an increase in sodium content in both healthy and patients. Compared with the empirical version of antihypertensive therapy, against the background of a targeted treatment option, the period of return of the values of the studied parameters, the level of oxygen utilization by tissues, the content of potassium and sodium in erythrocytes, as well as the degree of reaction of the body (according to the correlation analysis) were practically the same as in healthy individuals of the corresponding temperament, which indicates in favor of a higher efficiency of the treatment option targeted at the relief of psychosomatic features of the patient. Keywords: hypertension, solar activity, γ-background, erythrocytes, potassium, sodium, correlation.

Introduction. Arterial hypertension The contents of potassium and so- ies conducted by us using the criteria (AH) is one of the major independent risk dium (mmol/l) in er were determined by set out in [3] showed the prevalence of factors for development of complications ion-selective method on the apparatus sympathetic (SNS) Department of the of cardiovascular diseases [11, 13, 14]. “RAPIDLAB-865” (Bayer, UK) [8]. autonomic nervous system (ANS) and Psychoemotional tension, anxiety and To determine the coefficient of utiliza- hypothalamic-pituitary-adrenal system depression contribute to an increase in tion of oxygen by tissues (CUOT, %) ac- (GGNS, cortisol) in Ch and Sg, and para- the proportion of people with AH compli- count for the voltage of the oxygen (O2) sympathetic (PSNS) Department of ANS cations in the modern world [1, 11]. The in the blood (venous and venous arteri- with predominant activity of the renin- course of AH is closely related to sodium alization) (pO2, mm Hg. art.) according to angiotensin-aldosterone system (RAAS, accumulation and potassium decrease the approved and approved procedure aldosterone) in Ph and M persons. Based in blood [13,14]. Periods of increased [8], as well as saturation (saturation) of on the differences above, AHT included solar activity (SA) are also combined hemoglobin (Hb) with oxygen (SaO2,%), drugs that have been approved by order with changes in the electrolyte composi- which was determined using the blood No. 254 of the health Ministry of Rus- tion, rheological properties of blood and gas analyzer “STAT PROFILE. pHOx”. sia dated 22.11.2004 «On approval of an increase in the proportion of persons The content of Hb (g/l) was determined the standard of care for patients with with complications of hypertension [4, 5, by hemoglobincyanide method on the arterial hypertension» [7, 12]: selective

6, 16]. Studies have shown that mag- device CFC-2 [8]. The content of O2 in beta-adrenoblockers (β-AB), angiotensin netic storms (MS), as a consequence of the blood (СаО2) was calculated with the converting enzyme inhibitors (aceis), diu- changes in CA, are combined with chang- formula: retics (hydrochlorothiazide), cardiomag- es in the concentration of electrolytes, as СаО2 = 1.34 x Нb x SaO2 /100 + pO2, nyl. From β-AB patients in 96% of cases well as the trace element composition of mm Hg. art. x 0.0031, received metoprolol 200 mg/day (4% of blood (potassium, sodium, magnesium) where CaO2 – oxygen content in the its analogues), and LA/Ch and LA/Sg 100 in healthy and hypertensive patients [4, blood (in 1 ml per 100 ml); 1,34 – Hufner mg/day) and hydrochlorothiazide: HA/Ch 5, 16]. However, no studies have been constant; Hb – hemoglobin content in the and HA/Sg 25 mg/day, and LA 12,5 mg/ found on the relationship between the blood (in g per 100 ml); SaO2,% – satura- day. Of aceis patients in 96% of cases

γ-background of the external environ- tion of Hb with oxygen (in %); pO2 – oxy- took enalapril 20 mg/day (in 4% of cases ment in the MS period and the potassium gen tension in the blood (in mm Hg. art.); its analogues) + veroshpiron 100–200 and sodium content in erythrocytes (Er) 0,0031 – the coefficient of oxygen solubil- mg/day (in 75% of cases), rarely (25%) in people taking different variants of anti- ity according to Bunsen [8]. and hydrochlorothiazide 25 mg/day, be- hypertensive therapy (AHT). Blood sampling was performed from cause the content of potassium in the Material and methods of research. the cubital vein (in dry test tube without blood have been lower than those of Ch In the period from 1995 to 2017, 848 preservative) in the morning, fasting, be- and Sg. LA/Ph and LA/M were adminis- engineering and technical workers of fore treatment. The calibration curve was tered enalapril 10 mg/day + hydrochlo- men aged 44-62 years (average 54±1,8 obtained by measuring the optical den- rothiazide (hydrochlorothiazide) – 12,5 years) were examined in the polyclinic, sity of standard sodium nitrate solutions mg/day. All patients received Panangin who were diagnosed with stage II hy- with a concentration of 5 to 320 µmol. All 2 tab./day and cardiomagnyl on 1 tab./ pertension (GB-II, degree 2, risk 3) in studies were conducted from 8.00 am to day. Since Ch and Sg patients differed the cardiology Department. The disease 10.00 am, on an empty stomach, before from Ph and M patients PSNS Depart- duration averaged 11,6±1,4 years. The taking AHT. ment of VNS, as well as the activity of the presence of essential hypertension was Features of antihypertensive ther- hypothalamic-pituitary-adrenal system determined by the criteria set out in [13, apy. According to the method of Je.R. (GGNS cortisol), they were prescribed in 14]. 422 healthy men, compatible on the Akhmetzhanov [2] mild depression was 96% of cases of β-AB + hypothyazid. Pa- main anthropo-social indicators, served observed only in high-anxiety phlegmat- tients with phlegmatics and melancholy as control. The prevailing temperament – ics (HA/Ph) and melancholy (HA/M). differed from h and with the prevalence choleric (Ch) sanguine (Sg), phlegmatic According to the conclusion of psycho- of PSNS of the VNS Department and (Ph) and melancholic (M) was measured neurologists they did not need inpatient the predominant activity of the renin- using a psychological test [15] by 3 times treatment. Perfectionism choleric (HA/ angiotensin-aldosterone system (RAAS testing before treatment (0) and after 3, Ch) and sanguine (HA/Sg) received an- by aldosterone). In this regard, the latter 6, 9 and 12 months of AHT. The magni- xiolytic that 96% sibazon 2.5 mg in the was appointed in 96% of cases of ACEI tude of reactive and personal anxiety was morning and at night and HA/Ph and + veroshpiron. All other treatment options determined by [17]. Persons who scored HA/M antidepressant that 96% coaxil are called empirical (EAHT). In order to 32,0±0,6 points, to high-anxiety (HA) 12.5 mg in the morning and at night (in exclude the installation (on the result) from 42,8 ±0,4 points and above are re- 4% of cases the zoloft at 25 mg/day), attitude to the study, the authors did not ferred to low-anxiety (LA). except lowanxiety individuals [12]. Stud- appoint AHT, but only determined the 4’ 2018 23

temperament, anxiety and the presence of the accepted variant of AHT. The above variant of CAHT was success-

fully tested during vascular wall remodeling in patients 677 668 673 683 691 688 712 679 714 661 680 686 Table 1 Table Всего

with arterial hypertension [10]. 33.8±0.01 36.4±0.01 36.9±0.01 32.4±0.01 34.9±0.01 35.8±0.01 31.5±0.01 33.3±0.01 34.9±0.01 29.3±0.01 32.5±0.01 34.2±0.01 The values of γ-background power (µr/h) were ob- 8.58±0.007 tained daily by measuring γ-background of workplaces 45 44 46 47 47 46 48 48 48 46 44 44 (20 measurements, dosimeter «Master») from 8.00 to +7

10.00 and compared with the data of the Department 8.49±0.01 35.0±0.06 35.9±0.07 36.8±0.06 33.6±0.06 36.8±0.06 37.0±0.08 33.3±0.05 33.8±0.06 35.0±0.05 30.9±0.06 32.6±0.06 35.5±0.05 of ionospheric-magnetic forecasting of the West Sibe- rian Department of Hydrometeorology and environmen- 43 43 46 48 45 46 44 43 48 43 46 46 tal monitoring (Novosibirsk). Variations of γ-background +6 power from 1995 to 2017 (7,6-16,8±0,4 µr/h) did not ex- 8.62±0.01 35.3±0.07 38.0±0.08 38.2±0.05 33.8±0.06 37.6±0.06 38.6±0.05 31.7±0.06 33.6±0.06 36.2±0.05 30.2±0.05 32.8±0.06 35.5±0.06 ceed the permissible regional values.

The method of superimposed epochs was used in the 44 46 44 46 48 48 48 44 49 44 44 46 +5 work [9], which takes into account the days before the magnetic storm ( - ), in the period (0) and after the MB 8.47±0.01 35.2±0.07 35.8±0.05 36.7±0.05 32.7±0.07 34.9±0.07 35.6±0.07 33.2±0.07 33.4±0.05 34.9±0.04 27.4±0.06 29.8±0.07 34.5±0.05 (+): -7 -6 -5 -4 -3 -2 -1 - 0 - +1 +2 +3 +4 +5 +6- +7 accord- 43 43 44 43 48 46 49 43 49 43 43 47 ingly. The results were processed by methods of varia- +4

tion statistics (m±m) using a standard software package 8.59±0.01 33.7±0.05 37.7±0.06 37.6±0.06 29.6±0.05 33.9±0.07 37.0±0.06 28.5±0.07 31.3±0.06 32.7±0.04 27.0±0.04 29.7±0.06 32.5±0.05 “Statistica 7.0” and parametric student t–test, as well as the calculation of the correlation coefficient (r) Pearson. 44 48 46 45 44 44 46 44 46 44 44 46 Values at p<0,05 were considered statistically significant. +3 32.6±0.06 36.3±0.07 37.9±0.07 29.6±0.06 33.8±0.04 33.8±0.06 28.8±0.06 31.1±0.05 32.3±0.04 27.4±0.05 30.7±0.07 32.0±0.05 The study was carried out in compliance with the provi- 8.70± 0.01 sions of the Helsinki Declaration on treatment and examination of people and approved by the ethics Committee of 47 44 44 43 47 46 47 49 49 43 46 44 +2 the Novosibirsk state medical University on 20.11.2009, Protocol No. 18. 8.65±0.01 32.3±0.07 35.2±0.06 36.3±0.06 29.5±0.07 35.3±0.04 33.7±0.06 28.7±0.07 31.5±0.06 33.4±0.05 27.3±0.06 31.2±0.06 31.7±0.06 Results and discussion. The data obtained during 46 44 45 44 50 48 54 47 55 44 45 49 the study period showed that oxygen utilization by tissues +1

(according to COUT) and potassium content in Er signifi- 8.80±0.01 31.2±0.06 34.6±0.06 36.0±0.07 29.2±0.08 32.9±0.05 33.9±0.06 28.1±0.06 32.4±0.05 33.8±0.07 27.6±0.06 31.3±0.05 31.8±0.05 cantly decreased, and sodium concentration increased in the temperamental series HA(LA) Ch > Sg > Ph > M (ac- 0 cording to CUOT and potassium) and HA(LA) Ch < Sg < 48 46 44 49 48 45 52 48 49 47 48 48

Ph < M (according to sodium) (table. 1 – 3). Thus, in Er 8.78±0.01 31.6±0.06 34.8±0.07 35.5±0.06 29.3±0.05 33.6±0.06 34.4±0.06 32.3±0.05 33.4±0.06 35.1±0.06 28.6±0.05 32.4±0.06 35.3±0.05 HA(LA) of the melancholic content of sodium was higher

and potassium lower than that of others. Of the many fac- -1 49 44 46 48 47 46 49 46 45 44 45 45 tors that affect the utilization of oxygen and the content of electrolytes, the observed differences can be linked to the 8.70±0.01 32.1±0.05 35.0±0.06 35.7±0.05 30.8±0.06 35.1±0.05 36.6±0.06 32.5±0.04 34.5±0.07 35.9±0.05 28.9±0.04 33.2±0.04 35.0±0.06 prevalence of the activity of the RAAS (aldosterone) and -2 the parasympathetic section of VNS (index Kerdo and 43 45 44 43 43 44 48 46 44 43 48 44

initial vegetative tonus) in the Ph and M compared with 8.45±0.01 33.6±0.04 36.3±0.07 37.6±0.07 32.8±0.07 35.4±0.03 36.6±0.05 32.8±0.05 33.6±0.04 36.0±0.06 29.9±0.05 33.4±0.04 35.2±0.05 Sg and with individuals. The study showed a significant increase in the γ-background of the medium (within the -3 regional norm) for the day (-1) before, and a return to the 48 44 46 44 44 44 48 44 44 44 45 44 8.41±0.01 35.0±0.05 37.0±0.06 37.1±0.06 34.0±0.06 35.6±0.06 36.4±0.06 33.0±0.06 34.4±0.04 35.9±0.05 31.2±0.06 33.2±0.05 35.1±0.06

initial values on the (+4) day from the beginning of MS 1995 to 2017 the study period from storms during the study period over (table. 1). In the period of magnetic storms in healthy

individuals and against any variant of AHT, all patients -4 44 46 44 47 43 48 44 46 46 43 48 46 showed a significant decrease in the value of CUOT (%) and potassium content, but an increase in the concentra- 8.58±0.01 35.2±0.06 37.2±0.07 38.0±0.07 34.2±0.07 35.4±0.07 36.7±0.05 32.4±0.06 33.6±0.05 35.8±0.06 31.2±0.07 33.4±0.07 34.7±0.06 tion of sodium in er. In the groups of HA (LA) choleric -5 these changes were recorded per day (-1), in the groups 44 44 45 44 47 44 45 44 44 44 47 46 of HA (LA) sanguine in the first (0) day, and in the groups 8.46±0.01 36.2±0.06 37.0±0.06 34.2±0.06 35.6±0.06 37.5±0.06 36.0±0.07 31.0±0.05 35.1±0.06 34.9±0.05 35.0±0.07 36.9±0.05 32.9±0.05 of HA (LA) phlegmatic and melancholic on the second day (+1) from the beginning of MS (table. 1). In the context of the above, we note that ionizing radiation, including -7–6 44-43 45-44 44-46 48-45 44-43 49-49 44-45 44-43 46-45 γ-rays, contribute to the ionization and excitation of at- 44-45 46-46 44-46 oms and molecules, as well as the radiolysis of water to 8.5-8.50± 0.01 form active forms of oxygen. The consequence of oxida- 34.3-34.7±0.06 36.1-36.5±0.05 37.9-37.0±0.07 33.3-37.4±0.06 34.7-34.3±0.07 36.5-35.5±0.06 32.5-32.7±0.07 34.4-34.5±0.06 35.6-35.8±0.06 30.6-30.9±0.06 33.3-35.4±0.07 34.5-34.8±0.05 E E E E C C C C

tive stress is an increase in the permeability of cell mem- Zd Zd Zd Zd branes for electrolytes and a number of enzymes. The fact that the changes in Ch-individuals occurred a day

before MS is consistent with the results of the study [18], Days which found an increase in γ-background of the medium γ-phone Choleric Sanguines Phlegmatic

a day before MS and is associated with an increase in the Melancholic Dynamics of γ-background (ur/h) and the coefficient of utilization of oxygen by tissues (%) in HA individuals on the background of EAHT (E) and CAHT(C) in the days of magnetic of EAHT HA individuals on the background (ur/h) and the coefficient of utilization oxygen by tissues (%) in Dynamics of γ-background Note. Here and further: ZD-healthy persons; the denominator indicates total number of examined 24 YAKUT MEDICAL JOURNAL 677 668 673 682 690 691 715 679 708 661 684 686 677 668 673 682 690 691 715 679 708 661 684 686 Всего Table 2 Table 3 Table Всего 87.2±0.1 90.0±0.1 89.9±0.1 86.0±0.1 88.2±0.1 88.2±0.1 84.3±0.1 86.3±0.1 87.9±0.1 83.4±0.1 85.6±0.1 85.4±0.2 9.3±0.05 9.2±0.06 11.7±0.05 11.7±0.05 11.4±0.06 11.5±0.05 10.1±0.04 10.7±0.06 10.3±0.09 12.3±0.07 13.6±0.05 12.4±0.04 12.3±0.04 8.58±0.007 8.58±0.007 45 44 46 47 46 49 48 48 48 46 44 44 44 46 47 47 49 48 48 48 46 44 44 +7 +7 89.1±0.3 87.9±0.3 88.2±0.3 88.0±0.4 86.0±0.4 86.3±0.5 90.4±0.4 85.3±0.6 86.2±0.4 87.1±0.3 11.8±0.1 11.8±0.1 9.4±0.08 10.1±0.1 12.0±0.1 88. 5±0.4 9.1 ±0.07 8.49±0.01 91.5±0.01 11.0±0.08 11.0±0.08 11.5±0.07 11.9±0.08 8.49±0.01 10.1±0.08 10.8±0.07 13.1±0.08 9.2±0.1 45 43 43 48 45 46 44 43 48 43 46 46 +6 43 43 46 47 45 46 44 43 48 43 46 46 +6 8.7±0.08 8.9±0.09 9.9±0.07 12.1±0.1 88.2±0.4 93.4±0.3 92.5±0.3 87.8±0.4 91.1±0.3 90.4±0.3 89.7±0.4 88.7±0.3 84.5±0.6 87.6±0.3 87.3±0.4 11.0±0.07 11.0±0.07 8.62±0.01 10.0±0.08 10.0±0.09 12.0±0.09 10.8±0.08 13.2±0.09 12.0±0.08 8.62±0.01 84.1±0.04 8.5±0.1 46 44 46 44 46 48 46 48 44 49 44 44 46 46 46 48 46 48 44 49 44 44 46 +5 +5 89.6±0.4 91.4±0.3 90.9±0.4 86.8±0.3 87.9±0.4 83.9±0.4 86.0±0.4 90.4±0.4 82.5±0.4 86.5±0.4 86.3±0.3 11.8±0.1 11.8±0.1 9.4±0.09 10.0±0.1 8.47±0.01 88.6±0.05 11.2±0.08 11.2±0.08 11.8±0.09 8.47±0.01 10.0±0.07 14.1±0.09 12.1±0.08 12.0±0.08 9.1±0.1 44 9.2±0.1 44 11.3±0.008 11.3±0.008 43 43 44 43 46 48 49 43 44 43 43 47 +4 44 43 48 48 49 43 44 43 43 47 +4 86.9±0.3 91.9±0.3 91.2±0.4 84.8±0.4 91.0±0.4 89.9±0.3 83.0±0.4 82.9±0.3 85.3±0.5 80.0±0.5 83.7±0.3 83.3±0.4 8.6±0.09 12.8±0.1 10.2±0.1 13.3±0.1 8.59±0.01 8.59±0.01 10.2±0.09 12.0±0.09 12.8±0.08 14.4±0.08 13.8±0.06 13.9±0.09 9.1±0.1 43 9.4±0.1 43 44 48 46 45 44 46 46 44 46 44 44 46 +3 44 46 45 44 46 46 44 46 44 44 46 +3 85.2±0.3 92.2±0.3 91.6±0.4 81.9±0.3 86.6±0.4 85.5±0.3 80.2±0.3 82.1±0.5 83.0±0.4 80.0±0.4 83.0±0.4 81.1±0.3 11.9±0.1 11.9±0.1 8.8±0.08 13.2±0.1 9.2±0.08 11.2±0.08 11.2±0.08 14.3±0.08 12.3±0.09 13.0±0.09 15.0±0.07 14.6±0.07 14.4±0.09 8.70± 0.01 8.70± 0.01 8.9±0.1 48 47 44 44 43 46 44 47 49 49 43 46 44 +2 47 44 44 43 47 44 47 49 49 43 46 44 +2 84.9±0.3 87.2±0.4 86.2±0.4 81.7±0.4 83.4±0.2 83.8±0.3 80.0±0.3 82.2±0.3 82.5±0.5 81.2±0.3 81.1±0.3 81.3±0.4 12.1±0.1 10.6±0.1 9.6±0.07 13.5±0.1 12.9±0.1 13.5±0.1 14.2±0.1 8.65±0.01 8.65±0.01 12.9±0.08 14.0±0.09 13.4±0.06 14.9±0.06 14.3±0.08 46 44 45 44 44 46 54 47 55 44 45 49 46 45 44 50 46 54 47 55 44 45 49 +1 +1 11.9±0.1 11.9±0.1 83.3±0.4 85.8±0.4 85.9±0.3 82.0±0.5 84.0±0.2 84.0±0.4 81.9±0.3 82.7±0.3 86.8±0.4 82.0±0.3 81.0±0.4 81.6±0.4 9.9±0.06 13.3±0.1 12.4±0.1 13.7±0.1 12.8±0.1 8.80±0.01 8.80±0.01 12.4±0.07 12.6±0.06 14.9±0.07 13.1±0.09 12.8±0.01 9.8±0.1 44 0 0 48 46 44 49 48 48 52 48 49 47 48 48 48 46 44 49 48 48 52 48 49 47 48 48 11.5±0.1 11.5±0.1 11.6±0.1 11.6±0.1 11.8±0.1 10.1±0.1 9.9±0.07 12.0±0.1 83.5±0.3 85.5±0.4 86.6±0.4 84.2±0.4 84.6±0.3 88.9±0.3 85.1±0.3 85.2±0.4 89.2±0.4 82.3±0.5 87.0±0.4 86.7±0.3 11.6±0.09 11.6±0.09 11.1±0.08 11.2±0.07 8.78±0.01 12.6±0.08 13.6±0.08 12.0±0.08 8.78±0.01 -1 -1 49 46 48 45 49 46 45 44 45 45 49 44 46 48 45 45 49 46 45 44 45 45 11.6±0.1 11.6±0.1 11.4±0.1 9.6±0.08 9.1±0.08 84.1±0.3 89.0±0.4 87.4±0.3 87.1±0.3 90.9±0.4 89.0±0.4 85.7±0.4 87.9±0.2 90.2±0.3 84.3±0.3 87.3±0.4 87.7±0.4 11.1±0.07 11.1±0.07 11.0±0.09 11.7±0.09 8.70±0.01 10.7±0.09 10.9±0.08 13.0±0.09 8.70±0.01 9.9±0.1 44 9.7±0.1 47 -2 -2 43 45 44 43 43 44 48 46 44 43 48 44 43 45 44 43 43 44 48 46 44 43 48 44 storms during the study period from 1995 to 2017 storms during the study period from 1995 to 2017 storms during the study period from 88.3±0.3 89.8±0.3 89.4±0.2 87.0±0.4 88.9±0.4 85.8±0.3 85.8±0.3 90.0±0.4 84.5±0.4 86.9±0.3 9.4±0.07 9.2±0.08 9.0±0.06 10.8±0.1 9.9±0.08 11.0±0.09 11.0±0.09 11.5±0.07 11.0±0.09 11.8±0.09 11.6±0.08 8.45±0.01 88.8±0.05 86.2±0.05 8.45±0.01 10.9±0.09 12.8±0.09 -3 48 44 46 44 44 44 48 44 44 44 45 44 -3 48 44 46 44 44 44 48 44 44 44 45 44 88.6±0.4 89.6±0.3 89.8±0.4 87.3±0.3 88.7±0.3 89.4±0.3 86.0±0.4 87.0±0.3 90.3±0.4 84.6±0.3 86.7±0.4 86.0±0.3 11.1±0.1 11.1±0.1 9.7±0.08 9.4±0.08 9.2±0.09 9.9±0.09 8.41±0.01 11.3±0.09 11.3±0.09 11.7±0.09 11.5±0.07 8.41±0.01 10.8±0.09 10.9±0.08 10.6±0.06 12.6±0.06 -4 44 46 44 47 43 48 44 46 46 43 48 46 -4 44 46 44 47 43 48 44 46 46 43 48 46 88.2±0.3 91.5±0.4 91.0±0.4 86.8±0.4 90.2±0.3 90.1±0.4 85.4±0.3 88.4±0.4 89.7±0.5 84.0±0.3 87.2±0.3 86.7±0.4 8.58±0.01 8.9±0.07 8.9±0.08 8.6±0.08 9.7±0.08 9.5±0.06 11.8±0.08 11.8±0.08 11.6±0.09 11.4±0.07 8.58±0.01 10.6±0.09 10.8±0.08 10.7±0.06 13.3±0.07 -5 44 44 45 44 47 44 45 44 44 44 47 46 -5 44 44 45 44 47 44 45 44 44 44 47 46 89.1±0.3 89.4±0.3 89.3±0.4 88.3±0.3 88.6±0.4 88.7±0.5 88.0±0.4 87.7±0.3 89.7±0.4 85.0±0.4 86.9±0.3 86.0±0.4 8.46±0.01 11.5±0.1 11.5±0.1 9.7±0.07 9.3±0.09 9.2±0.06 11.1±0.08 11.1±0.08 11.0±0.07 11.3±0.09 11.1±0.06 8.46±0.01 10.1±0.07 12.5±0.07 12.1±0.08 12.1±0.09 -7–6 44-45 44-43 45-44 46-46 44-46 48-45 44-46 44-43 49-49 44-45 44-43 46-45 -7–6 44-45 44-43 45-44 46-46 44-46 48-45 44-46 44-43 49-49 44-45 44-43 46-45 8.5-8.50±0.01 89.7-89.5±0.4 91.1-90.0±0.4 91.4-89.9±0.4 88.1-88.0±0.4 89.3-88.1±0.4 89.5-88.8±0.4 86.8-88.4±0.4 89.4-89.0±0.4 89.1-88.7±0.4 85.5-85.3±0.3 86.7-86.6±0.3 86.9-86.2±0.3 9.1-9.2± 0.1 9.0-9.1±0.07 9.8-9.9±0.07 9.7-9.3± 0.08 10.8-10.9±0.1 9.9-10.0±0.07 11.7-11.5± 0.1 11.7-11.5± 8.5-8.50± 0.01 11.7-11.9±0.09 11.7-11.9±0.09 11.6-11.8±0.08 10.6-10.9±0.08 10.5-10.8 ±0.07 12.8-13.0± 0.08 E E E E E C C C C Zd Zd Zd Zd E E E E C C C C Zd Zd Zd Zd Days Days γ-phone γ-phone Dynamics of γ-background (ur/h) and the content of sodium in erythrocytes (mmol/l) in HA individuals on the background of EAHT (E) and CAHT(C) in the days of magnetic of EAHT individuals on the background (mmol/l) in HA (ur/h) and the content of sodium in erythrocytes Dynamics of γ-background Choleric Dynamics of γ-background (ur/h) and the potassium content in erythrocytes (mmol/l) in РФ individuals on the background of EAHT (E) and CAHT(C) in the days of magnetic of EAHT individuals on the background (mmol/l) in РФ (ur/h) and the potassium content in erythrocytes Dynamics of γ-background Sanguines Choleric Phlegmatic Sanguines Melancholic Phlegmatic Melancholic 4’ 2018 25

concentration of radioactive radon gas on tors (intense electromagnetic field of the these days several times. Earth and an increase in γ-background of Against the background of EAHT, a the medium), the obtained combination Table 4 Table significant return of the studied - param probably contributed to the development Healthy

+0.28±0.02 +0.27±0.03 +0.26±0.01 +0.27±0.02 eters to the baseline values in the groups of a cascade of SPOL reactions, which of HA cholerics was observed on (+4) resulted in an increase in the permeabil- day, sanguine on (+5), and HA phleg- ity of Er membranes and a decrease in Lowanxiety

matic and melancholic on (+6) day from magnesium [4, 16], potassium and CUOT the beginning of MS, and in the groups values, but an increase in sodium con- Patient

+0.47±0.02 +0.24±0.02 +0.46±0.03 +0.28±0.03 +0.47±0.02 +0.27±0.02 +0.38±0.02 +0.25±0.02 of LA persons-on the day before: LA/ centration in Er. In contrast to the em- Ch – Sg – Ph - M: +3 – +4 – +5 – +5 pirical AHT, against the background of (table. 1 – 3). Against the background of CAHT, associated with a decrease in the CAHT, compared with the EAHT variant, activity of SNS in Ch and Sg and the ac-

Sodium, mmol/days the return to the initial values was re- tivity of RAAS (aldosterone) in Ph and M

Healthy corded a day earlier: in the groups HA/ patients, the degree of response (accord- +0.420±0.02 +0.386±0.02 +0.456 ±0.03 +0.470 ±0.03 Ch – Sg – Ph - M at +3 – +4 – +5 – +5, ing to correlation analysis), as well as the and in groups LA/Ch – Sg – Ph - M on: coincidence of the timing of the return of

Highanxiety +2 – +3 – +4 – +4 day from the beginning the value of the CUOT and the electro- of MS, respectively (table. 1 – 3). In con- lyte content to the initial values, plus less

Patient trast to the groups taking EAHT, against significant differences in the magnitude of

+0.725±0.02 +0.438±0.02 +0.688±0.02 +0.430±0.02 +0.621±0.03 +0.450±0.03 +0.630±0.03 +0.449±0.03 the background of CAHT, the terms of changes in the CUOT and the content of return of the studied parameters to the the studied electrolytes in Er with those initial values approached those in healthy in healthy HA(LA) persons of the corre- HA(LA) persons of the corresponding sponding temperament, indicates in favor

Healthy temperament (table. 1 – 3).The correla- of greater efficiency of CAHT. -0.24±0.01 -0.25±0.01 -0.27±0.01 -0.27±0.01 tion analysis carried out on days using the method of superimposed epochs, be- References tween the change of γ-background and

Lowanxiety 1. Krasnov V.N., Vasyuk Yu.A., the content of potassium and sodium in Nesterova E.A., Dovzhenko G.V.,

Patient Er during MS in patients, regardless of Tarasovа V.K. Antidepressanty koaksil -0.48±0.01 -0.20±0.01 -0.49±0.01 -0.26±0.01 -0.43±0.01 -0.25±0.01 -0.37±0.01 -0.28±0.01 the variant of AHT, and in healthy indi- i zoloft v kompleksnom lechenii bol’nyh viduals, established a reliable inverse arterial’noj gipertenziej s rasstrojstvami correlation with the value of the CUOT affektivnogo spektra [Antidepressants and the concentration of potassium, but coaxil and zoloft in treatment of patients Potassium, mmol/l direct – with the content of sodium. But in with arterial hypertension with disorders Healthy the background, EAHT, correlation at the -0.447±0.01 -0.454±0.01 -0.482±0.01 -0.436±0.01 of the affective spectrum]. Rossijskij HA patients was high, and LA patients, medicinskij zhurnal [Russian medical the mean order of importance. On the journal]. Moscow, 2004, № 1, PР. 15 –

Highanxiety background of CAHT in HA patients cor- 18. relation was average, and in the groups 2. Akhmetzhanov Je.R. Shkala Patient of LA degree of importance, as well as in depressii. Psihologicheskie testy [De- -0.814±0.02 -0.478±0.01 -0.724±0.01 -0.485±0.01 -0.583±0.01 -0.567±0.01 -0.489±0.01 -0.463±0.0001 HA(LA) healthy individuals of the corre- pression Scale. Psychological tests]. sponding temperament (table. 4). Moscow: List, 1996, 320 p. These studies have shown that be- 3. Vejn A.M. Vegetativnye rasstro- tween the increase in γ-background of jstva: klinika, lechenie, diagnostika [Au-

Healthy the medium in the MS period, on the one tonomic disorders: clinical, treatment, -0.29±0.01 -0.23±0.01 -0.27±0.01 -0.25±0.01 hand, and the size of the CUOT, as well diagnosis]. Moscow.: Medicinskoe infor- as the content of electrolytes in Er, on macionnoe agentstvo, 2000, 752 p. the other, there was a reliable relation- Lowanxiety 4. Usenko G.A., Usenko A.G., ship. Based on these data, already the Vasendin D.V., Shakirova N.A. Vzai-

Patient day before the start and during the period mosvyaz’ mezhdu sostoyaniem magnit- -0.45±0.02 -0.27±0.01 -0.46±0.01 -0.27±0.01 -0.37±0.01 -0.25±0.01 -0.40±0.01 -0.29±0.01 of MS observed increase γ-background nogo polya Zemli i soderzhaniem mag- environment (within the boundaries of niya, temperamentom, trevozhnost’yu

CUOT, % CUOT, acceptable regional standards). And u bol’nyh stenokardiej napryazheniya the first the day before the MS reacted [Сorrelation between magnesium con- the body sympathotonics choleric, and Healthy tent, temperament, anxiety and earth’s AH-II with different temperament against the background of empirical (E) and targeted (C) AHT during the study period from 1995-2017 during the study period from AHT of empirical (E) and targeted (C) temperament against the background AH-II with different -0.477±0.01 -0.474±0.01 -0.394±0.01 -0.469±0.01 then the rest in the days of the MS and magnetic field condition in patients with increase γ-background environment. exertional angina]. Medicinskij vestnik It is unlikely to increase the activity of MVD [MIA Medical Bulletin]. Moscow, Highanxiety free-radiacal lipid peroxidation (SPOL) 2014, Vol. LXVIII, № 1, Р. 37 – 43. of membranes under conditions of in- Patient 5. Usenko G.A., Vasendin D.V.,

-0.830±0.02 -0.464±0.01 -0.745±0.01 -0.420±0.01 -0.638±0.01 -0.453±0.01 -0.585±0.01 -0.365±0.01 creasing γ-background of the medium Usenko A.G., Schakirova N.A., Makarova in the normal range. However, under the L.I., Machmudyan D.A. Vliyanie geliogeo- influence of these heliogeophysical fac- ME МC SgE PhE SgC PhC

ChE fizicheskih faktorov na minutnyj ob”em Correlation coefficients between the dynamics of γ-background, СUOT, potassium and sodium content in erythrocytes during magnetic storms in high-and low-anxiety patients with potassium and sodium content in erythrocytes СUOT, coefficients between the dynamics of γ-background, Correlation ChC 26 YAKUT MEDICAL JOURNAL

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Osobennosti soderzhaniya birsk, 108, Plakhotnogo str., 10; asso- nosti remodelirovaniya sosudistoj stenki magniya v organizme bol’nyh arterial’noj ciate Professor of mobilization training u bol’nyh arterial’noj gipertenziej v zavi- gipertenziej v zavisimosti ot psihoso- of health and disaster medicine of the simosti ot psihosomaticheskogo statusa maticheskogo statusa pacienta i varianta Federal state educational institution of i varianta lecheniya [Specifics of vessel antigipertenzivnoj terapii [The content higher professional education «Novosi- wall remodeling in patients with arterial of magnesium in the body patients with birsk state medical University» Ministry hypertension depending on psychoso- arterial hypertension depending on the of healthcare of the Russian Federation, matics status and treatment options]. psychosomatic status of the patient and 630091, Novosibirsk, 91, Krasny Av., Medicinskij vestnik MVD [MIA Medical alternative antihypertensive therapy]. 52; +7 (913) 9433792 (phone); E-mail: Bulletin]. 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E-mail: [email protected]. 4’ 2018 27

Z.N. Alekseeva, A.G. Egorova, N.S. Arhipova, E.D. Okhlopkova, V.M. Nikolaev GENDER FEATURES OF PSYCHOEMOTIONAL STATUS IN DOI 10.25789/YMJ.2018.64.07 CARDIOVASCULAR PATHOLOGY

ABSTRACT The article analyzes the psycho-emotional state of persons with cardiovascular disease, depending on gender and the socio-hygienic factors. The study analyzed the results of 140 people with cardiological diagnosis of various etiologies in terms of situational and personal anxiety, depression, hostility, and aggressiveness. The psychodiagnostic examination included Beck Depression Inventory, State-Trait Anxiety Inventory, and Buss- Durkee Hostility Scale. Among the surveyed there were 68 women (mean age = 43.7 years) and 72 men (47 years). The analysis showed that at the age of 41 to 50 years we found the highest indicators of situational and personal anxiety, and aggression. Significant depressive symptoms are more often noted between the ages of 31 and 40 years. Among women we’ve found significantly higher rates of anxiety and depression. There were no significant differences in indicators of hostility and aggression. A combination of high hostility and low aggressiveness is noted, which indicates a tendency to contain and suppress aggressive manifestations and may be a predictor of psychosomatic pathology. The main social risk factors in cardiovascular pathology affecting the psycho-emotional state of the subjects include the level of education, dissatisfaction with the state of health, financial situation, nutrition, lack of proper diet and sleep disorders in the nature of their aggression. Keywords: anxiety, depression, hostility, aggressiveness, cardiovascular diseases, gender.

Introduction. According to WHO, car- tion of a cardiologist, a neurologist, and Analysis of the psychodiagnostic diovascular diseases (CVD) are the lead- a therapist. With the help of a question- examination data depending on age ing cause of death worldwide. The study naire developed by the YSC CMP, data showed that high rates of SA (35.4%, of of risk factors of these diseases receive on the social status and living conditions the number surveyed of the correspond- great attention, among them a signifi- of the population were obtained. ing age) and PA (47.9%) are more often cant place is given to psychosocial fac- From the surveyed test data of 140 recorded between the ages of 41 and 50 tors. Researchers have found connection people with verified cardiological diag- years. Severe depressive symptoms oc- of CVD with affective disorders such as nosis were selected, of which 68 were cur between the ages of 31 and 40 years anxiety and depression, which most often women (48.6%) and 72 - men (51.4%). (29.4%). High rates of hostility were not- have the nature of comorbidity [7 - 9, 13, The age of the subjects ranged from 18 ed at the age of 18 to 30 years (43.7%), 14]. Depression is considered an inde- to 61 years. The average age of men and aggressiveness in the period from 41 pendent risk factor in the pathogenesis of was 47 ± 9.98, women – 43.7 ± 9.51. The to 50 years (8.3%). CVD and can both provoke a somatic dis- ethnic composition of the selection was Among the entire examined high SA ease and also be a factor worsening the represented mainly by indigenous people was registered in 25.7%, and moderate prognosis of cardiovascular events. It is – Yakuts -52.1% and low-numbered peo- in 55% of respondents. High PA was not- noted that chronic emotional stress and ples of the North 25%, and other nation- ed in 40% of subjects, and moderate in socioeconomic status are interrelated alities composed in total 22.9%. 48.6% (Table 1). Depending on the gen- and largely determine the integral risk of For the psychodiagnostic study, the der, statistically significant differences cardiovascular diseases [3]. Studying the Beck Depression Inventory (BDI), the were noted for SA (t = 2.19, p = 0.03) and phenomenon of hostility, J.C. Barefoot et Spielberger-Hanin Scale of Situational PA (t = 2, 77, p = 0.006) with the preva- al. confirmed that it is this trait that is sta- (SA) and Personal Anxiety (PA) Scale lence of indicators among women, which ble over time and helps to predict cardio- (State-Trait Anxiety Inventory), and Buss- is consistent with the data of many stud- vascular and overall mortality, including Durkee Hostility Scale, which differenti- ies. that associated with high blood pressure ates aggression and hostility, have been Many authors note that the preva- [12]. Regarding the effect of hostility on used. lence of anxiety in CVD is higher than CVD current research data are ambigu- Statistical processing of the research depression rates. Thus, in the study of ous and require additional testing. results was carried out using the IBM Antonysheva O.V. high SA was detected Research objective - study of the SPSS Statistics 23 software package in 43.5%, and PA in 55.5% of persons gender characteristics of psycho-emo- with the calculation of the Pearson cor- with arterial hypertension (AH) [1]. In the tional status of persons with cardiovas- relation coefficient and significance of work of Kiseleva M.G., it is indicated that cular pathology. differences for independent samples – in chronic CVD, outside the acute form, Materials and methods. Within the Student’s t-test. The significance of the anxiety magnitude is 25% [5]. The data framework of research at Yakut Science statistical differences was taken at a val- obtained by us, on average, correspond Center of Complex Medical Problems ue of p < 0.05. to the data of earlier studies and char- “Effect of Metabolic Syndrome to Devel- Results and discussion. The car- acterize a rather high frequency of PA opment of Coronary Arteries Atheroscle- diovascular pathology in the examined among the studied group. rosis Residents of Yakutia”, a medical, group was mainly represented by hy- An analysis of correlations showed social and psychodiagnostic examination pertension - 72.8% of subjects, 5% were that with an increase in the level of SA of the population was conducted during diagnosed with coronary heart disease & PA, there was a significant increase field trips from 2013 to 2016 in different and 22.2% - other CVD. The distribution in the degree of depression (r = 0.40, p areas of the Sakha (Yakutia) Republic. of CVD in age groups showed that more <0.01; r = 0.53, p < 0.01), hostility (r = A one-stage medical examination of the than 70% of patients were in the range 0.19, p < 0.05; r = 0.27, p < 0.01), ag- population was carried out with participa- from 40 to 60 years. gression (r = 0.18, p <0.05; r = 0.22, p < 28 YAKUT MEDICAL JOURNAL

Table 1 Table 2 Distribution of anxiety levels among respondents, n (%) Distribution of depression levels among Anxiety level Both genders Men Women respondents. n (%) SA PA SA PA SA PA Depression Both Men Women Mild 27 (19.3) 16 (11.4) 15 (20.8) 11 (15.3) 12 (17.6) 5 (7.3) level genders Moderate 77 (55) 68 (48.6) 46 (63.9) 40 (55.5) 31 (45.6) 28 (41.2) Absent 56 (40) 36 (50) 20 (29.4) Mild 39 (27.9) 15 (20.8) 24 (35.3) Expressed 36 (25.7) 56 (40) 11 (15.3) 21 (29.2) 25 (36.8) 35 (51.5) Moderate 27 (19.3) 16 (22.2) 11 (16.2) Total 140 (100) 140 (100) 72 (100) 72 (100) 68 (100) 68 (100) Expressed 18 (12.8) 5 (7) 13 (19.1) 0.01). The increase in the level of SA & were significantly higher among women Severe 0 (0) 0 (0) 0 (0) PA correlates with the level of education (t = 2.39, p = 0.018), which also corre- Total 140 (100) 72 (100) 68 (100) (r = - 0.19, p <0.05; r = - 0.28, p <0.01). sponds to the literature data. V.V. [10] revealed that the prevalence High SA was also associated with poor The data of the correlation analysis of hostility among men was 46.4%, and nutrition (r = 0.24, p <0.05), and PA with showed that the increase in the degree of among women – 43.6%, in our study, the lack of employment (r = 0.17, p <0.05). depression was associated with dissatis- rates are lower, but also do not have sig- In men, the increase in SA was associ- faction with the state of health (r = 0.18, nificant differences depending on gender. ated with a low financial position (r = 0.32, p < 0.05), low material position (r = 0.20, Also in the study of S.H. Hosseini it was p <0.05), low nutrition rating (r = 0.32, p p < 0.05), and lack of nutrition (r = 0.19, found that patients with arterial hyperten- <0.05), with frequent use of alcohol (r = p < 0.05) and a negative assessment of sion are characterized by the presence 0, 27, p <0.05), and also negatively cor- nutrition (r = 0.18, p < 0.05). In men, the of anger as a personality trait, as well as related with the number of children (r = degree of depression was associated its suppression [11], which also can be - 0.30, p <0.05). Indicators of SA posi- with dissatisfaction with living conditions traced in our study. tively correlated with ethnicity, i.e. for the (r = 0.28, p < 0.05). Among women, the High hostility was also associated with migrant population, high indicators were severity of depression correlated with a low material position (r = 0.21, p < 0.05), more characteristic (r = 0.31, p <0.05); a negative assessment of nutrition (r = and aggressiveness was correlated with with age SA indices decreased (r = - 0.27, 0.34, p < 0.01). smoking (r = 0.16, p < 0.05). High male p < 0.05). Among women SA had a nega- Thus, high rates of depression are hostility correlated with a short sleep du- tive correlation with ethnicity (high rates more associated with low material well- ration (r = 0.39, p < 0.01), and aggres- were more characteristic for the Yakuts (r being and the lack of nutrition associated sion with late bedtime (r = 0.30, p < 0.05). = - 0.24, p <0.05); it also correlated with with it. Among women, high hostility was associ- an increase in the level of education (r = According to the results of the Buss- ated with low material status (r = 0.28, p -0.24, p < 0.05). Durkee Hostility Scale (Table 3), high < 0.05) and lack of employment (r = 0.26, PA among women was also associat- hostility was noted in 23.6% of subjects, p < 0.05), and aggression correlated with ed with the level of education (r = - 0.27, and aggressiveness in 4.3%, i.e. with late awakening in the morning (r = 0.26, p < 0.05); among men, no significant cor- a sufficiently pronounced hostility, ag- p < 0.05). Thus, aggressive tendencies in relations were found. gressiveness is very low, besides that men were associated with a lack of sleep, Thus, in the structure of anxiety, the in more than half (58.6%) of the results and in women, on the contrary, with pro- most significant social factors are low of the subjects are at a level below the longed sleep, which most likely is derived financial standing and the associated norm. Based on the fact that hostility is from a lack of employment. lack of nutrition, and among women - a cognitive-emotional component, and Conclusions. Among the studied high level of education. In the studies of aggressiveness is more related to the women, significantly higher rates of situ- Gafarov V.V. it was noted that in women emotional-behavioral component, it can ational, personal anxiety and depression with higher and primary education with a be concluded that subjects with a nega- were found; there were no significant dif- high level of PA, there was a tendency to tive attitude, dissatisfaction with the life ferences with regard to hostility and ag- more frequent development of hyperten- situation cannot realize their aggressive gression. sion [10], which is also seen in our study, tendencies due to excessive self-control In the study group, there were high because our selection is dominated by and tendency to suppress negative feel- rates of hostility combined with low ag- individuals with hypertension. ings The presence of negative attitudes gressiveness, that may indicate the Mild depression by the Beck Depres- towards the world without the possibil- propensity of the subjects to suppress sion Inventory was observed in 27.9% of ity of their expression due to emotional negative feelings, increased emotional subjects, moderate depression – 19.3%, control causes internal tension, which control, which can lead to an accumula- expressed – 12.8%, severe depression creates the basis of psychosomatic pa- tion of psychological stress and may be a was not diagnosed (Table 2). According thology. predictor of psychosomatic pathology to literature data the frequency of depres- Depending on gender among indica- Main social risk factors in cardiovas- sive disorders at various cardiovascular tors of hostility and aggression, no signifi- cular pathology affecting the psycho- pathologies varies from 18 to 60% [4]. cant differences were found (ths = - 0.16, emotional state of the subjects include Thus, according to the data of the “Co- р = 0.86; tag = - 2.16, р = 0.16). In their the level of education, dissatisfaction with ordinate” program in patients with hy- research Akimova E.V. [2] and Gafarov the state of health, financial situation, nu- pertension severe depression occurs in Table 3 27.6%, an increase in the level of depressive disorders - in 52% of patients [6]. Hostility and aggressiveness levels, n (%) Our data, especially in men, are may be Both genders Men Women Level due to the fact that men ignore the ex- HS AG HS AG HS AG perienced difficulties due to the assigned Below average 11 (7.8) 82 (58.6) 6 (8.4) 39 (54.2) 5 (7.3) 43 (63.2) social role. In the case of gender distri- Average 96 (68.6) 52 (37.1) 50 (69.4) 29 (40.3) 46 (67.7) 23 (33.8) bution, significant differences were found Above average 33 (23.6) 6 (4.3) 16 (22.2) 4 (5.5) 17 (25) 2 (3) in the studied groups, depression rates Total 140 (100) 140 (100) 72 (100) 72 (100) 68 (100) 68 (100) 4’ 2018 29

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S. V. Poroyskiy, I. V. Firsova, D. V. Mikhalchenko, Yu. А. Makedonova, E. B. Fomichev COMPARATIVE STUDY OF REPARATIVE REGENERATION OF THE ORAL MUCOSA DOI 10.25789/YMJ.2018.64.08 IN EXPERIMENT

ABSTRACT At present, treatment of inflammatory-destructive diseases of the oral cavity is still a relevant problem. Despite the fact that any dentist disposes a wide range of medical preparations, it is difficult to choose one with the least amount of complications. While managing elderly patients with dental problems the goal is not only to facilitate healing of the oral mucosa, but also to prevent the recurrence of pathology. Injections of platelet autoplasma may be useful in treatment of inflammatory-destructive diseases of the maxillofacial region. Injections of platelet autoplasma for inflammatory-destructive diseases of the oral mucosa, effect of synergism of this method in combination with other therapeutic means justify the need for further study of this issue. In this work, in order to study the regenerative potential, the simulated wound defect in the oral cavity of 30 dogs was treated experimentally. Regeneration control, treatment and supervision lasted 14 days alongside with application of various pharmacotherapeutical methods. To exclude additional factors which might affect the final result of the experiment associated with individual physiological features, study of experimental local treatment methods was carried out within one body: traditional methods of treatment; application of Tysol composition with L-arginine; injections of platelet autoplasma were included in the treatment plan as well as a combined method of treatment. Platelet autoplasma injections combined with Tizol applications with L – arginine was proved to help restore and heal the oral mucosa much faster comparing to other treatment methods. Keywords: regeneration, experiment, dogs, platelet autoplasma, Tizol, pain, hyperemia, wound, treatment.

Introduction. Works on modeling and background of recombinant growth factor destruction of the oral mucosa [5], at pre- research into regeneration potential of therapy was evaluated planimetrically, sent researches are done into modern oral cavity wounds can be seen both in pathomorphologically and histologically. and effective methods of therapy restor- domestic and foreign sources being re- The research proved a favourable effect ing reparative regeneration of the dam- flection of the fundamental aims of the of the carried out therapy on the wound aged tissue [7]. research. [11]. Experiments provide the healing against the background of immu- In spite of the fact that medical science possibility of a deeper research into nodeficiency [2]. advances with seven-league strides and pathogenetic mechanisms of oral cavity In therapeutic dentistry application dentists possess accumulated experi- diseases, substantiation of efficacy and of electrochemically activated solutions ence, the issue of research into repara- directivity of new approaches to stimula- for comprehensive treatment of erosive tive process of the oral mucosa remains tion of the regeneration potential in the ulcerous OMH lesions in patients with pressing [8]. This is the reason for further oral cavity without affecting the patient lichen ruber planus was experimentally advanced researches into peculiarities of [12]. At present, there are some publi- explored to study the character of epi- reparative regeneration of oral mucosa cations on experimental works to study thelization. Experiments were performed in order to enhance clinical efficiency of regeneration potential of oral cavity tis- on chinchilla rabbits. The authors studied treatment and patients’ quality of life. sues. This trend became popular mainly effect of electrochemically activated so- These are platelets that release differ- in surgical practice. Works on predictabil- lutions on activity of antioxidant defense ent growth factors which enhance heal- ity of the oral mucosa healing (OMH) are enzymes in the rabbit’s isolated eryth- ing of regenerative potential. Fibroblasts, associated with the principle of guided rocytes in vitro. Laboratory data of the in turn, produce collagen, hyaluronic tissue regeneration. So, K.A.Aksenov et rabbit’s blood proved the effect of elec- acid and elastin. This process results al. (2011) carried out an experiment on trochemically activated solutions on the in formation of young connective tissue. mini-pigs of Svetlogorsk breed making activity of antioxidant defense which de- Growth factors also block osteoclasts a model of wound process to study the pends on oxidation-reduction potential of and stimulate osteoblasts proliferation, process of surgical wounds regeneration the solution possessing electron-donor thus suppressing bone loss and promot- in the oral cavity after their suturing and properties [3]. ing its regeneration [9]. to increase efficacy of treatment in surgi- The problem of developing new highly The data obtained with clinical re- cal dentistry clinics. This article reflects effective methods of OM diseases is searches substantiate therapeutic effect necessity to change the approach to the still pressing and important in therapeu- of PRP – therapy. Including injections of final stage of surgical interference - sutur- tic dentistry. Therefore, these are experi- platelet autoplasma into the treatment ing for positive result of treatment. [1]. mental studies that help obtain neces- plan, the researchers managed to re- To substantiate experimentally appli- sary data on efficiency of pathogenetic duce or eliminate inflammatory parodon- cation of recombinant epidermal growth impact of new medical compositions and tal diseases, prevent and arrest bone de- factor, an experiment on white Wistar methods of therapy directed to stimulate struction, enhance local immunity of the rats was performed. On the hard pal- reparative regeneration in the oral cavity oral cavity and normalize oral microflora ate of laboratory animals wounds of 5 prior to their clinical testing. [4,10] mm in diameter were made as deep as As alternative inflammation [6] - pre At present, PRP – therapy is performed to the bone. Healing progress under im- vail in the pathogenesis of inflammatory- either with injections or applications. Fol- munodeficiency conditions against the destructive geriatric diseases and lead to lowing centrifugal separation regime is 4’ 2018 31

an important integral part of the method upper and lower jaw, left and right from mental animals was photo documented [4]. At the same time application of this premolar 1 in the vestibule of the oral with a Sony digital camera (8 megapixel). method for inflammatory-destructive dis- cavity. Four wounds 1х1 cm each were During experiment 480 photos were ana- eases of the oral mucosa, efficiency of made on the mucosa. lyzed. PRP-therapy sinergism in combination The operation was performed under The data obtained were processed with other therapeutic methods prove the intravenous anesthesia by Zoletil and using the variational –statistical method, necessity of further studies of the issue. wounds made with a scalpel and pincers. a PC and Microsoft Excel program for Objective of the study: Experimen- To exclude additional factors associ- MS Windows ХР /Microsoft Corp., USA, tal evaluation of wound defect healing ated with individual physiological charac- as well as Stat Soft Statistica v6.0. ap- process in dogs’ oral cavity in conditions teristics which could affect the final result plication package (A.P. Kulaichev, 2006) of application of a new combined method of the experiment, research into experi- in accordance with standard methods of and traditional plans of treatment. mental methods of local treatment was medical statistics. Statistical analysis was Material and methods of the re- performed on one body. done using the method of variational sta- search. In the experiment, clinical evalu- Group 1 (control) – On the right lower tistics by determining mean (М), its mean ation of a standard wound defect in dogs’ jaw the dogs’ OM wound was treated error (±m), evaluation of significance of oral cavity was performed which helped with a traditional method (application of differences by group with Student’s test qualitatively evaluate dynamics of the Celestoderm: Solcoseril= 1:1). (t). Difference between compared indica- wound healing against the background Group 2 (experimental) – On the right tors was considered to be significant with of therapy. The study was performed in upper jaw applications of Tizol with L- р< 0,05, t≥2 (V.I.Sabanov, E.R.Komina, the laboratory of pathology modeling of arginine were use for the complex treat- 1996, I.F.Sprace et al. , 2006). SBI “Volgograd Center of Medical Sci- ment of OM would defect; Results and discussion. Morpho- ences”. The experiment was performed Group 3 (experimental) – On the left metric examination of the wound defect on 30 male dogs weighing from 2 to 16 upper jaw the treatment plan included in the oral cavity against the background kg, living in a vivarium (t° = 22-24 C°, injections of platelet autoplasma; of treatment showed neither complica- relative air humidity 40-50%), with a nat- Group 4 (experimental) – On the left tions nor side effects in all groups, posi- ural regime and standard diet (GOST Р lower jaw 2.0 ml of platelet autoplasma tive results were obtained in all groups, 50258-92), following rules of laboratory was administered into the OM wound de- though healing dynamics was different practice while carrying out pre-clinical fect by infiltration along the mucobuccal depending on therapy conducted. So, researches in the Russian Federation fold alongside with application of Tizol edema decreased more rapidly in the (GOST 3 51000.3-96 и 1000.4-96) as with L- arginine composition using sand- 4th group of dogs whose treatment plan well as rules of humane treatment of ani- wich-technique. included a combined method of treat- mals (Report of the AVMA Panel on Eu- Platelet plasma was made by taking ment (platelet autoplasma injections in thanasia JAVMA, 2001) and International 7 ml of venous blood from the labora- combination with Tizol and L-arginine recommendations of European conven- tory animals with a butterfly syringe into a applications). On the 3d day edema in- tion for Protection of Vertebrate Animals vacuum test-tube. The test-tube was put dicators in the 4th group were 1,5±0,09 in experimental researches (1997). Ex- into the centrifuge 80-2S (China) at 3 500 points which was 1.8 times less compar- periments were approved by the Ethi- rpm for 5 min. With this method 3.5 ml of ing with group 1 (2,7±0,08 points); 1.5 cal Review Committee of the Volgograd platelet autoplasma was obtained. times less comparing with group 2 (Ti- State Medical University (Proceedings Subsequently, the wound defect was zol with L-arginine applications) and 1.4 No 2036). treated by injecting platelet autoplasma times less comparing with group 3. This The animals were premedicated by into the lesion. difference was statistically significant 0.1% atropine injected in the left gas- The wound defect condition in the ani- (р<0,05). Significant difference was also trocnemius muscle in the amount corre- mals was clinically monitored daily for 2 obtained on determining this indicator sponding to the animal’s weight (under weeks. in groups 2 and 3 relative to the group the producer’s instructions). Anesthesia Hyperemia level was evaluated using with conventional treatment (р<0,05). was performed with “Zolitil-100” injected clinical evaluation scale: 0 - no hyper- The difference between group 2 and 3 intramuscularly in the amount of 8 mg/kg emia, 1 point– insignificant hyperemia, 2 was statistically insignificant (р>0,05). (under the producer’s instruction). When points – moderate hyperemia, 3 points– A week after the experiment began a the animal stopped reacting to stimula- marked hyperemia. Edema of the wound slight edema was noted in the first three tion, it was immobilized with a device edges was also evaluated using 4-point groups: group 1 – 1,8±0,13 points; group used for immobilization of the experimen- scale: 0 – no edema, 1 point – insignificant 2 – 1,3±0,07 points; group 3 – 1,1±0,11 tal animal for sampling bioptic material edema, 2 points – moderate edema, 3 points. In group 4 edema was estimated from the oral cavity (Patent No 62527 of points marked edema. Area of the wound as 0,3±0,08 points, that indicates ab- 10.06.2016). defect, OM regeneration index and OM sence of edema in the dogs’ oral cavity. Teeth of the immobilized animals were regeneration intensity were determined Differences between experimental cleaned with ultrasound, dental deposits using the technique developed by L.N. groups relative to group 4 were also sta- were removed manually, oral mucosa Dedova and I.N. Fedorova (2005), with tistically significant (р<0,01), so, it can be was treated with antiseptic solution of the help of our device to measure the le- noted that applying a combined method of 0.05% chlorhexidine bigluconate to elim- sion area in the oral cavity (RF Patent for wound treatment there is a clear tenden- inate a bacterial factor which could affect useful model No 66417 of 07.11.2016). cy towards marked decrease of edema the course of experiment. The results were considered on the 3d, against the background of the treatment Experimental modeling of the patho- 7th and 14th day of treatment and monitor- conducted. On the 14th day of the experi- logical process was performed by making. Photo documentation Dynamics of ment all dogs on all four sides showed no ing lesions on the oral mucosa of the OM wound defects treatment in experi- signs of edema in the oral cavity. 32 YAKUT MEDICAL JOURNAL

Significant difference was also ob- After 14 days the wound defect disap- erosive-ulcerative lesions of the mucous tained on evaluation of hyperemia in the peared in all four groups, no signs of in- membrane of the oral cavity in patients oral cavity. On the 3d day, hyperemia flammation were noted, the oral mucosa with lichen planus (clinical-experimental was 2,53±0,19 points in the group with of all dogs fully regenerated. study)]: avtoref. dis… kand.med.nauk conventional method of treatment which Conclusions. [author. dis ... cand. med. sciences]. Vla- was 10% higher than in group 2 and 3 Thus our experiment revealed that dikavkaz, 2014, 23 p; http://medical-diss. (2,3±0,05 points with р>0,05) and 58% Tizol with L – arginine applications ar- com/medicina/patogeneticheskoe-obos- significantly higher comparing with the rests inflammation much quicker in com- novanie-primeneniya-elektrohimicheski- group with treatment of platelet autoplas- parison with conventional therapy that is aktivirovannyh-rastvorov-v-kompleks- ma injections combined with Tizol and proved by significantly obtained differ- nom-lechenii-erozivno-yazv. L-arginine applications (1,6±0,09 points, ence on determining quantitative crite- 4. Ovechkina M.V. Izuchenie pato- р<0,05). ria. There was no significant difference morfologicheskih izmenenij tkanej desny On the 7th day signs of hyperemia between this group and the group where pri lechenii hronicheskih vospalitel’nyh i decreases in all groups. Significant dif- injections of platelet autoplasma were vospalitel’no-destruktivnyh zabolevanij ference was noted in group 4 comparing applied which proves the advantage of parodonta s ispol’zovaniem regenera- to other experimental groups (р<0,05). these two methods comparing with the tivnogo metoda na osnove autologichnoj Hyperemia in group 4 was 0,5±0,09 conventional therapy and efficacy of both trombocitarnoj plazmy. Chast’ II [Study points which was significantly 3 times methods to enhance regeneration of the of pathomorphological changes of gin- lower comparing with group 1 (1,5±0,09 oral mucosa. gival tissues in the treatment of chronic points), 2.6 times lower comparing with In spite of the fact that after 2 weeks inflammatory and inflammatory-destruc- the group whose treatment plan included full regeneration of the connective tissue tive periodontal diseases using a regen- applications of Tizol with L-arginine, and in the oral cavity was noted in all dogs, in erative method based on autologous 2.4 times less comparing with group 3. the group with combined method of treat- platelet plasma. Part II]. Parodontologi- Between groups 1,2 and 3 no significant ment there is a tendency towards more ya [Periodontology]. Vol.20, №3, (76), difference was noted р( >0,05) on evalua- marked and earlier epithelization, which 2015, p.23-26; https://elibrary.ru/item. tion of indicators of hyperemia in the oral is proved by significant difference in all asp?id=24365629 cavity. On the 14th day hyperemia in the periods of the experiment. One can sup- 5. Carev V.N. Eksperimental’noe dogs’ oral cavity was not noted. pose that injections of platelet autoplas- obosnovanie primeneniya biopolim- On the 3d day significant decrease ma alongside with applications of Tizol ernyh plenok, soderzhashchih pre- of the would defect diameter was not- with L-arginine more effectively influence paraty immunomoduliruyushchego i ed, though in the group with combined the process and healing comparing with antibakterial’nogo dejstviya, dlya lecheni- method of treatment the diameter was other methods of therapy. ya zabolevanij parodonta [Experimental 4,6±0,12 mm which was 34.7% lower justification of the use of biopolymer films comparing with group 1 with diameter References containing immunomodulatory and anti- of 6,2±0,18 mm which was 13% less 1. Aksyonov K.A. Eksperimental’noe bacterial drugs for the treatment of peri- comparing with group 2 (5,2±0,14 mm modelirovanie zazhivleniya hirurgich- odontal diseases]. Parodontologiya [Peri- and 15% less comparing with the group eskih ran v polosti rta [Experimental mod- odontology]. Vol.15, №1, 2010, p. 57-60; whose treatment plan included platelet eling of the healing of surgical wounds in https://elibrary.ru/item.asp?id=15244682 autoplasma injections (5,3±0,15 mm). the oral cavity]. Biomedicina [Biomedi- 6. Yurkevich A.V. Patomor- Groups 2 and 3 showed significant differ- cine]. №1, 2011, p.34-41; https://elibrary. fologicheskoe issledovanie slizistoj ence relative to group 1 (р<0,05). The ru/contents.asp?id=33663529. obolochki desny pri yazvennoj bolezni area of the wound defect also signifi- 2. Volozhin A. I. Zazhivlenie hirur- zheludka [Pathomorphological study of cantly decreased in all groups comparing gicheskoj rany slizistoj obolochki polosti the mucous membrane of the gums with with previously obtained data. It must be rta pod vliyaniem primeneniya rekom- ulcers of the stomach]. Sibirskij Konsilium stressed that regeneration of the oral mu- binantnogo ehpidermal’nogo faktora [Siberian Concilium]. №4, 2005, p.37-40; cosa in the first three groups correspond rosta v ehksperimente [the Healing of https://elibrary.ru/item.asp?id=28959556 to the 2nd degree of regeneration, and in surgical wounds of the mucous mem- 7. Yurkevich A.V. Patomorfologicheskij the group with combined method of treat- brane of the oral cavity under the influ- analiz slizistoj obolochki desny pri saha- ment the course of reparative processes ence of recombinant epidermal growth rnom diabete i yazvennoj bolezni zhe- was much more effective, degree III of factor in the experiment]. Rossijskaya ludka [Pathomorphological analysis of the regenerative potential being the evi- stomatologiya [Russian dentistry]. №31, the mucous membrane of the gums in dence. . 2011, p.32-37; https://www.medias- diabetes and gastric ulcer] avtoreferat A week after dynamic monitoring and phera.ru/issues/rossijskaya-stomatologi- dissertacii na soiskanie uchenoj stepeni treatment of the dogs the area of the ya/2011/1/032072-6406201115 doktora medicinskih nauk [abstract of the would defect significantly decreased in 3. Mrikaeva O. M. Patogenetiches- thesis for the degree of doctor of medi- all groups, though in group 4 the postop- koe obosnovanie primeneniya ehlektro- cal sciences]. Nauchno-issledovatel’skij erative would was not visually revealed, himicheski-aktivirovannyh rastvorov v institut regional’noj patologii i patomor- its area was 0,8 mm2. In the group with kompleksnom lechenii ehrozivno-yaz- fologii SO RAMN [Research Institute of conventional method of treatment the vennyh porazhenij slizistoj obolochki regional pathology and pathomorphology area of the wound defect was 8.7 mm2, polosti rta u bol’nyh krasnym ploskim SB RAMS]. Novosibirsk, 2005; https://eli- that was 2.4 times significantly higher lishaem (kliniko-ehksperimental’noe brary.ru/item.asp?id=32783602 comparing with group 2 (3.59 mm2) issledovanie) [Pathogenetic rationale for 8. Justification of the Effective- and 3.3 times higher comparing group 3 the use of electrochemically-activated ness of Plasmolifting TM Procedure in (2.57 mm2), with р<0,05. solutions in the complex treatment of Treatment of Patients with Erosive and 4’ 2018 33

Ulcerative Lesions of the Oral Cavity / and digestase / A.V. Timoshin, A.V. Sevbi- Medical University”, Volgograd, pin177@ Makedonova Iu.A., Firsova I.V., Temkin tov, E.V. Ergesheva, A.V. Boichuk, M.A. rambler.ru, 89047760825. Volgograd, E.S., Poroiski S.V., Mikhalchenko D.V. // Sevbitova // Asian Journal of Pharma- 400033, st. Ak. Bogomolets 1-177; Research Journal of Medical Sciences. ceutics. – 2018. – Vol.12. – №1. – P.284- 3. Makedonova Julia Alekseevna – 2016. – Vol. 10 (3). – Р. 64-68;DOI: 287. DOI: http://dx.doi.org/10.22377/ajp. - Candidate of Medical Sciences, 10.3923/rjmsci.2016.64.68.;http:// v12i01.2073. Associate Professor of the Department medwelljournals.com/abstract/?doi. 12. Zakharova G.P. Morphologi- of Therapeutic Dentistry of FGBOU VO 9. Mikhalchenko A.V. Using the cy- cal study of the biological fluid of nasal “Volgograd State Medical University”, tologic method for curing diseases of the polyps in patients with chronic rhinosi- senior researcher at the Laboratory of oral cavity mucous membrane after pros- nusitis polypous / G.P. Zakharova, Ye.V. pathology modeling of the Volgograd thetics / A.V. Mikhalchenko, V.F. Mikhal- Tyrnova, V.V. Shabalin, L.L. Kliachko Medical Scientific Center, Volgograd, chenko, A.V. Zhidovinov, E.N. Yarygina, // Rossiyskaya otorinolaringologiya. – 400105. St. M.Eremenko 98-9, mihai-m@ D.V. Mikhalchenko // Indo American Jour- 2006. – №6. – Р.1-6.DOI: 10.17116/ros- yandex.ru; nal of Pharmaceutical Sciences. – 2018. rino201523457-59. 4. Mikhalchenko Dmitriy – Vol.5. – №4. – С.2368-2375. DOI: Valerevich - Doctor of Medicine, Associate 10.5281/zenodo.1218233. The authors Professor, Head of the Department 10. Inchingolo F. Regenerative sur- 1. Poroyskiy Sergey Viktorovich of Propaedeutics of Dental Diseases gery performed with Platelet-Rich Plas- - Doctor of Medical Sciences, Associate FGBOU VO “Volgograd State Medical ma used in sinus lift elevation before Professor, Vice-Rector for Academic Af- University”, Volgograd, 400048, Zhukova dental implant surgery: an useful aid in fairs, FGBOU VO “Volgograd State Medi- Avenue 127-42, [email protected]; healing and regeneration of bone tissue cal University”, Head of the Laboratory 5. Fomichev Evgeniy Valentinovich / F. Inchingolo, M. Tatullo, M. Marrelli // of pathology modeling of the Volgograd - Doctor of Medical Sciences, Professor, European Review for Medical and Phar- Medical Scientific Center, Volgograd, Head of the Department of Surgical macological Sciences. – 2012. – Vol.16. 400081, ul. M. Rybalko д.12 кв.117, Dentistry and Maxillofacial Surgery – P.1222-1226; https://www.europeanre- [email protected]; FGBOU VO “Volgograd State Medical view.org/article/1455 2. Firsova Irina Valeryevna - Doctor University”, Volgograd, 400081, st. 11. Timoshin A.V. Еxperience of treat- of Medical Sciences, Associate Professor, Angarskaya 7B - 44, [email protected]. ment of aphthous lesions of oral mucosa Head of the Department of Therapeutic by preparations on the basis of collagen Dentistry FGBOU VO “Volgograd State E.A. Ubeeva, Y.G. Razuvayeva, D.N. Olennikov, I.P. Ubeeva, S.M. Nicolaev, L.D. Dymsheeva EXPERIMENTAL PHYTOCORRECTION OF ACUTE D-GALACTOSAMINE DOI 10.25789/YMJ.2018.64.09 HEPATITIS IN WHITE RATS

ABSTRACT The aim of our research was in defining hepatoprotective properties of new complex plant supplement on a rat model of D-galactosamine hepatitis. The new complex drug supplement is a dry extract consisting of Hypecoum erectus L., Hedysarum dauricum, Glycyrhhiza uralensis Fisch., Calendula officinalis and Scutellaria baicalensis. Intensity of the main pathogenetic syndromes was evaluated by biochemical tests, lipid peroxidation grade and morphological research. The use for the complex extract resulted in correction of functional state of the liver, inhibition of cytolysis and cholestasis, delay of LPO and enhancing synthetic function of liver manifested in albumin and fibrinogen increase. Keywords: acute experimental hepatitis, hepatoprotective drugs, complex drug of medicinal plants.

Introduction. A necessity in finding hepatitits. 120-5-C18 AQ (2 × 75 mm, 5 µm; Me- new hepatoprotective drugs and sup- Materials and methods of research. trohm AG, Herisau, Switzerland); mobile plements is dictated by the growing de- The researched plant supplement is a dry phase: 0.2 М LiClO4 with 0.006 M HClO4 mand: increasingly widespread liver pa- extract consisting of dry extracts of Hype- (А), MeCN (В). During the separation thologies tending to chronic forms being coum erectum L.; Papaveraceae grass, process profile of gradient elution was set caused by viruses, toxic agents including dry extract from Hedysarum alpinum L.; to 0–40` 5–100% В, 40–43` 100% В with some medication [8, 9, 10]. Under these Leguminosae grass, dry extract of Glyc- speed of 100 µl/min, temperature set to conditions, medicinal plants are of inter- yrrhiza uralensis Fisch.; Leguminosae 35°С with UV-detection at a wavelength est considering the wide range of their roots, dried flower extract of Calendula of 210 nm. Concentration of substances therapeutic effect, low toxicity and the officinalis L.; Compositae and dry root was measured with commercially avail- possibility of gaining amplified effect by extract of Scutellaria baicalensis Georgi; able samples (Sigma-Aldrich). Detected combining active components of complex Lamiaceae in proportion of 5:5:4:4:2. components included: glycyrrhizic acid plant supplements [1- 4]. Compounded preparations were 2.06 ± 0.04%, baikalin 1.85 ± 0.04%, The aim was in determining pharma- performed using HPLC with UV-detec- protopin 1.09 ± 0.03%, mangipyrin 0.68 ± cotherapeutical effectiveness of new tor on MiLiChrom A-02 by ECONOVA 0.02%, typhaneoside and narcissin com- complex medicinal supplement on a rat (Милихром А-02, Эконова), Novosi- bined 0.27 ± 0.01%. model of acute D-galactosamine toxic birsk, Russia with column ProntoSIL- The pharmacotherapeutical effective- 34 YAKUT MEDICAL JOURNAL

ness of complex plant supplement was significant when P<0.05. 18,9% and more (Table 1). studied after inducing acute hepatitis in Results and discussion. The use of In the comparison group (Carsil) on the rats by D-galactosamine infusion. The D-galactosamine model did not cause according dates ALT and AST decrease chosen model of acute liver damage is acute lethality in experimental animals. was 7,32-10,25% . In the groups of rats known to be close to viral hepatitis in its General condition, reaction and move- receiving the studied plant supplement morphological and biochemical features ability, appetite of the rats remained in- there was a more pronounced decrease [5]. tact. There was no weight loss during first of the activity of aminotransferases. D-galactosamine was injected intra- 7 days of the experiment in D-galactosa- The degree of cholestasis severity peritoneally in dose of 400 mg/kg [5]. The mine groups while the animals of the in- was measured by compex evaluation of researched supplement was injected intact group have gained 20-25 g. cholesterol concentration, ALP activ- tragastrically in doses 100 (group 1), 200 Biochemical tests performed on D- ity and GGTP in blood serum. As it is (group 2), 300 (group 3) mg/kg one hour galactosamine-exposed groups demon- known, lipid metabolism values in rats’ before D-galactosamine injection and strated drastic changes of the functional serum are lower than in human serum then daily for 14 days. Carsil (Silibinin) state of the liver (Table 1). A significant due to the functions of α-muricholic, and obtained from the milk thistle plant Sily- deviation of biochemical parameters β-muricholic acids that force cholesterol bum marianum (L.) Gaertn. was used as was observed in the groups of rats with metabolism [9]. However, despite that a reference agent in a dose of 100 mg/ D-galactosamine-induced liver toxicity fact in the experiment cholesterol level kg daily likewise. Control group of white pointing to the development of the main was still slightly growing because of the rats was injected with D-galactosamine pathogenic syndromes of liver damage: liver damage. In the comparison group but instead of pharmacological agents re- cytolysis, cholestasis, mesenchymal in- on the 7th day of the trial ALP activity ceived an equal volume of distilled water. flammatory reaction combined with hy- and GGTP level dropped by 9-10%. As Intact group received only distilled water. poalbuminemia and hypocoagulation. a result of using the complex drug sup- Functional state of the liver was evalu- The intensity of lipid peroxidation was plement a decrease in cholesterol levels ated by biochemical markers: Alanine evaluated by malondialdehyde and diene was more compelling than a decrease of aminotransferase (ALT) and aspartate conjugates concentration in blood serum it in the comparison group (Tab. 1). Ad- aminotransferase (AST), alkaline phos- of the experimental animals [9] wherein ditionally a decrease by 17,5-18,5% of phatase (ALP), gamma-glutamyl trans- in the experimental groups signs of lipid ALP and GGPT was demonstrated in the peptidase (GGTP), cholesterol, total peroxidation were significant. tested drug supplement group. Further- protein (reagents “Abris” and “Vital” on On the 7th day of the experiment in more in the group of the drug supplement analyser “VitaRay”). Lipid peroxidation the control group of the animals activity in dose 200 mg/kg demonstrated more intensity was determined with Malondial- of AST and ALT was amplified by 3,1-3,3 substantial decrease in ALP, GGTP and dehyde (MDA) and conjugated dienes in in comparison with the intact animals tes- cholesterol levels (in 6 out of 8 animals). serum [7]. In order to analyze the mor- tifying to the expressed cytolysis that had In the given period of the experiment af- phofunctional state of liver a set of histo- developed from an early date. Albumin ter injection with the studied supplement logical, histochemical and histoensymo- concentration was decreased by 14,9% relevant supression of peroxidation inten- logical methods was applied [5]. (down to 31,4-34,0 g/l in 6 rats of the con- sity manifested in a decrease of malondi- The pharmacotherapeutical effective- trol group) reflecting remarkable change aldehyde and diene conjugates concen- ness of complex plant supplement was in the functional state of hepatocytes tration by 18-24% studied on 7th, 14th and 21st days of while the level of total proteins remained Pathomorphological study showed experiment. Data were analyzed using on the same levels due to globulin frac- that in liver of animals from the control MedCalc version 18.5 statistical software tion growth. Furthermore, level of fibrino- group on the 7th day of the observa- [10]. Values were considered statistically gen and prothrombin index dropped by tion after injection with D-galactosamine

Table 1 Blood serum biochemical markers dynamics in D-galactosamine induced liver damage on rat model on the 7th day of the experiment (M±m, n=8) Groups with D-galactosamine induced liver damage Markers Intact group Group 1 + 100 Group 2 + 100 Group 3 + 100 Control+ Н2О Comparison mg/kg complex mg/kg complex mg/kg complex group + Carsil supplement supplement supplement ALT, U/l 58.6±5.4 152.9±9.2 141.7±9.7 132.6±8.2 123.5±7.9* 125.4±6.9 AST, U/l 73.5±4.7 242.7±10.2 217.8±11.4 205.7±9.1* 198.5±11.3* 203.3 ±9.2* Cholesterol, µmol/l 1.82±0.13 3.52±0.19 3.05±0.12 2.97±0.13 2.63±0.14* 2.90±0.12 ALP, U/l 308±21 742 ±41 667±43 612.0±27 604.7±25* 619±21* GGTP, U/l 7.13±0.31 23.94±2.10 21.83±1.34 19.45±0.89* 19.75±0.94* 18.38±1.25 Albumin, g/l 42.5±2.2 33.5±1.4 37.3±2.1 38.5±1.3* 39.2±1.2* 38.9±1.7* Total protein, g/l 72.9±3.9 64.3±2.4 64.5±4.1 65.7±3.8 68.7±3.9 66.7±2.1 Globulin, g/l 30.4±2.9 30.8±1.7 27.2±2.6 27.2±2.1 29.5±1.9 27.8±2.1 Fibrinogen, g/l 2.43±0.13 1.51±0.11 1.82±0.19 1.97±0.12* 2.03±0.14* 1.99±0.11* Prothrombin index (PI) % 84.4±4.7 50.3±2.4* 57.1±3.7 59.9±2.9* 64.7±3.8* 63.8±3.4* Note. In the Tables 1-2 * - the differences are statistically significant between the control and experimental groups at P <0.05; n is the number of animals in the group 4’ 2018 35

changes, characterized by dystrophic crease in ALP by 15,2% in dose 100 mg/ On the 3rd week of the experiment in and necrobiotic transformation of hepato- kg and by 17,84% in the group of the the control group deviation of biochemi- cytes, mesenchymal-inflammatory effect dose 200 mg/kg while in Carsil group cal markers was less evident than that coupled with activation of macrophages, ALP was decreasing by 9,16%. On the of the intact animals with ALT and AST accumulation of lymphocytes in portal 14-th day of the experiment hypoalbu- close to those of the intact group. At the tracts and deterioration of bile tract cells minemia in the groups of the studied sup- same time in the groups treated with the were present. The use of the complex plement was significantly less expressed studied plant supplement relevant de- drug supplement in doses from 100 mg/ than in the control gruop while coagula- crease in cholestasis was observed. The kg to 300 mg/kg and the comparison drug tion parameters were normalizing as a pathomorphological study of the speci- Carsil had limited the grade of necrobiotic result of increased synthetic ability of the mens taken on the 3rd week of the trial processes and mesenchymal-inflamma- liver. The grade of lipid peroxidation was showed no insignificant deviations. tory effects induced by D-galactosamine. decreasing. Conclusion. After experimental D-ga- Thus, in the observation group on the 7th On the 14-th day of the observation in lactosamine induced liver damage use of day moderate granular degeneration of animals’ liver of the control group the ex- the comparison drug influenced the path- hepatocytes prevailed. In the group of pression of structural changes decreased ological processes by decreasing cytoly- dose 100 mg/kg hepatocytes affected by in comparison to the previous control sis and cholestasis on the 2nd week of the hydropic dystrophy accounted for 2/3 of point. Dystrophic hepatocytes were experiment while levels of albumin and periportal lobe while in other drug sup- found locally but not diffusely. In three globulin and parameters of coagulation plement groups fractions of transformed specimens of the control group moderate remained constant. The use of the stud- hepatocyres were scarce and situated hydropic dystrophy was still observed. ied complex plant supplement had led to periportal. The data of morphometric re- In liver of the animals from experimental decrease of biochemical markers devia- search demonstrated that number of ne- groups was observed moderate expan- tions. The grade of cytolysis in the experi- crotic hepatocytes was lower in 1,9 times sion of sinusoidal spaces, local veno- mental group №2 (dose of the complex in average (compared to the data of the capillary erythrostasis, increased blood drug supplement 200mg/kg) was signifi- control group). filling of some vessels and granular de- cantly lower starting from the first control On the 14th day of the experiment generation of hepatocytes. Hepatocytes point (7 days after the beginning of the after D-galactosamine-induced damage with lipid degeneration were scarce in the experiment) with ALT and AST dropping the animals demonstrated weight loss several portal tracts. In the results of mor- by 15-18% compared to the comparison in comparison with the intact group by phometric research the number of fatty drug at 7-10%. Based on the complex 7-10%, lowered appetite and moveability. transformed hepatocypes was 5 times evaluation of cholesterol, ALP and GGTP Biochemical parameters reflected persis- lower than that of the control group. As levels the experiment had shown that tence of the main features of liver dam- a result of delayed destruction of hepato- the use of the drug supplement leads to age in experimental animals. After injec- cytes in the experimental groups signifi- significant growth of albumin, fibrinogen tion with Carsil a remarkable decrease of cant signs of reparation were observed. and prothrombin index levels evident of amynotranispherases was observed. Thus, in the group of studied supplement the improvements in synthetic function of During the second week of the experi- injected in dose 100 mg/kg and in the the liver starting from the first point of the ment signs of cholestasis were still ap- comparison group was found increased control. The use of the studied plant sup- parent. As a result of injection with the number of hypertrophic hepatocytes and plement contributed to a decrease in lipid complex drug supplement ALP, GGTP binucleate hepatocytes (by 22%), while peroxidation, inhibited the accumulation and cholesterol were lower than that of in groups with doses 200 mg/kg and 300 of malonialdehyde and diene conjugates the comparison group: the group of the mg/kg the increase was 31% in compari- with significant differences observed in studied supplement demonstrated de- son with the control group. the early periods of the experiment, on

Table 2 Blood serum biochemical markers dynamics in D-galactosamine induced liver damage on rat model on the 14th day of the experiment (M±m, n=8) Groups with D-galactosamine induced liver damage Markers Intact Group 1 + 100 Group 2 + 100 Group 3 + 100 group Control+ Н2О Comparison mg/kg complex mg/kg complex mg/kg complex group + Carsil supplement supplement supplement ALT, U/l 58.6±5.4 128.2±6.9 116.7±5.3* 103.6±5.4* 104.1±5.8* 105.1±4.9* AST, U/l 73.5±4.7 207.0±9.4 189.7±7.1* 172.9±8.7* 169.9±8.3* 170.5±8.2* Cholesterol, µmol/l 1.82 ±0.13 2.97±0.16 2.52±0.11* 2.44±0.15* 2.41±0.14* 2.43±0.15* ALP, U/l 308±21 585.5±25 532.4±17* 496.5±18* 481.5±24* 497.7±17* GGTP, U/l 7.43±0.31 18.82±0.8 16.31±0.7* 15.8±0.82* 15.43±0.72* 15.15±0.76* Albumin, g/l 42.5±2.2 35.3±1.7 38.8±1.9 40.9±1.2* 40.5±1.1* 41.8±1.3* Total protein, g/l 71.8 ±3.9 66.2±2.9 67.3±4.7 68.8±3.8 71.8±5.6 70.9±3.7 Globulin, g/l 29.34±2.9 30.9±3.7 28.5±2.8 27.9±2.1 31.3±1.4 29.1±2.1 Fibrinogen, g/l 1.93±0.11 1.97±0.11 2.05±0.10 2.51±0.12* 2.47±0.13* 2.53±0.12* Prothrombin index (PI) % 84.4±4.7 50.3±2.4 57.1±3.7 59.9±2.9* 64.7±3.8* 63.8±3.4* 36 YAKUT MEDICAL JOURNAL

the 7th and 14th days of the observation. logical substances]. Мoscow, 2012, 832 The authors Combined with ability to inhibit lipid p. URL: https://search.rsl.ru/ru/re- 1. Elena A. Ubeeva, research ass peroxidation and apparent limitation of cord/010026751366. istant at Buryat State University (Ulan- dystrophic and necrobiotic signs and 6. Sergienko V.I., Bondarenko I.B., Ude) October str., 36 a, tel. 8 (3012) lowered inflammatory intensity, improved Gaydyishev I.I. Matematicheskaya 448255.E-mail: [email protected]; reparation was observed. Consequently, statistika v klinicheskih issledovaniyah 2. Yanina G. Razuvaeva, doctor the researched complex drug supplement [Mathematical statistics for medical stud- of biological sciences, senior scientific demonstrated pronounced hepatoprotec- ies: practice guide]. Moscow: Medicina, researcher of laboratory of safety of tive effect in D-galactosamine-induced 2001, 256 p. URL: https://search.rsl.ru/ biological active substances of the liver damage. Dose elevation to 200 and ru/record/01002906597 Institutes of General and Experimental 300 mg/kg did not lead to the significant 7. Abrashova T.V. [et al.] Fizio- Biology of SB RAS. tel. 8 (3012)433713. improvement. logicheskie, biohimicheskie i biomet- E-mail: [email protected]; richeskie normyi eksperimentalnyih 3. Daniel N. Olennikov, doctor References zhivotnyih: spravochnik [Physiological, of biological sciences, senior scientific 1. Bykov V.A., Sokolskaya T.A., Zayko biochemical and biometric standards researcher of laboratory of the Institutes of General and Experimental Biology of L.N. [et al.] Atlas lekarstvennyih rasteniy of experimental animals: handbook]. SB RAS. tel. 8 (3012)433713. E-mail: Rossii [Atlas of medicinal plants of Rus- Saint-Petersburg: Lema, 2013, 116 [email protected]; sia]. Moscow: VILAR, 2006, pp. 122-124. p. URL: https://search.rsl.ru/ru/re- 4. Iraida P. Ubeeva, doctor of URL: http://www.ozon.ru/context/detail/ cord/01006676393 medical sciences, professor, the manager id/139961777 8. Yushchuk N.D., Vengerov Iu.Ya. chair of the infection diseases, FGBOU 2. Lesiovskaya E.E. Dokazatelnaya Infektsionnyie bolezni: natsionalnoe ru- VO Buryat State University, Ulan-Ude, fitoterapiya [Evidence-based phytothera- kovodstvo [Infectious diseases: national October str., 36 a, tel. 8 (3012) 448255; py]. Moscow: Medicina. P.1- 214 p., P.2 guideline] Moscow: GEOTAR-Media, professor chair of clinical pharmacology – 684 p. URL: https://search.rsl.ru/ru/re- 2010, 1056 p. URL: https://search.rsl.ru/ of Irkutsk state Institute for postgraduate cord/01007886081 ru/record/01004571032 education medical 664079, Irkutsk; 3. Nikolaev S.M. Fitofarmakoterapiya i 9. Yushchuk N.D., Klimova E.A. Lech- 5. Sergey M. Nicolaev, professor, fitofarmakoprofilaktika zabolevaniy [Phy- enie hronicheskogo gepatita C v Rossii: doctor of medical sciences, scientific topharmacotherapy and phytopharma- sovremennyie vozmozhnosti i blizhay- researcher of laboratory of safety of coprophylaxis of diseases]. Ulan-Ude, shie perspektivyi [Treatment of chronic biological active substances of the 2012, 286 p. URL: https://search.rsl.ru/ HCV infection in Russia: progress and Institutes of General and Experimental ru/record/01005481748 outlook] Infekcionnye bolezni: novosti, Biology of SB RAS, professor chair of 4. Nikonov G.K., Manuilov B.M. Os- mneniya, obuchenie [Infectious diseases: clinical pharmacology of Irkutsk state novyi sovremennoy fitoterapii [Basics of news, opinions, training]. Moscow, 2017, Institute for postgraduate education modern herbal medicine]. Moscow: Me- (2), pp. 86–95. doi:10.24411/2305-3496- medical, professor chair of pharmacology dicina - 2005, 520 p. URL: https://search. 2017-00039 FGBOU VO Buryat State University. rsl.ru/ru/record/01002757378 10. Sherlock S., Dooley J. Diseas- Ulan-Ude, October str., 36 a, tel. 8 (3012) 5. Khabriev R.U. Rukovodstvo po es of the Liver & Biliary System. 13th 448255 E-mail: [email protected]; eksperimentalnomu (doklinicheskomu) edition. London: Blackwell, 2002, 864 р. 6. Larisa D. Dymsheeva – PhD, izucheniyu novyih farmakologicheskih URL: https://onlinelibrary.wiley.com/doi/ docent FGBOU VO Buryat State Univer- veschestv [Manual on experimental book/10.1002/9780470986820 sity, Ulan-Ude, October str., 36 a. (non-clinical) study of new pharmaco- 4’ 2018 37

M.I. Gatilova, L.G. Chibyeva CLINICAL CHARACTERISTICS OF DOI 10.25789/YMJ.2018.64.10 ALCOHOLIC LIVER DISEASE

ABSTRACT The features of the clinical course of alcoholic liver disease in various ethnic groups were studied in comparison with chronic alcohol-viral and viral hepatitis B. All patients underwent clinical and laboratory examination. It was revealed that in indigenous patients chronic alcoholic hepatitis was formed in a shorter time, as evidenced by the high frequency of their detection in the age groups up to 20 and from 20 to 29 years and was characterized by more pronounced clinical manifestations. The main distinguishing features of alcoholic liver damage, regardless of the presence or absence of CVH infection, are hepatomegaly, the prevalence of pronounced extrahepatic manifestations, increased activity of AlAT in combination with GGT, and immunological changes. Keywords: alcoholic liver disease, chronic alcoholic hepatitis, alcoholic viral hepatitis, chronic viral hepatitis B.

Introduction. Alcohol abuse has a tected in patients with ACH and AVH. ic gastritis was observed in 34 (40.5%), complex negative effect on the human Hemorrhagic syndrome was detected pancreatic damage - chronic pancreatitis, body, especially on the liver. Alcoholic in ACH, AVH and CVH-B, respectively, more often calcifying in 28 (33.3), lesions liver disease (ALD) is manifested by al- in 25 (30.0%), 26 (36.4%), 10 (32.9%) of salivary glands in the form of mumps in coholic steatosis, acute and chronic alco- patients, without significant differences 21 (25.0%), kidney damage 25 (29.7%) - holic hepatitis, as well as alcoholic liver in groups. Jaundice was more often ob- alcoholic nephritis or pyelonephritis, in 14 cirrhosis [1, 2, 4, 5, 6]. Development of served in the ACH 18 group (21.4%) than (19.4%) heart disease - alcoholic cardio- ALD is also facilitated by excessive body CVH-B 4 (13.3%). myopathy with heart failure, quite often weight and obesity, hepatopathy virus in- Hepatic signs in the compared groups with arrhythmia in 16 (19.0%). Lung bron- fection and immune factors [6, 7]. were encountered in isolated cases. Ex- chitis with a protracted clinical course Purpose of the study- to study the trahepatic systemic manifestations were was observed in 7 (8.3%) patients. The features of the clinical course of alcoholic significantly more often detected in alco- Raynaud syndrome was found in isolat- liver disease in different ethnic groups in holic and alcohol-viral liver lesions com- ed cases at ACH and CVH-B. A moder- comparison with chronic alcohol-viral and pared with viral hepatitis (13.3%) (Table ate variant of the disease occurred in 82 viral hepatitis B. 2). (97.6%) patients with ACH, in 43 (59.7%) Materials and methods of research. Systemic lesions were detected at - AVH and in 17 (56.7%) CVH-B; frequent Groups of patients with alcoholic hepatitis ACH in 78 (92.9%), AVH in 51 (70.8%) clinical symptoms were not severe he- (84), alcoholic viral hepatitis (72), chronic and at CVH-B in 4 (13.3%) patients. In patomegaly in patients of viral and alco- viral hepatitis В (30) were examined. All indigenous people at ACH systemic man- holic-viral etiology, a more pronounced patients underwent clinical and labora- ifestations occurred in 53 (67.9%) and increase in the liver was noted at alco- tory examination. AVH - in 35 (68.6%), in non- indigenous holic chronic hepatitis, together with sys- Results of the study. In 84 patients patients ACH in 29 (37.2%) and AVH - in temic lesions, as well as pain, dyspeptic with chronic active alcoholic hepatitis 8 (15.6%) respectively. In indigenous pa- and asthenic-vegetative syndromes. A (ACH), clinical syndromes and symptoms tients at ACH and AVH, the frequency of significant clinical variant of the disease were analyzed in comparison with pa- systemic manifestations was much high- was found at ACH in 2 (2.4%), AVH in 8 tients with viral-alcoholic hepatitis (AVH) er than in the non-indigenous. (11.1%) and at CVH-B in 5 (16.7%) pa- and viral hepatitis B (CVH-B). Compara- The gastric lesion in the form of chron- tients (Table 3). At chronic viral hepatitis tive characteristics of clinical manifestations of chronic hepatitis of alcoholic, Table 1 alcoholic-viral and viral etiology are pre- Comparative characteristics of clinical manifestations of CH sented in Table 1. of alcoholic, alcohol-viral and viral etiology Asthenic-vegetative syndrome was ob- Number of patients in groups with the presence of signs served at ACH in 94,6%, at AVH in 90,3% Clinical signs ACH n – 84 AVH n – 72 HVG-В n – 30 and at CVH-B in 75,3% of patients, and % n. persons % n. persons % % with pain - 98,1%, hepatomegaly - 100%, Asthenic-vegetative 79 94.6±3.0 65 90.3±3.5 22 75.3±8.1 dyspeptic disorders - 66,6% at patients Dyspeptic 56 66.6±6.3 56 77.8±4.5 11 38.4±8.8 of two compared groups. Painful 83 98.1±1.8 57 79.2±4.9 15 49.3±9.1 Splenomegaly was observed in pa- Hepatomegaly 84 100 71 98.6±1.4 29 97.3±3.3 tients with ACH - 1.6 (1.9%), AVH - 2 Splenomegaly 2 1.9±1.8 2 2.8±1.9 2 6.6±4.6 (2.8%), CVH-B - 2 (6.6%). At alcoholic Hemorrhagic 25 30.0±6.1 26 36.4±5.7 10 32.9±8.6 hepatitis, splenomegaly was determined Jaundice 18 21.4±5.5 13 18.0±4.5 4 13.3±6.2 only by ultrasound examination. Asthen- Hepatic signs: 14 16.6±4.9 7 9.7±3.5 1 3.3±3.3 a) Vascular asterisks 5 5.9±3.4 3 4.2±2.4 1 3.3±3.3 ic-vegetative syndrome, hepatomegaly b) palmar erythema 9 10.7±3.8 4 5.5±2.7 - - occurred in practically all patients of the Systemic damage in total: 78 92.9±3.4 51 70.8±5.4 4 13.3±6.2 observed groups. At the same time, pain Clinical variants of CH: syndrome, dyspepsia disorders and sys- moderately severe 82 97.6±1.8 68 94.7±2.7 25 82.2±6.8 temic lesions were much more often de- severe 2.0 2.4±1.8 4 5.3±2.7 5 17.8±6.8 38 YAKUT MEDICAL JOURNAL

cases. An increase in the level of alkaline Table 2 phosphatase was noted in 26 (31.0%) in Comparative characteristics of systemic lesions in patients with chronic hepatitis patients with alcoholic chronic hepatitis of alcoholic, alcoholic-viral and viral etiology (ACH), with AVH and CVH-B significantly Number of patients with the presence of signs in groups less. Hypoalbuminemia was observed Clinical signs ACH n-84 AVH n-72 HVG- В n-30 in 19 (22.6%) patients with ACH, in 9 n % n % n % (12.2%) AVH and in 2 (6.6%) CVH-B. Systemic damage in total: 78 92.9±3.4 51 70.8±5.4 4 13.3±6.2 Hypergammaglobulinemia was noted Lymphadenopathy 2 1.8±1.8 1 1.4±1.4 3 10.0±5.5 in a small number of patients in all 3 Fever 12 14.3±4.4 3 4.2±2.4 1 3.3±3.3 groups. A significant increase in gamma- Articular syndrome 22 26±5.1 18 25.0±5.1 3 10.0±5.5 Skin syndrome 7 8.3±3.0 7 9.7±3.5 1 3.3±3.3 glutamyltranspeptidase (GGTP) was Renal damage 25 29.7±5.8 9 12.5±3.9 1 3.3±3.3 observed in patients with ACH, statisti- Heart Attack 16 19.0±4.9 14 19.4±4.7 1 3.3±3.3 cally significantly differed from those of Lung infection 7 8.3±3.0 2 2.8±1.9 1 3.3±3.3 the CVH-B group, and an increase in Stomach lesion 34 40.5±6.7 25 34.7±5.6 - GGTP was noted in patients with AVH. Pancreas lesion 28 33.3±6.5 29 40.3±5.8 - Hypocholesterolemia was observed only Lesion of the salivary glands 21 25.0±5.6 15 20.8±4.8 1 3.3±3.3 in patients with chronic hepatitis B 16 Raynaud's syndrome 3 3.6±1.8 - 1 3.3±3.3 (54%). Hypercholesterolemia was de- Nodular periarteritis - - 1 3.3±3.3 tected mainly in patients with alcoholic hepatitis. Anemia was more frequent in B in the clinical picture, systemic lesions hepatitis - severe variants of the disease. patients with alcoholic and alcohol-viral with unexpressed hepatomegaly mani- At studying laboratory indicators (Ta- hepatitis. Leukopenia, leukocytosis and fested themselves more vividly. ble 4) at ACH, AVH and viral hepatitis, it an increase in ESR occurred in isolated Thus, in the majority of patients with turned out that 100% of patients showed cases. From the laboratory indicators chronic alcoholic hepatitis, systemic le- hyperaminotransferase, more often than more characteristic for alcoholic hepatitis sions were observed at moderately se- 5 and 10 times higher than normal, but were hypoalbuminemia, increased activi- vere variants, and in patients with viral higher than 10 times only in isolated ty of gamma-glutamyltranspeptidase and

Table 3 Clinical variants of chronic hepatitis in different ethnic groups Number of patients in ethnic groups ACH AVCH CVH-В non-indigenous non-indigenous Clinical indigenous n=53 total n=84 indigenous n=45 total n=72 indigenous n=21 non-indigenous n=9 total n=30 option n=31 n=27 абс. % абс. % абс. % абс. % абс. % абс. % абс. % абс. % абс. % Latent 3 6.7±3.7 18 66.7±9.1 21 29.2±5.4 3 14.3±7.6 5 55.6±16.6 8 26.7±8.1 Moderately severe with systemic 53 100.0 29 93.5±5.1 82 97.6±1.8 35 77.8±6.2 8 29.6±8.8 43 59.7±5.8 14 66.7±10.3 3 33.3±15.7 17 56.7±9.0 manifestations severe 2 6.4±5.1 2 2.4±1.8 7 15.5±5.4 1 3.7±3.6 8 11.1±3.7 4 19.0±8.6 1 11.1±10.5 5 16.7±6.8

Table 4 Comparative analysis of laboratory parameters in patients with alcoholic, alcoholic-viral and viral etiology Number of patients in groups Indicator ACH n-84 AVCH n-72 CVH- B n-30 n % n % n % Hyperbilirubinemia (more than 20. 5 μmol / l) 21 25±5.5 5 6.8±3.0 4 13.7±6.2 Increase in the level of aminotransferases in total: 84 100 72 100 30 100 including less than 5 times 46 54.7±6.6 32 44.5±5.9 14 46.7±9.1 5 to 10 times 38 45.2±6.6 39 54.1±5.9 15 50.0±9.1 over 10 times - 1 1.4±1.4 1 3.3±3.3 Increase in the level of alkaline phosphatase 26 31.0±6.1х2.3 4 5.4±2.7 х1 2 6.6±4.6х1 Hypoalbuminemia (less than 32g.l) 19 22.6±5.6х3 9 12.2±3.9 2 6.6±4.6 х1 Hypergammaglobulinemia 3 3.6±5.0 3 4.2±2.4 1 3.3±3.3 Gammaglutamyltranspeptidase 80 95.2±3.0х3 61 84.7±4.2х1 1 3.3±3.3х1.2 Rheumatoid factor - - 1 3.3±3.3 Positive LE-cell test - - 1 3.3±3.3 Hypocholesterolemia 3 3.6±5.0х3 1 1.4±1.4х3 16 54.0±9.1х1.2 Hypercholesterolemia 57 67.8±6.2х3 40 55.5±5.9х3 1 3.3±3.3х1.2 Thrombocytopenia 1 1.2±1.8 1 1.4±1.4 1 3.3±3.3 Anemia 19 22.6±5.6х3 23 31.9±5.5х3 1 3.3±3.3х1.2 Leukopenia 4 4.7±3.0 2 3.1±1.9 2 6.6±4.6 Leukocytosis 1 1.2±1.8 - - Increased ESR 4 4.7±3.0 - 1 3.3±3.3 4’ 2018 39

hypercholesterolemia. gepatit [Alcoholic hepatitis] Klinicheskaya expression and viral replication. J Virol Conclusion. Thus, at chronic alco- gepatologiya [ Clinical hepatology]. Mos- -1996;70:5845-51. holic hepatitis, the presence of extrahe- cow, 2008, No. 4 (2), Р. 3-10. 7. O’Shea R.S. Alcoholic liver dis- patic systemic lesions is due to the toxic 2. Bueverov A.O. Pavlov A.I., ease /O’Shea R.S., Dasarathy S., Mc- effect of alcohol on the endocrine glands, Ivashkin V.T. Alkogol’naya bolezn’ peche- Cullough A.J.//Hepatology. -2010. -V.51. vessels, nervous system, and organs of ni: vozmozhno li uluchshenie prognoza? -Р. 307-328. the gastrointestinal tract, which was ob- [Alcoholic liver disease: is it possible to The authors served by other researchers. However, in improve the prognosis?] Klinicheskie per- YAKUTSK, REPUBLIC SAKHA indigenous patients they developed early spektivy gastroehnterologii i gepatologii (YAKUTIA), RUSSIA: and their number and severity were sig- [Clinical perspectives of gastroenterology 1. GATILOVA MARINA ILINICH- nificantly higher [1, 5, 7]. and hepatology]. Moscow, 2011, No. 2, Р. NA - post-graduate student of the depart- Pain syndrome in patients with chronic 3-10. ment of propaedeutic and faculty therapy alcoholic hepatitis in most cases is asso- 3. Mayer K.P. Gepatity i posledst- with endocrinology and exercise therapy ciated with the development of concomi- viya gepatita [Hepatitis and the conse- at the medical institute of the M.K. Am- tant secondary chronic pancreatitis, gas- quences of hepatitis]. Moscow, Geotar, mosov Northeastern Federal University. tritis and duodenitis. A number of authors 2004, Р.720. Tel.:89142873614. E-mail: Gatilova- have noted the presence of these dis- 4. Abittan C. Alcoholic liver disease [email protected] eases as the cause of the onset of pain. /Abittan C., Lieber C.//Clin. Perspect. in 2. Chibyeva Lyudmila Grigoryevna Chronic hepatitis combined with clinical Gastroenterol. -1999. -V. 2. -Р.57 -63. - Doctor of Medical Sciences, рrofessor, symptoms is closer to alcoholic than to 5. Achord J.L. Review and treat- Medical Institute of the M.K. Ammosov viral hepatitis. Very important was the ment of alcoholic hepatitis: a meta-analy- North-Eastern Federal University, fact that CVH replication markers were sis adjusting for confounding variables // рrofessor of the department of absent in all patients [2, 3, 6]. Gut. -1995. -V. 37. -P. 1138. propaedeutics and Faculty Therapy with 6. Buckwold V.E., Xu Z., Chen M., endocrinology and exercise therapy. References Yen T.S., Ou J.H. Effects of a naturally Tel.: 89241734445. E-mail: 1. Abdurakhmanov D.T. Alkogol’nyj occurring mutation in the hepatitis B vi- [email protected] rus basal core promoter on precore gene

D.K. Garmaeva, M.T. Buzinaeva, A.I. Pavlova MORPHOLOGY OF MUCOSA- ASSOCIATED LYMPHOID TISSUE (MALT) DOI 10.25789/YMJ.2018.64.11 OF LARYNX IN GENERAL HYPOTHERMIA

ABSTRACT We have studied the cytoarchitectonics of mucous-associated diffuse lymphoid tissue (MALT - mucosa-associated lymphoid tissue) of the larynx in persons who died from hypothermia. The material was collected in the summer (June, July, and August) and winter (December, January, and February) seasons of the year with the support from the State Budget Institution of the Bureau of Forensic Medical Examination of the Sakha (Yakutia) Republic. Death caused by low natural temperature occurred most often at ambient air temperatures ranging from -34°C to -40°C, less often at -31°C to -33°C. As one of the most frequent factors contributing to the onset of death from hypothermia is alcohol intoxication, for comparative characteristics of the morphology of lymphoid tissue, we also investigated the group of persons who died from general hypothermia with underlying alcohol intoxication. Significant changes in the cellular composition of the mucous-associated diffuse lymphoid tissue of the larynx were revealed: a decrease in T- and B- lymphocytes and plasma cells and an increase in the number of destructively altered cells and macrophages. Keywords: mucosa-associated diffuse lymphoid tissue (MALT), larynx, cytoarchitecture, hypothermia.

The study of the effects of low - tem vironments, the peripheral parts of the larynx, which are located at the surface of peratures on the human body is one of immune system provide sanitation to the the organ and are the first specific barrier the topical areas of basic and clinical tissue complex. Destroying foreign sub- to the penetration of antigens, in particu- medical sciences. The Sakha (Yakutia) stances and detoxification of the body [6, lar cold air. Republic is a region with extreme climatic 13] depends on the functional activity of In both domestic and foreign scien- and geographical conditions, where the these structures. tific literature, there is zero data on the cold is one of the main environmental When a person adapts to the condi- morphology of the mucosa-associated factors of adverse effects on the human tions of the North, the mucosa-associat- lymphoid tissue of the laryngeal walls body [1, 2, 5]. When activating protective ed lymphoid structures of the respiratory related to death from general hypother- reactions of the organism, an important organs are primarily affected by low tem- mia, as well as when this type of death is role belongs not only to the central or- peratures, as they are the first “target” in combined with alcohol intoxication under gans of the immune system, but also to the path of cold air penetration. In this conditions of low air temperatures in the its peripheral structures, in particular the regard, one of the promising areas of Sakha (Yakutia) Republic. The purpose immune (lymphoid) tissue of the walls research on the pathological influence of our study is to optimize the postmor- of hollow organs. Located on the border of the cold factor on the human body is tem diagnosis of death from general hy- between the external internal bodily en- the study of the immune structures of the pothermia by examining the cellular com- 40 YAKUT MEDICAL JOURNAL

position of the mucosa-associated diffuse cells in a state of mitosis, and destruc- of the larynx, both in persons who have lymphoid tissue of the laryngeal mucosa tively altered cells. The data obtained died from a general hypothermia of the in the climatic conditions of the Sakha were recorded as tables. Statistical pro- organism, and in persons who have died (Yakutia) Republic. cessing of the obtained data was carried from general hypothermia of the organ- Materials & Research Methods. The out according to the method of variation ism against the background of alcohol material for the study was samples of the statistics with the definition of arithmetic intoxication. Thus, a stratified squamous mucous membrane of the larynx from mean (X) and its margin of error (Sх). epithelium swells, a large amount of mu- the region of the vestibule, the left and The significance of differences with the cus is deposited in the epithelial cells, right ventricles and the sub-vocal region. p-95% reliability (p < 0.05) was estimated edema is observed in the mucosa itself, The object of the study was diffuse lym- by method of confidence intervals be- the glands and excretory ducts dilate, phoid tissue of the mucous membrane of tween Student’s t-distribution indicators and the accumulation of mucus in the lu- the larynx, recovered from bodies of de- [2, 8]. All mathematical calculations were mens (Fig. 1). ceased men in the territory of the Sakha carried using Microsoft Office Excel 2007 In the epithelium of the ventricles of (Yakutia) Republic. The material was table editor. the larynx with general hypothermia, the collected in the summer (June, July, and Immunophenotyping of T- and B- number of reticular cells decreases by August) and winter (December, January, lymphocytes and macrophages (CD3 1.2% compared to the control group, the and February) seasons of the year with +, CD20 +, CD68 +) was performed us- number of large lymphocytes decreases the support from the State Budget Insti- ing the PolyVue Mous/Rabbit HRP Kit by 36.6% compared to the control group tution of the Bureau of Forensic Medical (manufacturer Diagnostic BioSystems, and by 13.1% compared with the group Examination of the Sakha (Yakutia) Re- USA) imaging system according to the who died from alcohol intoxication. The public. Death caused by low natural tem- instructions of the manufacturer. Antigen number of medium lymphocytes decreas- perature occurred most often at ambient unmasking was performed for 2 minutes es by 0.3%, small lymphocytes – 1.6% air temperatures ranging from -34°C to in citrate buffer (pH 6.0). Primary anti- less compared with the control group and -40°C, less often at -31°C to -33°C. As bodies (CD20 +, CD3 +, CD68 +) were 4.5% less compared with alcohol intoxi- one of the most frequent factors contrib- incubated at 37°C for one hour. The re- cation, plasma cells – 1.2% more. Signifi- uting to the onset of death from hypother- sult of the reaction was visualized with di- cantly increase in the number of cells in mia is alcohol intoxication, for compara- aminobenzidine [4, 9, 10]. Microscopy of a state of destruction – 22.2% more com- tive characteristics of the morphology of immunohistochemical preparations was pared with the control group and 20.3% lymphoid tissue, we also investigated the carried out in transmitted light using a more compared with alcohol intoxication, group of persons who died from general Leica DMD microscope under oil immer- macrophages – 14.3% more compared hypothermia with underlying alcohol in- sion with 90x microscope magnification. with the control group and 1.7% more toxication. Photographing of microsections was car- compared to with alcohol intoxication. Thus, all studied deceased bodies ried out using a Leica digital microscope. In the lamina propria of the laryngeal were divided into 3 groups: the first – per- Research Results & Discussion. mucosa, the number of reticular cells de- sons who died in the summer from fatal The mucosa-associated lymphoid struc- creases by 2.1% compared with the con- mechanical injury, had no respiratory tures of the larynx are represented by trol and 2% compared with alcohol intoxi- system pathology (control group); the both diffuse lymphoid tissue and an ac- cation; the number of large lymphocytes second – persons who died from general cumulation of lymphoid cells. Diffuse decreases by 13.7% compared to the bodily hypothermia (GBH) in the winter lymphoid tissue is found season; the third – persons who died in in the epithelium, in the the winter season from alcohol intoxica- lamina propria of the tion (AI), who had no respiratory system mucous membrane and pathology during their lifetime. in the submucosal layer The material was fixed in a 10% neu- of all parts of the organ, tral formalin solution, embedded in “His- and lymphoid accumula- tomix” paraffin. Paraffin blocks were cut tions are located in the on a Leica HL 1210 microtome at slice region of the vestibule, thickness of 0.3-0.5 μm. Sections for his- the ventricles and the tological review were stained with hema- anterior wall of the sub- toxylin and eosin. Cytoarchitectonics of glot region. This article lymphoid structures were studied using presents the results of a a Leica DMD light microscope under oil morphological study of immersion at 90x magnification, using a cells of the diffuse lym- 25-node ocular morphometric grid of Ste- phoid tissue of the mu- fanov S.B. [14]. Counting of cells (per unit cous membrane of the area S = 0.016 mm2) was performed in ventricles of the larynx. surface epithelium, in laryngeal mucous Our research has Fig.1. The mucous membrane of the vestibule of the larynx in coat and in the submucosal layer. Dur- shown that the effect conditions of exposure to low natural temperatures in the winter ing the analysis and histological prepa- of low natural tempera- season. The epithelial layer is swollen, thickened, in the goblet rations we accounted for small, medium, ture on the human body cells the deposit of mucoid secretion (1), in the lamina propria large lymphocytes, immature and mature leads to significant mor- of the mucous membrane edema (2), the excretory ducts of the plasma cells, macrophages, mast cells, phofunctional changes in glands are enlarged, and in the lumens there is an accumulation of mucoid secretion (3). Stained with hematoxylin and eosin. eosinophils, neutrophils, fibroblasts, the mucous membrane Zoom of approximately 7 by 25 4’ 2018 41

control and 10.1% by compared with al- 3. Exposure to low natural tempera- cohol intoxication, medium lymphocytes tures in the Sakha (Yakutia) Republic – by 5.3% compared with the control and causes depletion of mucous-associated 3.2% compared with alcohol intoxication, diffuse lymphoid tissue of the laryngeal small lymphocytes – by 1.5% compared mucosa, which is expressed by a de- with the control. In the group of persons crease in the number of lymphoid cells, who died from general hypothermia of in particular T-lymphocytes, B-lympho- the organism, the number of plasma cells cytes, plasma cells, and also a significant in the mucosa itself was reduced by 3.2% increase in the number of destructive al- compared with the control group and tered cells, and as a result, macrophag- 2.4% compared with alcohol intoxication. es. The number of destructively altered cells 4. To improve the quality of pathologi- due to general hypothermia increased by cal diagnosis of death from general hy- 11.1%, macrophages by 5.4% compared pothermia when exposed to low natural with the control group, and compared temperatures, it is recommended to use with alcohol intoxication of cells in a state the study of the cellular composition of of destruction increased by 14.4%. diffuse lymphoid tissue of the mucous In the submucosal layer of the ven- membrane of the larynx. Fig.2. The immune status of diffuse lymphoid tricles of the larynx, the number of large tissue of the ventricles of the larynx in individuals who died from general hypothermia lymphocytes decreases by 4.9% com- References compared with the control group (CD3 + – pared with control and by 11.2% com- 1. Agadzhanyan N.A. Zhvavy N.F. T-cell antigen; CD20 + – B-cell antigen; CD68 pared with alcohol intoxication. Medium, Ananev V.N. 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Tik- nyy rezhim pri adaptatsii cheloveka na (CD68 +) - by 11% (Fig. 2). Our research homirov V.P. Fiziologo-gigiyenicheskiye Kraynem Severe [Oxygen Regimen for allows us to confirm the data of many au- aspekty akklimatizatsii cheloveka na Se- Human Adaptation in the Far North]. No- thors [1, 7, 11, 12], who claim that when vere [Physiological and Hygienic Aspects vosibirsk: Nauka [Science], 1987, 127 the body is exposed to low natural tem- of Human Acclimatization in the North]. pages. peratures, cellular and humoral immunity Leningrad: Meditsina [Medicine], 1979, 12. Petrova P.G. Zakharova D.A. is suppressed. 184 pages. Pavlova V.T. Kornilova V.V. Immuno- Conclusions 6. Garmaeva D.K. Osinskaya A.A., logicheskaya reaktivnost u korennykh 1. Peripheral immune structures Sapin M.R. Limfoidnyye struktury dykhat- zhiteley Yakutii [Immunological Reactiv- (MALT - mucosa-associated lymphoid tis- elnykh putey pri vozdeystvii almaznoy pyli ity in the Indigenous Peoples of Yakutia]. sue) are highly sensitive to the effects of v usloviyakh granilnogo proizvodstva re- Interuniversity Collection of Scientific Pa- low natural temperatures, which manifest spubliki Sakha (Yakutiya) v eksperimente pers “Aktualnyye voprosy klinicheskoy itself in the form of pathological changes [Lymphoid Structures of the Respiratory meditsiny v usloviyakh Severa” [Topical of diffuse lymphoid tissue in the mucous Tract under the Influence of Diamond Issues of Clinical Medicine in the North]. membrane of the larynx. Dust in the Conditions of Lapidary Work Yakutsk, 1992, pp. 19-25. 2. Changes in the mucosa-associated in the Sakha (Yakutia) Republic in Experi- 13. Sapin M.R. Nikituk D.B. Immun- diffuse lymphoid tissue in the mucous ment]. Yakutsk, 2010, pp. 10-17. naya sistema, stress i immunodefitsit membrane of the larynx when exposed to 7. Golderova A.S. Zakharova [Immune System, Stress and Immuno- low natural temperatures are character- F.A. Izmeneniya pokazateley immunnoy deficiency]. Мoscow: “Dzhangar” DSA, ized by a significant decrease in lympho- sistemy u bolnykh s kholodovoy travmoy 2000, 256 pages. cytopoietic processes, which results in a [Changes in the Immune System in Pa- 14. Stefanov S.B. Morfologiches- decrease in the percentage of lympho- tients with Cold Trauma]. Dalnevostoch- kaya setka sluchaynogo shaga kak sred- blastic cells and cells in a state of mitosis. nyy meditsinskiy zhurnal [Far Eastern stvo uskorennogo izmereniya elementov 42 YAKUT MEDICAL JOURNAL

[Morphological Grid of Random Step as erational Surgery with Topographic Anat- [email protected], Yakutsk, Rus- Means of Accelerated Measurement of omy and Forensic Medicine at NEFU’s sia; Elements]. Tsitologiya [Cytology], 1974, Medical Institute, [email protected], Ya- 3. Aleksandra Innoketyevna Pav- V. 26, No. 3, pp. 299-305. kutsk, Russia; lova, Doctor of Veterinary Sciences, Pro- 2. Mariya Telektezovna Buzi- fessor, Professor of the Department of Credits naeva, Candidate of Medical Sciences, Animal Physiology and Ecology of the 1. Darima Kyshektovna Garmae- Head of the Histology Laboratory of the Yakutsk Agricultural Academy, pavlova_ va, Doctor of Medical Sciences, Associ- Bureau of Forensic Medical Examina- [email protected], Yakutsk, Russia. ate Professor, Professor, Department of tion of the Ministry of Health of the Sakha Normal and Pathological Anatomy, Op- (Yakutia) Republic in City of Yakutsk, METHODS OF DIAGNOSIS AND TREATMENT

A. V. Antonov, V. E. Volovik, G. A. Palshin THE ROLE AND THE PLACE OF ARTHROSCOPY OF THE HIP JOINT IN TREATMENT OF ASEPTIC NECROSIS DOI 10.25789/YMJ.2018.64.12 OF THE FEMORAL HEAD

ABSTRACT Aseptic necrosis of the femoral head (ANFH) is one of current problems in orthopedics today. The arthroscopy of a hip joint in ANFH is a modern way of minimal-invasive surgery. We use the following staged means of arthroscopy: capsulotomy and synovectomy, debridement and sanation of a joint, revision of degenerative and dystrophic changes, resection of the affected cartilage, microfracturing, removal of free microscopic and macroscopic fragments of cartilage. The quality of life in operated patients before and after was estimated on Harris Hip Score (HHS). Arthroscopy of the hip joint has shown the positive clinical results and indeed improves quality of life in patients. It is necessary to revise more deeply all possibilities of arthroscopic surgery of the hip joint, to estimate all results, to improve treatment methods and to achieve long remission of a disease. On the basis of the orthopedic department of the KGBUZ Regional Clinical Hospital No. 2 in Khabarovsk, an analysis of the frequency of occurrence of aseptic necrosis of the femoral head, its various diagnostic methods, conservative and operative treatment, and the pathological picture of the disease among the adult population in various age categories was made. The obtained positive results of treatment indicate the need for further study of the problem in order to achieve a long lasting remission, and possibly a complete recovery of the patient. Keywords: arthroscopy, aseptic necrosis of the femoral head.

Introduction. Aseptic necrosis of the Materials and methods of research. rect interpretation at the ambulant stage femoral head (ANFH) is wide spread On the basis of Territorial state educa- of examination: permanent pain syn- multifactorial poliethiologic disease af- tional Health facility “Regional clinical drome (93%), increasing under weight fecting primarily men of working age, the hospital №2” in Khabarovsk we’ve ana- load (92), accompanied by a violation of initial link in the pathogenesis of which is lyzed the frequency of aseptic necrosis limb function (98) and requiring the use not exactly understood. ANFH diagnosis of the femoral head, different methods of of additional means of support in move- presents considerable difficulties, due its diagnostics, conservative and surgi- ment (64%). to the late-stage patients, late medical cal treatment, as well as the pathological Despite the development of modern care, and the absence of clear diagnostic picture of the disease among the adult highly informative radiographic methods symptoms. Edema of the bone marrow in population of different age. From 2015 to of diagnosis, the main standard of exami- the initial stage of the pathological pro- 2017, 97 patients diagnosed with aseptic nation is radiography of the affected joint, cess can be detected only on MRI inves- necrosis of the femoral head of the 2nd- and an additional method of investigation tigation. Traditional conservative treat- 4th degree (according to ARCO) were only in 4% of cases is magnetic reso- ment has not enough effectiveness and treated in the hospital, which is 25% of nance imaging. provides short-term improvement only all degenerative diseases of the hip joint. Late-stage pathological process, the in the early stages of the process due 53% of the cases were middle-aged severity of clinical symptoms lead to the to the use of drugs with low or unproven women (45-59 years). surgical treatment, which was performed effectiveness, and anyhow results the The purpose of the study is to analyze in 65% patients. Mostly total cementless complete replacement of the joint only for the frequency of ANFH occurrence. hip replacement (Zimmer, DePuy). In 1% a short period of time. Surgical methods Results and discussion. Detection of cases, due to instability of the acetab- mostly are traumatic and require long- of the disease ANFH at an early stage ular component, augments were used term rehabilitation, while not providing in most cases is extremely difficult and during the press-fit. Instability of the en- for long-term remission, and hip replace- formed 9 percent of cases, post-traumat- doprosthesis components in late follow- ment is associated with high risks of com- ic ANFH - 13% of patients and 4% had up occurred in 3% of cases, all around ponents’ instability. congenital abnormalities of the hip joint implants with a cement type of fixation. Nowadays, one of the little-known [3]. Intraoperational autopsy material was methods of surgical treatment in ANFH Complaints of patients after hospitali- taken for histological examination in 50 patients is arthroscopy of the hip joint [8, zation are usually non-specific, which is patients, both who undergone total hip 9]. probably is one of the reason for incor- replacement and core decompression. In 4’ 2018 43

Fig.1. Anterolateral and posterolateral Fig.2. Revision of the joint by a Shaver Fig.3. Revision of the joint by VAPOR- capsulotomy with an arthroscopic BEAVER (arthroscopic picture of the hip joint in ANFH) electrode, removal of degenerative changes knife of the cartilage elements

Fig.4. Diagnostics of degenerative changes in Fig.5. Visualization of free osteochondral Fig.6. Chondroid corps from the hip joint after the cartilaginous tissue of the femoral head for fragments in the hip joint removal subsequent microfracturing most cases, specimen had signs of fatty lems in modern orthopedics. Arthroscop- in the hip joint: current understanding of degeneration of the bone marrow in a ra- ic diagnostics of the pathological process the capabilities and roles of the various tio of 5: 1, with the presence of fibrous with subsequent revision of the hip joint, methods of X-ray diagnostics in determi- tissue, signs of resorption, necrobiosis, capsulotomy and synovectomy gives a nation of causes of the pain syndrome] lymphoid-plasmocytic and histocytic infil- decompressing effect, reduce the tension Luchevaya diagnostika i terapiya [Radia- tration of the stroma, and in some cases, of the joint capsule, makes it possible to tion diagnostics and therapy]. Saint-Pe- signs of an inflammatory reaction. remove free osteochondral fragments tersburg, 2014, № 2 (5), P. 37-44. Arthroscopic revision of the hip joint and areas of cartilage detachment with 3. Bolshakov O. P. Kornilov N.V. included the following stages: microfracturing if necessary, which allows Rasulov R.M. Znachenie funkcional’nyh i 1) anterolateral and posterolateral to preserve the cartilage of the femoral anatomicheskih faktorov v vybore metoda capsulotomy with an arthroscopic BEA- head, thereby ensuring its stable function lecheniya vzroslyh bol’nyh s aseptiches- VER knife (Fig.1), for an indefinite period of time. Positive kim nekrozom golovki bedrennoj kosti i 2) revision of the joint by a Shaver experienced results of treatment dictate detej s bolezn’yu Legga–Kal’ve–Pertesa (Fig.2), the need for further study of the problem, [Value of functional and anatomical fac- 3) revision of the joint by VAPOR-elec- observation of patients and analysis of tors in choosing a recovery method of trode, removal of degenerative changes long-term results of treatment in order to aseptic necrosis of the femoral head in of the cartilage elements (Fig.3), achieve the longest possible remission, adult patients and in children with Legg– 4) diagnostics of degenerative chang- and in some cases, complete recovery of Calve–Perthes disease] Vestnik trauma- es in the cartilaginous tissue of the femo- the patient. tologii and ortopedii imeni N. N. Priorova ral head for subsequent microfracturing [N.N. Priorov Journal of traumatology (Fig.4), References and orthopedics]. Moscow, 2007, № 2, P. 5) visualization of free osteochondral 1. Bashkova I. B. Madyanov I. 27-31. fragments in the hip joint (Fig.5), V. Mnozhestvennye netravmaticheskie 4. Pak J. Complete resolution of 6) removal of the chondroid corps from osteonekrozy krupnyh sustavov u avascular necrosis of the human femoral the hip joint (Fig.6). molodogo cheloveka, sprovocirovannye head treated with adipose tissue-derived Results were fixed and evaluated on neprodolzhitel’nym lecheniem glyukokor- stem cells and platelet-rich plasma / J. the Harris hip scoring system (HHS). tikoidami [Multiple non-traumatic osteo- Pak // The J. of Intern. Med. Research. – Before surgery HHS ranged from 24 to necrosis of large joints in a young man, 2014. – Vol. 42 (6): Dec. – P. 1353–1362. 70. According to preliminary results, we the treatment of glucocorticoids] Rus. 5. Pan Z.X. Effect of recombinant have got 60% positive results, 20% of med. zhurn. Revmatologiya [Rus. Med. human bone morphogenetic protein 2/ them correspond to the excellent result of journal. Rheumatology]. Moscow, 2016, poly-lactide-co-glycolic acid (rhBMP-2/ treatment, 20% – good and 20% – satis- № 2, P. 125-128. PLGA) with core decompression on re- factory, 40% of the results were assessed 2. Blisch O. Y. Bol’ v tazobedren- pair of rabbit femoral head necrosis / as unsatisfactory because of the persist- nom sustave: sovremennye predstav- Z.X. Pan // Asian Pacific J. of Tropical ing pain syndrome with up to 68 HHS. leniya o vozmozhnostyah i roli razlichnyh Medicine. – 2014. – Vol. 7 (11): Nov. – P. Conclusion. Aseptic necrosis of the metodov luchevoj diagnostiki v opre- 895–899. femoral head is one of the urgent prob- delenii prichin bolevogo sindroma [Pain 6. Wang L. Study on effect of sen- 44 YAKUT MEDICAL JOURNAL

sory neuropeptide in steroid-induced – 2010. – Vol. 24 (9): Sep. – P. 1072– Health facility “Regional clinical hospi- avascular necrosis of femoral head / L. 1077. tal №2” in Khabarovsk, post-graduate Wang // Chinese J. of Reparative and 9. Yassin M.A. Dasatinib Induced student of the Postgraduate Institute for Reconstructive Surgery. – 2010. – Vol. Avascular Necrosis of Femoral Head in Public Health Workers, Maeror... * neces- 24 (9): Sep. – P. 1078–1081. Adult Patient with Chronic Myeloid Leu- [email protected]; 7. Wang T. Analysis of risk factors kemia / M.A. Yassin // Blood Disorders. 2. Volovik Valery Evgenjevich - for femoral head necrosis after internal – 2015. – Vol. 8 : Jul. 23. – P. 19–23. MD, prof., acad. of Russian Academy of fixation in femoral neck fractures /T. 10. Zhang G.P. Correlation between Sciences and Russian Academy of natu- Wang // Orthopedics. – 2014. – Vol. 37 polymorphism of endothelial nitric oxide ral Sciences, Vice-Rector of Regional (12): Dec. – P. e1117–23. synthase and avascular necrosis of fem- State Budgetary educational Institution 8. Wang W. Study on relationship oral head / G.P. Zhang // Intern. J. of Clin- of additional professional education for between osteoporosis and mRNA ex- ical and Experimental Medicine. – 2015. Public Health Workers, head of Depart- pressions of vascular endothelial growth – Vol. 8 (10): Oct. 15. – P. 18849–18854. ment, [email protected]; factor and bone morphogenetic protein 3. Palshin Gennady Anatolyevich - 2 in nontraumatic avascular necrosis of The authors MD, prof., head of Department of medical femoral head / W. Wang // Chinese J. of 1. Antonov Alexander – orthopedic Institute of NEFU named after M. K. Am- Reparative and Reconstructive Surgery. surgeon of Territorial state educational mosov, [email protected].

A.N. Koval, N.V. Tashkinov, G.G. Melkonyan, A.Y. Marochko, B.M. Kogut, N.I. Boiarintsev, V.V. Ianovoi, P.M. Kosenko BASIC PRINCIPLES OF SURGICAL TREATMENT OF ARTIFICIAL PYOINFLAMMATORY DISEASES DOI 10.25789/YMJ.2018.64.13 OF SOFT TISSUES

ABSTRACT Aim. To identify the peculiarities of surgical treatment of APIDST. Material and methods. The analysis of treatment of 302 men with APIDST in the department of purulent surgery of the 301 Military Clinical Hospital of Khabarovsk from 1987 to 2013 was carried out. Results. Surgical emergency procedures were performed in 40 (13.2%) patients with APIDST before admission to the hospital and in 262 (86.8%) patients with APIDST immediately after admission to the hospital. Necrectomy was performed in 6 (2.0%) patients with APIDST before admission to the hospital and in 118 (39.1%) patients with APIDST immediately after admission at the hospital. The signs of anaerobic infection were found during the surgical procedures in 260 (86.1%) patients. During hospitalization 2 or more surgical procedures were required in 188 (62.3%) patients with APIDST due to the progression of the disease. Conclusions. In case of substantiated suspicion of APIDST surgical intervention should be based on the main principles of surgical treatment of anaerobic infections regardless of the duration of the disease. It is recommended to start the procedures with a small diagnostic incision through the site of introduction of the initiating substrate with a mandatory revision of the subfascial space and performing radical necrectomy. Keywords: artificial pyoinflammatory diseases of soft tissues, treatment. List of reductions: APIDST – artificial pyoinflammatory disease of soft tissues.

Introduction. The choice of treatment approach to the treatment of surgical most commonly used disease initiating strategy of APIDST is a very difficult soft tissue infections and does not have substrates were oral fluid (36.1%), dental problem due to insufficient knowledge any specific features [13]. Other authors plaque (15.6%) and liquid hydrocarbons of this pathology. It was established, stick to the opinion that the treatment (6.3%). that after deliberate introduction of of APIDST has some specific features, Results and discussion. Of non-sterile biological fluids into the soft particularly in patients after introduction 302 patients with APIDST, surgical tissues anaerobic infection develops of a chemical initiating substrate into the emergency procedures were performed in the majority of cases [3,16]. Various soft tissues of the body [9,15,18]. before admission to the hospital in 40 chemicals, introduced into soft tissues, The aim of this work is to identify the (13.2%) patients, and immediately after cause «chemical» necrosis, progressive peculiarities of the surgical treatment of admission to the hospital - in 262 (86.8%) ischemia, creating conditions for the APIDST. patients (Table 1). development of anaerobic infection Material and methods of the As is seen from the above table, [9,15]. It is well known that anaerobic research. The analysis of treatment of radical treatment of the surgical infection infection of soft tissues holds a special 302 men with APIDST who accounted for focus including not only an adequate place among surgical infections due to 6,1% of all patients with different forms incision but also necrectomy was the high morbidity and mortality [4,5]. of surgical infections of soft tissues and performed in 6 (2.0%) patients with Currently, some experts are sure that the had been hospitalized to the department APIDST before admission to the hospital treatment strategy of APIDST, caused of purulent surgery of the 301 Military and in 118 (39.1%) patients with APIDST by non-sterile biological fluids, does not clinical hospital of Khabarovsk from immediately after admission to the seriously differ from the conventional 1987 to 2013, was carried out. The hospital (Table 1). 4’ 2018 45

In the course of treatment, some patients required repeated operations Table 1 due to the progression of the inflammatory Surgical emergency procedures, performed in patients with APIDST before and after process (Table 2). admission to the hospital As is seen from the above table, 188 Before admission After admission Surgical procedures (62.3%) patients with APIDST required 2 n % n % or more surgical procedures (Table 2). The number of patients to have been 40 13.2 262 86.8 The distribution of patients with operated on APIDST depending on the area of the Cases of radical necrectomy performed 6 2.0 118 39.1 inflammatory process is presented in Table 2 Table 3 Table 3. The area of the inflammatory Number of surgical procedures The area of the inflammatory process in process indirectly indicates the average in patients with APIDST patients with APIDST length of the incision. The area of the inflammatory process The number of APIDST (n=302) The area of the APIDST (n=302) was limited and accounted for less than performed surgical inflammatory process in procedures per a patient n % 500 сm2 in 184 (60.9%) patients and patients n % 1 surgical procedure 114 37.7 Less than 500 сm2 more than 500 сm2 - in 118 (39,1%) 2 surgical procedures 95 31.5 (3% of the area of the 184 60.9 patients with APIDST (Table 3). 3-5 surgical procedures 72 23.8 person's skin) The signs of anaerobic infection were 6-9 surgical procedures 15 5 From 500 to 1000 сm2 found during the surgical procedures in 10 or more surgical (3-6% of the area of the 88 29.1 6 2 person's skin) 260 (86.1%) patients. procedures From 1000 to 1500 сm2 The peculiarities of surgical located close to each other is wrong, (6-9% of the area of the 21 7 procedures in patients with APIDST were because such incisions do not allow person's skin) as follows. Surgical intervention was to perform an adequate revision and More than 1500 см2 (>9% of the area of the 9 3 started from making a small (diagnostic) necrectomy, creating conditions for the person's skin) incision through the point of introduction progress of the purulent and destructive of the initiating substrate under local process. In addition, several small to surgical intervention in all cases anesthesia, which together with the other incisions often lead to the necrosis of the irrespective of the duration of the disease diagnostic procedures allowed to reliably tissues between them. if there is a substantiated suspicion of confirm APIDST. During necrectomy, the wound APIDST. In our opinion, an incision at some was carefully cleaned with antiseptic We share the opinion of M. J. DiNubile distance from the point of introduction solutions. Hemostasis was performed [8], that in case of a suspected anaerobic of the initiating substrate is the most using diathermocoagulation, as the infection of soft tissues, “an early or a too common mistake. ligation of vessels often promotes the extensive surgical procedure would be a The information obtained during a development of ischemia and increases much safer option”. small diagnostic incision was used to the contamination of viable tissues with Considering that it is not possible select the type of anesthesia in the main anaerobic microorganisms. to diagnose anaerobic infection with a stage of the surgical procedure as well After completing the surgical high degree of probability before the as to plan the direction of the operative procedures, the resulting wound was surgical procedure, the intraoperative access and to determine the borders of loosely packed with napkins soaked with assessment of tissues is needed [1,6,8], necrectomy. Besides, the material for anti-anaerobic activity ointments. which according to our observations emergency bacterioscopy and tissue The wound tamponade was performed allows to establish the anaerobic nature biopsy was taken from the wound for in such a way that there were no empty of the disease in 86.1% of patients. microbiological investigation. pockets and cavities left. The need for The above mentioned changes of In spite of the absence of visible repeated necrectomy and application of tissues include such well-known signs changes in the subcutaneous tissue and bandages was determined based on the of anaerobic infection as the stinking fascia in some patients, revision of the monitoring of the patients’ condition and smell of gray-green or brown exudate, a subfascial and intermuscular space was the development of the wound process. specific type of diseased tissues of gray, obligatorily performed. There was no mortality in this group of gray-green or black color, liquid pus, often During the main stage of surgery, the patients. diffusely saturating the inflamed tissues, pathomorphological form, the severity Currently, the active treatment the presence of gas and the presence of of the inflammatory process as well as strategy of anaerobic soft tissue infection wound anaerobic microorganisms in the the particular features of the soft tissues is accepted. It includes the early surgical smears [1,4,6]. destructive changes were clarified. The procedures, the removal of all necrotic The early diagnosis of anaerobic decision on whether additional incisions tissues, active drainage and aeration of infection of soft tissues is extremely should be performed was taken. the wound [5,13,7]. Such strategy allows important; therefore, we share the The maximum possible necrectomy, to reduce mortality from 40-67% [2, 4, 6] opinion of some authors who insist that debridement of the wound and its to 13–29.7% [8,7,17]. the diagnosis of anaerobic infection drainage were carried out if necessary. Considering that anaerobic must not be questioned when we can We avoided to perform additional microorganisms are involved in the find at least one of the above-mentioned incisions, particularly located close to majority of APIDST cases, the surgical signs. In such a case, the isolation of the each other. We think, that one or two procedures must be performed in all causative agent to prove the participation adequate incisions are sufficient for the patients according with fundamental of anaerobes in the infectious process is revision of the surgical infection focus. principles of surgical treatment of not of paramount importance [1]. It should be noted that, in our opinion, anaerobic infection of soft tissues. As far as the chemical substances the practice of making short incisions We deem it appropriate to resort are concerned, many authors agree 46 YAKUT MEDICAL JOURNAL

that the first step in the treatment of of treatment of anaerobic infection. East J Fam Med. – 2010. – Vol. 8. – P. APIDST caused by chemicals, for 35–39. example, by liquid hydrocarbons, is the Reference 12. Kennedy J. The management urgent hospitalization of patients to the 1. Bel’skih A.N. Samohvalov I.M. of hydrocarbon toxicity following hospital for observation and prevention Ukazanija po voenno-polevoj hirurgii subcutaneous injection: case report and of systemic complications [9,15,18]. [Instructions for military surgery]. SPb.: literature / J. Kennedy // Orthopaedics. At the same time, the analysis of VMedA, 2013, 474 p. – 2010. – Vol. 7. – Electronic resource modern publications on APIDST reveals 2. Gorjunov S.V. Gnojnaja hirurgija URL: http://www.jortho.org (Date of the lack of a common approach. A number (Atlas) [Purulent surgery (Atlas)]. M.: access: 7/3/2010). of researchers support the conservative BINOM, 2004, 558 p. 13. Liu H. Parasuicidal poisoning approach consisting in the forming of the 3. Kuzin M.I. Rany i ranevaya by intramuscular injection of insecticide: elevated position and immobilization of infekciya: rukovodstvo dlya vrachej A case report / H. Liu, B. Kan, X. Jian the affected limb, dynamic observation [Wounds and wound infection: a guide // Exp.Ther. Med. – 2013. – Vol. 6. – P. and symptomatic therapy without denying for doctors]. M: Medicina, 1990. – 591 p. 696–698. doi: 10,3892 / etm.2013.1216. surgery in case of the negative dynamics 4. Melkonyan G.G. Koval’ A.N. 14. Nelson M. Parenteral of disease and the development of local Tashkinov N.V. et al. Klinicheskie hydrocarbon injection and associated complications [15,18]. osobennosti iskusstvennyh gnojno- toxicities: two case reports / M. Nelson, At the same time, other authors point vospalitel’nyh zabolevanij mjagkih I. Nasr // West J. Emerg. 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Clinical features and prognostic [email protected], phone +7 (914) be performed taking into account the factors of anaerobic infections: a 7-year 191-53-28 (responsible for contacts with main principles of treatment of anaerobic retrospective study / Y.Park, J. Choi, edition), Khabarovsk, 35, Muravyev- infections, regardless of the stage of the D.Yong, K. Lee, J. Kim // Korean J. Intern. Amursky St., 680000; disease. Med. – 2009. – Vol. 24. – P. 13–18. doi: 2. Tashkinov Nikolai Vladimirovich 3. Surgical intervention should 10.3904 / kjim.2009.24.1.13. – Doctor of Medical Science, professor, begin with a small diagnostic incision 10. Di Nubile M. Complicated head of the Department of general and through the site of introduction of the infections of skin and skin structures: clinical surgery of the Far Eastern State initiating substrate with a mandatory when the infection is more than skin deep Medical University Khabarovsk, 35, revision of the subfascial space and / M. Di Nubile // J. Antimicrob. Chemother. Muravyev-Amursky St., 680000; performing a radical necrectomy. – 2004. – Vol. 53. – P. 1137–1150. doi: 3. Marochko Andrei Yurievich – 4. In surgical treatment of patients 10,1093 / JAC / dkh202. Doctor of Medical Science, professor of with APIDST induced by chemicals one 11. Kafaween H. Necrotizing fascitis the Department of general and clinical should resort to active surgical treatment induced by self-injection of kerosene / H. surgery of the Far Eastern State Medical with consideration for the basic principles Kafaween, H. Rbehat, M. Sweis // Middle University Khabarovsk, 35, Muravyev- 4’ 2018 47

Amursky St., 680000; education of the Institute of continuous Khabarovsk, Muravyev-Amursky 35; 4. Kogut Boris Michailovich – professional education and accreditation 7. Melkonyan Gegam Genrikovich Doctor of Medical Science, professor of the Far Eastern State Medical – doctor of surgical department of the 301 of the Department of normal and University Khabarovsk, 35, Muravyev- Military Clinical Hospital, Khabarovsk, 1, topographic anatomy with the course Amursky St., 680000; Seryshev St., 680028; of operative surgery of the Far Eastern 6. Kosenko Pavel Mikhailovich, 8. Ianovoi Valerii Vladimirovich – State Medical University Khabarovsk, 35, FGBOU VO “FGMU” of the Ministry of Doctor of Medical Science, head of the Muravyev-Amursky St., 680000; Health of Russia, Associate Professor Department of hospital surgery with a 5. Boiarintsev Nikolai Ivanovich – of the Department of General and course of pediatric surgery of the Amur Doctor of Medical Science, professor of Clinical Surgery, Candidate of Medical State Medical Academy, Blagoveschensk, the Department of additional professional Sciences, kosenko @ inbox.ru, 680000g. 95, Gorky St., 675000.

V.G. Pshennikova*, F.M. Teryutin*, N.A. Barashkov, N.N. Gotovtsev, A.A. Nikanorova, A.V. Solovyev, G.P. Romanov, O.L. Posukh, L.U. Dzhemileva, E.K. Khusnutdinova, S.A. Fedorova POSTLINGUAL DEAFNESS IN EVENO- BYTANTAYSKY NATIONAL DISTRICT OF THE SAKHA REPUBLIC (YAKUTIA): AUDIOLOGICAL AND CLINICAL- DOI 10.25789/YMJ.2018.64.14 GENEALOGICAL ANALYSIS

ABSTRACT In this paper we present for the first time the results of the audiological and clinical-genealogical research of the population of settlements Batagai-Alyta and Kustur of the Eveno-Bytantaisky National District (ulus) of the Sakha Republic (Yakutia) for studying the postlingual form of deafness of unknown etiology, which we for the first time have identified earlier in 3 Evens. As a result of an audiological examination of 72 people, 10 patients from 6 nuclear families who met the criteria of postlingual form of hearing loss were found. The segregation analysis carried out in these families confirmed the autosomal recessive type of inheritance of this form of postlingual hearing loss. The distant relationship of the examined patients with postlingual hearing loss living in two villages of the Eveno-Bytantaisky National District of the Sakha Republic can indicate to the role of the founder effect in the local prevalence of this pathology. The results of present study and obtained expedition material will be the basis for further research of the molecular genetic etiology of this form of deafness and the discovering of mechanisms of its accumulation in this region of Yakutia. Keywords: рostlingual deafness, audiological analysis, clinical-genealogical analysis, segregation analysis, Eveno-Bytantaisky National District, Sakha Republic (Yakutia).

Introduction. Mutations of the GJB2 for the Yakuts - с.-23+1G>A and for the logical analysis) for these 3 patients from gene are the main reasons of congeni- Russians - с.35delG. Nevertheless, the the Eveno-Bytantaysky National District tial and prelingual nonsyndromic hearing biallelic GJB2 mutations were not de- of the Sakha Republic allowed us to sug- loss (HL) in many countries [5, 10]. Cur- tected in 51% of examined deaf patients gest the hereditary cause of this postlin- rently the territory of Eastern Siberia (the (GJB2-negative patients), and the reason gual form of deafness. Sakha (Yakutia) Republic) is character- of their HL remained unknown. Consid- The objective of this study is to con- ized by the spectrum and frequency of ering the genetic diversity of known he- duct audiological and clinical-genealog- mutations of the GJB2 (Cx26) gene on reditary forms of deafness, there is a high ical analysis of the families with post- the large cohort of patients (n=393) with probability that HL of some patients may lingual form of deafness of unknown congenital hearing impairments and indi- be due to the mutations in other genes etiology from Eveno-Bytantaysky Na- viduals with normal hearing (n=187) from since about 100 genes are known in as- tional District for the further confirmation Yakut and Russian populations [1, 9]. Re- sociation with non-syndromic hearing of hereditary nature of this disease and cently it was shown that the pathogenic impairments (Hereditary Hearing loss clarification of its inheritance type. contribution of biallelic GJB2 gene muta- Homepage - http://hereditaryhearingloss. Materials and methods of the re- tion to the etiology of HL in Yakutia was org). search. During the field work in the equal to 49%; and this rate was the larg- Our detailed clinical-genealogical Eveno-Bytantaysky National District of est in comparison with the earlier studied analysis of the sample of GJB2-negative the Sakha (Yakutia) Republic (April, 2018) regions of Asia (10213 probands from 23 patients from different districts of the the staff of the Yakut Science Center of countries) [4]. In the spectrum of identi- Republic of Sakha (Yakutia) revealed Complex Medical Problems (Yakutsk) fiedGJB2 mutations, three mutations: c.- 3 Evens with late onset HL from the vil- examined 106 inhabitants of the villages 23+1G>A, с.35delG and c.109G>A were lage Batagay-Alyta (Eveno-Bytantaysky Batagay-Alyta and Kustur. Among them, the most common. These mutations ac- National District): 2 sibs (proband A and 72 individuals were selected for the study count for 98% out of all pathogenic GJB2 sibs A) whose HL became noticeable at 7 of the etiology of the postlingual form of alleles. The major GJB2 mutations spe- years in proband A and at 4 years in sibs deafness - 65 from Batagay-Alyta, 4 from cific for the main ethnic populations of A, and also one patient (proband B) with Kustur, and also 3 previously examined Sakha (Yakutia) Republic were identified: the same onset of HL (at 4 yrs). GJB2-negative patients (proband A, sibs All collected data (medical history, the A, proband B) from Batagay-Alyta were * - These authors contributed equally to this work results of molecular-genetic and audio- taken for further examination. Among 48 YAKUT MEDICAL JOURNAL

them, males accounted for 34.7% (n=25), participant and his parents and grandpar- females - 65.2% (n=47). The average age ents; age; ethnicity (up to the third gen- Table 1 was 44±17.21 years. Ethnic composition eration); place of birth and residence as Data for segregation analysis in families of the sample: Evens - 48 (66.6%), Ya- well as the profession was filled out for of patients with signs of postlingual form kuts - 22 (30.5%), one Evenk (1.4%), and each participant. The information about of deafness/hearing loss one individual of mixed ethnicity (Even/ otorhinolaryngologic diagnosis, potential Nuclear Affected siblings Yakut) (1.4%). cause of HL, onset of HL, presence or ab- Sibship’s (r) size (s) families/ Audiological examination sence of relatives with HL, and concomi- probands (а) 1 2 3 Complaints about the condition of tant diseases was also included in the 2 2 2 - - hearing such as the presence of a dis- individual patient’s card. The pedigrees 3 2 1 1 - charge from the ear, noise in the ears, compiled on the basis of all obtained data 7 1 - - 1 dizziness were clarified through an in- were subjected to subsequent clinical- 9 1 - 1 - terview with patients. Medical and life genealogical analysis. Total 6 3 4 3 histories including past illnesses, injuries To confirm the heritability of postlin- and/or surgeries, contacts with industrial gual form of HL and ascertain the type pected value of the segregation frequen- noise, and information about allergic re- of its inheritance we conducted a seg- cy (0.25 for recessive inheritance) falls actions was ascertained for all examined regation analysis in six nuclear families into this interval. subjects. The otologic examination was selected through the proband (Table 1). All examinations provided in this study carried out by unified algorithms on the All parents in these families were healthy have been conducted after written con- KaWe Combilight otoscope. A full audio- that suggests a recessive type of the in- sent of all participants or their parents. logical survey was conducted with the heritance of this trait. This study was approved by the local use of a tympanometer and an audiome- The Weinberg formula for a single Biomedical Ethics Committee of Federal ter “AA222” (“Interacoustics”, Denmark). choice was used for calculation of the State Budgetary Scientific Institution “Ya- Hearing thresholds were measured by air segregation frequency (SF) of the trait in kut Science Centre of Complex Medical conduction at frequencies of 0.25, 0.5, families [11]: Problems”, Yakutsk, Russia (Protocol No. 1.0, 2.0, 4.0, 8.0 kHz and bone conduc- SF = (r – n) / (s – n), (1) 16, April 16, 2009). tion at frequencies of 0.25, 0.5, 1.0, 4.0 where r - the number of affected sub- Results and discussion kHz in 5.0 dB increments. Severity of jects in all siblings, n - the total number Audiological analysis HL was defined by hearing thresholds of of probands, s - the total number of de- Among 72 examined individuals 35 better hearing ear in the voice frequency scendants in the sample. subjects did not complain about HL and range (VFR) in accordance with interna- The standard deviation was calculated audiological examination has not re- tional classification under which I degree as: SF(1− SF) /(s − n) vealed any objective otologic problems is equal to 26-40 dB in VFR, II - 41-55, σ = (2) (normal hearing thresholds were de- III - 56-70, IV - 71-90, deafness > 90 dB. To test the hypothesis about the type tected). Unilateral or bilateral HL was Clinical-genealogical analysis of inheritance, a confidence interval (CI) observed in 37 individuals (the possible We had developed an individual card, was calculated as: causes of HL are shown in Fig. 1). Among which included information about last CI = SF ± 1.96 * σ (3) them, the pathology of the sound-con- name, first name, middle name of the The hypothesis is accepted if the ex- ducting system and unilateral or bilateral

Fig.1. Schematic representation of the results of audiological analysis. Note: 26 individuals from all examined subjects are relatives (of different degree of kinship) of probandA with postlingual form of deafness. 4’ 2018 49

conductive or mixed HL were objectively with sensorineural HL, 9 patients showed sibs A, proband B) (Table 2). detected in 14 patients. 23 patients had signs of presbyacusis, 2 patients showed These patients were predominantly unilateral or bilateral sensorineural HL in signs of noise exposure, 2 patients had Evens (Evens - 8, Yakuts - 2) that prob- the absence of a visual otological prob- a prelingual (before 1 year) HL, and 10 ably indicates the ethnic specificity of in- lem. Among these 23 patients with sen- had signs of postlingual HL that had vestigated form of HL. sorineural HL, 12 patients had no opin- become noticeable at the age of 3 - 48 Clinical-genealogical analysis ion about causes of their HL, 2 patients years. In total, as a result of the audio- Based on the initial analysis of person- supposed otitis media in childhood, 2 logical analysis 10 patients (5 males and al data, we found that 72 examined indi- patients - possibly toxic exposure to an- 5 females from 18 to 65 years old, whose viduals belonged to 24 families with 718 tibiotics, 2 patients - head injury in child- average age at the time of the study was family members in total. Among them, hood, 1 patient - hereditary HL, 1 patient 43.3±13.7 years), showed the signs of 10 patients with signs of postlingual form - colds, 1 patient - age, 1 patient - indus- postlingual form of HL which firstly -de of HL belonged to three extended pedi- trial noise exposure. Among 23 patients tected by us in 3 patients (proband A, grees (355 relatives in total) (Fig. 2). At

Table 2 Characteristics of patients with signs of postlingual form of deafness/hearing loss

Diagnosis Subjective Accompanying illnesses Ethni Onset of Patients Code Sex GJB2 genotype Age (otorhinolaryngo cause of Speech city hearing loss logical) hearing loss Otorhinolaryn Other gological Systemic 1 Proband Not Residual Sign-dactylic А - IV2 Female c.[Wt];[Wt] Even 19 Bilateral deafness 7 hypoplasia of A determined encephalopathy language speech Microtia and Not Sign-dactylic 2 Sibs A А - IV1 Male c.[79G>A];[Wt] Even 20 Bilateral deafness 4 external auditory - determined language canal atresia Probably a Glaucoma Sign 3 А - III7 Male c.[Wt];[Wt] Even 65 Bilateral deafness 7 trauma in Speech is absent (Blindness) language childhood Dense eardrum; Chronic Sign-dactylic 4 А - III13 Female not investigated Even 59 Bilateral deafness 9 Antibiotics Chronic gastritis dystrophic language rhinopharyngitis Rinoskoliosis. 5 Proband Not Sign А - III17 Male not investigated Even 57 Bilateral deafness 4 Curved nasal - B determined language septum

Chronic gastritis; Colds; due Neurodermatitis; Sign-dactylic 6 А - III18 Male not investigated Even 29 Bilateral deafness 4 to otitis Dense eardrum Hepatitis language media B; Lumbar osteochondrosis Vegetative Bilateral vascular dystonia sensorineural Not 7 В - IV3 Male not investigated Yakut 38 36 Dense eardrum according to the Intact hearing loss III determined hypertonic type; degree Myopia Chron. Bilateral Pyelonephritis; sensorineural Hereditary 8 В - IV8 Female not investigated Yakut 42 30 - Cholecystitis; Intact hearing loss IV burdening Chronic degree pancreatitis Arterial hypertension; Diabetes II; Bilateral Psoriasis; sensorineural Not 9 С - II7 Female not investigated Even 54 8 - Chronic Intact hearing loss III determined pyelonephritis; degree Lumbar osteochondrosis; Goiter Bilateral sensorineural Not Mental 10 С - II9 Female not investigated Even 50 30 - Intact hearing loss III determined retardation degree Мale Bilateral deafness Middle age: Not - 5 GJB2-negative Even - 8 Middle Three people - 6 (60%) Bilateral Juvenile - determine Absent - 6 (50%); - 30%; not (80%); age: report dense Total sensorineural 5,6±1,9; Middle - 6 (60%) - (60%); Intact Female investigated - Yakut - 43,3± eardrum - 3 hearing loss - 4 age: Mature Other - 4 - 4 (40%) - 5 70% 2 (20%) 13,7 (30%) (40%) - 36±6 (40%) (50%) 50 YAKUT MEDICAL JOURNAL

the first stage of pedigree’s analysis, it was revealed that proband B (A-III17) was a paternal relative for proband A (A-IV2) and sibs A (A-IV1) (Fig. 2, A). It should be also noted that mothers (A-III1 and B-III1) of probands A-IV2 and B-IV3, respectively, are cousins (Fig. 2, A, B). For segregation analysis we used the data on six nuclear families which included 10 patients with postlingual HL, their siblings and parents (Fig. 2). We assumed an autosomal recessive type of transmission of postlingual HL in these six nuclear families since all affected probands had hearing parents who did not complain about hearing impairment and also both deaf and hearing siblings (including cousins). To confirm or disprove the hypothesis about autosomal recessive type of inheritance of post- Fig.2. Pedigrees of probands with signs of postlingual form of hearing loss: A - pedigree of probands 1, 2 and 3, lingual HL the segregation B - pedigree of probands 4 and 5, C - pedigree of proband 6. analysis was carried out in Family members with signs of hereditary postlingual form of deafness are indicated by black symbols; family six siblings. Only siblings members with other forms of deafness/hearing loss (congenital or conductive) – by gray symbols; family members from each nuclear family who have signs of postlingual hearing loss (on information from close relatives) - by plus into symbols; nuclear were taken into account families are highlighted by dotted lines; probands in nuclear families are denoted by arrow and number on the top. (without half-sibs and indirectly registered (on information from tients is later (in comparison with con- III2 for six years, from the first audiometry relatives) affected family members (Ta- genital HL) onset of this form of HL that (at the age of 10 years) to the latest (at ble 1). As a rule, the Weinberg proband occurred after the end of a sensitive pe- the age of 16 years), revealed significant method is used for calculation of the riod of speech development (after 4-5 deterioration of hearing (from II-III to IV segregation frequency (SF) [2, 6-8, 11]. years and older). In this period of sen- degree of HL) that allowed us to suggest The essence of this method consists in sory ontogeny, verbal speech is already the progressive nature of this form of HL calculating of the ratio of the total number formed, and the thinking development (Fig. 4). It is also interesting to note that of affected siblings to the total number of of young patients approximately corre- the majority of patients (6 out of 10) could their unaffected siblings with correction sponds to the level of their hearing peers not determine the possible cause of their for the number of probands (formula 1). [3]. However the earlier debuts of the HL HL. They denied the hereditary cause The segregation frequency (SF), calcu- cause the sooner complete degradation despite the fact that some of them had lated from formula (1) with using the data of verbal speech. HL in 6 patients from deaf close relatives (Table 2). Most likely, from Table 1, was 0.20: our sample occurred in juvenile age (on this fact is due to that hearing problems SF = (r – n) / (s – n) = 4/20 = 0.20 the average 5.6±1.9 years), and in 4 of these patients began against a back- Subsequently, the obtained segrega- patients with verbal speech without any ground of preserved hearing and de- tion frequency (0.20) was compared with special distortions - at adulthood (on the veloped speech. In addition, 3 cases of the segregation frequency expected ac- average 36±6 years). Patients with dif- observation of a dense eardrum in adult cording to the recessive type of inherit- ferent onset of HL are characterized by patients are of interest since this peculi- ance (SF = 0.25). The confidence inter- 0 different degree of HL. Profound HL (up arity is mainly found only in children (Ta- val calculated using formulas (2) and (3) to deafness) (in the range from 98 to 108 ble 2). for the obtained estimation of the segre- dB in VFR) is common in patients with To confirm the hereditary nature of this gation frequency is equal 0.026 - 0.374. juvenile onset of HL while III-IV degree postlingual form of HL and ascertainment Theoretically expected value of segrega- of HL (in the range from 58 to 75 dB in of its type of inheritance, a segregation tion frequency (SF = 0.25) falls into this 0 VFR) is detected in the patients having analysis was carried out. The segrega- interval that allows to accept the hypoth- HL with onset in adulthood (Fig. 3). In tion frequency (SF), estimated using esis about autosomal recessive type of addition, a comparative analysis of the Weinberg’s proband method, was 0.20 inheritance of trait under study. audiometric data available for proband A- and matched the expected one for auto- A common characteristic for all pa- 4’ 2018 51 A - patients with juvenile onset of hearing loss; A B - patients with onset of hearing loss in adulthood. Audiograms of patients with signs post-lingual form deafness/hearing loss. Fig.3. The progression of hearing loss by the example of audiograms of patient A-IV2 (proband A) with postlingual form of deafness. A-IV2 (proband The progression of hearing loss by the example audiograms patient Fig.4. 52 YAKUT MEDICAL JOURNAL

somal recessive type of inheritance (SF0 V. 6, No. 156, P. 10-23. URL: https:// 2nd printing edition (June 17, 1982) - P. = 0.25) (CI 0.026 - 0.374). www.medgen-journal.ru/jour/issue/view- 700. ISBN-10: 3540094598. Thus, we revealed 10 patients (mostly Issue/30/30. Evens) with postlingual bilateral senso- 2. Ginter E.K. Medicinskaya gene- The authors rineural form of HL of unknown etiology tika [Medical genetics] Izdatel’stvo: “Me- Title of the manuscript «Postlingual which inheriting as autosomal recessive dicina” [Publishing: “Medicine”]. Moscow, deafness in Eveno-Bytantaysky Na- trait. Moreover, the distant relationship 2003, P. 448. ISBN: 5-225-04327-5 tional District of the Sakha Republic of the examined patients with postlingual 3. Karpova G.A. Osnovy sur- (Yakutia): audiological and clinical- HL living in two villages of the Eveno- dopedagogiki: ucheb. posobie dlya stud. genealogical analysis» Bytantaisky National District of the Sakha vyssh. ped. ucheb. zavedenij [Funda- 1. VERA G. PSHENNIKOVA - Republic may indicate the role of the mentals of audio-pedagogy: textbook for Ph.D., Head of laboratory, Yakut Scientific founder effect in the local prevalence of stud. of ped. higher educational institu- Center of Сomplex Мedical Рroblems, 4, this pathology. tions] Izdatel’ Kalinina G.P. [Publisher Ka- Sergelyakhskoe shosse, Yakutsk, Sakha We hope that the results obtained linina G.P.]. Ekaterinburg, 2008, P. 354. Republic, 677010, Russian Federation. during this work will allow us not only to ISBN 978-5-901487-46-4. Phone: +7 (4112) 32-19-81, e-mail: further reveal the molecular and genetic 4. Pshennikova V.G. Mutacii [email protected]; cause of postlingual form of HL in ex- genov GJB2 (Cх26), GJB6 (Cх30) i GJB3 2. FEDOR M. TERYUTIN - Ph.D., amined families, but also to uncover the (Cх31) u pacientov s vrozhdennymi na- Researcher, Yakut Scientific Center mechanism of its accumulation in Eveno- rusheniyami sluha v Yakutii [Mutations of Сomplex Мedical Рroblems, 4, Bytantaysky National District of Yakutia. of the GJB2 (Cx26), GJB6 (Cx30) and Sergelyakhskoe shosse, Yakutsk, Sakha Acknowledgments GJB3 (Cх31) genes in patients with con- Republic, 677010, Russian Federation. We are sincerely grateful to all medi- genital hearing impairment in Yakutia] Phone: +7 (4112) 32-19-81, e-mail: cal staff of the hospital of the Eveno- avtoref. diss. … k-ta biol. nauk: 11.01.17 [email protected]; Bytantaysky National District of the [Author’s abstract. diss. ... cand. biol. 3. NIKOLAY A. BARASHKOV - Sakha Republic and chief therapist of the sciences: 11.01.17]. Ufa, 2017, Р. 24. Ph.D., Head of laboratory, Yakut Scientific Ministry of Health of the Sakha Republic URL: http://ibg.anrb.ru/wp-content/up- Center of Сomplex Мedical Рroblems, 4, N.I. Everstova for their participation and loads/2016/12/2016_07_Pshennikova_ Sergelyakhskoe shosse, Yakutsk, Sakha assistance in field work. This study was dissertacia_1.pdf. Republic, 677010, Russian Federation. supported by the Project of the Ministry 5. Chan D.K. GJB2-associated Phone: +7 (4112) 32-19-81, e-mail: of Education and Science of the Russian hearing loss: systematic review of world- [email protected] Federation (#6.1766.2017), the Project wide prevalence, genotype, and auditory 4. NYURGUN N. GOTOVTSEV of the Yakut Science Center of Complex phenotype / D.K. Chan, K.W. Chang // - Researcher, Yakut Scientific Center Medical Problems “Studying the genetic Laryngoscope - 2014. - Vol. 124(2). - P. of Сomplex Мedical Рroblems, 4, structure and load of hereditary patholo- 34-53. doi: 10.1002/lary.24332. Sergelyakhskoe shosse, Yakutsk, Sakha gy of populations of the Sakha Republic”, 6. Fisher R.A. The effect of meth- Republic, 677010, Russian Federation. the Project of the NEFU in Yakutsk “Ge- ods of ascertainment upon the estimation Phone: +7 (4112) 32-19-81, e-mail: netic features of the population of Yakutia: of frequencies / R.A. Fisher // Ann. Eu- [email protected] gene pool structure, cold adaptation, psy- gen. - 1934. - Vol. 6. - P. 13. https://doi. 5. ALENA A. NIKANOROVA - chogenetic characteristics, prevalence of org/10.1111/j.1469-1809.1934.tb02105.x. Researcher, Yakut Scientific Center certain genetic and infectious diseases”, 7. Моrton N.E. Genetic tests under of Сomplex Мedical Рroblems, 4, and also was supported by the Russian incomplete ascertainment / N.E. Моrton Sergelyakhskoe shosse, Yakutsk, Sakha Foundation for Basic Research (#17-29- // Am J Hum Genet. - 1959. - V. 11(1). Republic, 677010, Russian Federation. 06-016_ofi_m, #18-015-00212_А, #18- - Р. 1-16. 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Novosibirsk, 630090, Russian (3472) 35-60-88, e-mail: dzhemilev@ 11. SARDANA A. FEDOROVA - Federation. Phone: +7 (383) 363-49- mail.ru; Ph.D., Head of Laboratory of Molecular 63*3413, fax 8-(383) 333-12-78, e-mail 10. ELZA K. KHUSNUTDINOVA - Biology, Ammosov Institute of Natural [email protected] Ph.D., Director, Institute of Biochemistry Sciences, North-Eastern Federal 9. LILYA U. DZHEMILEVA - Ph.D., and Genetics, Ufa Scientific Centre, University, 46, str Kulakovskogo, Researcher, Institute of Biochemistry and Russian Academy of Sciences, 71, Yakutsk, Russian Federation, Sakha Genetics, Ufa Scientific Centre, Russian Octyabrya Ave., Ufa, Bashkortostan Republic, 677010, Russian Federation. Academy of Sciences, 71, Octyabrya Republic, 450054, Russian Federation. Phone: +7 (4112) 49-68-42, e-mail: Ave., Ufa, Bashkortostan Republic, Phone: +7 (3472) 35-60-88, e-mail: [email protected]. 450054, Russian Federation. Phone: +7 e-mail: [email protected]

N.S. Arkhipova, E.K. Popova ESTIMATION OF BODY MASS INDEX IN PATIENTS WITH CORONARY HEART DISEASE AGED OVER 60 IN THE CASE DOI 10.25789/YMJ.2018.64.15 OF YAKUTIAN CITIZENS

ABSTRACT An analysis of the body mass index (BMI) revealed the ethnic, gender, age differences among the groups of hospital patients with coronary heart disease (CHD) aged over 60. Significantly higher value of BMI was identified in non-indigenous patients compared to Yakut group that was respective to the obesity of p <0,001. Maximum values of BMI were established in the older group aged between 60 and 74 years. The decrease in BMI can be observed with the age in the senile age group and more clearer dependency on age in the indigenous group. When comparing the BMI among the age groups: older, senile age and long-livers, the lower value of BMI was noted among long-livers (p <0,001). The obesity was identified significantly more often among women. Keywords: body mass index, obesity, chronic coronary heart disease, non-indigenous, indigenous (Yakut), older, senile age, long-livers, Yakutia.

Introduction. Obesity is an independ- divided based on gender – men (n=187) differences, namely Kruskal – Wallis H- ent risk factor of cardiovascular diseases, and women (n=167), age – older (from test and single-factor analysis of variance including arterial hypertension, coronary 60 to 74 years old, n=154), senile (from (ANOVA) were also used. The analysis heart disease and heart failure, and is 75 to 89 years old, n=149) and long-livers of the dependence between the indica- related to the increased risk of morbid- (90 years and older, n=51) (WHO, 1963). tors was performed using the Pearson ity and mortality [4]. The prevalence of Body mass index (BMI) or Quetele II r-test, Spirmen’s rs-test and the Pearson obesity increases with age [6] and there index was used to assess the ration of c2-criterion. Statistical processing of the is enough evidence to consider the de- weight and height. BMI was calculated material was carried out on a computer crease in body mass as an important ac- using the following formula: BMI (kg/m2) using the standard software package of tion preventing cardiovascular, endocrine = weight (kg)/height (m2). Body weight the statistical analysis (Statistica for Win- and other diseases. The obesity is com- was considered excessive with the BMI dows, v. 6.0). The critical level of validity mon among the patients with CHD and of ≥25 kg / m², and the presence of obe- of the null statistical hypothesis (about higher death rate is observed at values sity was indicated with the BMI value of the absence of significant differences or of BMI equivalent < 20 kg/m2 and ≥ 30 ≥30 kg / m² (European Guidelines for the factorial effects) was taken as 0.05. kg/m2 [5]. Epidemiological studies have III review, 2003). Results and discussions. The prob- proven the overweight and obesity to be The research was conducted as part ability of the development of cardiovas- the risk factors of increased human mor- of research work program “The contri- cular disease increases with the rise of tality [7]. bution of metabolic syndrome to the de- BMI [8]. Higher BMI was found in non- The purpose of study - the exami- velopment of coronary arteries athero- indigenous group compared with Yakut nation of overweight and obesity preva- sclerosis among Yakutian residents” of group (Table 1). lence on BMI in the group of patients with Yakut Science Center of Complex Medi- The estimation of BMI in patients (aged CHD aged 60 and older living in Republic cal Problems and was approved by the from 60 to 106 years old) revealed more of Sakha (Yakutia). local committee on biomedical ethics at frequent presence of obesity (p <0,001) Material and research methods. The the YSC CMP. All the surveyed voluntar- in non-native patients while Yakut group research included 354 patients under the ily gave the approval to take part in bio- had normal BMI (p <0,001) (Table 2). age of 60 and older with verified diagno- medical research. An analysis of the dependence of BMI sis of CHD, who passed the examination Statistical processing of the results on age, taking into account ethnicity, was and treatment in cardiological depart- was performed using the methods of carried out in order to monitor the amount ment of Geriatric center, Yakutsk city. parametric and non-parametric statistics. of body weight with age. It has been re- The examined population consists of na- Student’s t-criterion was used to assess vealed that BMI decreases with age and tive group - Yakuts (100%) (n=205, aver- the intergroup differences in the values most significantly traced in the Yakut age age 77,6±0,6) and European group of indicators with the continuous distribu- group compared with non-indigenous – Russians (91,3%), Ukrainians, Tatars tion and Pearson’s c2-criterion was ap- people (r = –0.27, p <0.001 and r = –0.16, and Germans (8,7%) (n=149, average plied for the comparison of the frequency p = 0.058, respectively) (Figure 1). age 75,5±0,7). The studied groups were values. Methods of multiple intergroup The significant decrease in BMI was 54 YAKUT MEDICAL JOURNAL

detected when comparing the BMI values of older, senile age groups and long-liv- Table 1 ers regardless to ethnicity (Table 3). The value of BMI in both native and non-native group of patients with CHD aged 60 and older (n=354) By the age of 90 years and older, the Population majority (80.4%) of long-livers have a Indicator t p z * p normal body weight – significantly more non-native (n=149) native (n=205) often than the older (36.9%) and senile BMI. kg/m² 27.3±0.4 25.0±0.3 4.57 <0.001 4.38 <0.001 age groups (37.0%); they were signifi- * - z-approximation for the non-parametric Wilcoxon-Mann-Whitney U-test cantly less likely to be overweight and obese. The maximum values of BMI in Table 2 the examined patients were found in the The estimation of BMI in non-native patients with CHD aged 60 and older (n=354) group of older people aged between 60 Population and 74 years (Table 4). BMI, кг/м2 non-native (n=149) native (n=205) Х2 p Statistically significant differences in abs. rel., % abs. rel., % BMI (c2 = 33.68; p <0.001) were found 18.5–24.9 48 32.2 105 51.2 11.94 <0.001 between the groups of patients of older, 25.0–29.9 60 40.3 74 36.1 0.47 >0.10 senile age and long-livers (Table 4). 30.0 and more 41 27.5 27 13.2 10.54 <0.001 Applied non-parametric Kruskal-Wallis Note: BMI < 18,5 кг/м2 – body mass deficit; 18,5–24,9 кг/м2 – kg/m2 – normal; 25,0–29,9 test and univariate analysis of variance kg/m2 – excessive body weight; ≥ 30,0 kg/m2 – obesity. for the determination of the value of BMI revealed statistically significant differences in BMI in the group of men and women Table 3 (Table 5). The value of BMI in the non-native and Yakut groups of patients of older, The highest BMI is significantly more senile age and long-livers with CHD (n=354) often registered in the older group among Age (years) Indicator H p F p women, compared with representatives 60–74 (n=154) 75–89 (n=149) ≥90 (n=51) of other age groups. BMI, kg/m² 26,8±4,8 26,3±3,8 23,4±2,8 30,60 <0,001 13,23 <0,001 Significantly lower values of body 2. The maximum values of 2 mass and BMI were established in men BMI, kg/m BMI are established in the old- among long-livers compared with men of er group (between 60 and 74 older and senile age (H = 11.97; p = 0.003 BMI (age) years old). Significantly lower and H = 10.15; p = 0.007, respectively). BMI is found among long-livers In the group of women significantly lower compared with the older and body weight and BMI were also found senile age groups. among long-livers (H = 23.68; p <0.001 3. The decrease in BMI is and H = 19.79; p <0.001, respectively). observed with age and is more BMI (age) Similar indicators were obtained in the pronounced in the Yakut group, Khanty-Mansiysk Autonomous region as in the non-native group there a result of a study of 109 long-livers hav- is only a tendency to the de- Age, years ing cardiovascular pathology. The age of crease in body weight. Native population Non-native population long-livers at the time of the survey was 4. Obesity is significantly 90-101 years [2]. Dependence of BMI on age in non-native and Yakut more common in women than it was noted that a large proportion patients with CHD aged 60 years and older (n=354) in men. of men and women have normal body weight (44.9%; 41.3%, respectively) when evaluating the BMI of men and Table 4 women, without regard to ethnicity and The estimation of BMI in older, senile age groups and long-livers with CHD (n=354) age, (Table 6). Age, years At the same time, women are signifi- BMI, kg/m2 60–74 (n=154) 75–89 (n=149) 90 and more (n=51) Х2 p cantly more likely to have obesity than абс. отн., % абс. отн., % абс. отн., % men (25.7% and 13.4%, respectively; c2 18.5–24.9 57 37.0 55 36.9 41 80.4 33.55 <0.001 = 7.93; p <0.005), and their BMI is higher 25.0–29.9 63 40.9 63 42.3 7 13.7 14.50 <0.001 than in men (c2 = 9.11; p = 0.011) (see 30.0 and more 34 22.1 31 20.8 3 5.9 6.90 =0.032 Table 6). Similar results were also obtained in Note: c2=33,68; p<0,001. the works of other researchers while iden- tifying ethnic differences in BMI, where Table 5 the most common BMI corresponding to The BMI value in the non-native and Yakut group of men and women with CHD aged obesity was found among the non-native 60 years and older (according to the results of the Kruskal-Wallis test and single-factor population compared to the native and in analysis of variance) (n=354) the group of women unlike men [1, 3]. Gender Conclusions. 1. Significantly higher Age, years men n=187) women (n=167) H p F p BMI values corresponding to obesity n M±m n M±m were found in patients of non-native na- 60–74 83 25.9±0.4 71 27.8±0.7 30.60 <0.001 13.23 <0.001 tionality compared to Yakut group of pa- 75–89 79 25.9±0.4 70 26.8±0.5 tients. 90 and older 25 23.7±0.5 26 23.0±0.6 4’ 2018 55

6. Kuk JL, Ardern CI. Influence of Table 6 age on the association between various The estimation of BMI in men and women with CHD aged 60 and older (n=354) measures of obesity and all-cause mor- Gender tality. J Am Geriatr Soc., 2009. no. 57. pp. 2077– 2084. DOI: 10.1111/j.1532- 2 BMI, kg/m2 men (n=187) women (n=167) Х p 5415.2009.02486.x. abs. rel., % abs. rel., % 7. Samaras T.T., Storm L.H., Elrick 18.5–24.9 84 44.9 69 41.3 0.33 >0.10 H. Longevity, mortality and body weight. Ageing Res. Rev, 2002, vol. 1, no 4, pp. 25.0–29.9 78 41.7 55 32.9 2.54 >0.10 673-691. 30.0 and more 25 13.4 43 25.7 7.93 <0.005 https://pdfs.semanticscholar.org/e397/ a3316268d5cd203f6f880cffb071b9b- Note: Х2=9,11; p=0,011. teristics of long-livers of the Khanty-Man- 1fad3.pdf. 8. WHO. Prevention and Manage- References siysk autonomous region: abstract of Ph. 1. Mulerova T.A, Filimonov S.N, D thesis.]. Tyumen, 2005, 24 p. ment of the Global Epidemic of Obesity. Onishchenko E.G et al. Klinicheskoe 3. 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J Cardi- Medical Problems, cardiologist, Yakutsk, tal-research.ru/pdf/2012/4-2/20.pdf ometab Syndr, 2008, no. 3. pp. 155–161. Russia; [email protected]; 2. Rupcheva I.N. Sostoyanie kar- DOI:10.1111/j.1559-4572.2008.00001.x. 2. Popova Elena - Candidate of diorespiratornoj sistemy, social’no-fizio- 5. Kragelund C., Hassager C., Medical Sciences, associate professor logicheskaya harakteristika dolgozhitelej Hildebrandt P [et al.]. Impact of obesity Мedical Institute of the M. K. Ammosov Hanty-Mansijskogo avtonomnogo okru- on long-term prognosis following acute North-Eastern Federal University, cardi- ga-YUgry, Avtoref. dis. … kand. med. myocardial infarction. Int J Cardiol, ologist, Yakutsk, Russia, ecapopova@ nauk [The state of the cardiorespiratory 2005, no. 98. pp. 123-31. DOI:10.1016/j. yandex.ru. system, the socio-physiological charac- ijcard.2004.03.042. S.I. Semenov, K.M. Stepanov, F.A. Platonov, S.S. Shadrina, M.M. Pisareva, A.B. Komissarov, A.V. Fadeev, A.A. Egorova, S.N. Kuzin SEROLOGICAL AND MOLECULAR- BIOLOGICAL VERIFICATION OF VIRAL HEPATITIS B, C, D AND E IN VARIOUS POPULATIONS OF THE REPUBLIC DOI 10.25789/YMJ.2018.64.16 SAKHA (YAKUTIA) ABSTRACT The purpose of the study is the serological and molecular-biological monitoring of the latitude of viral hepatitis B, C, D and E in the Republic of Sakha (Yakutia). Materials and methods. Used official statistics and annual reports. The analysis of the incidence of acute and chronic viral hepatitis B and C, hepatitis carriers for the period from 1999 to 2016, as well as serological and molecular biological monitoring of the latitude of viral hepatitis B, C, D and E in the Republic of Sakha (Yakutia). Results and discussion. In the dynamics of the incidence of AVG B, the carriage of VGV and VG C in Yakutia, there is no existence of any of their own laws that are not inherent in many regions of Russia. In general, based on the level and dynamics of the incidence of chronic viral hepatitis In the country, it is possible to characterize the overall epidemiological situation as unfavorable, even despite a noticeable decrease in the incidence. The unstable undulating nature of the incidence and their increase in recent years indicate the persistence of epidemiological tension with respect to viral hepatitis B. A distinctive feature of the structure of chronic viral hepatitis in the Republic of Sakha (Yakutia) is the high incidence of chronic viral hepatitis B and the steady growth of chronic viral hepatitis C. The infection of the population of the Republic with hepatitis B and C viruses can be determined as high. This situation, given the high frequency and severity of the adverse effects of HBV, HCV infections, as well as the endemicity of HDV infection, poses a threat to public health. According to the results of serological, molecular biological studies, a high incidence and infection rate of the population of the republic with all known hepatitis viruses was stated. An increased circulation of hepatitis E virus, previously considered a tropical infection, was also detected in the Arctic zone of Russia. Conclusion. In general, an epidemiological analysis of the incidence of acute and chronic viral hepatitis showed that in the Republic of Sakha (Yakutia) a highly endemic area with respect to viral hepatitis C, B, D and E, and such a tense epidemiological situation requires urgent appropriate measures. Studies of the genetic heterogeneity of the identified hepatitis viruses and the pathogenetic mechanisms of the development of the disease among the indigenous people of the Russian North are also required. Keywords: acute hepatitis B and C, chronic hepatitis B and C, hepatitis D, hepatitis E, HBsAg, HBV DNA, a-HCV, HCV RNA, a-HDV, a-HEV. 56 YAKUT MEDICAL JOURNAL

Introduction. In recent years, the epidemic process of parenteral viral hepatitis B, C and D in the world and Russia is AVH B AVH C changing. There is a sharp decline in the prevalence of acute forms of viral hepatitis B and D, which is associated with the widespread use of vaccine prevention of viral hepatitis B. However, the proportion of chronic hepatitis B in the overall structure of chronic viral hepatitis in Russia, in particular, in the Republic of Sakha (Ya- kutia) remains [1, 19]. Against the background of a decrease in the incidence of viral hepatitis B, the prevalence of the incidence of chronic viral hepatitis C is Fig.1. Dynamics of the incidence of acute forms of viral hepatitis B and C in the period from 1999 commonly observed [21, 9, 3]. It is es- to 2016 (figures per 100,000 population) pecially relevant for Yakutia to study the from 1999 to 2016 have been carried out. HDV-qualitative RNA. Statistical analy- patterns of the spread of infection caused Serological and molecular biological sis of laboratory results was performed by viral hepatitis D. Earlier studies have studies were carried out in two groups of using Statistica 8.0 statistical software shown an extremely high frequency of the population of the Republic. The first package. detection of antibodies to the hepatitis D group consisted of “conditionally healthy” Results and discussion. In the Re- virus in different regions of the country people in the amount of 71 people, of public of Sakha (Yakutia), the epide- [17, 7, 5]. whom 13 were men (18.3%) and 58 were miological situation regarding acute viral Hepatitis E is an important public women (81.7%). The average age of the hepatitis has now improved significantly health problem throughout the world subjects was 41.6 years (the median of (Fig. 1). The incidence of acute hepatitis and by some estimates, one third of the the age of the conditionally healthy was B from 1999 to 2002 was characterized world’s population is infected with HEV 42 years, the range was 12-65 years, by a gradual decrease in indicators from infection [18]. Studies show the wide- the interquartile range was 35-53 years), 24.3 per 100 thousand to 18.2, then there spread prevalence of viral hepatitis E. while the median age of men was 39 was a sharp decline in 2003 to 10.1 per Mainly it manifests itself in an outbreak years old with an interquartile range of 100 thousand people, followed by a grad- of acute hepatitis in tropical, subtropical 32-45 years women - 43.5 and 32-53, re- ual decrease in up to 0.53 per 100 thou- countries [2, 4, 8]. In many European spectively; no statistically significant age sand population. In 2014, only 7 cases of countries, the detectability of serological differences were found by sex (Z = 0.85; acute hepatitis B were registered in the markers of viral hepatitis E among do- p = 0.39). The second group (group II) republic, in 2015 and in 2016, 6 and 5 nors varies from 1.3% in Italy to 52% in included 78 patients with various etiologi- cases, respectively. France, and in risk groups among farm- cal forms of viral hepatitis (B, C and D), In the dynamics of hepatitis B virus ers and hunters this range varies from among whom there were 24 men (30.7%) infection, there is a markedly noticeable 1.3% to 52 % [12,15]. people, women - 54 (69.3%). The aver- trend of a sharp decrease in infection of Russia is considered a non-endemic age age of patients was 50.3 years (the the population with the hepatitis B virus region for hepatitis E, especially the median age of patients was 52 years, the (Fig. 2). This is due to the implementa- northern territories. Often, HEV infection range was 28-83 years, the interquartile tion of preventive work against hepatitis is found in immunosuppressed patients range was 43.5-59 years), the median B. The level of virus-carrying indicators in who may have a delay or absence of a age of men was 49 years old with an in- 1999 was 322.1 per 100 thousand pop- pronounced humoral immune response terquartile range of 41-58 years, women ulation, which was significantly higher to the infection [6]. Recent studies have - 53 and 45-60 respectively; in this group than the average level of the all-Russian shown that viral hepatitis E is not only of subjects, there were also no statistical- indicator. This exceptionally high level an anthroponotic disease, as previously ly significant differences in age by gender exceeded the average Russian figure by thought, but may also be zooanthro- (Z = 0.92; p = 0.36). about 3 times. In 1999, the virus infection ponotic [13]. Moreover, genotypes 1 and By ELISA studies were performed for rate in the Russian Federation was 88.0 2 cause disease in humans, and geno- the presence of HBsAg, a-HBsAg (mU / per 100 thousand people. A decrease in types 3, 4 - in various wild and domestic ml), a-HBc-total, a-HBs IgM, a-HBeAg, a- virus infection rates of more than 19 times animals (pigs, cows, horses, deer, dogs, HBe IgG, a-HDV, a-HDV-IgM, a-HCV , a- in 17 years (from 322.1 to 16.91 per 100 ducks) [20, 11, 14, 10, 15]. HEV-IgG. For detection of viral hepatitis thousand people) indicates a significant The aim of the study is the serologi- markers, Gepascan HBsAg and Gepas- breakthrough effect of preventive work cal and molecular-biological monitoring crin test systems were used, manufac- and a high efficacy of hepatitis -B vac of the latitude of viral hepatitis B, C, D tured by Bioservice, Moscow, Vektogep cination, especially with the introduction and E in the Republic of Sakha (Yakutia). D - antibodies-strip, manufactured by of hepatitis B vaccination The national Methods and materials of the re- Vector-Best, Novosibirsk, Anti -HBc calendar of prophylactic vaccinations in search. To study the incidence of acute EIA »Cobas Core, Hoffmann La Roche 2002, which pledges three-time vaccina- and chronic viral hepatitis B and C in (Switzerland). Anti-HBs were quantified tion of newborns against hepatitis B ac- the Republic of Sakha (Yakutia), data of using the anti-HBs Quant EIA II Roche cording to the scheme 0-6-12 (the first 12 official statistics, annual reports of the ELISA test system on a Cobas Core II hours of life - 6 months - 12 months). Republican Center of Rospotrebnadzor automatic analyzer from Hoffmann La The incidence rate of acute hepatitis C were used. The analysis of the incidence Roche (Switzerland). HCV-quantitative in 1999 was 9.5 per 100 thousand peo- of acute and chronic viral hepatitis B and RNA was isolated by PCR, followed by ple (Fig. 1). In subsequent years, there C, and the carriage rates of hepatitis B HCV genotyping, HBV-quantitative DNA, was a decline in indicators to 2.0 per 100 4’ 2018 57

the studies in both selected groups for the study are shown in Table 1. Analysis of the results of detection of markers of viral hepatitis B, C, D and E according to serological studies showed a high intensity of the course of the epidemic process of viral hepatitis among various population groups of the Repub- lic of Sakha (Yakutia). Analysis of the presented studies found that among the population of the republic there is a high proportion of seropositive individuals for all viral hepatitis with the highest rates of hepatitis C in the group of patients (I group) up to 71.8%, hepatitis B up to Fig.2. The long-term dynamics of the decrease in the carriage of hepatitis B (figures per 100,000 24.3% and hepatitis E up to 23, 0% of population) cases. High infection of HBsAg-positive thousand population in 2003 and a slight atitis B were at 63.3 per 100 thousand individuals with hepatitis D virus markers increase in indicators to 5.0 in 2005. population in 2003, the minimum de- (a-HDV — 42.1%) was particularly alarm- Since 2007, there has been a gradual crease to 33.13 in 2007. In recent years, ing. steady decline in the incidence of acute there has been a trend of a moderate For the purpose of diagnostic verifica- viral hepatitis to 0.52 per 100 thousand steady increase from 27.83 per 100 thou- tion in the group of patients with viral hep- people in 2012. Moreover, in 2008-2012, sand people in 2013 to 37.15 per 100 atitis, he was examined for hepatitis B vi- the incidence rates of acute viral hepatitis thousand people in 2016. rus markers (Table 1). The main marker B and C were compared and amounted In general, based on the level and dy- of viral hepatitis B HBsAg was detected to 1.0-2.0 per 100 thousand people. namics of the incidence of chronic viral in a quarter of patients (24.3%). At the Since 2013, there has been a change in hepatitis B in the country, it is possible to same time, out of 19 HBsAg-positive pa- the epidemiological situation with respect characterize the overall epidemiological tients, HBV DNA was detected in 13 pa- to acute viral hepatitis B and C. The in- situation as unfavorable, even despite a tients, which was 68.4%, which indicates cidence of acute viral hepatitis B contin- marked decrease in the incidence. The an increased replicative activity of virus ues to decline gradually, reaching 0.52 unstable undulating nature of the inci- B. Moreover, a quantitative analysis of per 100 thousand people in 2016. At the dence and their increase in recent years HBV DNA showed an average viral load same time, the incidence of acute viral indicate the persistence of epidemiologi- of 2.6 × 10 4 copies / ml the maximum in- hepatitis C gradually, steadily increases cal tension with respect to viral hepatitis dicators 3.1 * 102, with the minimum - 1.7 from 1.36 in 2013 to 1.98 per 100 thou- B. Against the background of a general * 104. These patients require long-term sand people in 2016. It should be noted decrease in the incidence of hepatitis B, systematic treatment, regular follow-up, that in recent years an unfavorable situ- the incidence of viral hepatitis C increas- taking into account clinical manifesta- ation has been created for viral hepatitis es. 13 per 100 thousand population for tions, biochemical and serological indica- C, there is a tendency to an increase in chronic hepatitis C versus 37.15 chronic tors. the incidence rate, prevailing over acute hepatitis B in 2016). This tendency is In group I, HBsAg was detected in hepatitis B. observed everywhere, since there is no 9.8% of the subjects. Of 7 HBsAg-posi- Thus, in the dynamics of the incidence specific prophylaxis for viral hepatitis C tive people, HBV DNA was detected in 5 of AVH B, the carriage of VGV and VG (Fig. 3). (71.4%). Moreover, the viral load of HBV C in Yakutia, there is no existence of In order to detect infection of the popu- DNA was higher than in the group of pa- any own patterns that are not inherent in lation with hepatitis B, C, D, and E virus- tients, and the rates ranged from 1.9x102 many regions of Russia. es, selected groups studied serological to 3.0x102. Hepatitis B markers, such as The dynamics and incidence of chron- and molecular biological markers with the a-HBeAg IgG and a-HBcor-cumulative, ic forms of viral hepatitis B and C are aim of etiological verification, as well as were found in 21.1 and 28.1% of cases, significantly different from acute forms. determining the virological activity of the respectively, which are now estimated to From 1999 to 2013, the incidence rates pathological process. The total results of be a sign of chronic latent HBV infection. of chronic hepatitis B rose steadily, and CVH B CVH C significantly, due to improved diagnostics and the widespread introduction of immunological laboratories in health care facilities, mandatory testing for the first time applied for a viral hepatitis marker - HbsAg. The epidemiological situation in relation to chronic hepatitis B is the same as in acute hepatitis B: with the maintenance of hepatitis B vaccination in the national immunization schedule since 2003, a decrease in incidence has been observed. The decrease in the incidence of chronic hepatitis B was undulating. The Fig.3. Dynamics of incidence rates of the registered forms of chronic viral hepatitis B and C in maximum incidence rates of chronic hep- the Republic of Sakha (Yakutia) in the period from 1999 to 2016 58 YAKUT MEDICAL JOURNAL

The significantly high detection rate of a- HBc IgG in both groups of patients also Table 1 indicates a history of acute hepatitis B, Serological and molecular biological markers of viral hepatitis B. C. D. E among the presence of chronic hepatitis B, and various population groups (n-149) the carriage of HbsAg. Conditionally One of the aspects of HbsAg-positive Number of Sick Number of healthy Chi- VG markers examinations examinations apt. р viral hepatitis, which cause worsening of n % n % the disease and a high degree of chro- Markers of viral hepatitis В nicity, is the addition of HDV infection. In HBsAg 19 24.3 7 9.8 5.4 0.02 the group of patients, the proportion of a- a-HBsAg* 21 26.9 35 49.2 7.9 HDV among HBsAg positive was 42.1%, a-HDcor-суммарные 78 42 53.8 20 28.1 10.1 0.002 and the marker of replicative activity, HBeAg 0 - 71 0 - showing active viral replication, a-HDV a-HBeAg IgG 34 43.5 15 21.1 8.5 0.004 IgM was detected in 10.5% of the studied Of 19 HBsAg ДНК HBV** positive 13 68.4 5 7.0 6.7 0.01 (Table 1). The identified indicators of the Markers of viral hepatitis D presence of hepatitis D virus markers in a-HDV IgM Of 19-HBsAg 2 10.5 Of 19-HBsAg 0 - the structure of chronic viral hepatitis are a-HDV positive 8 42.1 positive 0 - unprecedentedly high in the Republic of Markers of viral hepatitis С Sakha (Yakutia). Usually HDV infection is a-HCV 78 56 71.8 71 9 12.6 52.8 <0.001 registered in 5-7% of cases in the Euro- core 12 21.4 1 1.4 10.0 0.002 pean part of Russia. NS3 10 17.8 0 - Of particular concern is the fact that Of 56 HCV Of 9 HCV NS4 positive 7 12.5 positive 0 - the hepatitis D virus causes, as a rule, NS5 6 10.7 0 - very severe forms of chronic hepatitis, РНК HCV*** 38 48.7 7 77.7 which in a short time lead to cirrhosis Markers of viral hepatitis Е of the liver. It is necessary to note the a-HEV IgG 78 18 23.0 71 14 25.3 0.3 0.6 alarmingly high proportion of HDV infection in the structure of chronic viral hepa- Note: a-HBsAg * - quantitative analysis on average 122.09 MU / ml. maximum indicators -> 263.9 MU / ml. minimum - 12.7 MU / ml titis 42.1%, which indicates an obvious HBV ** DNA - quantitative analysis of an average of 2.6 * 10 ^ 4. the maximum of 3.1 * 10 ^ 2. the increase in the intensity of the epidemic minimum - 1.7 * 10 ^ 4 process in recent years of viral hepatitis HCV *** RNA - quantitative analysis of an average of 2.6 * 10 ^ 4. the maximum performance of 7.0 * B in the territory of Yakutia. 10 ^ 4. the minimum - 5.4 * 10 ^ 2 In Yakutia, as well as throughout the given the high frequency and severity of C in the country are distinguished by an country, the proportion of the incidence of the adverse effects of HBV, HCV infec- increased replicative activity of viruses in viral hepatitis C is increasing and prevail- tions, as well as the endemicity of HDV more than 3/4 of patients and a high de- ing over the incidence of viral hepatitis infection, poses a threat to public health. gree of infection by 2, 3, and even 4 other B. In the study of the breadth of preva- The viral hepatitis E endemic to tropi- viruses. hepatitis at the same time (mixt lence in patients with chronic hepatitis cal countries in the republic was not sub- infection). So among 19 patients with and healthy individuals, the serological ject to testing for patients with hepatitis, chronic hepatitis B, hepatitis C markers markers of viral hepatitis C (a-HCV) were as well as during monitoring studies. Our were found in 31.5% of cases, while the detected in most patients and accounted studies showed a high circulation of the virus (HCV RNA) was detected in 21.0% for 71.8%. Among conditionally healthy E virus among conditionally healthy and of cases. Anti HEV IgG was detected in individuals, this indicator was 12.6%, sick VH - 25.3% and 23.0%, respectively. 21.0% (4 of 19). A similar situation occurs while HBsAg in this group was detected In addition, patients with acute viral hepa- in patients with chronic viral hepatitis C. in only 9.8% of cases. The wide distribu- titis with unclear etiology may have cases Among 68 patients with chronic hepatitis tion of a-HCV and the core, NS3, NS4, of acute viral hepatitis E, which is cur- C, markers of hepatitis B (HBsAg), hepa- NS5 spectrum among patients and the rently not routinely diagnosed in Russia titis D, and hepatitis E are often detected high proportion of hepatitis C virus (HCV in routine practice. (in fact, a fourfold infection (HCV + HBV RNA) detected in seropositive individuals In connection with the detection of se- + HDV + HEV) in 11.7% , 4.4% and 25% among patients and conditionally healthy rological markers of hepatitis E in domes- of cases, respectively (table 2). 67.8% and 77.7%, respectively, indicates tic and wild animals, which can be food Thus, according to the results of se- a significant intensity Hepatitis C epidem- of the population, these animals can be rological, molecular-biological studies, a ic process among the population of the a source of infection of acute hepatitis E, high incidence and infection of the popu- republic. (Table 1). The group of condi- which can be especially dangerous for lation of the republic with all known hepa- tionally healthy individuals consisted of pregnant women. titis viruses was stated. An increased the studied, not belonging to the groups Our further studies have shown that circulation of hepatitis E virus, previously at high risk of infection with viruses of the serological and molecular biological considered a tropical infection, was also parenteral hepatitis. The detection of up characteristics of chronic hepatitis B and detected in the Arctic zone of Russia. to 71.4% of HBV DNA and 77.7% of HCV RNA in seropositive, conditionally healthy Table 2 subjects indicates a high activity of viral 4-fold infection (HBV + HCV + HDV + HEV) among patients B and C infections in the studied popula- with chronic hepatitis B (n-19) and C (n-68). in% tion. a-HBcor a-HBe DNA РНК a-HEV Thus, the infection of the population of Patients HBsAg amounts IgG HBV a-HDV a-HCV HCV IgG the republic with hepatitis viruses B and Hepatitis В 84.2 100.0 68.4 57.8 1.4 31.5 21.0 21.0 C can be defined as high. This situation, Hepatitis С 11.7 45.5 35.3 7.3 4.4 97.0 57.3 25.0 4’ 2018 59

Conclusion characteristics of viral hepatitis B, C and 20. Perez-Garcia M.T. Modern In general, an epidemiological analy- Delta in the Republic of Sakha (Yakutia): knowledge about hepatitis E / M.T Perez- sis of the incidence of acute and chronic MD thesis]. Moscow, 2007, p. 42-48. Garcia, B.Suay, M.L.Mateos-Lindemann viral hepatitis showed that in the Repub- 8. Solonin S.A. Cirkulyaciya virus- // Int. J Mol. Sci..2015 Oct; 16 (10): lic of Sakha (Yakutia) a highly endemic nogo gepatita E sredi svinej na territorii 25711-43. area with respect to viral hepatitis C, B, Rossijskoj Federacii: avtoref.dis. … kand. 21. The past incidence of hepatitis D and E, and such a tense epidemiologi- med.nauk [Circulation of viral hepatitis E C virus infection: implications for the cal situation requires urgent appropriate among pigs in the territory of the Russian future burden of chronic liver disease in measures. Studies of the genetic hetero- Federation: PhD thesis]. Moscow, 2010. the United States / G.L Armstrong, M.J. geneity of the identified hepatitis viruses 9. Berkes J., Cotler S.J. Global Alter, G.M.McQuillan [et al.] // Hepatol- and the pathogenetic mechanisms of the Epidemiology of HCV Infection. // J. Ber- ogy. 2000; 31: Р. 777–782. development of the disease among the kes, S.J. Cotler / Current Hepatitis Re- indigenous people of the Russian North port, 2005, vol. 4, pp. 125–129. The authors are also required. 10. Cross-species infections of 1. SEMENOV Sergey Innokentevich, This work was supported by the RFBR cultured cells by hepatitis E virus and MD, Leading Researcher, Scientific Re- grant No. 18-415-140005 p_a. discovery of an infectious virus-host research Institute of Health, NEFU them. combinant. // P. Shukla, H.T. Nguyen, U. M.K. Ammosova, 677000, Yakutsk, Be- References Torian [et al.] /Proc Natl Acad Sci US A. linsky, 56, E-mail: [email protected] 1. Uchajkin V.F. Cherednechenko 2011 Feb 8; 108(6):2438-43. 2. 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HEALTHY LIFESTYLE. PREVENTION

M.S. Avdeeva PHYSICAL DEVELOPMENT AND PHYSICAL FITNESS OF 7-8-YEAR-OLD GIRLS WITH PECULIARITIES OF PERINATAL DOI 10.25789/YMJ.2018.64.17 DEVELOPMENT PERIOD

ABSTRACT Aim. The purpose of the research is to study the characteristics of the physical development of 7-8-year-old girls with non-physiological perinatal period. Materials and methods. 236 girls of 7-8-year-old girls from Kirov (Russia) were divided into groups: group I - control (n = 60, physiological perinatal period), group II (n = 58, late gestational hypertension in the anamnesis), group III (n = 61, placental insufficiency in the anamnesis), group IV (n = 57, maternal anemia in the anamnesis). We measured their physiometric characteristics (heart rate, blood pressure, vital capacity of lungs, flexion muscle strength of the right and left hand, maximum oxygen consumption) and anthropometric ones (length, body weight, chest circumference, its excursion). Then the corresponding indices and coefficients were calculated. Results. Girls with late gestational hypertension have lower mass-growth index, the Quetelet index and dynamometry indicators; girls with placental insufficiency have higher systolic blood pressure and lower work power; girls with maternal anemia in the anamnesis have low mass-growth index, the Quetelet index and the power of work. Conclusion. It is shown that the studied perinatal pathologies have a similar remote effect on physical development: gestational hypertension and anemia of a mother during pregnancy affect the mass-growth index and the Quetelet index, placental insufficiency and anemia influence the work power. Thus, we consider these indicators of 7-7-year-old girls (mass-growth index, the Quetelet index and work power) to be the most sensitive to pathologies of the perinatal period. Keywords: physical development, perinatal period pathologies, gestational hypertension, placental insufficiency, pregnancy anemia.

Introduction. A number of studies mother’s gestational hypertension are at anamnesis). Groups II-IV included chil- have shown that complications of the risk for cardiovascular disease. dren with only one of these pathologies. perinatal period negatively affect the In addition to gestational hyperten- To measure the physical development of morphophenotype and adaptation of sion, placental insufficiency has a distant girls, physiometric and anthropometric in- newborns [4], and the sexual develop- influence on the state of children’s CVS. dicators were measured logically: at the ment of adolescents [5]. The increase in It causes an increase in blood pressure beginning of the first grade (1st measure the period of gestation is connected with [20] and has a long-term effect on the in October), in the middle (2d measure in an increase in body mass and its index CVS status [14]. Moreover, placental January), at the end (3d measure in May) in adulthood, especially among girls [7]. insufficiency remotely reduces memory and at the beginning of the second grade According to research, gestational hy- [10] (when a child is 12). (4th measure in September). Anthropo- pertension in the anamnesis affects the In addition to the above pathologies, metric indicators included measurements physical development of children. Chil- the mother’s anemia during pregnancy of length, body weight, chest circumfer- dren with a gestational hypertension (n = has a remote negative impact on the ence, its excursions and the calculation 343) have a higher body mass index and health of children. A study of 78,923 of weight-growth indices: mass-growth, a greater circumference of the chest than women showed that if a mother had ane- Rohrer, Pignet, Quetelet [8]. According to those with a physiological perinatal pe- mia (hemoglobin concentration in the anthropometric indicators, we compared riod [6]. The research [22], which aimed blood was 70-99 g/l), then the risk of ane- the increase between measurements 1 to identify the relationship between ges- mia of 3-5-year-old children increased and 2 (October-January), 2 and 3 (Janu- tational hypertension of mother and obe- [21]. Mother’s anemia during pregnancy ary-May), 3 and 4 (May-September). sity in 4-7-year-old children (n = 88406), affects the motor abilities of 1-year-old The physiometric parameters were showed that mother’s increase in pres- children [9]. In addition, it has an inverse studied in February-March, measuring sure by 10 mmHg during pregnancy in- correlation with the Tiffno-Pinelli index the heart rate, blood pressure [15], vi- creases the risk of children’s obesity. of 8-9-year-old children, i.e. they have tal capacity of the lungs [11], the flexion In addition, gestational hypertension a smaller airway patency [18] up to 10 muscular strength of the right and left in the anamnesis affects the state of the years old [13]. hand [12]. We calculated life and strength cardiovascular system (CVS). A study The purpose of our study is to study index, pulse pressure, coefficient of ef- [16] showed that in 979 children (median the characteristics of the physical devel- ficiency of blood circulation, coefficient age of 7 years) children with gestational opment of 7-8-year-old girls with non- of endurance [3]. The level of general hypertension of mother had a higher sys- physiological perinatal period. endurance was assessed by the maxi- tolic blood pressure. Also, Tenhola S and Materials and methods of the re- mum oxygen consumption (MOC), us- co-authors [19] write about higher systolic search. In retrospect, according to the ing the method of indirect calculation of and diastolic blood pressure of 12-year- data of the registration form No. 112-U the MOC for power and heart rate during old children with a mother’s gestational “The history of the development of the the performance of the test step (climb- hypertension in the anamnesis, the cause child” and 026/u “Medical card of the ing the bench at a height of 0.35 m for 4 of it may be the elevated concentration of child” we studied the perinatal period de- minutes with a frequency of 20 cycles per adrenaline in children’s blood. In addition velopment of 236 first-year schoolgirls minute ) [1]. Using the MOC, the level of to high systolic blood pressure, children in the city of Kirov (Kirov region, Rus- physical working capacity was assessed with gestational hypertension have a sia). Girls were divided into 4 groups: I according to Apanasenko [2]. The results higher level of triglycerides in the blood - control (n = 60, physiological perinatal of the research were subjected to statisti- plasma, which confirms the presence of period), II (n = 58, late gestational hyper- cal processing using parametric statistics a metabolic syndrome [17]. According to tension), III (n = 61, placental insufficien- methods in the Microsoft Excel software Alsnes I.V. et al. [6], all children with a cy), IV (n = 57, maternal anemia in the package on an Intel Pentium computer. 4’ 2018 61

Then the arithmetic mean (M) and the standard error of the mean (m) were cal- Table 1 culated. The differences were assessed Indicators of physical development of the group I (control) and the group II by the Student’s criterion (t) for indepen- (late gestational hypertension) dent samples, and they were considered Late gestational reliable at р<0,05 (in text it is indicated Measurement Control hypertension Indicators № p as «*»). M m M m Results and discussion. When com- Mass-growth index. g / cm 2 206.57 6.02 189.76 3.52 <0.05 pared with the group I (control) for girls Quetelet index. kg / m2 2 15.77 0.38 14.67 0.22 <0.05 from the group II (late gestational hyper- Dynamometry of the right hand. kg 4 14.20 0.44 12.68 0.63 <0.05 tension), lower values of weight-growth Dynamometry of the left hand. kg 4 13.34 0.48 11.59 0.59 <0.05 indices and dynamometry indicators Table 2 were revealed (Table 1). Indicators of physical development of the group I (control) and the group III The obtained data contradict the lit- (placental insufficiency) erature data on the higher body weight Control Placental among children with a mother’s gesta- Indicators Measurement insufficiency p tional hypertension in the anamnesis [6, № M m M m 22]. We have not confirmed the data on the influence of gestational hypertension Systolic blood pressure. mmHg - 95.45 1.32 99.81 1.71 <0.05 on the cardiovascular system [16, 17, Working power. kg * m / min - 227.52 13.31 192.10 5.74 <0.05 19]. For the first time the effect of gestational hypertension on dynamometry was Table 3 established. Indicators of physical development of the group I (control) When comparing groups I (control) and the group IV (maternal anemia) and III (placental insufficiency), no - dif Control Anemia ferences in anthropometric parameters Indicators Measurement № p were revealed, but differences in cardio- M m M m vascular parameters were established Mass-growth index. g / cm 3 206.57 6.02 189.63 5.25 <0.05 (Table 2). The group III has higher sys- Quetelet index. kg / m2 3 15.77 0.38 14.66 0.30 <0.05 tolic blood pressure and lower exercise Working power. kg * m / power. min - 227.52 13.31 194.17 7.22 <0.05 We have confirmed the literature data growth index and work power. All three “mat-platsenta-plod” [Morphophenotype on the increase of blood pressure of chil- indicators are calculated and determined and adaptation of newborns depending on dren with placental insufficiency [14, 20]. taking into account the body weight. Con- the stages of circulatory disturbances in For the first time, it has been established sequently, perinatal period pathologies “maternal-placental-fetal” system] Clinical that placental insufficiency has a nega- remotely affect the body weight, reducing Practice in Pediatrics, 2008, Vol 3, № 6, p. tive effect on the power of the work. its value in comparison with the control 33-37. Comparison of the group I (control) at 7-8 years. It should be noted that two 5. Mirlas E.M. Zaritskaya E.N. and IV (maternal anemia) has revealed pathologies of the perinatal period (ges- Shulzhenko E.V. Sostoianie ploda differences in three indices (Table 3). tational hypertension and anemia) affect i perinatalnye iskhody u materei The group IV has the lower mass-growth the mass-growth index and Quetelet in- s khronicheskoi platsentarnoi index, the Quetelet index and the work dex, while placental insufficiency and nedostatochnostiu [Fetus state and power. anemia affect the work power. Thus, perinatal outcomes in mothers with We have not confirmed the literature we consider these indicators (the mass- chronic placental insufficiency] Bulletin data on the negative impact of the mater- growth index, Quetelet index and work Physiology and Pathology of Respiration, nal anemia in the anamnesis on the state power) in 7-8-year-old girls to be most 2008, № 30, p. 68-72. https://cfpd.amursu. of the child’s airways [13,18] - differences sensitive to perinatal period pathologies. ru/attachments/article/80/N30.pdf in the magnitude of the vital capacity of 6. Hypertension in Pregnancy and the lungs, the vital index, the Stange and References Offspring Cardiovascular Risk in Young Gentcha tests between groups I and IV. 1. Avdeeva M.S. Tulyakova O.V. 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A.M. Cherdonova*, V.G. Pshennikova*, A.V. Solovyev, N.A. Barashkov, A.M. Rafailov, G.P. Romanov, S.K. Kononova, S.A. Fedorova, F.M. Teryutin OPINION OF YOUNG PEOPLE ON THE POTENTIAL RISK OF THE BIRTH DOI 10.25789/YMJ.2018.64.18 OF DEAF CHILD

ABSTRACT In Yakutia, the contribution of GJB2 mutations to the etiology of hereditary deafness is 48.8% and is one of the highest in Asia, due to a significant accumulation of the mutation of the splice site c.-23+1G>A in the GJB2 gene due to the founder effect in the Yakut population (“age” of mutation ~ 800 years). The results of scientific research in the field of genetic forms of deafness are actively introduced into practice in the form of various test systems of routine DNA diagnostics. However, the bioethical, social and psychological problems arising from the application of these genetic technologies are less well understood than the molecular genetic aspects of deafness. We conducted a questionnaire and a selection of buccal epithelium of 241 people, whose mean age is 21, in order to analyze their opinion on the potential risk of a deaf child’s birth and conduct genetic testing for the presence of the mutation c.-23+1G>A in the GJB2 gene. The frequency of heterozygous carriage of the mutation c.-23+1G>A of the GJB2 gene among hearing young people (n = 241) in the Yakut population was 10.8%, which is comparable to the previously obtained data. Analysis of data from the questionnaire with genotypes shows that there are no statistically significant differences in the respondents’ responses (p>0.05). As a result of the questionnaire, it is shown that most young hearing people think that deafness can be a hereditary disease (62.6%). Most young people assume the possibility of birth of a deaf child from hearing parents (81.33%), but only 2.49% of respondents agree with this risk. Such an answer can be explained by the protective internals of the psyche, when a person assumes the existence of the same risk of the birth of a deaf child in all people, but denies such a possibility in himself. Keywords: opinion of young people, GJB2 gene, c.-23+1G>A mutation, frequency of heterozygous carrier.

Introduction. In recent years, in con- sibilities of DNA testing, much attention regions of the world, the bioethical and nection with the expansion of the pos- has been paid to the molecular genetic social aspects of this disease remain in- causes of hereditary forms of deafness. sufficiently studied. At present, genetic * - Equivalent contribution of authors However, at the same time, in many technologies are ahead of the informa- 4’ 2018 63

tion space, as a result of which there is Institution of Higher Education “North- Table 1 no formed opinion in Russian society in Eastern Federal University named after relation to the heavy moral and ethical M.K. Ammosov “. A total of 241 people Data of interviewed young hearing respondents issues that entail genetic technologies. took part in the questionnaires, who were Work in this direction was carried out in students. Of these, 44% were men and Young hearing people Number % the United States and a number of Eu- 56% women, the average age of partici- (n=241) ropean countries [5,6,9], in Russia such pants was 21 years. The urban popula- Gender studies are practically absent. tion was 24%, rural - 74%, did not specify Male 106 43.98 Earlier in the Republic of Sakha (Ya- the place of residence / birth - 2%. All the Female 135 56.02 kutia), the main cause of congenital deaf- respondents were Yakuts (Table 1). Place of residence Urban 57 23.65 ness was identified, which is caused by Questions in the questionnaires were Rural 178 73.86 the mutation c.-23+1G>A in the gene closed alternatives with a choice of one No response 6 2.49 GJB2 [3]. In the Yakut population, this answer option. By completeness of cov- Nationality mutation occurs with an extremely high erage, the questionnaire is selective, Yakut 241 100 incidence of heterozygous carriage conducted among hearing people. By Average age – 21 (10%) [3]. In Yakutia, the contribution of type of contact with respondents - full- GJB2 mutations to the etiology of heredi- time. According to the number of respon- a chance to give birth to a deaf child?”. tary deafness is 48.8% and is one of the dents, there is an auditor, that is, the si- Respondents answer: “Yes”, “No” or “I do highest in Asia, due to a significant ac- multaneous filling in of questionnaires by not know.” cumulation of the mutation of the splice a group of people gathered in the same We correlated the respondents’ an- site c.-23+1G>A in the GJB2 gene due to room in accordance with the rules of a swers about the hypothetical risk of a the founder effect in the Yakut population selective procedure. Surveys foreseen deaf child’s birth with their real risks, by (“age” of mutation ~ 800 years) [3,4,11]. by the scope of this research work were testing their presence of the mutation c.- The results of scientific research in the carried out after informed written consent 23+1G>A of the GJB2 gene, since this field of genetic forms of deafness are ac- of the participants or their parents. The mutation among the Yakuts is the most tively introduced into practice in the form research work was approved by the lo- common [11]. The frequency of heterozy- of various test systems of routine DNA di- cal committee on biomedical ethics under gous carrier mutation c.-23+1G>A of the agnostics. However, the bioethical, social the YSC of the Commission in 2014 (Ya- GJB2 gene among hearing young people and psychological problems arising from kutsk, minutes No. 41 of November 12, (n = 241) in the Yakut population was the application of these genetic technolo- 2014). 10.8% (Table 2). gies are less well understood than the Isolation of DNA from the buccal epi- To the question “What do you think, molecular genetic aspects of deafness. thelium was carried out by phenol-chlo- deafness is a hereditary disease?” More In clinical practice, 90% to 95% of roform extraction. Amplification of frag- than half of the respondents (62.66%) deaf children are born in hearing families ments of the GJB2 gene, including exon answered “Yes” and 37.34% do not agree [7,10]. An analysis of the voices of hear- 1 with 5’-CCGGGAAGCTCTGAGGAC-3 with this (Fig. 1 - A). When comparing re- ing parents about the possible causes ‘and 5’-GCAACCGCTCTGGGTCTC-3’ sponses to genotyping data, there were of hearing loss in their child indicates primers and exon 2 with 5’-TCG- no significant differences in respondents’ that the majority of hearing respondents GCCCCAGTGGTACAG-3 ‘and answers. Thus, heterozygous carriers of in Yakutia (86.1%), Tuva (73.8%) and 5’-CTGGGCAATGCGTTAAACTGG-3’ the mutation c.-23+1G>A of the GJB2 Bashkortostan (76.2%) do not consider primers of the GJB2 gene with flanking gene are larger (76.92%) in the group hearing loss in a child hereditary [1, 8]. regions was performed by PCR. The veri- of respondents who agree that deafness If we take into account this opinion of the fication of the amplificate on electropho- is a hereditary disease, and in a group parents, then the hearing loss in their resis was carried out in a 2.5% agarose of those who disagree with this hetero- children in 73.8-86.1% of cases is due ei- gel and stained with ethidium bromide zygous carriers of this mutation, 23.08% ther to environmental factors or the cause for 25 minutes. When detecting the mu- (Fig. 1-B). remains unknown [1.8]. At the same time tation of c.-23+1G>A in the GJB2 gene, To the question “Do you think there among respondents who participated in we amplified exon 1 of this gene with an is a probability of giving birth to a deaf the survey, there is a tendency to deny intron portion containing a polymorphic child from hearing parents?” The majority the hereditary nature of the disease in restriction site (restriction site - GGTGA (81.33%) consider that hearing parents the absence of deaf relatives in the fam- (N) 8/7). To do this, the amified sample have such a probability, 17.43% exclude ily [1,8]. In this context, the analysis of with restriction enzyme and buffer was such a possibility and 1.24% did not re- the opinion of young people about the placed in a thermostat for 12 hours at 37 spond to this question (Fig. 2 - A). In the hypothetical risk of the birth of a deaf ℃ and the next day electrophoresis of the group of respondents who agree with child is important from the point of view of amplifications was performed. this probability, heterozygous carriers forming a reference group of individuals, Results and discussion are larger (88.46%) than in the opposite who for the most part did not face similar In this paper, we consider three ques- group (7.69%) (Fig. 2 - B). moral and ethical problems [1]. tions related to the purpose of the study. To the question “Is there a probability of The aim of this work is to analyze the The first question: “Do you think deaf- opinion of young people about the hypo- ness is a hereditary disease?” Respon- Table 2 thetical risk of a deaf child’s birth. dents answer: “Yes” or “No”. The second The frequency of heterozygous carriers Materials and methods. We con- question: “Do you think there is a chance of mutation c.-23+1G>A in the gene GJB2 ducted a questionnaire and a selection of giving birth to a deaf child from hearing Number of buccal epithelium in students of the parents?”. Respondents answer: “Yes” or (n=241) % Federal State Autonomous Educational “No”. The third question: “Do you have [wt]; c.[-23+1G>A] 26 10.79 [wt];[wt] 215 89.21 64 YAKUT MEDICAL JOURNAL

a deaf child’s birth?” More than half of the respondents (66.8%) do not know what to answer, they exclude this probability of 29.88% and only 2.49% of respondents agree with this (Fig. 3 - A). When corre- lating responses with genotypes, it turns out that heterozygous carriers are larger in the group of respondents who do not know whether they have a probability of giving birth to a deaf child (80.77%), less Fig.1. Answers to the question: «What do you think, deafness is a hereditary disease?»: A - the in a group that do not agree with such general distribution of answers; B - the answers of young people in relation to their genotypes. a probability (19.23%) and in a group, which agreed with this heterozygous carriers was not (Fig. 3 - B). The carrier frequency of the mutation c.-23+1G>A of the GJB2 gene among hearing young people (n = 241) in the Yakut population was 10.8% (Table 2), which is comparable to earlier data. Ear- lier in Yakutia, the carrier frequency of Fig.2. Answers to the question: «Is it possible to give birth to a deaf child from hearing parents?»: mutation c.-23+1G>A, in a population A - the general distribution of answers; B - the answers of young people in relation to their sample of Yakuts of 350 people, was genotypes. 10.2% [3, 11]. Most young hearing people think that deafness can be a hereditary disease (62.6%) (Fig. 1). In a study conducted among deaf adults and hearing parents of deaf children [1,8], it is shown that these groups think the opposite. That is, most deaf adults (84%) and hearing parents of deaf children (78%) think that Fig.3. Answers to the question: «Do you have a chance to give birth to a deaf child?»: A - the their deafness or deafness of their child general distribution of answers; B - the answers of young people in relation to their genotypes. is a non-hereditary disease [1,8]. The general tendency in denying the heredi- there are no statistically significant dif- c.-23+1G>A in the gene GJB2, there is tary nature of the disease in the study ferences in the respondents’ responses a tendency to assume the hereditary na- groups is attributed to the respondents’ (p>0.05). However, heterozygous car- ture of deafness more often than in peo- low awareness of the genetic causes of riers of the mutation c.-23+1G>A in the ple without this mutation. deafness and psycho-emotional reasons GJB2 gene are more likely (79%) than Acknowledgments - “unwillingness to be guilty of deafness people without this mutation (60%), We thank all participants of this study. of the child” [1,8]. Consent that deaf- agree that deafness is a hereditary dis- The study was supported by the Minis- ness can be a hereditary disease among ease (Fig. 1-B). To question number 2, try of Education and Science of the Rus- young hearing people may indicate that “Do you think there is a probability of sian Federation №6.1766.2017, Project this group of respondents underesti- giving birth to a deaf child from hearing NEFU M.K. Ammosov “Genetic features mates the importance of this issue, and parents?” Heterozygous carriers of muta- of the population of Yakutia: the struc- is ready to agree with such an abstract tion c.-23+1G>A are half as rare (7.6%) ture of the gene pool, adaptation to cold, statement (that deafness is a hereditary than people without this mutation (18, psychogenetic characteristics, the preva- disease). On the contrary, people with 6%) answer “no” (Fig. 2-B). In addition, lence of certain hereditary and infectious hearing loss or having a deaf child / deaf heterozygous carriers of the mutation diseases”, Programs of Bioresource col- relatives (faced with this problem) are c.-23+1G>A are uncertain in answering lections of the FASO Russia “Genome more likely to deny the hereditary nature the question about the probability of pro- of Yakutia” (BRK: 0556-2017-0003) and of hearing loss (78-84%) [8]. ducing a deaf child in themselves (Fig. Russian Foundation of Basic Research It is interesting that most of the young 3-B). Such an answer can be explained (#17-29-06016-ofi_m, #18-54-16004_ respondents interviewed believe that by the presence of close or distant deaf NCNIL_a, #18-015-00212_А, #18-013- hearing parents may have a deaf child / hard-of-hearing relatives, and thus car- 00738_А, #18-05-60035_Arctica). (81.33%) (Fig. 2), but only 2.49% (Fig. 3) riers of the mutation c.-23+1G>A in the of the respondents agree with this risk. gene GJB2 assume these risks in them- References Such a response can also be explained selves. Perhaps, statistical results can be 1. Barashkov N.A., Dzhemileva by the protective internals of the psyche, achieved by increasing the sample, and L.U., Posukh O.L., Solov’yev A.V., Bady- when a person assumes the existence of then this trend can be statistically con- Hoo M.S., Pshennikova V.G., Terjutin the same risk of the birth of a deaf child firmed. F.M., Lobov S.L., Neustroyeva A.B., Kur- in all people, but denies such a possibility Сonclusion. Most young people think tanov H.A., Vasil’yeva L.M., Fedotova Je. in himself. that a deaf child may be born to hear- E., Rafailov A.M., Solov’yeva N.A., Ko- Analysis of the data from the questioning parents (81.33%), but only 2.49% nonova S.K., Alekseyev A.N., Fedorova naire with GJB2 genotypes shows that of respondents agree with this risk. In S.A., Khusnutdinova Je.K. Analiz anke- heterozygous carriers of the mutation tirovaniya roditeley detey-invalidov po 4’ 2018 65

slukhu v Yakutii, Tyve i Bashkortostane: nal.pone.0100848 a Large Cohort of Patients with Hearing mneniye slyshashchikh roditeley o prichi- 5. Effect of Pre-test Genetic Coun- Impairment Living in a Subarctic Region nakh poteri slukha u rebonka s posleduy- seling for Deaf Adults on Knowledge of of Russia (the Sakha Republic) / N.A. ushchim sravneniyem s rezul’tatami Genetic Testing / Baldwin E.E [et al.] // Barashkov, [et al.] // PLoS One. - 2016. DNK-testirovaniya gena GJB2 (Sh26) J Genet Counsel. - 2012. - Vol. 21, №2. - Vol. 11(5):e0156300. DOI: 10.1371/jour- [Analysis of the survey of parents of hear- - P.256-272. DOI: 10.1007/s10897-011- nal.pone.0156300 ing-impaired children in Yakutia, Tuva 9398-1 and Bashkortostan: the opinion of hear- 6. Middleton A. Prenatal diagnosis The authors ing parents about the causes of hearing for inherited deafness: what is the poten- M.K. Ammosov North-Eastern Fed- loss in the child, followed by a compari- tial demand? / A Middleton, J Hewison, eral University: son with the results of DNA testing of the R. Mueller // J Genet Couns 2001; 10: 1. CHERDONOVA Alexandra gene GJB2 (Cx 26)] Meditsinskaya gene- 121–131. https://www.ncbi.nlm.nih.gov/ Matveyevna - student, cherdonovasa- tika [Medical genetics]. Moscow, 2014, pubmed/11767801 [email protected], SOLOVYEV Aisen V.13, №1, p.8-17 https://www.medgen- 7. Mitchel R.E. When parents are Vasilievich - junior researcher, nelloann@ journal.ru/jour/issue/viewIssue/13/13 deaf versus hard of hearing: patterns mail.ru, 2. Barashkov N.A., Teryutin F.M., of sign use and school placement of 2. RAFAILOV Adum Mikhaylovich Pshennikova V.G., Solov’yev A.V., Fe- deaf and hard-of-hearing children / R.E. - Ph.D, assistant professor, archinay@ dorova S.A. Molekulyarno-geneticheski- Mitchel, M.A. Karchmer. // J Deaf Stud mail.ru, ROMANOV Georgii Prokopievich ye metody izucheniya nasledstvennykh Deaf Educ. - 2004; 9(2):133–152. DOI: - engineer, [email protected], bolezney na primere autosomno-ret- 10.1093/deafed/enh017 3. FEDOROVA Sardana sessivnoy glukhoty 1 A tipa [Molecular 8. Opinions of hearing parents Arkad’evna - Ph.D, head lab, genetic methods for studying hereditary about the causes of hearing impairment [email protected]/ diseases on the example of autosomal of their children with biallelic GJB2 muta- Yakut Science Center of Complex recessive deafness type 1 A] Izdatel’skiy tions / Solovyev A.V. [et al.] // Journal of Medical Problems: dom SVFU [SVFU Publishing house]. Ya- Community Genetics. 2017. Jul;8(3):167- 4. PSHENNIKOVA Vera kutsk, 2017. 171. DOI: 10.1007/s12687-017-0299-3 Gennadiyevna - Ph.D, head. lab., 3. Autosomal recessive deaf- 9. A Prospective, Longitudinal [email protected], BARASHKOV ness 1A (DFNB1A) in Yakut population Study of the Impact of GJB2/GJB6 Ge- Nikolay Alekseevich - Ph.D, head. lab., isolate in Eastern Siberia: extensive ac- netic Testing on the Beliefs and Attitudes [email protected], cumulation of the splice site mutation of Parents of Deaf and Hard-of-Hearing 5. KONONOVA Sardana IVS1+1G>A in GJB2 gene as a result of Infants / C.G. Palmer, A. Martinez, M. Fox Kononovna - Ph.D, senior researcher, founder effect / N.A. Barashkov [et al.] // [et al.] // Am J Med Genet A. - 2009 - Vol. [email protected]. Journal of Human Genetics. – 2011. – 149A, №6. - P.1169-1182 DOI: 10.1002/ 6. TERYUTIN FEDOR M. - Ph.D., V.56. – N-8. – P. 631-639. DOI: 10.1038/ ajmg.a.32853 Researcher, Yakut Scientific Center jhg.2011.72 10. Schein JD. The deaf population of Сomplex Мedical Рroblems, 4, 4. Associated with GJB2 Single of the United States / J.D. Schein, M.T. Sergelyakhskoe shosse, Yakutsk, Sakha Mutation IVS1+1G>A in the Yakut Pop- Delk // National Association of the deaf: Republic, 677010, Russian Federation. ulation Isolate in Eastern Siberia / N.A. 1–336 https://eric.ed.gov/?id=ED101517 Phone: +7 (4112) 32-19-81, e-mail: Barashkov [et al.] / PLoS One. - 2014. - 11. Spectrum and Frequency of [email protected]. Vol. 9(6). - e100848 DOI: 10.1371/jour- the GJB2 Gene Pathogenic Variants in ORGANIZATION OF HEALTH, MEDICAL SCIENCE AND EDUCATION

S.S. Sleptsova, N.M. Gogolev, O.M. Zamorshchikova ANALYSIS OF THE INFECTIOUS SERVICE DOI 10.25789/YMJ.2018.64.19 IN THE REPUBLIC OF SAKHA (YAKUTIA)

ABSTRACT The main results of the infectious service were analyzed for the study of its state in the Republic of Sakha (Yakutia) during 2000-2017. Also there were given comparative characteristics with analogical indicators in the Russian Federation. According to results of 2017, the growth of morbidity in 12 infections was recorded in the Republic. Due to persisting unfavorable situation, the problem of realization of medical service to infectious patients demands to take system arrangements on deficit reduction of infectious diseases’ specialists and infectious beds in hospitals; to increase financing of current medical care in the Republic of Sakha (Yakutia). Keywords: infectious service, morbidity, infectious diseases, personnel, the death rate from infectious diseases.

Introduction ing; tuberculosis indicators have a steady in the Russian Federation by 45%, in the The epidemiological situation is inten- downward trend. However, comparing Far Eastern Federal District by 50%. Last sive in the Republic of Sakha (Yakutia). with the average of Russian indicators, two years expansion of the incidence of The spread of the human immunodefi- they continue to keep a sufficiently high whooping cough and enterovirus infec- ciency virus among the population and level. The incidence of acute respiratory tion is noted in the Republic, which is an increase in the cumulative number viral infections in the Republic of Sakha connected with contiguous cyclical rise in of infected and sick people are continu- (Yakutia) is higher than the incidence rate the incidence rate. In 2017, the incidence 66 YAKUT MEDICAL JOURNAL

rate of acute viral hepatitis in the country pound in the Republic, statistic data of chronic virus hepatitis C in 1.5 times, is 18.5% higher than last year, which is basic indicators of diseases in Russia; careering of chronic virus hepatitis B on caused by an increase in the incidence also, materials of case studies of infec- 32,7%, whooping cough in 2.9 times, of viral hepatitis A 3.9 times, while a de- tious service issues. There was used varicella on 11,7% [3]. crease in the incidence of hepatitis B vi- graphical method of comparative analy- Total death rate from infectious dis- rus by 2.5 times, hepatitis C in 2,1 times. sis and Software of MS Excel to show eases in the Republic of Sakha (Yaku- The epidemiological and epizootic situa- line chart of data. tia) has grown in 1.15 times from 2000 tion of natural focal and zooanthroponotic Results and discussion. In agree- to 2017 and consisted 13.2 cases per infections continues to be also complex ment with official facts, dynamics of im- 10000 population. The Figure 2 presents and intensive. According to retrospective provement of demographic and health comparative diagram of death rate from epizootic-epidemiological analysis, 14 indicators of population from 2005 to infectious diseases in the Russian Fed- nosological forms of infectious diseases 2013 in Russia slowed down for last eration, where the results in the Republic pathogens circulate, including tularemia, three years [5]. For the last 3 years, the is lower in 1.5-2 times comparing with na- leptospirosis, listeriosis, pseudotubercu- tendency of reducing the death rate is ob- tional indicators [4]. losis, iersiniosis and hemorrhagic fever served by demographic of the Republic Now, constitutional and primordial with kidney syndrome [3]. of Sakha (Fig. 1). As reported by Russian incidences of infectious diseases in the The problems, which were arisen in Statistics from 2017, in the Republic the Republic have tendency to constant re- the Health Care System of the Russian main reasons of the death were non-in- duction. Thus in studied period, consti- Federation since the beginning of 90s, fectious diseases: as circulatory system tutional incidence of infectious diseases are insufficient financing by Government illness – 44, 4%, neoplasia – 16, 8%, in- decreased on 37,1%, from 4274,3 to and shortage of medical stuff. Thereby, ner causes – 16, 1%, that correspond the 2685,2 per 100000 population respec- capacity of infectious service of Russia mortality compound in Russia and Far tively (Figure 3). Here with constitutional substantially decreased during the pre- Eastern Federal District. Specific gravity incidence of population in the Republic vious period. Provision index of infec- of the main reasons of the population’s increased on 25,8% by the main classes tious beds in hospitals has reduced to death is 77, 3%. 127 people have died by of diseases from 2000 to 2016; 7735,0 to 52% from 1990 to 2014; provision indi- infectious and parasitic diseases, which 10438,4 per 10000 population [4]. cator of infectious diseases’ specialists is more than 1% of the whole number of Organization of infectious services in decreased by 16% from 2010 to 2015. deceased. In the Republic of Sakha (Ya- the Russian Federation presented by in- According to Russian Statistics, in 2016 kutia), expected life duration grows up to fectious diseases rooms, infectious units the number of specialists, working at the 71, 68 years old on 2017 that is lower in of multi-field hospitals, municipal and state medical organizations, shortened in 1.02 year than national indicators [4]. regional infectious hospitals, some of 2122 people [5]. In the Republic of Sakha Confirming to results of 2017, in the which are the platform for the department (Yakutia) the number of infectious beds Republic the growth of acute intestinal of infectious diseases and scientific re- decreased to 30,8% from 2010 to 2017; infections incidence is checked up ad- search institutes [2]. Adult infectious unit and number of infectious diseases’ spe- justed etiology on 12,8%, including virus of the “Municipal Hospital” for 123 beds cialists keeps 0.6 per 10.000 population intestinal infectious on 22,9%, rotavirus in Yakutsk, and 24 infectious units for without significant dynamics. infections of them on 25,6%, enterovirus 164 beds hosted by municipal and cen- Research aim - to study contempo- infections on 12,2%, acute hepatitis in tral regional hospitals introduce in-patient rary state of the infectious service in the 3.8 times, whooping cough in 2.3 times, infectious service of the Republic. In total Republic of Sakha (Yakutia) based on infectious mononucleosis on 34,3%, 390 infectious beds are in Yakutia. analysis of its main indicators during the ARVI on 5%, bacterial community-ac- As of 2017, 65 specialists work in in- period 2000 to 2017. quired pneumonia on 32,9%, as well as fectious service of the Republic of Sakha Data and methodology of the study. caused by pneumococci in 2.6 times. (Yakutia). They are infectious diseases’ Reporting data of medical organizations Excess of Russian indicators of diseases specialists of republican and administra- and the Ministry of Health of the Repub- in average is registered by infections as tive faculties, members of the department lic of Sakha for 2000-2017 are applied in follows: enterovirus infections in 2 times, of the infectious diseases, phthisiology the analysis, as well as statistic data of salmonellosis on 27,7%, ARVI on 31,2%, and dermathovenerology of the NEFU demographic state and morbidity com- chronic virus hepatitis B in 3.6 times, Institute of Medicine, medical residents

Fig.1. Overall death rate dynamics in the Republic of Sakha (Yakutia) Fig.2. Dynamics of the death rate from infectious diseases in the comparing with the Russian Federation Republic of Sakha (Yakutia) in comparison with Russian Federation 4’ 2018 67

Fig.4. The dynamics of the overall death rate (ODR) and supply of Fig.3. Dynamics of infectious diseases incidence in the Republic of infectious diseases’ doctors and infectious beds in the Republic of Sakha Sakha (Yakutia) (Yakutia) in the period of 2000 to 2017 and graduate students, from which 25 ering of the number of beds in infectious Moscow: GEOTAR-Media, 2015, pp. 17- specialists (47,2%) work in Yakutsk, 29 hospitals on 52% from 1990 to 2014; and 20. URL: http://www.rosmedlib.ru/book/ specialists (52,7%) are in regions. Staff decreasing of infectiologists sufficiency ISBN9785970432655.html composition consists of 46, 4% doctors on 16%from 2010 to 2014. This regres- 3. O sostoyanii sanitarno- with a higher qualifying category, 16, 1% sive analysis shows that redundancies of e`pidemiologicheskogo blagopoluchiya a first level and 7, 1% a second-level infectiologists bring to one more case of naseleniya v Rossijskoj Federacii po qualifications. the death from infectious diseases [1]. Respublike Saxa (Yakutiya) za 2017 god [On the state of sanitary and General categorization of doctors Conclusion.Epidemiological situation epidemiological welfare of the population equals 69, 6%, that is explained by a of infectious diseases in Yakutia that has in the Russian Federation for the large number of young specialists under developed in recent years continues to Republic of Sakha (Yakutia) in 2017] 35 years old (36, 6%) in staff, the num- be unstable in spite of significant achieve- Gosudarstvenny`j doklad Federal`noi ber of retirement specialists is 43, 6 %. ments in the Health Care System. In ad- sluzhbyi po nadzoru v sfere zashhity` prav Among infections disease specialists in dition, the growth of sickness rate from potrebitelej i blagopoluchiya cheloveka the Republic, there are 12 excellent work- 12 infectious nosology is observed in po Respublike Saxa (Yakutiya) [State ers (17,9%) of Public Health of Yakutia, the Republic as in the Russian Federa- report of Federal service on surveillance 9 excellent workers (13,4%) of Public tion. The death rate from infectious dis- for consumer rights protection and human Health of Russia, 3 candidates of Medi- eases increased in 1.15 times from 2010 wellbeing] Yakutsk, 2017, pp 98-191. cal Science (4,5%); 2 habilitated doctors to 2017 and was 13.2 cases per 100000 URL: http://fguz-sakha.ru/gos_doklad (2,9%). On the territory of the Republic population. This is followed by reduction 4. Baza danny`x Rosstat [ Database of 9 regions from 34 do not have infectious of bedspace on 30, 8%. Rosstat] URL: http://www.gks.ru specialists; there are Allaikhovskiy, Aby- In view of the above, organization of 5. Baza danny`x Saxa (Yakutiya) iskiy, Anabarskiy, Eveno-Bytantaiskiy, medical service to infectious diseases stat [Database of Sakha (Yakutia) stat] Momsky, Ust-Mayskiy, Kobyayskiy, Zhi- calls for systemic actions in lowering the URL:http://sakha.gks.ru ganskiy, Namsky regions. deficit of infectious beds and hospitals of There were applied comparison of the Republic with appropriate increase of The authors sufficiency indicators of infections spe- funding in the given medical care. 1. Sleptsova Snezhana cialists and beds in hospitals on the dy- Spiridonovna - MD, Doctor of Medical Sciences, Head of Department of namics of the death rate from infectious References Infectious Diseases, phthisiatrics and diseases. As it is shown on the Figure 4, 1. Yushchuk N.D. Ulumbekova dermatovenerology of Medical Institute the growth of the death rate from infec- G.E. Palevsky S.A. Ginoyan A.B. Ka- the North-Eastern Federal University tious incidence was followed by reduction lashnikov A.V. Akberdieva E.A. Аnaliz named after M.K. Ammosov, 677016, of bedspace on 30,8% during the studied osnovnykh pokazatelej deyatel’nosti Yakutsk, ul. Oyunsky, 27, Russia. Tel. period. infektsionnoj sluzhby Rossijskoj Fed- 8-914-2718770. E-mail:sssleptsova@ Analogical works on the analysis of eratsii [Analysis of the main indicators yandex.ru the indicators of infectious service in of infectious diseases Service of the 2. Gogolev Nikolai Mihailovich - the Russian Federation were made by Russian Federation] Zhurnal Infektsion- candidate of Medical Sciences, Director group of authors under the supervision nye bolezni [Infectious illness journal], of Medical Institute the North-Eastern of Academic of RAS (Russian Academy №3, Moscow: GEOTAR-Media, 2016, Federal University named after M.K. of Sciences) N. D. Yushchuk and prin- pp. 13-22. URL:https://cyberleninka.ru/ Ammosov, 677016, Yakutsk, ul. Oyunsky, cipal of High School Organization and article/n/analiz-osnovnyh-pokazateley- 27, Russia. Tel. 8-924-1687966. E-mail: Management of Health Care Service G. deyatelnosti-infektsionnoy-sluzhby- [email protected] E. Ulumbekova, where the similar results rossiyskoy-federatsii 3. Zamorshchikova Olga were taken. According to their analysis, 2. Yuschuk N.D. Vengerov Y.Ya. Mihailovna - resident of Medical Institute unsatisfactory indicators of the death rate Infekcionny`e bolezni: nacional`noe the North-Eastern Federal University from some of infectious and parasitic dis- rukovodstvo [Infectious diseases: named after M.K. Ammosov, 677016, eases connect with steady reduction of national leadership] Seriya Nacional`ny`e Yakutsk, ul. Oyunsky, 27, Russia, 8-924- infectious service capacity; namely low- rukovodstva [National guidelines] 866-41-95. E-mail: [email protected]. 68 YAKUT MEDICAL JOURNAL

M. Yu. Rykov MEDICAL CARE FOR CHILDREN WITH CANCER IN THE FAR EASTERN DOI 10.25789/YMJ.2018.64.20 FEDERAL DISTRICT

ABSTRACT Background. The analysis of the quality of medical care for children with cancer is based on statistical data. Evaluation of the results is also the basis of the strategy for the development of medical care for this category of patients. Aim. Analysis of the main indicators characterizing medical care for children with cancer in the Far Eastern Federal District. Methods. The operative reports for 2017 of the executive authorities in the sphere of health protection of 7/9 (77,8%) subjects of the Russian Federation that are part of the Far Eastern federal districts have been analyzed (The Ministry of Health of the Republic of Sakha (Yakutia) and the Khabarovsk Territory did not provide the data). Results. The number of children was 790855 (0-17 years), the number of children’s oncological beds was 60 (0.7 for 10 thousand 0-17 years), the average number of days of berth employment in the year was 283.7 days. In 4 (57.1%) subjects of the department of pediatric oncology are absent, in 2 (28,6%) - there are no children’s oncological beds. The number of doctors providing medical care to children with cancer is 13, of them 7 (0.8%, 0.08 for 10 thousand 0 - 17 years) have a certificate of a doctor-pediatric oncologist. In 5 (71.4%) subjects there are no doctors-children oncologists. The incidence of malignant tumors was 15 (per 100,000 0-17 years), the prevalence was 90.1 (per 100,000 0-17 years), the mortality rate was 2.9 (per 100,000 0-17 years), the one-year mortality rate - 7.6%. 5% of patients were actively detected. 52 (43.7%) of primary patients were sent to medical organizations of federal subordination, 8 (6.7%) of primary patients left the territory of the Russian Federation. Conclusion. Low morbidity and mortality are attributable to defects in the account and the lack of reliable follow-up data. It is advisable to introduce electronic accounting systems. For reliable estimation of the level of provision of the population with children’s cancer beds and the percentage of patients sent for treatment in medical organizations of federal subordination, audit of patients’ illnesses is necessary. Deficiency of children’s oncologists and a low percentage of patients identified shouldbe eliminated by reforming the training of medical personnel. Keywords: pediatric oncology, malignant tumors, morbidity, mortality, one-year mortality.

Introduction. The analysis of the ern Federal District are analyzed: the Ka- logical beds and doctors-children’s on- quality of medical care for children with mchatka and Primorsky Territories, the cologists by 10 thousand 0 - 17 years, the cancer is based on statistical data. Eval- Amur, Magadan and Sakhalin Regions, percentage of patients hospitalized in chil- uation of the results is the basis for the the Jewish Autonomous Region, the dren’s oncology departments and aimed development strategy of medical care for Chukotka Autonomous Okrug (Ministry of at treatment in federal medical organiza- this category of patients. It is also impor- Health of the Republic of Sakha (Yaku- tions. The morbidity, mortality, and one- tant to coordinate the activities of regional tia)) and the Khabarovsk Territory did not year mortality rates were also calculated and federal authorities aimed at increas- provide reports). The reports contained by the author to monitor the reliability of ing continuity in the provision of various the following information: the size of the the information contained in the reports. stages of medical care, since pediatric child population (0 - 17 years); number of As the object of the study, aggregated oncology is a centralized area, but at the primary patients; morbidity (by 100 thou- data served: morbidity; mortality; one- same time, the routing of patients must sand 0 - 17 years); the total number of year mortality; active detectability; num- be dispersed throughout the country, that children with oncological diseases on the ber of doctors of children’s oncologists is, high-tech stages of treatment are con- register; the number of patients identified and children’s oncological beds; average ducted in medical organizations of the actively; number of deceased patients, number of days of berth employment per third B level, routine - under the condi- of them among those identified in 2017; year; the percentage of patients sent for tions of the second - the third A levels [4]. one-year mortality (%); mortality (per 100 treatment in medical organizations of fed- For this reason, a particularly important thousand 0 - 17 years); presence in the eral subordination and left for treatment assessment of the level of medical care subject of the Department of Pediatric outside the territory of the Russian Fed- in the subjects and federal districts of the Oncology; number of children’s onco- eration. Russian Federation. logical beds; number of days of berth Methods of statistical data analysis. The purpose of the study - an analy- employment per year; number of doctors The sample size, which was not calculat- sis of the main indicators characterizing providing medical care to children with ed in advance, according to the submit- medical care for children with cancer in cancer, including the number of doctors ted reports, is as complete as possible. the Far East Federal District. who have certificates of pediatric oncolo- However, it is impossible to establish this Materials and methods. From gists; the number of patients referred fact precisely, since the study included all 01.01.2017 to 31.12.2017, an environ- for treatment in medical organizations children with morphologically confirmed mental study was conducted in which the of federal subordination; the number of malignancies and reported in statistical units of analysis were aggregated data, patients who left for treatment outside reports. Considering the low incidence rather than individual individuals [5]. the territory of the Russian Federation. in the analyzed subjects, it is reasonable The operative reports of executive au- Based on the obtained data, the author to assume that some patients were not thorities in the sphere of health protection calculated the prevalence of malignant included in the reports. This fact, as well of 7 constituent entities of the Russian neoplasms (by 100 thousand 0 - 17 as the absence of patients’ catamnesis, Federation that are part of the Far East- years), the number of children’s onco- do not allow to guarantee the reliability 4’ 2018 69

of data on morbidity, mortality and doctors-children’s oncologists is one-year mortality. the same - 0.1 per 10 thousand The statistical processing of the children’s population 0-17 years. material was carried out on a per- The number of primary patients sonal computer using the program with malignant tumors was 119, n/d n/d 0/0 1/0 0/0 1/0

1/n/d STATISTICA v. 7.0 (StatSoft Inc., on dispensary registration (who

4/2/50 (0.1) USA). For the value of statistical had reached remission and con- 6/5/83.3 (0.1)

13/7/60.8 (0.08) significance, the value p <0.05 tinuing treatment) - 712. Thus, the Number of doctors

children with cancer / of was assumed. An estimate of the incidence rate in the Far Eastern them have a certificate of providing medical care for pediatric oncologist /% (**) reliability of the relative frequency Federal District in 2017 was 15, difference was carried out by the the prevalence was 90.1 100 thou- Student’s test. sand children (0 - 17 years). Results. The main indicators The highest incidence was

n/d n/d 0/0 0/0 characterizing medical care for registered in the Chukotka Au- year children with cancer in the sub- tonomous District (53.8 per Number of 0/5 (0.8)/285 1/25 (0.7)/20 0/8 (0.8)/440 departments / 0/10 (7.6)/ n/d

0/12 (0.7)/389.8 1/60 (0.7)/283.7 jects that make up the Far Eastern 100,000 0-17 years), the lowest pediatric oncology bed occupancy per / number of days number of children's

oncological beds (**) Federal District are presented in in the Magadan Region (3.3 per Table. 100,000 0-17 years), the high- The number of children’s popu- est prevalence in the Sakhalin 0 0 0 n/d n/d n/d (%) The 6 (5) 2 (25)

1 (4.3) lation was 790855 people (0 - 17 Oblast (120.6 for 100 thousand patients actively 4 (57.1) identified number of years). The maximum number of 0 - 17 years) the lowest - in the children was recorded in the Pri- Amur region (82.6 per 100 thou-

3 0 morsky Territory (363902 people), sand 0 - 17 years) (Fig. 22, 23). 3.3 2.8 2.9 2.7 2.9 n/d n/d n/d the minimum in the Chukotka Au- The number of deceased patients Mortality* tonomous Okrug (13245 people). in the FEFD was 23, of them among There was 1 children’s oncol- the identified in 2017 - 9. Thus,

0 ogy department (Primorsky Krai). the death rate was 2.9 per 100 25 4.3 7.4 8.7 7.6 n/d n/d n/d 16.7 In 4 (57.1%) subjects of the de- thousand 0 - 17 years, a one-year One-year mortality.% partment of pediatric oncology are mortality rate of 7.6%. The highest Indicator absent: medical care for children mortality was registered in the Pri- with cancer falls on beds allocated morsky Territory (3.3 per 100,000 0 n/d 2/2 n/d 5/2 n/d 3/2 1/1 12/2 23/9 2017 in other departments of multidisci- 0-17 years), the lowest in the Jew- of dead Number patients / out of those identified in plinary children’s clinical hospitals. ish Autonomous Region (2.7 per The number of children’s on- 100,000 0-17 years) (Figure 22). cological beds was 60 (0.7 per The largest one-year mortality was 10 thousand 0 - 17 years). In 2 recorded in the Kamchatka Ter- (28.6%) subjects (Magadan Oblast ritory (25%), in the Chukotka Au- n/d n/d 0/0 (%) and the Jewish Autonomous Re- tonomous District it was 0%. 1 (100)/0 6 (85.7)/0 gion) there are no children’s onco- The number of patients detect- 4 (50)/1 (12.5) 23 (100)/3 (13) 11 (40.7)/1 (3.7) 11 17 (36.2)/3 (6.4) 52 (43.7)/8 (6.7) logical beds. The smallest number ed actively was 6 (5%). In a num- to federal medical organizations (%) / organizations Number of patients referred for treatment who left for treatment

outside the territory of of beds was noted in Primorsky ber of subjects (Primorsky Krai, the Russian Federation Krai and the Amur Region (0.7 per Amur Oblast, Jewish Autonomous 10,000 0-17 years), the largest in Region), during planned preven- the Chukotka Autonomous District tive examinations of the child pop- n/d n/d 7/11 8/59 1/15 6/33

47/324 27/147 23/123 (7.6 per 10,000 0-17 years). ulation of malignant neoplasms, 119/712 children patients / of primary The number of registered total number The average number of days of there was no evidence. The maxi- berth employment in the year was mum percentage of patients identi- 283.7 bed days. The largest num- fied actively was registered in the ber of days of berth employment Chukotka Autonomous District n/d n/d 3.3/50

15/90.1 in the year was noted in the Amur (57.1%). 12.3/90.8 12.9/89.3 15.2/82.6 16.2/89.2 53.8/84.6 22.5/120.6 prevalence* Incidence * / Region (389.8), the smallest - in 52 (43.7%) patients were sent the Primorsky Territory (20). to medical organizations for fed- The main indicators characterizing medical care for children with cancer in the Far East Federal District in 2017 in the Far with cancer children for The main indicators characterizing medical care The number of doctors pro- eral subordination. The highest in- n/d n/d Child

65432 30132 37597 13245 viding medical care to children dex was registered in the Magadan 363902 178297 102250 790855

population with cancer was 13, of which 70 and Sakhalin regions (100%), the (60.8%, 0.08 for 10 thousand 0 lowest in the Primorsky Territory - 17 years) are certified as a pe- (36.2%). diatric oncologist. In 4 (57.1%) For treatment outside the terri- subjects (Magadan and Sakhalin tory of the Russian Federation, 8 regions, the Jewish Autonomous (6.7%) of primary patients left. Region, the Chukotka Autono- Discussion. Operative reports Federation mous Okrug) there are no doctors- 5 (71.4%) of the subjects con- children oncologists and children’s tained 6 errors in the calculation of

Subjects of the Russian oncological beds. The number of some indicators. The Republic of Sakha (Yakutia) Kamchatka region Primorsky region Khabarovsk region Amur region Magadan region Sakhalin region Jewish Autonomous Region Autonomous Chukotka District Total Note: * - per 100 thousand children population aged 0–17 years. ** 10 n/d no data 70 YAKUT MEDICAL JOURNAL

In the reports of the Kamchatka and in the US and Europe, but higher than in ment tactics and patient routing [3, 5]. Primorsky Krais, the Amur Region and the countries with low reliability of statistical Although the reports were signed by Jewish Autonomous Region, the figures data, for example, in the Central Asian the heads (deputy heads) of the execu- for a one-year mortality are not true: 9.1%, Republics (Kyrgyzstan, Uzbekistan, Ta- tive bodies in the sphere of health protec- 1.86%, 3.17%, 100% with true values of jikistan) [1, 7]. tion of the subjects of the Russian Fed- 25%, 4.3%, 7, 4%, 16.7%, respectively. The provision of the population with eration, most of the data were provided Also in the reports of the Jewish Autono- pediatric oncological beds has slightly in- by the main freelance pediatric special- mous Region and the Chukotka Autono- creased (2013 - 0.53, 2017 - 0.7 per 10 ists oncologists, which does not exclude mous Okrug, incidence rates were erro- thousand 0 - 17 years) [3]. the subjective factor, and as a result, mis- neously calculated: 15.9 and 52.9, with The provision of the population by takes in completing the questionnaires true values of 16.2 and 53.8 per 100,000 doctors-pediatric oncologists decreased that were have been identified. population 0-17 years, respectively. from 0.11 to 0.08. It, obviously, is due to From conversations with some compil- Some reports do not contain informa- the fact that in 2017 the number of doc- ers, it was found that some of them did tion in full: The Kamchatka Krai did not tors with certificates of children’s oncolo- not know how to calculate the levels of provide data on the number of doctors gists was indicated in the reports [2]. morbidity, mortality and one-year mortal- who have a certificate of a pediatric on- The percentage of patients sent for ity, while others cited a lack of time for the cologist, Magadan Oblast did not provide treatment in medical organizations of correct filling in questionnaires. Another data on the number of deaths, one-year federal subordination decreased from reason for respondents was the lack of mortality, mortality and active detectabil- 75.3 to 43.7%. It is quite difficult to as- reliable statistics (the number of primary ity, the Chukotka Autonomous District did sess this indicator, since pediatric oncol- patients, the total number of children reg- not provide data on average number of ogy is a centralized field of medicine and istered, etc.). days of employment of a berth in a year. patients should receive many stages of Conclusion. The incidence rates in The time characteristics in the reports treatment on the basis of federal medical the RF subjects of the FEFD are sig- (the average time taken to establish the organizations. For this reason, the actual nificantly lower than those in Europe diagnosis, the average time elapsed from value seems to be quite low. Although and the United States, but higher than the moment of verification of the diagnosis this is only a subjective assessment and in countries with low statistical reliabil- to the start of treatment, and the average it requires an audit of patients’ illness his- ity. This indicates the remaining defects time spent on diagnosing patients who tories [2]. of detectability. But there is a positive died of malignant neoplasms of patients) It is not possible to compare preva- trend. The mortality rate is at an accept- are untrue, since it is highly doubtful that lence, mortality, one-year mortality, ac- able level, which may be due to the lack the average The quantities calculated, as tive detectability, the average number of of reliable follow-up data. The percent- is known, by adding the numbers and di- days of occupancy of a child cancer cage age of patients identified actively, it is viding the obtained number by the num- in a year, and the percentage of patients necessary to increase, including by the ber of terms, can be integers, whereas in leaving for treatment outside the Russian wide introduction in the clinical practice most of the reports comrade values are Federation, since in 2013 the reports did of the algorithm for referring the patient to 7, 1 and 7, respectively. It is obvious that not contain this information. a consultation with a pediatric oncologist. in some cases the morphological verifica- The average number of days of berth For a reliable assessment of the level of tion of the diagnosis takes up to 14 days. employment per year is at an extremely provision of the population with children’s In the Far East Federal District, the “lead- low level-283.7 bed days, respectively. cancer beds, audit of patient records is er” in terms of the incidence rate in 2013 In some subjects, this indicator is necessary. - the Sakhalin region - has maintained a at an extremely low level. For exam- Conflict of interest. The author of the high incidence rate (18.5 and 22.5 per ple, in the Primorsky Territory - 20 bed article confirmed the absence of a conflict 100,000 0-17 years, respectively), but is days, in the Kamchatka Territory - 285 of interests, which must be reported. in second place behind Chukotka Auton- bed days. This indicates that in these omous District (53.8 per 100 thousand 0 subjects there is an excess of pediat- References - 17 years), the incidence of which is the ric oncological beds that are not filled. 1. Aksel E.M. Zlokachestven- highest among all subjects of the Rus- In some subjects, this indicator is at an nye novoobrazovaniya u detej: statistika sian Federation. At the same time, the extremely high level and exceeds 365 zabolevaemosti i smertnosti detej v Ros- largest number of children’s oncological hospital days. For example, the Amur re- sii i stranah byvshego SSSR v 2015 g. beds in the Chukotka Autonomous Okrug gion - 398.8 bed days, the Sakhalin re- [Malignant tumors in children: statistics of is 7.6 per 10,000 0-17 years, but not a gion - 440 days. Obviously, in these sub- morbidity and mortality of children in Rus- single pediatric oncologist. jects, several patients are hospitalized for sia and the countries of the former USSR Morbidity in the Jewish Autonomous children’s oncological beds at the same in 2015] Evrazijskij onkologicheskij zhur- Region, which in 2013 was minimal in time, which indicates the inadequacy of nal [Eurasian journal of Oncology], 2017, the Far East Federal District, increased children’s oncological beds in these sub- V.5, No 2, p. 349 – 357. significantly (2013 - 8.1, 2017 - 16.2). In jects. 2. Rykov M.Y., Susulyova N.A., 2017, the lowest incidence in the federal In order to eliminate the identified data Chumakova O.V. [et al.] Onkologiches- district was registered in the Magadan defects and the reasons leading to the kaya zabolevaemost’ detskogo nas- Region - 3.3 per 100 thousand 0 - 17 appearance of such data, it is necessary eleniya Rossijskoj Federacii i ego obe- years [2]. This indicates that the detect- to expand informatization, to introduce an spechennost’ medicinskoj pomoshch’yu ability and accounting for the past 5 electronic database of children with onco- (vrachami, koechnym fondom, diagnos- years in some entities have increased. logical diseases, which will eliminate the ticheskimi i lechebnymi tekhnologiyami): Although the incidence in the analyzed “subjective” factor both in the preparation analiz statisticheskih dannyh za 2013 g. federal district is significantly lower than of reports and during the choice of treat- [Cancer incidence of child population of 4’ 2018 71

the Russian Federation and its provision Russian Federation: analysis of key indi- named after I.M. Sechenov], 2017, 210 p. of medical care (doctors, bedspace, dicators and ways to overcome the statisti- 7. Siegel R., Miller K., Jemal A. agnostic and therapeutic technologies): cal data defects] Onkopediatriya [Onco- Cancer statistics. CA Cancer J Clin., analysis of statistical data for 2013] Vo- pediatrics], 2017, V. 4, No 3, p. 159-176. 2016, No 1, p. 7−30. prosy sovremennoj pediatrii [Current pe- 5. Rykov M.Y., Baibarina E.N., diatrics], 2015, V. 14, No 6, p. 686 – 691. Chumakova O.V. [et al.] Sovershenst- The author: 3. Rykov M.Y., Turabov I.A., Zhe- vovanie organizacionno-metodicheskih Rykov Maxim Yu., PhD, Deputy Di- ludkova O.G. Vnedrenie ehlektronnoj podhodov k okazaniyu medicinskoj po- rector of the Research Institute of DOG bazy dannyh detej s onkologicheskimi moshchi detyam s onkologicheskimi FGBU “NMI of Oncology named after. zabolevaniyami v pilotnyh medicinskih zabolevaniyami [Improvement of the N.N. Blokhin”of the Ministry of Health of organizaciyah: rezul’taty prospektivnogo organizational and methodological ap- Russia, associate professor of the De- kogortnogo issledovaniya [Set-up of the proaches to healthcare delivery for chil- partment of Oncology of the First Moscow electronic database of pediatric cancer dren with cancer] Onkopediatriya [Onco- State Medical University of the Ministry of patients in pilot medical facilities: a pro- pediatrics], 2017, V. 4, No 2, p. 91-104. Health of Russia (Sechenovsky Universi- spective cohort study] Onkopediatriya 6. Epidemiologiya zlokachestven- ty), the chief freelance children’s special- [Oncopediatrics], 2018, V. 5, No 1, p.5- nyh novoobrazovanij u detej: osnovnye ist oncologist of the Ministry of Health of 12. pokazateli v 2011 – 2016 gg [Epidemiol- Russia in the Central Federal District 4. Rykov M.Y., Baibarina E.N., ogy of malignant tumors in children: the Address: 115478, Moscow, Ka- Chumakova O.V., Polyakov V.G. Epide- main indicators in 2011 – 2016] Pod. red. shirskoye sh., 24, e-mail: wordex2006@ miologiya zlokachestvennyh novoobra- Rykova M.Yu., Polyakova V.G. [edited rambler.ru zovanij u detej v Rossijskoj Federacii: by M.Y. Rykov, V.G. Polyakov]. Moscow: ORCID: http://orcid.org/0000-0002- analiz osnovnyh pokazatelej i puti preo- Izdatel’stvo Pervogo MGMU im. I.M. 8398-7001, SPIN-код: 7652-0122 doleniya defektov statisticheskih dannyh Sechenova [The publishing house of the [Сancer epidemiology in children in the First Moscow State Medical University ACTUAL TOPIC

S.S. Sosina, J.V. Vinokurova, E.P. Yakovleva, I.N. Nikolayeva, A.P. Sleptsov THE DETECTABILITY OF HELICOBACTER PYLORI CAGA STRAIN IN ADULTS AND CHILDREN ACCORDING TO THE DATA OF DOI 10.25789/YMJ.2018.64.21 RH№1-NCM

ABSTRACT The Republic of Sakha (Yakutia) belongs to Arctic territories. Hard social and economic conditions cause broad development of helicobacter infection in the republic. A comparative analysis of detectability of Helicobacter pylori CagA strain among adults and children with chronic gastritis since 2012 to 2016 according to Republic hospital №1 - National center of medicine (RH №1-NCM) revealed a distinct decrease in these indexes among adults and children with chronic gastritis. Thus it demands its further identification and treatment for prevention of stomach diseases of oncological risk group. This article presents research data of detectability of Helicobacter pylori among adults and children for 6 years in RH №1- NCM clinical-immunological laboratory by method of enzyme immunoassay on antibodies to antigen Cag A Helicobacter pylori. The blood serum of patients from the National center of medicine was the material for this research. 15868 patients were examined, 6993 of them were revealed Helicobacter pylori Cag A that made 44,1%. The detectability for the research period decreased from 49,6% to 40%. 3827 adults out of 8272 patients were revealed Нр (+) Cag A that made 46,3%, and detectability decreased from 52% to 42% for this period. Among 7596 sick children a decrease in detectability of Нр (+)CagA was from 47,4% to 39,1%. Thus, a comparative analysis of detectability of Нр (+)CagA for the reporting period proved a distinct decrease in indexes among adults and children with chronic gastritis. Serological diagnostic methods for diagnosing the pathology of the upper digestive tract are of great importance for mass medical examinations. They allow diagnosing the disease in the early (asymptomatic) stage. There is a tendency to reduce the rates of Helicobacter pylori infection among patients with chronic gastritis, which requires further identification, treatment and prevention among the population. Keywords: Far North, Republic of Sakha (Yakutia), Helicobacter pylori, Cag A antigen, clinical and immunological laboratory, RB N1-NCM (Yakutsk), screening, diagnosis, immunoassay, antibodies to Cag A Helicobacter pylori antigen, treatment.

Introduction. In most cases, Helico- 90% of cases is the cause of peptic ulcer antral forms of gastritis at young age. bacter pylori infection which is always [1]. According to researchers of the Yakut associated with gastritis is the cause of According to researches, chronic gas- scientific center, Russian Academy of atrophic gastritis. Almost 50% of the pa- tritis among indigenous people of Yaku- Medical Science of the Republic of Sakha tients infected with Helicobacter pylori tia is characterized by the considerable (Yakutia), Helicobacter pylori infection develop atrophic gastritis which in most specific gravity of atrophic gastritis (38,5- among adult population of Yakutia was cases leads to stomach carcinoma and 57,1) with a larger frequency of atrophic 76,1% [2]. In the common structure of the 72 YAKUT MEDICAL JOURNAL

examined children and teenagers Heli- Detectability of Helicobacter pylori among adults and children for the period cobacter pylori infection was 58,5% [3]. from 2012 to 2017 years Atrophic gastritis were at 8,5% of teenag- Year Нр(+)/% Всего детей Нр(+)/% ers and 34% of adults among indigenous Total Total Нр(+)/% Total adults Нр(+)/% children Нр(+)/% people of the North. It was combined with 2012 2996 1487/49.6 1434 747/52 1562 740/47.4 intestinal metaplasia, stomach mucosa 2013 2722 1233/45.3 1317 620/47 1405 613/43.6 dysplasia. Authors emphasize HP infec- 2014 2482 1166/47 1290 647/50.2 1192 519/43.5 tion value in the development of stomach 2015 2555 1041/40.7 1569 680/43.3 986 361/36.6 mucous restructuring. A distinct correla- 2016 2635 1050/40 1376 580/42 1259 470/37.3 tive connection between HP infection and 2017 2478 1016/41 1286 553/43 1192 466/39.1 precancerous state was established: at- Mean % 15868 6993/44.1 8272 3827/46.3 7596 3169/41.7 rophy, dysplasia, intestinal metaplasia GERD, and HP (+) was in 61 cases. tics of chronic gastritis in children of the of stomach mucous at patients with HP According to the detectability of He- Republic of Sakha (Yakutia)] Materialy gastritis. licobacter pylori among adults and chil- nauchno-prakticheskoj konferencii «Pre- According to Kurilovich S.A., Reshet- dren since 2012 to 2017 it turned out that kancerogennye sostojanija organov pish- nikov O.V. atrophy frequency in a stom- 6993 out of 15868 were revealed Helico- hevarenija v uslovijah Krajnego Severa» ach body at the population of Novosibirsk, bacter pylori Cag A that made 44,1%. The [Materials of the scientific-practical con- urban and country people of Yakutia was detectability for the research period de- ference “Pre-carcinogenic states of the respectively 10,1, 16,7 and 25,6%, and creased from 49,6% to 41%. 3827 adults digestive organs in the conditions of the in antral department – 10,7, 25,6 and out of 8272 patients were revealed Нр(+) Far North”]. Bulletin of Novosibirsk State 8,9%. “GastroPanel” was used [4]. The CagA that made 46,3%, and detectability University. Series: Biology, clinical medi- total atrophy was registered in 1% in all decreased from 52% to 43% for this peri- cine, Novosibirsk, 2009, V. 7, № 1, P. 72- groups. Helicobacter pylori infection was od. Among 7596 sick children a decrease 76. revealed at 78 – 88%. in detectability of Нр(+) CagA was from 3. Reshetnikov O.V. Kurilovich S.A. Nowadays the question of differentia- 47,4% to 41,7%. Thus, a comparative Krotov S.A. Krotova V.A. Neinvazivnaja tion of various strains of H.pylori on the analysis of detectability of Нр(+)CagA diagnostika hronicheskogo atrofich- basis of their heterogeneity on virulence for the reporting period proved a distinct eskogo gastrita pri pomoshhi serologich- factors is being studied. decrease in indexes among adults and eskogo issledovanija [Noninvasive diag- Materials and research methods. children with chronic gastritis. nostics of chronic atrophic gastritis with We revealed a helicobacter infection at Conclusion. Serological diagnostic serological testing] Klinicheskaja labora- various diseases of inner organs of pa- methods for diagnosing the pathology of tornaja diagnostika [Clin. lab. Diagnos- tients by noninvasive respiratory method the upper digestive tract are of great im- tics]. Moscow, 2007, №11, P. 39-41. - “Helic-test”. The analysis of 748 proto- portance for mass medical examinations. 4. Kurilovich S.A. Jepidemiologija cols of clinical trial, esophagogastroduo- They allow to diagnose the disease in the zabolevanij organov pishhevarenija v Za- denoscopy and “Helic-test” at adults and early (asymptomatic) stage. padnoj Sibiri [Epidemiology of diseases children in RH №1-NCM (306 adult pa- There is a tendency to reduce the rates of the digestive system in Western Si- tients (137 males and 169 females from of Helicobacter pylori infection among beria] Pod redakciej akademika RAMN 19 to 79 years old) and 442 children (239 patients with chronic gastritis, which re- Ju.P. Nikitina [ed. acad. RAMS Yu.P. Niki- girls and 203 boys, aged from 1 year to quires further identification, treatment tin]. Novosibirsk, 2000, 165 p. 18 years) was carried out. and prevention among the population. We made a comparative analysis The authors of detectability of HP infection indexes References 1. Sosina Svetlana S., Associate among patients with chronic gastritis 1. Loskutova K.S. Morfologicheskie professor NEFU, Institute of Medicine, e- for the last 5 years by Republic hospital aspekty mestnogo immunnogo otveta pri mail: [email protected], Yakutsk, №1 data, Yakutsk. The research on de- Helicobacter pylori – associirovannom Russia; tectability of Helicobacter pylori among gastrite u naselenija Jakutii [Morphologi- 2. Zhanna Vinokurova, RH №1 adults and children since 2012 to 2016 cal aspects of the local immune response – NCM, chief of clinical and diagnostic was done on the basis of Republic hospi- in Helicobacter pylori-associated gastritis laboratory, Yakutsk, Russia; tal №1 clinical-immunological laboratory in the population of Yakutia] Materialy II 3. Ekaterina Yakovleva, RH№1 – by EIA method on antibodies to antigen mezhregional’noj nauchno-prakticheskoj NCM, chief of clinical and immunological CagA Helicobacter pylori. konferencii «Jekologija i zdorov’e na Se- laboratory, Yakutsk, Russia; Results and discussion. Helicobac- vere» Materials of the II Interregional sci- 4. Irina Nikolaeva, RH№1 – NCM, ter pylori was revealed at 74% out of 270 entific and practical conference [“Ecology doctor of clinical and immunological adults patients (males - 72%, females - and Health in the North”]. Yakutsk, 2007, laboratory, Yakutsk, Russia; 76%). 79% of cases were HP (+) among P. 31- 34. 5. Alexander Sleptsov, Associate 164 patients with chronic gastritis. 67% 2. Lehanova S.N. Argunov V.A. Mor- professor NEFU, Institute of Medicine. were HP at 24 patients with peptic ulcer fologicheskaja harakteristika hronich- E-mail: [email protected], Yakutsk, of stomach and duodenum. In 28 cases eskih gastritov u detej respubliki Saha Russia. chronic gastritis was combined with (Jakutija) [Morphological characteris- 4’ 2018 73

G.E. Evdokimov, V.N. Egorova, S.P. Vinokurova MEDICAL AND SOCIAL ASSISTANCE DOI 10.25789/YMJ.2018.64.22 TO HIV-INFECTED PATIENTS

ABSTRACT The purpose of research is to study the quality of medical and social care and the attitude of the population towards HIV-infected people in Yakutsk in the Republic of Sakha (Yakutia). The main methods of research are the analysis of normative and legal acts and statistical data, a sociological questioning. A study of the opinion of HIV-positive people about their satisfaction with the quality of medical and social services, living standards and social status showed that 90% of patients receive the necessary medical care and often attend the AIDS Center. The results of the research showed that the majority of HIV-infected people in Yakutsk, young people aged 19 to 29, contracted sexual intercourse, which in turn indicates that there are still many young people who are poorly informed about the threat HIV infection and other STDs. Survey of HIV-infected and medical workers of the State Bank of the Yakut Republican Center for AIDS Prevention and Control revealed that in our republic a sufficiently effective and qualified medical and social work is carried out, providing crucial help to HIV-infected people, but not enough social assistance is provided. It has been found that the society is generally benevolent towards HIV - infected patients and is ready to provide some form of support to a person living with HIV, regardless of whether they know him or not. However, the responses also showed that HIV-positive status appears as an extremely strong social label, significantly worsening the attitudes of others around it. It was noted the need to open a sanatorium-type rehabilitation center for HIV-infected people. Keywords: HIV - infected, medical and social services, medical aid, psychological help.

Introduction. In the modern world, a of the spread of the disease caused by The purpose of our study is to study serious danger to life and health of peo- the human immunodeficiency virus HIV the quality of medical and social care and ple is represented by diseases denoted infection). «In addition to this law, at the the attitude of the population towards by the term “socially dangerous diseas- present stage, the organization of medi- HIV-infected people in Yakutsk in the es”. In the Russian Federation, diseases cal and social care for people with HIV Republic of Sakha (Yakutia). The main approved by Government Decree No. and AIDS is implemented in accordance methods of research are the analysis of 715 of 1 December 2004 on the approval with the Fundamentals of the Russian normative and legal acts and statistical of the list of socially significant diseases Federation legislation on the protection data, a sociological survey. and a list of diseases that pose a danger of public health and Federal Law No. A study of the opinion of HIV-positive to others are considered socially danger- 38-FZ of 30 March 1995 “On preventing people about their satisfaction with the ous diseases. The resolution lists the fol- the spread of the disease in the Russian quality of medical and social services, liv- lowing diseases: HIV, viral fever, hepatitis Federation, caused by the human immu- ing standards and social status showed B, hepatitis C, sexually transmitted infec- nodeficiency virus (HIV infection) “. that 90% of patients receive the neces- tions, tuberculosis, cholera, and others Thus, medico-social work with HIV- sary medical care and often attend the [1]. In the Republic of Sakha (Yakutia), infected and AIDS patients is based on AIDS Center. Half of the respondents the most dangerous and widespread, dif- the legal framework that determines the believe that they receive social assis- ficult to cure or completely incurable, are social status, rights and duties of this tance, 30% of the subjects found it dif- the diseases of the human immunodefi- contingent. Expansion of the list of nor- ficult to answer this question, 20% of the ciency virus, tuberculosis and hepatitis B mative legal acts and clarification of their patients answered negatively. Patients and C. content is associated with an increase have a fairly complete picture of the con- HIV is a slowly progressing disease in the number of the disease, as well as sequences of AIDS and 80% of them caused by the human immunodeficiency awareness of the need to provide social believe that it is incurable. Half of the virus. The virus affects the cells of the and medical assistance to HIV-infected patients do not hide their positive diag- immune system. As a result, the work of and AIDS patients. nosis of HIV infection from their relatives, the immune system is inhibited, the syn- According to the statistics of 2016, friends and close people, receive moral drome of acquired immune deficiency all HIV cases in the Republic of Sakha support and discuss with them problems (AIDS) develops, the patient’s body loses (Yakutia) are 1752, of which 1332 Rus- related to the disease. the ability to protect itself from infections sian citizens, including 833 men and 489 To the question “What kind of help and tumors, secondary opportunistic dis- women, the remaining 420 patients are would you like to receive from the pub- eases that are not characteristic of peo- migrants from other countries. In the first lic?” many refrained from answering, ple with normal immune status. AIDS, in place in terms of the number of HIV in- some answered: “Understandings” and turn, is the terminal stage of HIV infec- fected is Mirninsky district - 495, then the “Calm attitude towards HIV-positive peo- tion, the period from infection with the city of Yakutsk - 467 and in third place ple”. Naturally, people are different, and human immunodeficiency virus to the de- Neryungri district - 207. The greatest pro- react differently to the fact that their close velopment of AIDS lasts an average of 9 portion of HIV-infected falls on the age of person, relative, friend, friend is suffering to 11 years. 19-29 years-55.1%. It should be noted from HIV and because of insufficient in- The main normative legal act regulat- that analysis of HIV-positive statistics formation about the illness, and possibly ing the provision of medical and social shows that the number of people infected lack of psychological preparedness, they assistance to persons affected by HIV with this virus is growing rapidly in the may get scared and turn away from the in the Russian Federation is the Federal Republic of Sakha (Yakutia) and through- latter. Law of 30 March 1995 on the prevention out the Russian Federation. Nevertheless, 70% of the polled pa- 74 YAKUT MEDICAL JOURNAL

tients noted that they do not feel a sense that HIV-infected people have a greater swer. 96% of the interviewed people of discrimination by the society. sense of rejection and loneliness, which noted that they could provide some form Half of the respondents are satisfied in turn is more likely due to the attitude of of help to HIV-infected people, perhaps with the help provided by the state, the society towards their diagnosis. Employ- such a positive attitude of almost all re- patients additionally suggested that they ees of the AIDS Center, as profession- spondents is due to the fact that there would like to receive assistance in the als in their case on HIV in our country, were no such items as “would not help” form of cash payments. It was also noted believe that people most affected by HIV in the answers. 4% chose the answer the desire of patients to establish a san- are lacking effective social assistance “other” without specifying the reason. atorium-type rehabilitation center for HIV- from the state, as well as subsequent re- 47% of respondents would advise inten- infected people. Perhaps opening such habilitation work. sive treatment, 33% - not to give up and a facility would help many people living According to the medical staff of this fight for life, 15% - to live a normal life with HIV raise their spirits, help them to institution, HIV-positive people badly and not “fixate” on the problem, 2% - turn intensify their internal forces to prolong need psychological help, which is in- to a psychologist and 2% - refrain from their lives. cluded in the complex of the concept advice. All the advice was benevolent, no Based on the results of the study, it of “medical and social assistance”, and one showed a negative attitude, which can be concluded that a larger number equally need social assistance, intensive indicates that there is no discrimination of people suffering from HIV in Yakutsk, treatment and support of the community. against HIV-infected people. namely 80% have sexually transmitted The degree of rendering medical care However, when questions relate to infections, which indicates that there are to HIV-infected people in the Republic of close, contact with HIV-infected indi- still a lot of people who do not adhere to Sakha (Yakutia) “by the AIDS Center staff viduals, the answers become less com- safe sex and lead a lascivious lifestyle. is not very high-an average of 7.1 points prehensible and compassionate. So, to Perhaps this is due to the lack of public out of 10, and medical and social assis- the question “What would you do if you awareness about the threat of HIV infec- tance by 6 points. learned that your child goes to a kinder- tion and irresponsible treatment of their The results of the research also re- garten or to a school where a child with health by individuals. vealed personal qualities of employees, HIV is living?”, Some gave negative an- As the study showed, in general, peo- such as tolerance, compassion and swers until the child was excluded from ple are exposed to HIV at a young age goodwill. Doctors, nurses and a psychol- the institution of an HIV-infected child (10 - from 17 to 25 years. This indicator is ogist of this institution in the process of %). Also, there are answers that are close confirmed by the data of the statistical communicating with their patients gently in meaning to the previous one (5%) - department of the AIDS Center, accord- learn to “live with a diagnosis”, “adhere to they would arrange a scandal. 20% of ing to which 60% of patients are under an optimistic attitude”, “observe a healthy the subjects would transfer their child to 30 years old. lifestyle”, “trust doctors” and “do not give another group or class, 38% would trans- The next stage of our study was a up”. fer to another institution. 9% refrained survey of medical personnel of the State Summarizing the above, it can be con- from responding, and only 17% did not Budgetary Agency of the Republic of cluded that HIV-infected patients could take any action. These results also indi- Sakha (Yakutia) “Yakut Republican Cent- learn to live with this status. Overcom- rectly show that there is a label placed er for AIDS Prevention and Control” to ing the attendant difficulties, as well as on people living with HIV. Respondents’ identify and assess the quality of medical maintaining the old way of life are possi- answers indicate that HIV-positive status and social services for HIV-infected peo- ble with timely psychological support and is an extremely strong social label that ple in the Republic of Sakha (Yakutia). comprehensive rehabilitation work. makes a person “not desirable” a mem- GBU “Yakut Republican Center for One of the tasks of our study was to ber of society, thereby significantly wors- AIDS Prevention and Control” as a mul- study the attitude of Yakutsk residents to ening the attitude towards him. tidisciplinary medical and prophylactic HIV-infected people. A total of 53 women, Conclusion. HIV infection affects all institution conducts, mainly, medical, di- 47 men, were interviewed with different major aspects of the life of an infected agnostic and medico-preventive work, members of the community: 25 school- person. The severity of the patient’s which was confirmed by the conducted children, 25 students, 25 workers and 25 condition is due not only to physical research. pensioners. causes. Feelings, thoughts, experiences In the survey, 5 doctors from the AIDS An analysis of the answers of the sub- of people living with HIV, their changed center clinic, 4 nurses and 1 psycholo- jects found that the majority of respond- social status, relationships with others gist who were directly involved with HIV- ents (66%) feel compassion and pity for are no less important for their future life infected patients participated. HIV-infected people, and also revealed than the presence or absence of clinical An analysis of the responses of the that the society is ready to provide some symptoms of the disease. Adaptation of survey participants showed that the main form of support for a person living with HIV-infected people to the changed con- activity of the AIDS Center is the provi- HIV, regardless of whether they are he ditions of life depends on many factors, sion of medical care (56% of responses) knows them or not. Many subjects (62%) first of all on the timely provided psycho- to infected patients, followed by psycho- noted that they would not turn away from logical support, which is indicated in their logical support (25%) and social (13%). a relative or someone with strong con- answers by patients and AIDS doctors of Legal assistance is not rendered at all, nections if the latter were found to have the Yakutsk Center. which, in principle, does not fall under the HIV-positive status, but would support It is known, although at the moment responsibility of this institution. them. 74% of respondents are ready to this disease is not yet curable, the suc- AIDS Center’s medical professionals, provide moral support and help in the cesses of rapidly developing antiretrovi- as specialists who most often contact fight against the virus, and 19% could ral therapy give hope to these patients. people with HIV-positive status, are sure help financially and only 4% did not an- Currently, the life expectancy of an HIV- 4’ 2018 75

infected person with active participation zhennosti antiretrovirusnoj terapii sredi 2. Egorova Valentina Nikiforovna, of a patient in the treatment process can VICH – inficirovannyh pacientov v RT cand. psychological science, Associate be equal to the life expectancy of an aver- [Individually conditioned factors for the Professor of the Department of Psychology age healthy person. HIV-infected patients formation of adherence to antiretroviral and Social Sciences, Institute of could learn to live with this status [1]. therapy among HIV-infected patients in Psychology, NEFU, contact information: Overcoming the psychological and social Tajikistan] Sbornik materialov konfer- 677013, Yakutsk, Kalandarashvili street difficulties that have arisen, as well as the encii «Aktual’nye voprosy infekcionnoj 21/2, flat6 8241663788, VE373@mail. restoration and preservation of the old patologii» [Collection of materials of the ru; way of life are possible with timely psy- conference “Actual issues of infectious 3. Vinokurova Svetlana Petrovna, chological support and comprehensive pathology”]. Kazan: Otechestvo, 2007. cand. medical science, Associete rehabilitation work. That is why the prob- Professor of the Department of lem of social rehabilitation is relevant. The authors «Propedeptic and Faculty Therapy with 1. Evdokimov Harry Eduardo- Endocrinologists and LFK», Medical References vich, student of the Institute of Psy- Institute, NEFU, contact information: Bikmuhametov D.A. Anohin V.A. chology, contact information: 677016, 677907, Yakutsk, Khatassy village, Severnaya street 4, 89142207804 , Mendelevich V.D. Individual’no-obus- Yakutsk, Kulakovsky street 46/2, room 26 [email protected]. lovlennye faktory formirovaniya priver- 89644299617, [email protected];

E.Yu. Sizykh, N.A. Solovyova, M.A. Varlamova, A.T. Dyakonova, Kh.A. Kurtanov, N.I. Pavlova MOLECULAR GENETIC STUDIES AS AN AUXILIARY METHOD FOR DETERMINING RISK FACTORS IN THE CLINICAL EXAMINATION DOI 10.25789/YMJ.2018.64.23 OF THE ADULT POPULATION

ABSTRACT Indicators of morbidity of adult population according to out-patient office of Hospital of the Yakut Science Center of Complex Medical Problems (Yakutsk) during 2015-2017 are presented in article. The characteristic of dynamics and structure of cases of the general and primary incidence is given. Decrease in level of the general incidence for all analyzed period is established. In structure of the general incidence of adult population the prevalence of diseases of respiratory organs and the blood circulatory system is revealed. The analysis of dynamics of indicators of primary incidence has shown the stable growth of her level with prevalence a case of diseases of respiratory organs. The obtained data on the dynamics and distribution patterns of diseases have served as the basis for selecting the directions of molecular genetic research, the search for associations of genetic markers of the system of cytokines responsible for the development and maintenance in the body of chronic systemic inflammation, the genes B2 - adrenoreceptor and genes of cold receptors involved in the hereditary predisposition to hyperreactivity of the respiratory and the cardiovascular system in response to the effects of low temperatures. Keywords: clinical examination, morbidity general and primary, structure and dynamics of morbidity, genes of cytokines, adrenoreceptor genes, cold receptor genes.

Introduction. Clinical examination documents, a clinical examination is risk of developing diseases long before is a method of systematic medical designed to identify and correct the the first clinical, laboratory and functional observation of the health status of certain main risk factors for the development changes appear, in other words using groups of the healthy population or of diseases, such as elevated blood high-tech diagnostic methods, it is patients with chronic diseases with the pressure, cholesterol and glucose in possible to carry out not only accurate aim of preventing and early detection of the blood, smoking, harmful alcohol molecular diagnostics, but also to diseases, timely treatment and prevention consumption, overweight or obesity [3]. determine a person’s predisposition to a of exacerbations. But, taking into account that even minimal particular disease [2]. Clinical examination is aimed primarily deviations from the norm of laboratory The use of the results of molecular at the early detection of chronic non- or functional indicators, and even more genetic testing can significantly facilitate infectious diseases, which include: so the initial clinical manifestations of the solution of the task of conducting all diseases of the circulatory system and diseases occur when there are already citizens with a history of risk factors for especially ischemic heart disease and established pathological processes in brief preventive counseling, as well as cerebrovascular diseases, malignant the human body, the question arises of for individuals with high and very high neoplasms, diabetes, chronic lung the timeliness of clinical examinations total risk of individual in-depth and group diseases, diseases of the musculoskeletal regarding the prevention of risk factors. (patient’s school) preventive counseling system, gastrointestinal tract and urinary To improve the effectiveness of in the context of dispensarization . Such system. These diseases cause more measures to identify predisposing active prophylactic interventions make than 75% of all mortality in our country. risk factors, modern medicine has it possible to quickly and significantly In addition, according to the regulatory technologies that are able to calculate the reduce the likelihood of the development 76 YAKUT MEDICAL JOURNAL

of dangerous chronic non-infectious Table 1 diseases in each particular person, and in those already suffering from such Population distribution by health groups for 2015 - 2017 diseases significantly reduce the severity of the course of the disease and the Patients from the 3rd group. Period Health group transferred to groups 4 and 5 incidence of complications [3, 4]. (year) 2 group n. The introduction of active medical 1 group n. (%) (%) 3 group n. (%) 4 group n. (%) 5 group n. (%) examinations using the capabilities of 2015 25 (4.5) 7 (1.3) molecular genetic methods will enhance 2016 175 (22.1) 189 (24) 425 (53.9) 19 (4.5) 8 (1.9) the effectiveness of preventive measures 2017 115 (13.2) 123 (14.1) 636 (72.7) 17 (2.7) 21 (3.3) to reduce mortality and disability of the risk factors (smoking, increased weight, characterizes the totality of new, nowhere population, reduce economic losses, by elevated blood cholesterol, etc.); Group previously recorded, and for the first restoring labor potential. 3 - a patient who needs to be examined time in a given calendar year, diseases For an informed choice and correction or treated in a polyclinic; 4 patient group detected per 1,000 people and registered of the directions of molecular genetic who needs inpatient treatment; 5 patient among the population. The analysis of studies to determine biological predictors group needs a high-tech type of medical the dynamics of the indicators of primary of susceptibility, in order to optimize care. morbidity showed a steady growth of its measures for the organization of Indicators of the distribution of the level, with the maximum rates in 2016, preventive measures, an analysis of the attached population are presented which is explained by the increase in the indicators of the clinical examination of in table 1. According to the results of number of the attached population of the the outpatient department of the Hospital clinical, laboratory and instrumental older age group during this period, as well YSC CMP was carried out. examination, the largest number of as the active detection of diseases in the Materials and methods. To assess people were identified in the 3rd group newly attached population. It should be the organization of the dispensarization of health, and amounted to 53.9 - 85% noted that the primary incidence rates of carried out, we used the method of of the total number of those undergoing 2017 with the same size of the attached analyzing the indicators of the clinical medical examination. The analysis of population decreased compared with examination of adults aged 18 to 80 the dynamics of population distribution the previous figures of 2015 -16, which years based on the statistical reports of indicators by groups showed an annual may indicate a systematic and effective the outpatient department of the Hospital increase in the number of population medical examination, as well as the of the Nuclear Physics Center for the assigned to groups 1 or 2 of health, organization of preventive measures period 2015-2017. which indicates the timely prevention and aimed at reducing the incidence of whole. All participants of the clinic were diagnosis of diseases. Analysis of the structure of the examined by a therapist and narrow Table 2 presents the dynamics of primary morbidity for the entire analyzed specialists: a neuropathologist, the level of general morbidity of the period revealed the following features, obstetrician gynecologist, surgeon, attached population. General morbidity first place in frequency is occupied by oculist. is the totality of all the diseases among respiratory diseases, second - diseases Laboratory and functional studies the population, both newly diagnosed of the genitourinary system, third place - were performed: clinical blood analysis, in a given calendar year and registered diseases of the circulatory organs (table urinalysis, biochemical blood analysis in previous years, about which patients 5). The maximum increase in the rates (cholesterol, sugar, total protein, again applied in a given year. Analysis of newly diagnosed diseases of the creatinine, fibrinogen, bilirubin, AST, of the dynamics of indicators of general urogenital system and circulatory system ALT, sodium, potassium), blood test for morbidity showed a certain increase in is in 2016, which may be associated with tumor marker PSA (for men older 51 its level in 2017 compared to the level of an increase in the number of assigned years old); fecal occult blood; cytological 2016, which is explained by the increase population and the active detectability examination of a smear from the cervical in the number of attached population of these diseases. Despite the fact that canal; electrocardiography (ECG); of the older age group in this period. respiratory diseases occupy a leading fluorography (FLG), mammography (for However, the overall incidence rate for place throughout the analyzed period, in women over 39 years old). Statistical the entire analyzed period decreased by general, they tend to decline. data processing was carried out using 1.3 times, which is the result of timely descriptive statistics methods [1]. preventive work aimed at early detection Conclusion. Thus, an analysis Results and discussion. Аccording and treatment of diseases. of the organization of the outpatient to the results of the analysis, for 3 An analysis of the overall morbidity dispensation of the attached population of years, 2348 people were subject to structure according to the data of the the Hospital of the YSC CMP has shown planned medical examination. In 2015, outpatient department showed that that the systematic implementation of dispensaryization was carried out in diseases of the respiratory system and preventive measures helps to reduce the relation to - 657 people, in 2016 - 789 circulatory system are in the lead among incidence rate in general. people, in 2017 - 874 people, thus, for adult diseases, which may be due both the period from 2015 to 2017. 2320 to the high level of this pathology among Table 2 people underwent medical examination, the population and to the diagnostic or 98.8% of the planned volume. The general incidence capabilities and active identification of for the years 2015 - 2017 According to the results of research patients with these diseases. organs and and examinations of medical specialists, systems (table 3). 2015 2016 2017 each patient was determined by the health The analysis of the dynamics of Absolute figure 15 971 10 914 12 060 group: Group 1 - the patient is healthy; the indicators of primary morbidity is Group 2 - the patient is healthy, but has presented in table 4. Primary morbidity Per 1000 population 1651,6 1091,4 1246,9 4’ 2018 77

The obtained data on the dynamics Table 3 and structure of the distribution of The rating of registered diseases for 2015 – 2017, % diseases served as the basis for choosing the directions of molecular genetic 2015 2016 2017 studies, the results of which will be Diseases of the Diseases respiratory organs Diseases respiratory organs used as an additional factor in planning 1 place cardiovascular system (17,6) (19,4) (19,6) personalized prevention and treatment Diseases respiratory organs Diseases of the Diseases of the programs, taking into account the genetic 2 place (14,6) cardiovascular system cardiovascular system characteristics of patients. (15,7) (18,0) Diseases of the urogenital Diseases of the urogenital Diseases of the urogenital Currently, the staff of the laboratory 3 place system (11,3) system (13,4) system (12,9) of population genetics and hereditary pathology of the YSC CMP within the Table 4 framework of the research «Study of the genetic structure and load of the Indicators of primary morbidity for 2015 - 2017 hereditary pathology of populations 2015 2016 2017 of the Republic of Sakha (Yakutia)» Absolute figure 3197 5603 4490 are conducting research on the Per 1000 people 303,6 579,4 464,3 formation of bronchopulmonary and cardiovascular pathologies prevalent in patients according to dispensary data. Table 5 An association of genetic markers of The rating of newly diagnosed diseases for 2015-2017 the cytokine system responsible for the 2015 2016 2017 development and maintenance of chronic Год abs.(%) abs.(%) abs.(%) systemic inflammation, adrenoblocker genes and cold receptor genes involved in 1 place Diseases respiratory organs Diseases respiratory organs Diseases respiratory organs hereditary susceptibility to hyperreactivity 1589 (49,7) 1533 (27,3) 1481 (33) of the respiratory and cardiovascular Diseases of the Diseases of the Diseases of the systems in response to the effects of low 2 place genitourinary system 310 genitourinary system 927 genitourinary system 714 temperatures. (9,7) (16,4) (16) Diseases of the Diseases of the Diseases of the References 3 place cardiovascular system 140 cardiovascular system 197 cardiovascular system 151 1. Naglyadnaya mediczinskaya (4,4) (3,5) (3,4) statistika [Evident medical statistics] Pod. red. Leonov V.P. [edited by V.P. Leonov]. [the Order MZ Russian Federation from population genetics of department of Moscow: Izdatel’skaya gruppa GEOTAR 26.10.2017 № 869n]. Moscow, 2017. molecular genetics of YSC CMP, contacts: media [Publ.group « GEOTAR -media»], https://www.rosminzdrav.ru/ [email protected], 8-924- 171-34- 2015, p. 217. http://www.biometrica. 4. Shchepin O.P. Rol’ 89, 677010, Yakutsk, Sergelyakhskoye tomsk.ru dispancerizacii v snizhenii zabolevaemosti Highway 4, FGBNU “The Yakut science 2. Novikov P.V. DNK–testirovanie: naseleniya [A dispantserization role in center of complex medical problems”; monogenny`e i mul`tifaktorial`ny`e decrease in incidence of the population] 3. Pavlova Nadezhda Ivanovna - bolezni [DNA testing: monogenic Zdorov’e i obshchestvo [Health and сandidate of biology sciences, the leading and multifactorial diseases] Russkij society]. Moscow, 2015, No. 23(6), p. researcher - the head of laboratory of medicinskij zhurnal [Russian medical 3-6. http://www.medlit.ru/journalsview hereditary pathology of department of journal]. Moscow, 2011, No. 12, p. 794. molecular genetics of YSC CMP; https://www.rmj.ru/articles/genetika The authors 4. Kurtanov Khariton Alekseyevich - 3. Ob utverzhdenii poryadka 1. Sizykh Elena Yuryevna - junior candidate of medical sciences, the chief provedeniya dispancerizacii researcher associate of laboratory of researcher – head of department of opredelennyh grupp vzroslogo population genetics of department of molecular genetics of YSC CMP; naseleniya [About the statement of an molecular genetics of YSC CMP; 5. Varlamova Marina Alekseevna order of carrying out a dispantserization 2. Solovyova Natalya Alekseevna - - research associate of laboratory of of certain groups of adult population] candidate of medical sciences, senior hereditary pathology of department of Prikaz MZ RF ot 26.10.2017 g. №869n research associate of laboratory of molecular genetics of YSC CMP. 78 YAKUT MEDICAL JOURNAL

A.G. Egorova, T.E. Burtseva, S.A. Evseeva TOTAL DYNAMICS OF CHILD MORTALITY RATES IN THE REPUBLIC OF SAKHA DOI 10.25789/YMJ.2018.64.24 (YAKUTIA) FOR THE PERIOD 2006-2015

ABSTRACT The article provides a retrospective analysis of child mortality in the Republic of Sakha (Yakutia) for the period 2006-2015. According to the analysis, there is an evolution of child mortality rates, a steady trend towards a decrease in child mortality rates for many groups of diseases, the presence of gender differences in the structure of child mortality, high child mortality rates in the Arctic regions of the Republic of Sakha (Yakutia). Insertion of high-tech methods of medical care, input of pediatric and prenatal centers played a huge role for decreasing child mortality rate. Especially it is up-to-date issue in the conditions of the Arctic region, where children’s destinies are sometimes resolved by long distance and possibility of ambulance aircraft. Sufficiently huge number of child and adolescent mortality in RS (Y), due to external causes, makessocial component of loss. Thus, in the modern stage of development of the Republic of Sakha (Yakutia) the peculiarities of child mortality include, at first, huge demographic significance, at the second-dependence on social life conditions. Because child health is a social category, child mortality rate and structure are integral criterions of population life quality rating and the quality of medical care in the region. Keywords: children, mortality rate, Republic of Sakha (Yakutia), Arctic, injuries and poisoning, external causes. Introduction. Children’s and adoles- Table 1 cents’ health care and its’ preservation is one of the main state problems, solving Child mortality in the Republic of Sakha (Yakutia) for the period 2006-2015 of it provides presence of work force and Rate 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 defensive potential of a country. Conven- Total children’s death 0-17 412 387 361 280 232 206 220 220 217 194 tion on the Rights of the Child, which is years undertaken almost in all countries of the Mid-year child population 0 -17 years 261.6 265.2 259.0 251.6 250.6 252.9 253.7 254.9 256.9 259.6 world, involves realization of wide range Child mortality rate per 1.000 of legislative, administrative and other children 1.5 1.4 1.3 1.1 0.9 0.8 0.8 0.8 0.8 0.7 measures for serving of the interests of children, first of all, of their health care. specific structure within 10 years had The problems of health preservation, de- found out sustained tendency of child Table 2 crease of death rate and children’s dis- mortality’s decrease in all ages group. Gender differences of child mortality ability were declared as priority directions The Table 3 shows the significant chang- in the Republic of Sakha (Yakutia) by the President of the Russian Federa- es in the structure of total child mortality tion [2, 3]. The problem of child mortality since 2006, thus, the ratio of child mortal- Years Boys Girls assumes an up-to-date importance [1]. ity of 0-1 ages had decreased, the mor- 2006 254 (61,65) 158 (38,35) Nowadays, it is evident, that the fact of tality rates of 15-17 ages’ children were 2007 244 (63,05) 143 (36,95) medical care is not the only issue in the stable, and we noted the tendency of in- strategy of national development that is creasing child mortality of 1-4,5-9,10-14 2008 209 (57,89) 152 (42,11) responsible for healthcare, because the ages (Table 3). 2009 160 (57,14) 120 (42,86) main reasons, determining children’s ill- According to the data, in 2006 we 2010 136 (58,62) 96 (41,38) being, refer also to social and economic could find in the structure of 412 total child spheres. mortalities the following disease classes: 2011 132 (64,08) 74 (35,92) The aim of the study was to present perinatal causes are prevailed (154 in- 2012 140 (63,64) 80 (36,36) the evolution of child mortality rates for cidents), then consequences of external the period 2006-2015 in the Republic of causes (137), and on the third place- 2013 148 (67,27) 72 (32,73) Sakha (Yakutia). congenital malformations,deformations 2014 133 (61,29) 84 (38,71) We ana- Materials and methods. and chromosomal abnormalities (56). 2015 116 (59,79) 78 (40,21) lyzed child mortality rate by all disease In 2015 the structure of 194 total structure, according to the data of the official statistics of Yakut Republican Medi- Table 3 cal informative-analytic center for the pe- Age pattern of child mortality in 2006-2015. % riod 2006-2015. Results. Nowadays the decreasing of Year 0-1 year 1-4 years 5-9 years 10-14 years 15-17 years child mortality rate is one of the main is- 2006 53.64 13.83 8.50 9.47 14.56 sues of the demographic development in 2007 55.81 14.73 7.75 7.75 13.95 the Republic of Sakha (Yakutia). For the 2008 57.89 13.57 5.82 5.82 16.90 period 2006-2015 common child mortal- 2009 38.57 13.93 11.79 12.86 22.86 ity rate had decreased. Thus, in 2006 it 2010 34.48 15.95 13.79 12.07 23.71 was 1,5 %, in 2006 and at the beginning 2011 36.89 14.08 8.74 11.17 29.13 of 2015 reached a historic low of 0,7 %. 2012 38.64 22.27 11.82 12.73 14.55 Mortality rates of male children had increased in dynamics: in 2006 - 61%, in 2013 41.82 15.45 11.82 15.00 15.91 2015 -59% (Table 2). 2014 39.17 15.21 9.68 12.44 23.50 Primary analysis of mortality’s age- 2015 39.18 17.53 15.46 13.40 14.43 4’ 2018 79

Table 4 Infant mortality rate dynamics in 2006-2015 per 1000 child population

Total system diseases poisoning Injury and Congenital Neoplasms system and and parasitic Diseases of the malformations Diseases in the Diseases of the Diseases of the Diseases of the Diseases of the Diseases of the external causes forming organs nervous system and subcutaneous perinatal period Dis eases of the musculoskeletal laboratory findings digestive system Consequences of blood and blood- connective tissue Diseases of the skin Certain infectious Symptoms.signs.and circulatory system respiratory system abnormalclinical and genitourinary system Endocrine diseases 2006 1.535 0.030 0.048 … 0.019 0.034 0.019 0.045 0.019 0.574 0.209 0.030 … 0.510 … … … 2007 1.472 0.015 0.027 0.004 0.011 0.065 0.030 0.068 0.004 0.487 0.183 0.095 … 0.475 0.008 … … 2008 1.399 0.015 0.023 … … 0.054 0.008 0.054 0.004 0.496 0.221 0.043 … 0.473 0.004 0.004 … 2009 1.101 0.024 0.020 0.004 0.008 0.063 0.075 0.055 0.008 0.114 0.083 0.122 0.499 0.016 0.004 … 0.008 2010 0.918 0.028 0.028 0.008 … 0.087 0.055 0.055 0.008 0.047 0.044 0.071 0.479 0.004 … … 0.004 2011 0.815 0.012 0.032 0.008 0.004 0.063 0.059 0.040 0.012 0.071 0.059 0.055 0.395 0.004 … … … 2012 0.867 0.016 0.004 0.008 0.004 0.083 0.059 0.051 0.020 0.067 0.075 0.067 0.406 … 0.008 … … 2013 0.863 0.016 0.012 0.008 0.004 0.125 0.078 0.039 0.004 0.094 0.024 0.098 0.345 0.012 0.004 … … 2014 0.844 0.012 0.016 … 0.004 0.078 0.121 0.070 0.008 0.125 0.027 0.047 0.339 … … … … 2015 0.747 0.019 … … … 0.108 0.058 0.062 0.023 0.081 0.019 0.039 0.339 … … … … child mortalities included following dis- Table 5 ease classes: at first -injury and poison- Infant mortality rate dynamics in 2006-2015 per 1000 child population according ing (88 incidents), on the second place- to the regions of RS (Ya) diseases of the nervous system (28), Region 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 then perinatal causes (21). Yakutsk 1.320 1.070 1.179 0.797 0.650 0.571 0.567 0.750 0.781 0.734 The total child mortality rate de- Arctic 2.486 2.114 2.000 1.588 1.754 2.222 1.647 1.607 1.257 1.024 creased in 2015 from 1,535 to 0,747 per Industrial 1.356 1.317 1.115 0.854 0.842 0.581 0.796 0.553 0.806 0.698 1000 children (Table 4). In 2006 the most Agrarian 1.598 1.815 1.639 1.302 1.065 0.943 1.014 1.093 0.742 0.750 significant increase was found in the fol- Mixed zone 1.657 1.472 1.524 1.494 0.817 0.691 0.900 0.709 1.119 0.714 lowing disease classes,such as diseases Total 1.535 1.472 1.399 1.101 0.918 0.815 0.867 0.863 0.844 0.747 in the perinatal period, consequences of external causes and congenital malfor- distance and possibility of ambulance №271. mations.In 2015 we noted the greatest aircraft. Sufficiently huge number of child 3. D. A. Chichachov, V. I. Gordeev, increase for such disease classes,like in- and adolescent mortality in RS (Y), due A. F. Potapov [et al.]. Mladencheskaya jury and poisoning, diseases of the nerv- to external causes, makes social compo- smertnost’ v Respublike Sakha Yakutiya ous system, diseases in the perinatal pe- nent of loss. Thus, in the modern stage [Infant mortality in the Republic of Sakha riod. Thus, there is an evolution of child of development of the Republic of Sakha (Yakutia)] Dal’nevostochnyy meditsinskiy mortality rates, connected with many fac- (Yakutia) the peculiarities of child mor- zhurnal [Far Eastern medical journal]. tors of society development and health- tality include, at first, huge demographic 2009, №1, p.55-57. care system. significance, at the second-dependence 4. Chichahov D. A. Verbitskaya L. I. There is the highest mortality rate in on social life conditions. Because child Detskaya smertnost’ v Respublike Sakha the Arctic region of the Republic of Sakha health is a social category, child mortality Yakutiya [Infant mortality in the Republic (Yakutia) (Table 5). rate and structure are integral criterions of Sakha (Yakutia)] Dal’nevostochnyy Conclusion: According to the analy- of population life quality rating and the meditsinskiy zhurnal [Far Eastern medi- sis of child mortality rates in the RS (Ya) quality of medical care in the region. cal journal]. 2010, №4, p. 42-43. there is an evolution of many groups of 5. Chichachov D. A. Sistemnaya diseases. As a whole, child mortality rate References organizatsiya pediatricheskoy reanimat- has clearly decreased following the com- 1. Baranov A. A. Albitsky V. Yu sionnoy sluzhby Respublike Sakha Yaku- mon pattern [3- 5]. In fact all differences Detskaya smertnost’ (tendentsii,prichiny tiya [Systematic organization of pediatric in the structure of child mortality show i puti snizheniya [Child mortality (trends, intensive care service of the Republic real innovations and daily hard work of causes and ways of reduction)] The IX of Sakha (Yakutia)] Sbornik materialov republican pediatric care. Congress of pediatricians of Russia. respublykanskoy naucno praktiches- Insertion of high-tech methods of Moscow, 2001, p. 256. koy konferencii - Organizatsiya medico medical care, input of pediatric and pre- 2. Medvedev D. A. Poslanyi pre- sotsial’noy pomoshi detyam I podrostkam natal centers played a huge role for de- zidenta RF federal’nomy sobraniyu Respubliki Sakha Yakutiya problemy per- creasing child mortality rate. Especially 2010 [Message of the President of the spektivy razvitiya [The Collection of Re- it is up-to-date issue in the conditions of Russian Federation to the Federal As- publican scientific-practical conference the Arctic region, where children’s des- sembly 2010] Rossiyskaya Gazeta [Rus- materials ‘Organization of medico-social tinies are sometimes resolved by long sian Newspaper].Moscow, 01.12.2010, assistance to children and teenager’] 80 YAKUT MEDICAL JOURNAL

Print servis [Print service]. Yakusk, 2010, ter of Complex Medical Problems, Yakusk, lems, Yakusk, Russia, 8(914)294-32-44, p.187-188. Russia, 8(914)2346411, [email protected]. [email protected] 2. Tatyana E. Burtseva – PhD, MD, 3. Sardana A. Evseeva – junior re- The authors M.K.Ammosov North-Eastern Federal search scientist, Yakut Science Center of 1. Aytalina G. Egorova – Ph.D, University, a laboratory chief of Yakut Sci- Complex Medical Problems, Yakusk, Rus- head of department of Yakut Science Cen- ence Center of Complex Medical Prob- sia, 8(967)911-11-95, [email protected].

E.Z. Zasimova, A.S. Golderova, Z.N. Krivoshapkina, L.D. Olesova, S.D. Efremova, E.D. Okhlopkova, A.I. Sivtseva RISK FACTORS FOR THE DEVELOPMENT OF METABOLIC SYNDROME AMONG EMPLOYEES OF RIVER DOI 10.25789/YMJ.2018.64.25 TRANSPORT OF YAKUTIA

ABSTRACT 221 employees of river transport of Yakutia at the age 20-49 years old were examined simultaneously. Metabolic syndrome (MS) was verified in 7.7% of employees of non-indigenous nationality. One of the most significant risk factor for MS was the age (F = 8.24, p = 0.005), 58.8% of people with MS belong to the age group from 40 to 49 years old. A sign of disadaptation of an organism - metabolic disorder was observed among people with the experience of 10 and more years. The degree of disorder of metabolic processes is mostly noticed among employees of non-indigenous nationality with an experience of residence in Yakutia of 15-20 years. Revealed age, severe arterial hypertension and the degree of dyslipidemia among river transport employees with MS in comparison with the population with MS indicate the acceleration of mechanisms of metabolic disorder in Yakutia. Keywords: metabolic syndrome, river transport, Yakutia.

Introduction. WHO experts described natives of the North, which can manifest it was shown that the former population the metabolic syndrome (MS) as a «pan- themselves in the specific features of mi- died more often than indigenous people demic of 21st century”. Prevalence of MS grants and natives [1]. from diseases of the circulatory system, is 20-40%. It is more common among The specific nature of the operation including acute myocardial infarction and middle-aged and older people (30-40%). of the floating structure of river vessels malignant neoplasms. According to the Cardiovascular morbidity and mortality has stringent requirements for the health results of studies conducted in the Re- among people with MS are significantly of workers in the fleet. The shortcomings public of Sakha (Yakutia), the frequency higher than among those without MS. in the organization of the regimes of la- of metabolic syndrome (MS) is higher in The presence of MS in 3-6 times increas- bor, life, food, habitation on ships, etc., non-indigenous residents than in indig- es the risk of developing both 2 type of have a significant effect on the morbid- enous ones [9]. The intensification of the diabetes and hypertension. MS is associ- ity of crews. The leading factors in this lipid metabolism necessary for adapta- ated with a subclinical lesion of vital or- are the impact of occupational hazards tion to the climatic and geographic con- gans. MS is characterized by an increase - noise, vibration, high humidity, various ditions of the North with insufficient re- of visceral fat, a decrease in the sensi- climatic and geographical and meteoro- plenishment of body reserves, can lead tivity of peripheral tissues to insulin and logical factors. In addition, the employees to pre-pathological changes in the body. hyperinsulinemia, which cause the de- of water transport have high psychoemo- Thus, the study of the characteristics of velopment of violations of carbohydrate, tional load [13]. According to Petrova T.B. metabolic processes of the newcomers lipid, purine metabolism and arterial hy- and co-authors [2] in addition to climatic who are working in the water transport in- pertension [8]. and geographic factors, there are specif- dustry of Yakutia is an urgent task for the As in conditions of the Far North dis- ic occupational and socio-environmental development of therapeutic and preven- comfort factors act continuously, deplet- factors, which influence on the floating tive measures for early detection of risk ing the adaptive reserves of the body, crew of the Northern water basin, which groups. The aim of this study was to esti- the risk of developing metabolic disor- doubles the probability of disturbances mate the features of metabolic syndrome der increases, it leads to the formation in metabolic processes, especially car- among river transport workers of Yakutia, of pathology [4, 6]. The formation of a bohydrate and lipid metabolism, among depending on the medical and social fac- specific “polar metabolic type” [5] among ship specialists. Due to increasing age tors, ethnicity and length of stay. northerners are postulated, which is and work experience, the activity of cho- Material and methods of investiga- characterized by a complex restructuring lesterol esterification decreases, imbal- tion. During the planned medical exami- of the hormonal-metabolic profile, active ance of lipid transport system and carbo- nation, we examined 221 water transport use of lipid energy carriers, a decrease hydrate metabolism is increased, more workers of the Republic of Sakha (Yaku- of carbohydrates as energy substrates noticeable among seamen, river birds tia) at the age of 20 to 49 years (mean and a change in the need for vitamins. and fishermen. According to the com- age 35.03 ± 7.95 years) (men - 184, It is shown that there are significant dif- parative analysis of the main causes of women - 37). There were 25 people of ferences in metabolic processes among mortality in the Republic of Sakha (Ya- the indigenous nationality (Yakut people migrants unadapted to the North and kutia) at the working age of 2005-2011, - 21, indigenous people of the North - 4’ 2018 81

4). The non-indigenous population was tion “Yakut Scientific Center of Complex comfortable apartments (F = 4.65, p = represented by 196 people (Russians, Medical Sciences” and carried out from 0.032). Comparative analysis found that Ukrainian, Tatar and many others), 85 of the consent of the subjects in accord- the mean age (40.41 ± 7.67 years) of them turned out to be born in Yakutia. 111 ance with the ethical norms of the Hel- people with MS (n = 17) was statistically people arrived from other regions of Rus- sinki Declaration (2000). In the process significantly higher (p = 0.005) than of sia and the CIS. Depending on the length of conducting the statistical analysis, test those without MS (34.58 ± 7.82 years) (n of stay in Yakutia, they were distributed for the distribution of the quantitative in- = 204). As it can be seen from the pre- as follows: up to 1 year - 3 people; up to dicators was carried out according to the sented figure 1, the highest frequency of 5 years - 13; from 5 to 10 years - 15; from Kolmogorov-Smirnov test. The data are MS was found in the age group from 40 10 to 15 years - 12; from 15 to 20 years - presented in the form of M ± m, where M to 49 years old and constituted 13.5% (n 17; more than 20 years - 51 people. is the mean value, m is the standard error = 10) of all people of this age group; in To identify the features of the meta- of the mean value. the group of people from 30 to 39 years bolic syndrome among river transport When comparing the quantitative indi- old - 4.82% (n = 4), in the group from 20 workers, a comparative analysis was car- cators of the groups, the significance of to 29 years old - 4.68% (n = 3). It should ried out with selective allocation (Lensky the differences was assessed using the be noted that 58.8% of people with MS District, Republic of Sakha (Yakutia)), Student’s t-test for the normal distribution (10 people out of 17) were in the age consisting of alien men (n = 20). and the Mann-Whitney test for the ab- group from 40 to 49 years old. Blood for biochemical research was normal distribution. To compare the fre- For further analysis of the features of taken from the ulnar vein in the morn- quencies of qualitative characteristics in the formation of MS among river trans- ing on an empty stomach. Laboratory unrelated groups, the χ2 criteria were ap- port workers, we excluded indigenous research was conducted in conditions plied. The results were considered to be residents and women from the general of constant internal and external quality statistically significant with the values of sample (n = 221), MS was detected in control. Activity of aspartate and alanine the achieved significance level p <0.05. 100% of cases among the newcoming aminotransferases (asAT, ALAT), alkaline Results of the study and its dis- population and in 94% of cases in men. phosphatase, gamma-glutamyltrans- cussion. MS was diagnosed among 17 To study the metabolic characteris- ferase (γ-HT), lactate dehydrogenase patients, (16 men and 1 woman), which tics, depending on the length of stay, four (LDH), creatine kinase, glucose levels, was 7.69% of the total sample (n = 221) comparison groups were formed accord- total cholesterol (cholesterol), high- of the examined individuals. It should be ing to the age: group 1 - 11 men with a density lipoprotein cholesterol (HDL-C), noted that among the representatives of residence period from 1 to 5 years old triglycerides were performed by the en- the indigenous nationality, MS was not (mean age 33.63 ± 1.97); group 2 - 12 zymatic method on the automatic bio- identified; all 17 people were representa- men from 5 years to 10 years old (31.83 chemical analyzer CobasMiraPlus by tives of the newcomers. 7 men were born ± 1.91); group 3 - from 10 to 15 years old LaRoche (Switzerland) using Biocon in Yakutia, 8 people had a length of resi- (32.40 ± 2.77) and group 4 - from 15 to reagents (Germany). The levels of low- dence in Yakutia for more than 20 years, 20 years (33.06 ± 1.43). In these com- density lipoprotein cholesterol (LDL-C) 1 person was from 15 to 20 years old parison groups we did not include arrivals and cholesterol of very low density lipo- and 1 person was from 5 to 10 years old. from other regions and people who were proteins (C-VLDL) were calculated by the There was only one 48-year-old woman born in Yakutia (n = 67), because adapta- formula Friedewald et al. [14]. The coeffi- with MS, native of Yakutia, who was of tion mechanisms to the conditions of the cient of atherogenicity was calculated by non-indigenous nationality. Analysis of North will to some extent be formed and the formula proposed by Klimov A.N. [3]: the frequency of MS, depending on the may have significant differences; people Ka = (C-C-HDL) / HDL-C. For hypercho- position and the profession, did not re- who lived in Yakutia for up to 1 year (n = lesterolemia, the level of total cholesterol veal any significant differences. This pa- 3) due to the small sample size; people ≥ 5.0 mmol / L was taken, elevated LDL thology was detected among 4 steering who have lived more than 20 years (n = cholesterol level ≥ 3.0 mmol / L, reduced motorists (8.8% of all 49 steering motor- 43) as the mean age (40.27 ± 1.05 years) level of HDL-C ≤ 1.0 mmol / L among ists); 3 captains (15% out of 20); 3 me- was statistically higher than in other com- men and HDL-C ≤ 1.2 among women. chanics (20% out of 15), 2 administrative parison groups. To hypertriglyceridemia, the level of TG ≥ and management personnel (10.5% out It is known that the main task of the 1.7 mmol / l was referred. The presence of 19), 1 gas electric welder (33.3% out organism in the process of adaptation of the MS among the examined individu- of 3), 1 skipper (33.3% out of 3), 1 cooker to the climatic and geographic condi- als was verified according to the criteria (5.88% out of 17), 1 coast worker (7.7% tions of high latitudes is the mobilization of the Russian Scientific Society of Car- out of 28). diology (2010). Single-factor variance The main sign of the diagnosis of met- analysis showed signifi- abolic syndrome was abdominal obesity, cant dependence of MS in which the waist circumference is more frequency on age (F = than 80 cm among women and more than 8.24, p = 0.005), mar- 94 cm among men. Additional criteria for ried life (F = 7.98, p = our study were: arterial hypertension (BP 0.005), duration of oc- ≥130 / 85 mmHg) and an increase in the cupational hazard (F = level of TG> 1.7 mmol / l. 6.25, p = 0.013), as well The study was approved by the deci- as on housing conditions, sion of the local ethical committee at the i.e. MS is more common Federal State Budget Scientific Institu- among people living in Fig.1. Grouping of people according to their age 82 YAKUT MEDICAL JOURNAL

of resources and the enhancement of Table 1 energy metabolism in general, and the activity of the organism participating in Biochemical parameters of blood in non-indigenous men - river transport workers, depending on the length of stay in Yakutia metabolic reactions can be judged on the functional state of the organism [11]. Group The Impor The comparative analysis of biochemical Index, reference values 1 1-5 y.o. 2 5-10 y.o. 3 10-15 y.o. 4 15-20 y.o. tance of parameters, depending on the length of n=11 n=12 n=10 n=15 Differences stay in Yakutia, showed that the activity of the main enzymes (creatine phospho- Age, y.o. 33.63±1.97 31.83±1.91 32.40±2.77 33.06±1.43 kinase, lactate dehydrogenase and alka- Lactate dehydrogenase, (225- ## 450 U / l) 335.9±15.9 376.5±22.5 366.0±20.7 374.0±11.59 0.006 line phosphatase) is significantly more Creatine phosphokinase, (˂ pronounced among men of the second 190 U / l) 110.8±11.1 150.2±13.91 116.8±13.96 117.7±20.0 0.043* group than among other groups indicat- Alkaline phosphatase, (˂ 258 ing the intensity of biochemical process- U / l) 193.2±15.28 205.6 ±12.08 187.8±17.7 194.20± 13.8 es. Gamma-glutamyltransferase, 23.00±2.42 45.4±8.25 53.6±23.58 45.6±5.23 0.029* Thus, the concentrations of creatine (11 to 50 U / l) 0.002## phosphokinase (p = 0.043), γ-HT (p = 0.05* ALT, (˂ 30 U / l) 11.81±1.12 22.2 ± 4.53 20.8±4.43 24.46±5.6 ## 0.029), and ALT (p = 0.05) among men of 0.044 the 2 group were significantly higher than AsAT, (˂ 40 U/l) 20.36±1.28 28.20±6.43 34.88±8.9 26.53±53 among men of group 1 (Table 1). 0.042* Coefficient de Ritis, (the 1.81±0.13 1.37±0.14 1.87 ± 0.26 1.30±0.14 0.048** There are low values of the enzyme norm is 1.3 - 1.5) 0.019## st level among men of the 1 group in com- Glucose, (3.3 to 5.5 mmol / l) 4.95±0.14 4.64±0.12 5.00±0.16 5.18±0.2 0.082# parison with other groups indicating signs Triglycerides, (0.5-1.7 mmol of an emergency phase of adaptation. In / l) 1.26±0.24 1.10±0.15 1.55±0.25 1.27±0.12 this phase, the molecular processes in the 0.002## cells and membranes of the body do not Cholesterol, (3.6-6.5 mmol / l) 4.27±0.26 4.52±0.14 5.05±0.28 5.27±0.28 0.028 ° change; it is required significantly more 0.036°° time for their thorough restructuring. The HDL-C, (0.78-2.2 mmol / l) 1.13±0.14 1.18±0.12 1.18±0.08 1.34±0.09 increased activity of key enzymes among # men of the 2nd group corresponds to the 0.085 LDL-C, (1.68-4.53 mmol / l) 2.79±0.29 2.82±0.15 3.40±0.27 3.49±0.25 0.087## transition phase of adaptation, for which 0.04° the intensity of metabolic processes is typical for increasing the energy, plastic HS-VLDL, (0.8-1.5 mmol / l) 0.63±0.11 0.50±0.07 0.65±0.11 0.61±0.10 and protective maintenance of the organ- The coefficient of ism. Considering the fact that creatine atherogenicity, (˂ 3) 3.47±0.52 3.22±0.27 3.46±0.47 3.60±0.47 phosphokinase is considered to be an *-between 1 and 2 group; # - between 2 and 3 group; **- between 3 и 4 group; ## - between absolutely stress-dependent enzyme and 1 and 4 group; ° - between 2 and 4 group; °°- between 1 and 3 group an indicator of the realized energy potential due to the synthesis of a unique of 10-15 years in comparison with other transport forms of fat-lipoproteins of all endogenous membrane protector of cre- groups, which provides energy-depen- classes are intensified [12]. Taking into atine phosphate [11], it can be assumed dent amino acid transport to maintain the account the fact that it was revealed con- that non-indigenous men of the 2 group level of total protein. It is known that with tent of enzymes γ-HT, AST, glucose, total with a residence period of 5-10 years ex- the enhancement of adaptive mecha- cholesterol, atherogenic fraction of LDL- perience a strain of metabolic processes nisms, glucose appears in the blood due C and atherogenicity coefficient among in the greatest degree in comparison with to gluconeogenesis, in its turn, its inten- non-indigenous men of the 3rd group other groups. With different intensity of sification is possible only with the optimal with the experience of 10-15 years it can metabolic processes, one can judge the supply of the necessary substrates for be stated about the depletion of adaptive prevalence of catabolic and anabolic this - amino acids [11]. reserves and the development of disad- metabolic pathways by the De Ritis co- It should be noted that in the phase aptation. Violations of carbohydrate and efficient (the ratio of ASAT to ALAT), the of stable adaptation, which is associ- lipid metabolism are most pronounced adaptation range of which varies from 1.2 ated with constant voltage of the control among people the 4th group with a resi- to 1.6, its reference value is 1.5. In our mechanisms, the restructuring of the dence time of 15-20 years (Table 1). study, the de Ritis coefficient was signifi- nerve humoral ratios, the formation of Thus, the data obtained by us show cantly different among compared groups, new functional systems, adaptive pro- that the length of stay in the North is one so in men of the 1st group and of the 3rd cesses can be depleted. Depletion of of the main risk factors for metabolic dis- groups its value exceeded 1.8. In the 1st control mechanisms, on the one hand, orders, i.e. the higher the length of ser- group, this indicator was increased due as well as cellular mechanisms associ- vice, the greater the degree of violations. to a low value of ALAT, i.e. decrease in ated with increased energy costs, leads To assess the characteristics of the anabolic processes, and in 3 groups - to disadaptation [7]. With chronic effects metabolic syndrome among river trans- due to increase of ASAT, i.e. catabolic on the body of sub-extreme and extreme port workers, a comparative analysis was processes. There is an increased content factors, the role of lipids in energy supply made between the data of non-indige- of γ-HT enzymes among non-indigenous of adaptation reactions increases. The nous men: river transport workers (n = men of the 3rd group with an experience fat-mobilizing effect and the formation of 16) and population sampling (n = 20) with 4’ 2018 83

MS. The population sample was chosen criteria for MS. With respect during a comprehensive medical survey to MS and coronary athero- in the expeditionary conditions of resi- sclerosis, the high levels of dents of the village of Vitim in the Lensk LDL-C and, especially TG, District, the Republic of Sakha (Yakutia). reduced levels of HDL-C are The results of the comparative analy- the dominant disturbances sis indicate that the mean age (38.44 ± in the lipid transport system 2.12 years) among river transport work- [9]. Hyperuricemia is one of ers is significantly (p = 0.001) lower than the most important compo- among population sample (53.40 ± 1.32 nents of MS and is involved years), which may indicate the earliest in the pathogenetic mecha- formation of the metabolic syndrome nisms of atherogenesis, among non-indigenous men working activating the processes of Fig.2. Indices of blood pressure among river transport in the water transport industry. In terms lipoperoxidation with the workers and population sampling with metabolic syndrome of anthropometric parameters (height, formation of peroxide-modi- rience of 15-20 years. weight, BMI, waist circumference, hips), fied LDL-C [9]. Oxidative stress and an The average age of the river transport a significant difference was revealed only increase in the oxidative modification of workers with MS (38.44 ± 2.12 years) by height (p = 0.026). The value of height lipids in the wall of the arteries can play was significantly lower (p = 0.001) than among river transport workers (176.68 ± a significant role in the progression of among the population sample with MS 1.26 cm) was higher than among popula- atherosclerosis. It was also found that (53.40 ± 1.32 years), which probably in- tion group (170.35 ± 2.21 cm). uric acid is capable to activate the adhe- dicates early formation of MS among the The indices of arterial pressure among sion and aggregation of platelets. These newcomers working in the branch of the river transport workers were higher than mechanisms demonstrate the active par- river transport of Yakutia. among population group. Thus, the mean ticipation of uric acid in the processes of Comparative analysis of people with diastolic pressure among river transport atherogenesis and confirm the significant MS indicates that arterial hypertension workers was significantly (p = 0.001) role of hyperuricemia in the formation of and degree of dyslipidemia are more pro- higher (94.62 ± 2.09 mm Hg), and sys- a high risk of cardiovascular pathology in nounced among river transport workers tolic blood pressure (142.00 ± 2.62 mm patients with MS. than among population sample, which Hg) tended to an increase (p = 0.085) in Undoubtedly, the length of stay of an may indicate a negative impact of work- comparison to the population sampling alien population in the North is one of ing conditions of river transport workers, (82.00 ± 0.92 and 135.00 ± 2.94 mmHg, the main risk factors for the formation of which provokes acceleration of metabolic respectively) (Fig. 2). metabolic disorders and leading to pre- disturbances in Yakutia. There is a significant increase of tri- pathological conditions. glyceride content (p = 0.001), total choles- Conclusion. MS was verified in 7.7% References terol (p = 0.023), and uric acid (p = 0.001) of river transport workers, indicated data 1. Boyko E.R. Fiziologo-bio- in the serum of river transport workers in refer to non-indigenous residents of Ya- khimicheskiye podkhody k otsenke comparison with the population sample. kutia. One of the significant risk factors funktsional’nogo sostoyaniya cheloveka They also showed a significant reduction for MS was the age (F = 8.24, p = 0.005) na Severe [Physiological and biochemi- in the content of the antiatherogenic frac- of the examined individuals. 58.8% of cal approaches to the assessment of the tion - high-density lipoprotein (HDL-C) (p people with metabolic syndrome were in functional state of a person in the North] = 0.006) and the associated significant the age group from 40 to 49 years old. Problemy adaptatsii cheloveka k eko- increase in the atherogenic index (p = Among non-indigenous people work- logicheskim i sotsial’nym usloviyam Se- 0.003). The average values of LDL-C ing in the river transport of Yakutia, the vera [Problems of human adaptation to and C-VLDL among river transport work- signs of disadaptation of metabolic pro- the environmental and social conditions ers exceed those of the population sam- cesses (dyslipidemia, increase in blood of the North]. Syktyvkar. – SPb.: Politekh- ple although they do not have significant glucose) begin to be observed among nika-servis, 2009, pp.30–34. statistical differences. Thus, the obtained people with experience of residents of 2. Petrova T.B. Bichkayev Ya.I. results of a comparative analysis of bio- 10 years or more. The degree of distur- Bichkayeva F.A. [et al.] Izmeneniye chemical parameters indicate an unfa- bance of metabolic processes is most parametrov uglevodnogo obmena u plav- vorable atherogenic background among pronounced in newcomers with an expe- sostava Severnogo vodnogo basseyna river transport workers in comparison to [Changes in the parameters of carbohy- the population sample (Table 2). Table 2 The obtained data to some extent Biochemical parameters of blood in people with metabolic syndrome confirm the data of Khasnulin V.I. and co-authors (2011) [12] indicating that lipid Biochemical parameters River workers Population sample with р= .... metabolism disorders among alien resi- with MS (n=16) MS (n=20) dents of the North, with the impossibility Uric acid. mmol / l 443.92 ± 17.14 261.58 ± 21.2 0.001 of switching to the northern type of me- Triglycerides. mmol / l 2.67 ± 0.32 1.24 ± 0.18 0.001 tabolism, become one of the important Cholesterol. mmol / l 6.03 ± 0.29 5.24 ± 0.13 0.023 links in the progression of arterial hyper- HDL-C. mmol / L 0.99 ± 0.03 1.24 ± 0.07 0.006 tension in high latitudes. LDL-C. mmol / L 3.69 ± 0.29 3.44 ± 0.23 Dyslipidemia is one of the main and C-VLDL. mmol / l 1.26 ± 0.15 1.24 ± 0.18 most frequently encountered diagnostic Atherogenicity index 5.01 ± 0.42 3.44 ± 0.23 0.003 84 YAKUT MEDICAL JOURNAL

drate metabolism in the navigation per- 81- 101. cholesterol in plasma, without use the sonnel of the Northern aquatic basin] 9. Romanova A.N. Voyevoda M.I. preparative ultracentrifuge // Clinical Ekologiya cheloveka [Human Ecology.]. Gol’derova A.S. Metabolicheskiy sin- chemistry. 1972. V.18. pp. 499–502. Arkhangelsk, 2009, V.8., pp. 12–18. drom i koronarnyy ateroskleroz u zhiteley 3. Klimov A.N. Nikul’cheva N.G. Yakutii [Metabolic syndrome and coro- The authors Lipidy, lipoproteidy i ateroskleroz [Lipids, nary atherosclerosis in Yakutia residents] 1. Zasimova Ekaterina Zakharovna – lipoproteins and atherosclerosis]. SPb.: Byulleten’ SO RAMN [Bulletin of the Rus- Deputy Chief Physician for Clinical Expert Piter Press., 1995, 304 p. sian Academy of Medical Sciences]. No- Work of the Yakut Hospital Federal State 4. Manchuk V.T. Nadtochiy L.A. vosibirsk, 2011, V.5 (31), pp.90–99. Budgetary Health Care Institution «Far Sostoyaniye i tendentsii formirovaniya 10. Romanova A.N. Voyevoda M.I. Eastern District Medical Center» of the zdorov’ya korennogo naseleniya Severa Krivoshapkina Z.N. Assotsiatsiya moche- Federal Medical and Biological Agency» i Sibiri [The state and trends in the forma- voy kisloty s koronarnym aterosklerozom of Russia. tion of health of the indigenous popula- u zhiteley Yakutii [Association of uric acid 2. Golderova Aitalina Semenovna – tion of the North and Siberia] Byulleten’ with coronary atherosclerosis among res- Ph.D. of Medical Sciences, Professor of SO RAMN [Bulletin of the SB RAMS]. idents of Yakutia] Yakutskiy meditsinskiy Federal State Autonomous Educational Institution of Higher Education «North- Novosibirsk, 2010, V.3 (30), pp. 24–32. zhurnal [Yakut Medical Journal]. Yakutsk, Eastern Federal University named after 5. Panin L.Y. Energeticheskiye 2013, V.2 (42), pp. 28-31. M.K. Ammosov» aspekty adaptatsii [ Energy aspects of 11. Roslyy I.M. Abramov S.V. Pok- 3. Krivoshapkina Zoya Nikolaevna adaptation] Leningrad: Meditsina [Medi- rovskiy V.I. Fermentemiya - adaptivnyy – Ph.D. of Biological Sciences, Senior cine], 1978, 192 p. mekhanizm ili marker tsitoliza? [Is fer- Researcher of Federal State Budget 6. Avtsyn A.P. Zhavoronkov A.A. mentemia an adaptive mechanism or a Scientific Institution «Yakut Scientific Marachev A.G. [et al.]. Patologiya che- cytolysis marker?] Vestnik RAMN [Bul- Center of Complex Medical Sciences» loveka na Severe [Human pathology in letin of the Russian Academy of Medical 4. Olesova Liubov Dygynovna – the North]. Moscow: Meditsina [Medi- Sciences.]. Novosibirsk, 2002. V. 8. pp. Ph.D. of Biological Sciences, head of cine], 1985, 461 p. 3–8. the laboratory of Federal State Budget 7. Petrova P.G. Ekologiya, adap- 12. Khasnulin V.I. Gevorshyan Scientific Institution «Yakut Scientific tatsiya i zdorov’ye: Osobennosti sredy M.M. I.A. Bakhtina. Osobennosti lipid- Center of Complex Medical Sciences» obitaniya i struktury naseleniya Re- nogo obmena u prishlykh zhiteley Severa 5. Efremova Svetlana Dmitrievna spubliki Sakha [Ecology, adaptation and bol’nykh arterial’noy gipertenziyey [Fea- – Junior Researcher of Federal State health: Features of the environment and tures of lipid metabolism in newcomers of Budget Scientific Institution «Yakut population structure of the Republic of the North of patients with arterial hyper- Scientific Center of Complex Medical Sakha] pod redaktsiyey N.A. Agadzh- tension] Mir nauki, kul’tury, obrazovaniya Sciences» anyana. Yakutsk: NIPK «Sakhapoli- [World of science, culture, education], 6. Okhlopkova Elena Dmitrievna - grafizdat» edited [ by N.А. Aghajanyan. 2011, V. 4-2, pp. 280-283. Ph.D. of Biological Sciences, head of Yakutsk: NIPK “Sakhapoligraphizdat”], 13. Chinyak V.N. Yegiy V.V. Vliya- the laboratory of Federal State Budget 1996, 272 p. niye faktorov proizvodstvennoy sredy na Scientific Institution «Yakut Scientific 8. Rekomendatsii ekspertov Vse- stomatologicheskuyu zabolevayemost’ u Center of Complex Medical Sciences». rossiyskogo nauchnogo obshchestva plavsostava [The influence of the factors 7. Sivtseva Anna Innokentevna - kardiologov po diagnostike i lecheniyu of the working environment on the den- Doctor of Medicine, Head of the Mobile metabolicheskogo sindroma. Vtoroy tal morbidity among the crew members Expedition Center, Federal State peresmotr. [Recommendations of ex- ] http://tele-conf.ru/zhiznedeyatelnost- Autonomous Educational Institution perts of the All-Russian Scientific Soci- organizma-i-zdorove-chelovka/vliyanie- of Higher Education «North-Eastern ety of Cardiology for the diagnosis and faktorov-proizvodstvennoy (01.07.2009) Federal University in Yakutsk», sannai@ treatment of metabolic syndrome. Sec- 14. Friedewald W. T., Levy R. I., inbox.ru. ond revision] Prakticheskaya meditsina Fredrickson D. S. Estimation of the [Practical medicine]., 2010, V. 5(44), pp. concentration of low-density lipoprotein 4’ 2018 85

ARCTIC MEDICINE A.I. Kodochigova, S.S. Parshina, S.N. Samsonov, P.G. Petrova, A.A. Strekalovskaya, E.S. Olenko, K.O. Belousova, A.R. Magomedova, Z.T. Gadzhieva, T.N. Afanas`eva SPACE WEATHER EFFECTS ON THE FEATURES OF PERSONAL RESPONSE OF VOLUNTEERS DOI 10.25789/YMJ.2018.64.26 IN A MULTIPLE-LATITUDE MONITORING

ABSTRACT The article presents a comparative analysis of psycho-emotional peculiarities of persons from polar, sub-polar and middle latitudes, taking part in multiple-latitude monitoring, in relation to a psychological sensitivity to heliogeomagnetic factors. 64 relatively healthy persons, males and females, have been examined using the following tests: State-Trait Anxiety Inventory (STAI) (Ch. Spielberg, U. Khanin), E. Heim Test, Psycho-Geometric Test. Reactive anxiety and integral index of heliogeomagnetic activity (Kр-index) have been determined by a two-month phase of monitoring, other tests have been checked once in the beginning of a phase. Group I consisted of persons with maximum coincidences in Kр-index peaks and in reactive anxiety. Group II consisted of persons with no coincidences. It is found that the volunteers from the group I and II, as in northern (polar and sub-polar) as in middle latitudes, had a number of similarities depending on a psychological sensitivity to heliogeophysical factors (tending to analyze problems, emotional suppression, agreeableness, purpose). The findings of the study allow organizing patient-specific preventive methods for psycho-somatic diseases and neuroticisms in relatively healthy persons taking into consideration their psychological sensitivity to changes in heliogeomagnetic activity, and the latitude of their place of living. Keywords: heliogeomagnetic activity, anxiety, polar, sub-polar and middle latitudes, stress-overcoming behavior.

Introduction. The given research was the Earth environment – there are no two effect of heliogeomagnetic factors on a controlled by a multiple-latitude monitor- days of a kind. So, as a grey rainy day in psycho-emotional condition of a healthy ing of the study of heliogeophysical fac- November differs from a sunny May day, person actual. tors effects on psycho-emotional and so- as two days may not be the same from A detailed studying of personal psy- matic (cardiovascular system, primarely) the space weather and its factors point chological features of people from polar state of inhabitants of auroral (Tiksi), sub- of view [12]. and middle latitudes from the point of their auroral (Yakutsk) and middle latitudes The main targets for heliogeophysical stress-overcoming behavior differentiat- (Saratov). The monitoring is being held factors are human nervous and cardio- ed according their spheres and types of simultaneously during two months in fall vascular systems. During the geomag- personality, with the space weather effect and/or spring periods (October-Novem- netic activity there are: arrhythmia, heart on them, had not been held earlier. ber, March-April) – the periods of a maxi- rate changes, BP peaks, blood viscosity Aim: make a comparative analyze of mal activity of heliogeomagnetic factors and erythrocytes aggregation increases, psycho-emotional features and to deter- [5], in groups of volunteers from the given capillary slow flow, and a number of other mine them in persons living in polar, sub- latitudes, with a daily recording for a uni- pathological changes happen [3, 9]. polar and middle latitudes, and taking form protocol. Alongside with traditional risk factors part in a multiple-latitude monitoring in The monitoring started in 2014 and it of cardiovascular pathology developing 2015, in dependence of a presence of a is a follow-up to the previous unique in- (smoking, adiposity, hypodynamia, etc.), psychological sensitivity to a changeable ternational project “Heliomed”, which was today there are data about psycho-social geomagnetic state. organized by an interdisciplinary project- risk factors accumulated (anxiety, de- Methods of research and objects. team of physics, biologists, informational pression, alexithymia) [4, 6, 8], and data Relatively healthy persons took part technologies specialists, psychologists about increased indices of a solar and in the research – males and females and physicians [1]. geomagnetic activity on blood circulation (n=64), age - 44, 8 (40,7; 45,2) years. A combined research of a psycho- organs diseases [3, 5, 9]. At the same The observation of the volunteers was emotional status and of a cardiovascular time, complex influence of these - fac organized in a spring monitoring phase in system condition of volunteers in space tors on physiological and psychological 2015, in March and April, in Saratov (mid- weather changes [5]. characteristics of healthy people are not dle latitude), Yakutsk (sub-polar latitude), “Space weather” or “cosmic weather” enough studied. Tiksi (polar latitude). is a phenomena in an upper atmosphere, Over the last years, there are innova- To achieve the goal the following tests in an ionosphere and in the near-Earth tive abilities of registering and analyzing were used: environment. Space weather, as well space weather parameters by artificial • State-Trait Anxiety Inventory as the weather as a common notion of satellites of the Earth. These data ana- (STAI) (Ch. Spielberg, U. Khanin) [2, 7]; this word, is characterized by a cycle of lyze, further studying the effect of the so- • E. Heim Test, building a stress- calm periods (the minimum of a solar lar and geomagnetic activity parameters overcoming behavior [11]; activity cycle) which can be comparable on a cardiovascular system and personal • Psycho-Geometric Test [10]. to a stable summer weather, and a cycle psychological features may allow to opti- Reactive anxiety of the volunteers ac- of abrupt changes (in high solar activity) mize measures of a primary prevention cording to Spielberg-Khanin had been which may be analogical to an change- of cardiovascular diseases leading to a determined every day during a two- able fall weather. A changeable weather high mortality percent of an adult popula- months observation (March-April), the in the near-Earth environment links with tion on Earth. All these make studying the other tests had been given once at the 86 YAKUT MEDICAL JOURNAL

beginning of the monitoring phase. An in- lus material of a Psycho-Geometric Test The peculiarities of building stress- tegral parameter of geomagnetic activity in the observing persons living in north- overcoming behavior by E. Heim in the had been used daily - Kp-index. ern latitudes are presented on Pic. 4-5. volunteers from Saratov are presented Statistical processing of the findings As we can see from the Pic. 4-5, the on Pic. 6-8. was done by an application program volunteers from the both groups living in As we can see from the data on Pic. package Statistica 6.0, Microsoft Excel northern latitudes preferred triangle and 6, the persons with psychological sensi- 7.0. for Windows, checking zero hypoth- refused zigzag (p<0,05). Among the in- tivity to heliogeomagnetic factors chang- esis of conformity with a normal distribu- habitants of middle latitudes taking part es, living in middle latitudes, preferred tion law based on a Shapiro-Wilk crite- in the monitoring, 46,7% (40,6; 47,2) of choosing non-adaptive cognitive coping- rion, and following use of nonparametric persons were in the group I, 53,3% (49,3; behavior (dissimulation and submission), mathematical methods (as the distribu- 54,1) – in the group II. the volunteer without sensitivity – adap- tion of variables was non-normal). The data are presented as a median (Me) with values of quartile range (25%, 75%) for samples. Reliability of the used statistical estimating was no less than 95%. Results and discussion. We divided all of the observing persons into two groups depending on coincidence (no less than 60%) in absolute and pinnacled increase of the values of reactive anxiety by Spielberg-Khanin, and Kp-index values. In the group I there were people who had such coincidences – volunteers with a psychological sensitivity to heliogeomagnetic factors changes. In the group II there were volunteers with no coincidences mentioned above – without psychological sensitivity to geomagnetic factors changes. During the examination of the volunteers living in polar and sub-polar latitudes we established the followings: group I with persons having a psychological sensitivity to changeable heliogeophysical factors consisted of 42,9% (39,2; 43,7) people. In the group II there were 57,1% (52,7; 58,6) persons with no psychological sensitivity. The results of examination of auroral and sub-auroral inhabitants by the use of E. Heim test are presented below on Pictures 1-3. From the data on Pic. 1 we can see that in the group II as in the group I adaptive coping-cognitions predominate, which is keeping self-control (p<0,05). As it follows from the data on Pic. 2, the volunteers with a psychological sensitivity to heliogeomagnetic factors changes had chosen adaptive coping-forms more seldom than those one with no sensitivity (in both groups this was optimism), and it’s interesting that persons from the group I had chosen mostly non-adaptive coping-behavior – emotion suppression (p=0,04). As for the choice of behavior coping- responds (Pic. 3), there should be noticed a number of prevailing choice of non-adaptive coping-behavior (retreat) in the group I, and the choice on a par with adaptive (asking for help) and non- adaptive (active escape) coping-behavior in persons from the group II (p<0,05). The results of the research with stimu- 4’ 2018 87

tive (problem analyzing and II chose circle and triangle establishing own value) with the same frequency, (p<0,05). and refused zigzag and cir- The volunteers from cle (p<0,05). the group I chose adaptive It stands out that on the emotional coping-strategies given stage of the monitor- (optimism, protest) of nearly ing we established practi- the same frequency as the cally the same frequency of persons from the group II episodes of a psychological (latter ones – only optimism). sensitivity to heliogeophysi- Among non-adaptive coping- cal activity in persons as strategies the representa- from middle as from northern tives from both groups, living latidudes. in middle latitudes, preferred On the base of the find- emotional suppression and ings of a psychological ex- blamed themselves in any amination, it seems as if troubles, and what’s interest- inhabitants of polar and sub- ing, persons with no psycho- polar latitudes, regardless of logical sensitivity to helioge- the presence or absence of omagnetic factors did that a psychological sensitivity more often (p<0,05). to heliogeophysical activ- As we can see from the ity changes, are representa- Pic. 8, in persons with psy- tives of a composed manner chological sensitivity to of behavior, they are serious, changeable heliogeomag- organized, highly responsi- netic factors, in building their ble, tend to analyze prob- own coping-behavior, adap- lems, they don’t get rattled in tation coping-strategies pre- any situations. At the same dominated (asking author- time they are optimists, and ity figure for help), and the they are sure as in positive volunteers without sensitivity results as in their own possi- chose adaptive (ask for help) bilities. It stands out that the and non-adaptive (retreat) persons with a psychological coping-behavior in the same sensitivity to heliogeomag- frequency. netic factors, comparing to That is interesting to no- those ones who do not have tice that the findings from sensitivity, are more patient the volunteers of the group and self resrained, have I, living in middle latitude, in a strong will power, self- work with the stimulus mate- esteemed, they never ever rial of the psycho-geometric show off their emotions even test, are analogical to the if they are ill, and cover all same results from the per- symptoms. sons of northern latitudes Compared to persons (group I): they chose trian- from polar and sub-polar gle and refused zigzag. The latitudes, between the rep- representatives of the group resentatives of the group I 88 YAKUT MEDICAL JOURNAL

and II from middle latitudes there is no sosudistoi` sistemy` u zdorovy`kh liu- Gibt es Geeignetes oder Ungeeignetes as much common which is limited by op- dei` i bol`ny`kh ishemicheskoi` boleznìu Coping? / E. Heim // Psychoter Psycho- timism, emotion suppression, submission serdtca: avttoref. dis. … kand. biolog. som Med. Psychol, 1988.- №1.- Р. 8-17. and asking for help in difficult situation. nauk [Heliogeomagnetic activity effect on 12. http://ipg.geospace.ru/what-is- As for the difference in the groups, we a functional condition of a cardiovascular space-weather.html. should notice high behavior adaptation system in healthy people and in people in persons with psychological sensitivity with an ischemic heart disease: author’s The authors to heliogeomagnetic factors, and their abstract]. St. Petersburg, 2009. 22 p. 1. Kodochigova A.I. – Saratov less cognitive adaptation, comparing to 4. Kodochigova A.I Psiho- State Medical University n.a. V.I. Ra- those who has no such sensitivity. The fiziologicheskie kriterii riska razvitiia zumovsky, member of the Council of representatives from the group I more arterial`noi` gipertenzii i ishemicheskoi` Eastern European Psycho-Somatic So- often then those ones from the group II, bolezni serdtca: avttoref. dis. … dokt. ciety, Department of Therapy, Gastro- tended to analyze problems, suppressed biolog. nauk [Psychophysiological risk enterology and Pulmonology, Professor, emotions, though, protested sometimes, criteria of arterial hypertension and isch- M.D.; mail address: 410012, Russia, and could dissimulate when they were ill. emic heart disease developing: author’s Saratov, ul. B. Kazach’ya, 112; Phone: Regardless of the latitude, the volun- abstract]. Saratov, 2005. 38 p. +7(903)0222198, e-mail: kodochigov- teers with a psychological sensitivity to 5. Parshina S.S. Samsonov S.N. [email protected]; changeable heliogeomagnetic factors, Many`kina V.I. etc. Osobennosti grup- 2. Parshina S.S. – Saratov State were kind and purposeful, preferred ana- povoi` reaktcii serdechno-sosudistoi` Medical University n.a. V.I. Razumovsky, lyzing cause-and effect relationship of sistemy` na izmenenie kosmicheskoi` member of the Council of Eastern Euro- problems, tended to dissimulation and pogody` [Peculiarities of a group cardio- pean Psycho-Somatic Society, Depart- emotion suppression. Those who had no vascular respond on the space weather ment of Therapy and Gerontology of sensitivity were, as a rule, contradictory changes]. IT + M&Ec International Con- the Institute of Continuing Professional and tended to ignore problems. ference information package; Innovative Education, Associate Professor, Profes- Conclusion. From there, in 2015 dur- information technologies in medicine, bi- sor, M.D.; mail address: 410012, Russia, ing monitoring there had been revealed ology, pharmacology and ecology, 2015. Saratov, ul. B. Kazach’ya, 112; a coincidence of frequency of presence pp. 316-322. 3. Olenko E.S. – Saratov State of psychological sensitivity and non-sen- 6. Kirichuk V.F. Kodochigova Medical University n.a. V.I. Razumovsky, sitivity in volunteers among inhabitants of A.I. Olenko E.S. etc. Sovladaiushchee member of the Council of Eastern Eu- northern and middle latitudes, to changes povedenie u clinicheski zdorovy`kh ropean Psycho-Somatic Society, De- in geomagnetic activity. litc i bol`ny`kh arterial`noi` giperten- partment of Normal Physiology n.a. I.A. On the base of this research there had ziei` razlichny`kh sotcial`ny`kh grupp i Chuevsky, Associate Professor, Profes- been established that among the volun- adaptatcionnyè rezervy` ikh serdechno- sor, M,D.; mail address: 410012, Russia, teers who took part in multiple-latitude sosudistoi` sistemy` [Coping-strategy be- Saratov, ul. B. Kazach’ya, 112; monitoring had as similarities as differ- havior in clinically healthy persons and 4. Magomedova A.R. – Saratov ences, taking to account the latitude, psy- in persons of various social groups with State Medical University n.a. V.I. Razu- chological sensitivity to heliogeophysical arterial hypertension, and adaptation re- movsky, III –year Student of the Faculty of factors. Many similar features are sub- sources of their cardiovascular system]. General Medicine; mail address: 410012, jected, first of all, by the latitude of living, Saratov Journal of Medical Scientific Re- Russia, Saratov, ul. B. Kazach’ya, 112; though, there are some close features in search 2009; No. pp. 108-111. 5. Gadzhieva Z.T. – Saratov State volunteers with psychological sensitivity 7. Hanin Yu.L. Kratkoe rukovod- Medical University n.a. V.I. Razumovsky, to heliogeomagnetic activity (tendency stvo k primeneniiu shkaly`reaktivnoi` III –year Student of the Faculty of Gener- to analyze problems, suppress emotions, i lichnostnoi` trevozhnosti Ch.D. Spil- al Medicine; mail address: 410012, Rus- kindness, focus). bergera [Summery guide for the use of sia, Saratov, ul. B. Kazach’ya, 112; Conflict of interests in the study was the scale of reactive and personal anxiety 6. Afanasèva T.N. – Saratov State not stated. by Ch.D. Spielberg]. LNII FK, 1976. 18 p Medical University n.a. V.I. Razumovsky, 8. Chapala T.V. Psihologicheskie Department of Therapy and Gerontology References faktory` riska v clinicheskoi` dinamike of the Institute of Continuing Professional 1. Ragul`skaya M.V. Biotropnoe ishemicheskoi` bolezni serdtca: avtoref. Education, Assistant Professor, Ph.D. vozdei`stvie kosmicheskoi` pogody` (po dis. … kand. psihol. nauk [Psychologi- (Medicine); mail address: 410012, Rus- materialam rossii`sko-ukrainskogo moni- cal risk factors in clinical dynamics of sia, Saratov, ul. B. Kazach’ya, 112. toringa «Geliomed» 2003-2010) [Biotro- an ischemic heart disease: author’s ab- 7. Samsonov S.N. – Yu.G. Sha- pic effect of the space weather (adapted stract]. St. Petersburg., 2012. 25p fer Institute of Cosmophysical Research from the materials of the Russian-Ukraine 9. Parshina S.S. Samsonov S.N. and Aeronomy of Siberiam Branch of monitoring “Heliomed” 2003-2010)]. Mos- Reutov V.P. Sorokina E.G. Е`ffekty` kos- Russian Academy of Sciences, Leading cow, Kiev – St. Petersburg: VVM, 2010, micheskoi` pogody` i sistema oksida Researcher, Ph.D. (Physics and Math- p. 312. azota [Space weather effect and nitrogen ematics); mail address: 677980, Russia, 2. Karandashev V.N., Lebedeva oxide system]. XII Intrnational Crimea the Republic of Sakha (Yakutia), Yakutsk, M.S., Spielberg Ch.D. Izuchenie oce- Conference information package: Space Lenin Pr., 31; nochnoi` trevozhnosti: rukovodstvo po and Biosphere. Alushta, Crimea Arial, 8. Petrova P.G. – M.K. Ammo- ispol`zovaniiu [Study of estimate anxi- 2017 pp. 140-143. sov North-Eastern Federal University, ety: instruction for use]. St. Petersburg., 10. Dellinger, S. Psychogeomtrics. Head of the Department of Normal and 2004. p. 80. How to use geometric psychology to in- Pathologic Physiology, Academician of 3. Kameneva E.G. Vliian- fluence people / S. Dellinger. - New Jer- the Academy of Science (the Republic of ie geliogeomagnitnoi` aktivnosti na sey: Prentice-Hall, 1989. - 199 p. Sakha (Yakutia)), Professor, M.D.; mail funktcional`noe sostoianie serdechno- 11. Heim E. Coping und Adaptivitat: 4’ 2018 89

address: 677000, Russia, the Republic of Physiology, Associate Professor, Ph.D. cho-Somatic Society, The Ministry of In- Sakha (Yakutia), Yakutsk, Ojunskij Str., (Medicine); mail address: 677000, Rus- ternal Affairs of the Russian Federation, 27; sia, the Republic of Sakha (Yakutia), Ya- Saratov Branch, Clinical Psychologist, 9. Strekalovskaia A.A. – M.K. Am- kutsk, Ojunskij Str., 27; Psychotherapist; mail address: 410012, mosov North-Eastern Federal University, 10. Belousova K.O. – member of Russia, Saratov, ul. Moskovskaya, 156 B. Department of Normal and Pathologic the Council of Eastern European Psy-

I.V. Averyanova, S.I. Vdovenko INDICATORS OF THE CARDIOVASCULAR SYSTEM IN THE CAUCASIAN RESIDENTS OF MAGADAN REGION DEPENDING ON THE TERM OF RESIDING UNDER DOI 10.25789/YMJ.2018.64.27 CONDITIONS OF RUSSIA’ NORTHEAST

ABSTRACT The climatic conditions of the North have been forcing the human body to use additional social and biological means of protection against the adverse effects of environmental factors. It should be noted that, first of all, the cardiorespiratory system undergoes the influence of these abiotic factors. In this regard, the purpose of the research was to study and identify the characteristics of the cardiovascular system in young male residents of Magadan Region who differ in terms of residence in the northeast of Russia. 1632 young male subjects aged 17 to 21 and permanently residing in the city of Magadan, were examined in 2005–2017 using standard methods for determining cardiovascular parameters. Depending on the length of residing in the region all the subjects were divided into 4 groups. They represented three generations as well as migrant Caucasians who were not born in Magadan Region but came there from the central regions of the country. Residents of the northeast of Russia with short periods of residence in the North demonstrated a state of stress in the cardiovascular system manifested by an increase in systolic pressure, total peripheral vascular resistance, heart rate, and a decrease in the blood stroke volume. At the same time, the representatives of the 3rd generation had better functioning of the system. They were significantly lower in blood pressure (both systolic and diastolic) and the heart rate. In addition, the subjects of this group had minimal cardiac output, which indicated a more economical functioning of the cardiovascular system in the conditions of the northeast of Russia. Keywords: cardiovascular system, generations of residence in the North, adaptive changes

The territory of Magadan Region that unfavorable natural conditions [4]. At the nisms of the development of early stages is located in the northeast of Russia same time, much less attention is paid to of hypertension, called “near-disease” (59.33 northern latitude) belongs to the the study of adaptive rearrangements in or “prehypertension” became of special subarctic region (55-66.5 north latitude) the activity of the cardiovascular system relevance. This condition is more often according to modern concepts of circum- in different periods of residence under demonstrated by young men [14; 22]. Ac- polar regions [20]. Circumpolar regions the northern conditions. cording to the authors, one of the preno- create a unique set of negative environ- The circulatory system serves as a sological conditions is the so-called “high mental factors affecting humans, includ- marker of the nature of the adaptation normal pressure” of 130-139 / 85-89 mm ing prolonged and severe cold stress with processes in the body and is one of the Hg [23]. negative monthly temperatures, which in first to reflect a state of stress, exhaus- Based on the above, the purpose of some regions may drop to -40Cº [20]. tion, and pathology [10]. Acute exposure this work was to study the cardiovascular Living in the conditions of the northeast of to cold is associated with a decrease in system in young residents of Magadan Russia can be considered as life with ad- peripheral blood flow and an increase region differing in terms of residence in ditional functional tension. So the climatic in metabolic heat production to main- Russia’ northeast. characteristics of the North are defined tain body temperature. The vasomotor Materials and methods. By random by researchers as uncomfortable, severe response of the cardiovascular system sampling, 1,632 young men aged 17 to [1], and even extreme [12] as they make is mediated by sympathetic activation 21, permanent residents of the Magadan significant demands to the human body, directed toward peripheral vasoconstric- Region, were examined. Depending on forcing it to use additional social and bio- tion which results in the body heat loss the term of residence in the territory of logical means of protection against unfa- decrease at the expense of a decrease Magadan Region all the examinees were vorable environmental factors [18]. in peripheral blood flow [16]. This is a divided into 4 groups. The I group (n = The physiological mechanisms of ad- necessary term for the functioning of the 62) included migrant-Caucasians moved aptation changes in the cardiovascular cardiovascular system since peripheral here from the central regions of the coun- system under northern conditions have cold stress due to sympathetically con- try and characterized by a short period of been studied fairly well and are pre- trolled vasoconstriction increases arterial residence in the North (average 7.1 ± 1.3 sented in numerous works [3, 4, 7, 19]. pressure by increasing the peripheral re- years). We designated this group as the The results of such studies are aimed at sistance [17]. Of note that chronic vaso- “zero generation”. The II group included creating the conditions for maintaining constriction leads to the development of those born in Magadan Region in the 1st health and increasing the life expectancy hypertension [15]. At the end of the 20th generation from among Caucasians but of people living and working in the arc- and beginning of the 21st centuries, the whose parents were migrants (n = 924). tic and subarctic climatic zones under identification and study of the -mecha The III group included young people born 90 YAKUT MEDICAL JOURNAL

in the region in the second generation (n the lowest indices of the arterial pressure rate, and a decrease in the blood stroke = 580) whose parents were born in the against the backdrop of the lowest values volume. At the same time, the represen- territory of Magadan region in the 1st of the total peripheral resistance of the tatives of the 3rd generation have dem- generation. And the IV group are the sub- vessels. onstrated more optimal parameters in the jects with the longest term of residence in Statistically higher heart rate indices work of the system, which is seen in sig- Magadan region, which are representa- were observed in groups of young men of nificantly lower values of the arterial pres- tives of the population that is just start- the 0th, 1st, and 2nd generation, relative sure (both systolic and diastolic), and the ing to form (due to the “relative youth” of to their age mates from among the rep- heart rate. In addition, the subjects of this our region). They are young males of the resentatives of the 3rd generation. It is group have had minimal blood cardiac third generation (n = 66) whose parents known that a faster heart rate is potential- output, which indicates a more economi- belong to the representatives of the 2nd ly unfavorable for the optimal circulatory cal functioning of the cardiovascular sys- generation. All studies were conducted state, in particular, due to the shortening tem under Russia’ northeast conditions between 2005 and 2017. of the period of the diastolic phase and and characterizes the strategic orienta- Characteristics of the cardiovascular the increased tension with respect to the tion of adaptive rearrangements associ- system were determined using an auto- cardiac output (CO) which is metaboli- ated with the body functional systems’ matic blood pressure tester Nessei DS- cally much more expensive for the body, energy minimization under the cold fac-

1862 (Japan). The systolic (BPS, mmHg) requires a significant increase in oxygen tor, which is well shown in animal studies and diastolic (BPD, mmHg) values of ar- intake [5], and indirectly may indicate a [8]. In this regard, the direction of chang- terial pressure were measured at rest as reduced effectiveness in the work of the es in the circulatory system has become well as the heart rate (HR, bpm). In ad- cardiovascular system. Cardiac output reasonable. The tension of the system dition, the Starr stroke volume (SV, mL), is an extremely important variable in functioning in migrants proved to be sig- cardiac output (CO, L/min) and the total the cardiovascular system which is con- nificantly higher than that of representa- peripheral vascular resistance (TPVR, stantly regulated so that the this system tives of the 1st and the subsequent gen- dyne2 s cm-5) were calculated [11]. can satisfy the gas transporting needs of erations. At the same time, the vector of Results and discussion. The pa- the organism at particular time, and the functional physiological rearrangements rameters of the cardiovascular system higher the potential energy expenditure among migrants and different genera- in young men with different degrees of of the organism, the more pronounced tions of the north born Caucasians allows adaptation to the conditions of Russia’s the proportional increase in CO. From us to state that in the current conditions, northeast are presented in the table. Our this position, the lower values of this indi- a new population is forming in the north- study has found the young male subjects cator in the group of young men, the rep- east of Russia which we have designated of the 0th generation to be very close resentatives of the third generation who as rooted individuals. to the upper limit of the normal systolic are most adapted to the abiotic factors blood pressure. These values reflected of the North, have become clear, which References high normal blood pressure [21] and sig- is consistent with the principle of econo- 1. Agadzhanjan N.A. Ermakova nificantly exceeded the indices typical for mizing the energy functions of the or- N.V. Jekologicheskij portret cheloveka residents of the central part of the coun- ganism in conditions of extreme climatic na Severe [Ecological portrait of a man try and the European North [2, 9, 13]. characteristics. In the series from the 0th in the North]. Moscow: KRUK, 1997, We have concluded before that, modern generation to the 3rd generation, a sig- 212 p. http://www.biblus.ru/Default. young male Caucasians of Magadan re- nificant dynamics of the increase in the aspx?book=876a1i1i1 gion are oriented towards hypertensive blood stroke volume was noted, which re- 2. Buduk-ool L.K. Ajzman values in their blood pressure [6]. The flects the effective provision of the blood R.I. Sravnitel’naja dinamika reaction of the cardiovascular system cardiac output circulation due to the high kardiorespiratornoj sistemy studentov in individuals with the shortest period of value of the stroke volume against the Juzhno-Ural’skogo regiona [Comparative adaptation to the conditions of the north- significantly lower values of heart rate in dynamics of the cardiorespiratory system east of Russia was due to the increased the young male subjects of the 3rd gen- of students of the South Ural region]. systolic blood pressure. We assumed the eration. Rossijskij mediko-biologicheskij vestnik latter to be a compensatory mechanism Conclusion. The analysis has shown, im. I.P. Pavlova [I.P. Pavlov Russian under the action of low ambient tempera- that Russia’ northeast subjects with short Medical and Biological Bulletin]. 2008, tures. It should be noted that the young periods of residence in the North have № 4, pp. 28-33. https://elibrary.ru/item. male residents among the representa- been experiencing the state of stress in asp?id=12229750 tives of the third generation character- the cardiovascular system manifested 3. Djomin D.B. ized by the longest period of residence by an increase in systolic pressure, to- Klimatojekologicheskie uslovija severnyh in the Northern conditions demonstrated tal peripheral vascular resistance, heart territorij i ih vlijanie na serdechno- Cardiovascular system indices in subjects with different rates of adaptation to the conditions of the northeast of Russia (M ± m) Examined subjects Significance of differences among examined groups Parameter 0th generation 1st generation 2nd generation 3rd (1). (2) (3) generation n I–II II–III III–IV I–III I–IV II–IV n = 56 n = 924 n = 580 = 66 BPS. mmHg 129.7±0.6 128.0±0.4 128.0±0.4 127.8± 0.8 p=0.18 p=1.00 p=0.94 p=0.18 p<0.05 p=0.86 BPD. mmHg 77.1±1.0 76.0±0.3 75.0±0.3 71.8 1.2 p=0.29 p<0.05 p<0.001 p<0.05 p<0.001 p<0.001 HR. bpm 78.2±1.1 79.6±0.4 79.0±0.5 71.8 1.6 p=0.61 p=0.34 p<0.001 p=0.32 p<0.001 p<0.001 SV. mL 69.8±1.3 70.4±0.3 71.1±0.3 75.1 1.0 p=0.48 p=0.09 p<0.001 p=0.19 p<0.001 p<0.001 CO. L/min 5594.5±92.5 5575.2±34.3 5510.6±43.8 5362.3±96.6 p=0.82 p=0.24 p=0.26 p=0.39 p<0.05 p<0.05 TPVR. dyn2 s cm-5 1579.6±46.1 1532.9±12.5 1467.4±14.8 1434.1±31.1 p=0.32 p<0.05 p=0.33 p<0.05 p<0.05 p<0.05 4’ 2018 91

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Sergei Igorevich Vdovenko, DVO RAN, 2003, V. 1, 373 p. https:// cold test. J. Appl Physiol, 1961, v.16, Ph. D. (Biology), Junior Researcher, elibrary.ru/item.asp?id=19488956 pp. 401-404. https://doi.org/10.1152/ Laboratory for Physiology of Extreme 9. Pushkina V.N. Gribanov A.V. jappl.1961.16.3.401 States, Scientiic Research Center Sezonnye izmenenija vzaimootnoshenij 17. Pickering T.G. Gerin W. “Arktika”, Fareastern Branch of the pokazatelej kardiorespiratornoj sistemy Cardiovascular reactivity in the laboratory Russian Academy of Sciences (SRC u junoshej v uslovijah cirkumpoljarnogo and the role of behavioral factors in “Arktika” FEB RAS), 24 Karl Marx street, regiona [Season-related changes in hypertension: a critical review. Ann. 24, Magadan, 685000, http://orcid. the relations between cardiorespiratory Behav. 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M.S. Soboleva, K.V. Zhmerenetsky, N.V. Voronina, E.E. Loskutova, V.A. Dobryh USAGE OF THE FIXED-DOSES COMBINATIONS FOR DRUG THERAPY OF ARTERIAL HYPERTENSION IN NORTHERN REGIONS OF THE FAR DOI 10.25789/YMJ.2018.64.28 EASTERN FEDERAL DISTRICT

ABSTRACT Aim. To analyze the usage of the fixed-doses combinations for treatment of arterial hypertension in three northern regions of the Far Eastern Federal District. Material and methods. The pharmacoepidemiological study of realization of antihypertensive drugs in the pharmaceutical organizations of the Magadan region, Kamchatka Krai, the Sakha Republic (Yakutia). The studied period was 2013-2017. Total sales were calculated based on the amount of drugs and defined daily doses, acquired by patients. The range of international nonproprietary names has been divided into therapeutic classes. Further calculation of indicators in group for each combination was carried out. The analysis was performed with usage of Microsoft Office of Excel 2015. Results. In a therapeutic class of combinations β-blockers with diuretics or calcium channel blockers the combination atenolol+сhlortalidone remained the leader in three regions. Shares of sales of other international nonproprietary names were insignificant, and did not exceed totally 10%. Valsartan+amlodipin had the greatest indicators of realization in the therapeutic class of аngiotensin II antagonists with calcium channel blockers. Among combinations of аngiotensin II antagonists and diuretics, the combination of losartan+hydrochlorothiazide had more than a half of the acquired defined daily doses. Since 2017 in the Sakha Republic (Yakutia) were more actively used valsartan+hydrochlorothiazide, azilsartan medoxomil+chlortalidone. In a therapeutic class of angiotensin-converting-enzyme inhibitors with calcium channel blockers in the Magadan region and in the Sakha Republic (Yakutia) the leader of the market was the combination of lisinopril+amlodipine, in Kamchatka Krai - perindopril+amlodipine. Acquisition of the drugs containing ramipril and amlodipine has increased in all three regions. In a therapeutic class of combinations of angiotensin- converting-enzyme inhibitor with diuretics, the redistribution of preferences from drugs containing enalapril+hydrochlorothiazide in favor of perindopril+indapamid was observed. The combinations lisinopril+hydrochlorothiazide had the considerable share of sales in the Sakha Republic (Yakutia). Usage of a combination of hydrochlorothiazide+triamterene and drugs of a reserpine is characteristic of the Magadan region and Kamchatka Krai. In the Sakha Republic (Yakutia), in comparison with other explored regions, triple-component drugs are more actively applied. Conclusions. The greatest part of realization of the defined daily doses of the modern antihypertensive fixed-doses combinations was the share of only seven international nonproprietary names, on condition of presence in the pharmaceutical market of 43 variants. Current situation proves expediency of prescription of the applied schemes of drugs therapy, taking into account the available range of drugs in the pharmaceutical organizations of regions. Keywords: arterial hypertension, fixed-doses combinations, pharmaceutical market, Far Eastern Federal District, defined daily dose, epidemiology. List of reductions: β – AB – β-blockers AH – arterial hypertension BP – arterial blood pressure AC – calcium channel blockers ARA – аngiotensin II antagonists D – diuretic FEFD – the Far Eastern Federal District ACE inhibitor – angiotensin-converting-enzyme inhibitor INN – international nonproprietary name FDC – the fixed-dose combination Introduction. The high morbidity of districts (figure1) [4]. pressure (BP) has to be reached no cardiovascular system, risk of develop- The main in structure cardiovascular later than in 3 months after an initiation ment of fatal complications, results of nosologies are circulatory system dis- of treatment. At the same time less than modern randomized studies, data of eases. Indicators in Kamchatka Krai till 50% of the patients receiving antihyper- meta-analyses, registration in the phar- 2016 remain higher in comparison with tensive therapy reach the level of sys- maceutical market of new drugs and im- Russian and Far East. The tendency tolic BP<140 mmHg. It proves relevance provement of their forms of usage, cause to their decrease can be explained with of a problem of increase in compliance need of systematic revision of the exist- implementation of federal and regional of patients. One of the easiest ways of ing recommendations, standards, other target programs, medical examination growth of this is use of the multicom- regulations regulating approaches of ex- of the population, promoting of a healthy ponent drugs. In the recommendations perts to drugs therapy [1]. The Far East- lifestyle, improvement of diagnostics and of 2018 the class and level of validity ern Federal District (FEFD) is also char- treatment. of initiation of therapy from the double acterized by high rates of presence of The Arterial Hypertension (AH) is one fixed-dose combination is raised to IB. cardiological pathology among the popu- of the most widespread chronic diseases. There are recommended combinations lation. In northern regions heavy climate, Around the world, researches on optimi- of inhibitors of – angiotensin-converting- low temperatures and small duration of zation of therapy are actively conducted enzyme inhibitor (ACE inhibitor) or the light day complicate the situation. Difficult [14]. According to the last recommenda- аngiotensin II antagonists to blockers geographical conditions can negatively tions of the European Society of Cardiol- (ARA) with calcium channel blockers of influence on epidemiological situation in ogy, the target level of the arterial blood a dihydropyridine structure (AC) or thia- 4’ 2018 93

zide diuretic (D), it is preferable in «one tablet» (IA) [2]. In the Russian Federation researches of features of a current of AH [1,6,9] are also actively conducted. The recommendations of the All-Russian scientific organization of cardiologists and the Russian Medical Society of Arterial Hypertension [12] are revised. The combinations of ACE inhibitors+AС/D [5,8,10,11,13] are the most studied. Advantages of use of combinations of ACE inhibitors and β – blokers (β – AB) [7], three-component antihypertensive drugs are analyzed [3]. The analysis of the pharmaceutical market is one of the most reliable ways Fig.1. Indicators of incidence of circulatory system diseases on 100000 all population of northern of assessment of introduction of the ex- subjects of the FEFD (with the diagnosis established for the first time in life) isting regulations in real clinical practice cal standards developed according to the and telmisartan+amlodipine have begun and also usage by patients of antihyper- Helsinki declaration of the World medical to be applied by patients in Kamchatka tensive medicines. The of the purpose association “Ethical Principles for Medi- Krai and in the Sakha Republic (Yakutia). conducted research: comparison of ap- cal Research Involving Human Subjects” At the same time, totally their share has proaches to drugs therapy of AH with use with amendments of 2000. The epidemi- made less than 5%. of the fixed-doses combinations in three ological research was conducted without Changes that are important in northern regions of the FEFD. participation of people and animals. the data of sales were observed in a The epidemi- Material and methods. Acknowledgements: none. therapeutic class of combinations the ological research was conducted based Results and discussion. In a thera- ARA+D. More than 80% of realization on data on realization of antihypertensive peutic class of combinations β-AB+AC/D intra-group remains the leader - INN medicines in the pharmaceutical organi- more than 90% of realized amount by losartan+hydrochlorothiazide. Since zations (n=17) during 2013-2017 in the DDD were from the leader - an atenolol 2017 patients buy combination INN Magadan region, in Kamchatka Krai, with сhlortalidone in all three analyzed valsartan+hydrochlorothiazide were: in in the Sakha Republic (Yakutia). Based districts. Only in 2017 the share of sales the Magadan region - 4,8%; in Kamchat- on the obtained data the general base bisoprolol+amlodipine in the Sakha ka Krai - 7,8%; in the Sakha Republic (Ya- of sales in a quantity equivalent (by the Republic (Yakutia) has increased to kutia) - 11,02%. Shares of sales kande- number of packing’s) has been carried 11,11%. Indicators of acquisition of INN sartan/telmisartan+hydrochlorothiazide out with use of Microsoft Office of Excel bisoprolol+hydrochlorothiazide in Yaku- in the Magadan region have increased to 2015. Injection medicines, in connec- tia and the Magadan region were less 3,4% in 2017, and combinations azilsar- tion with their use, generally in a hospital than 3%. Patients in northern regions tan medoxomil+сhlortalidone to 12,18% segment have been excluded from the of the FEFD did not demand combina- in the Sakha Republic (Yakutia). list. At the following study phase the to- tions atenolol + amlodipine, metoprolol The therapeutic group of combinations tal indicators of sales of the established + felodipine, nebivolol + amlodipine for of ACE inhibitors+AC is one of the most daily doses (DDD) all international non- the studied period. The narrow list of the demanded in the pharmaceutical market proprietary name (INN), were calculated fixed-doses combinations acquired by in regions. The structure of realization of on the basis of DDD, presented on the patients characterizes therapeutic group these fixed combinations for the studied website of World Health Organization. In of the ARA+AC. The leader of the market period in three districts is presented in the analysis of the fixed-doses combina- is the combination valsartan+amlodipine. the figure 2. In the Magadan region more tions, the rule is followed: 1 tablet - DDD More than 95% of an intra-group indica- than 50% of intra-group volume acquired for the combinations applied once a day; tor of realization are the share of this INN. by DDD were the share of a combination 2 tablets - DDD for the combinations ap- Only since 2017, losartan+amlodipine of lisinopril with amlodipine, and sales plied twice a day and 3 tablets DDD for the combinations applied three times a day, etc. This principle means what the DDD of fixed-doses combination can differ from the DDD of its active ingredients [15]. Further the average indicator of realization of each INN in the specific region on 1 drugstore sold for a year (for align- ment of differences of population density in regions) was calculated. The “Analysis of Data” and “Intermediate Results” package was used. Conflict of interests: authors declare lack of the obvious and potential conflicts of the interests connected with the publi- cation of the present article. Financing source: authors declare lack of financing. Compliance to the principles of ethics: research work conforms to the ethi- Fig.2. Structure of realization of the DDD fixed-doses combinations ACE inhibitors+АС 94 YAKUT MEDICAL JOURNAL

of perindopril+amlodipine decreased. In 2017 was increased to 35% the indicator of sales of rather new fixed-doses combination ramipril+amlodipine and has occurred come a redistribution of preferences. The share of this INN in the Sakha Republic (Yakutia) in 2017 has made more than 10%. In general, the structure of realization in regions was similar. At the same time, patients in Sakha Republic (Yakutia) actively bought the fixed combinations of a perindopril+amlodipine. Their share has made about 25% in 2016 and 18% in 2017. Preferences of experts and patients in Kamchatka Krai differed from the regions described above. The leader of the therapeutic group of ACE inhibitors+AC was perindopril+amlodipine. More than 50% of sales were the share of this INN in Fig.3. Structure of realization of the DDD fixed-doses combinations ACE inhibitors+D the district. Since 2015 there is a market redistribution - realization of a combination lisinopril+amlodipine decreases to 30% in favor of INN ramipril+amlodipine – his indicator increases to 10%. Com- binations of trandolapril+verapamil and also rather new drugs, which containing enalapril+lercanidipine and enalapril+nitrendipine, were not demanded among patients in regions. In general, decrease in demand for drugs of an enalapril is noted. It can be connected with feature of pharmacokinetics of the substance (applied twice a day). It is reduces at patients commitment to treatment, while there are effective,long acting ACE inhibitors (perindopril, ramipril,fozinopril) in the market. Dynamics of realization of the fixed doses combinations in the ACE inhibitors+D group is presented in the figure 3. The leader was the combina- Fig.4. Structure of realization of the DDD fixed-doses combinations of antihypertensive drugs of tion perindopril+indapamide. The share other therapeutic classes of its sales varied from 20% (in 2015 in the Magadan region) up to 60% (in and hydrochlorothiazide+dihydralaz tors of sales have increased to 10%. 2017 in Kamchatka Krai). Indicators ine+reserpine. Despite emergence Despite existence in the pharmaceuti- of sales of INN enalapril+indapamide of modern multicomponent medical market of combinations of more selec- were insignificant (no more than 10%) cines ACE inhibitors+AC+D, ACE tive β-AB (bisoprolol, metoprolol, nebivo- and decreased in three studied dis- inhibitors+AC+statins, the ARA+ AC+D, lol), till 2017 year the most acquired by tricts. Use by patients of a combina- AC+D, AC+statins, ACE inhibitors+D+β patients there is an atenolol combination. tion enalapril+hydrochlorothiazide was – AB+nootropic in the pharmaceutical It can be explained with the accumulated also decreased in the Magadan region market, their total share made no more experience of its clinical application, pres- and in Kamchatka Krai. Shares of oth- than 10%. The situation in Kamchatka ence duration in the regional pharmaceu- er representatives of this therapeutic Krai was similar, but at the same time, tical markets and also rather low cost of class remained insignificant - totally no high rates (over 60% intragroup in 2013 the concrete trade name «Tenoric». more than 10%. The increase in real- year) characterized sales of alkaloids of a The significant proportion of realiza- ization was also observed for combina- Rauwólfia serpentína (trade name “Rau- tion of INN valsartan+amlodipine among tions of ramipril+hydrochlorothiazide natine”). combinations of the ARA+AC can be and lisinopril+hydrochlorothiazide in the The pharmaceutical market of the caused by recent registration and, re- Sakha Republic (Yakutia). Sakha Republic (Yakutia) also differed in spectively the entry to the regional phar- At the following study phase the view of considerable acquisition of com- maceutical markets, trade names of sales of the fixed-doses combina- binations of a reserpine with hydrochloro- combinations of an irbesartan, losartan, tions of drugs from various therapeutic thiazide. At the same time, market redis- olmesartan medoxomil and telmisartan classes have been analysed. Dynam- tribution nevertheless happened, and an with amlodipine. Till 2017 in drugstores ics of realization is presented in the intra-group share of a combination lisinop this group has been presented, generally figure 4. In the Magadan region the ril+amlodipine+rosuvastatin by 2017 has by the trade name «Exforge». most acquired there were combina- made more than 40%. At INN valsartan In the therapeutic class ARA+D re- tions hydrochlorothiazide+triamterene +amlodipine+hydrochlorothiazide indica- distribution of preferences from a com- 4’ 2018 95

bination of a losartan with hydrochloro- 2013-2017 years and insignificant usage of Health of the Russian Federation. thiazide, in favor of rather new INN was of the drugs containing three and/or four Department of monitoring, analysis and observed. Current situation can be a con- active ingredients, except for the Sakha strategic development of health care. sequence of increase in interest of spe- Republic (Yakutia), still takes place. Re- Federal State Budgetary Institution Central cialists and patients to group of sartans in sults of a research prove slow introduc- Research and Development Institute of the general, an active promotion, acquisition tion of recommendations in real practice Organization and Informatization of Health of practical experience of use of medi- of the antihypertensive therapy, which Care of the Russian Ministry of Health] cines by doctors and patients in northern is appointed to patients, in the remote Moscow, 2017, P. 67-68. Ehlektronnyj regions of the FEFD. northern regions of the Russian Federa- resurs URL: https://www.rosminzdrav. In group of the fixed-doses combination. The structure and dynamics of de- ru/ministry/61/22/stranitsa-979/ tions ACE inhibitors+AC remained high a velopment of the pharmaceutical market statisticheskie-i-informatsionnye- share of realization lisinopril+amlodipine. shows need actions for expansion of materialy/statisticheskiy-sbornik-2016- It can be caused by the fact that this com- knowledge of doctors about new stan- god Data obrashcheniya 11.02.2018. bination was one of the first in the regional dards of therapy, about the registered [Electronic source URL: https:// pharmaceutical markets. Nevertheless, multicomponent drugs with the fixed-dos- www.rosminzdrav.ru/ministry/61/22/ entery of new options of combinations es, which allow increasing compliance of stranitsa-979/statisticheskie-i- has attracted interest of specialists. This patients to the appointed treatment. informatsionnye-materialy/statisticheskiy- can be connected with a later registra- sbornik-2016-god Date of the address tion (only in 2015year) of a full-doses References 2/11/2018]. combination «Ekvator» (20 mg +10mg), 1. Bojcov S.A., Andreev E.M., 5. Kravchenko A.Ya., Alimhanova and also the increase in number of re- Samorodskaya I.V. Ocenka vozmozh- Z.Z. Ocenka ehffektivnosti perevoda na searches devoted to efficiency and safety nosti sravneniya pokazatelej smertnosti fiksirovannuyu kombinaciyu Prestans of a combination perindopril+amlodipine ot boleznej sistemy krovoobrashcheniya u pacientov s nedostatochnym [5,8,10,11,13]. The lack of sales of INN v Rossii i SSHA [Assessment of the pos- kontrolem arterial’nogo davleniya enalapril+nitrendipine/lercanidipine can sibility of comparing mortality rates from drugimi antigipertenzivnymi preparatami be explained with recent registration of diseases of the circulatory system in the i ih kombinaciyami: regional’naya medicines (2016-2017) and need of ac- United States and Russia] Kardiologiya programma ob”ektiv [Efficacy evaluation cumulation of practical experience of [Cardiology]. Moscow, 2017, №57 (1), P. of the transition to fixed combination usage in the form of singlecomponent 5-16. DOI: 10.18565/cardio.2017.1.5-16. drug prestance in patients with drugs. 2. Villeval’de S.V., Kotovskaya insufficient control of blood pressure by In a therapeutic class of combina- Yu.V., Orlova Ya. A. Rekomendacii other antihypertensive medications or tions of ACE inhibitors+D consider- po vedeniyu arterial’noj gipertonii combinations: regional program objective] able and stable share of sales at a Evropejskogo obshchestva kardiologov i Kardiovaskulyarnaya terapiya i profilaktika perindopril+indapamide what can be Evropejskogo obshchestva po arterial’noj [Cardiovascular Therapy and Prevention]. explained with synergism of action due gipertonii 2018 goda [Guideline for Moscow, 2018, №17(2), P.10-16. https:// to vasodilating properties, additional at management an arterial hypertension doi.org/10.15829/1728-8800-2018-2-10- diuretic. Decrease in demand for com- of the European Society of Cardiology 16. binations of enalapril can be caused and European society about an arterial 6. Krivoshapova K.E., Cygankova by registration and entry into the phar- hypertension of 2018] Ehlektronnyj resurs D.P., Barbarash O.L. Rasprostranennost’, maceutical market of combinations of a URL: http://rgnkc.ru/novosti/new-novye- osvedomlennost’ i priverzhennost’ ramipril, a fosinopril and quinapril and evropejskie-rekomendatsii-po-arterialnoj- lecheniyu arterial’noj gipertenzii: mify also growth of interest in combinations gipertonii-2018-goda Data obrashcheniya i real’nost’ [Prevalence, awareness of ACE inhibitors+AC and ARA+D and 08.08.2018. [Electronic source URL: http:// and adherence to treatment of arterial ARA+AC. rgnkc.ru/novosti/new-novye-evropejskie- hypertension: myths and reality] Sistemnye Traditional preference of acquisitions rekomendatsii-po-arterialnoj-gipertonii- gipertenzii [Systemic Hypertension]. by patients of combinations of diuret- 2018-goda Date of the address 8/8/2018]. Mockow, 2018, №15(1), P. 63–67. DOI: ics and medicines with reserpine shows 3. Nedogoda S.V., CHumachek 10.26442/2075-082X_15.1.63-67. need of informing doctors about new E.V., Ledyaeva A.A. i dr. Vozmozhnosti 7. Ostroumova O.D., Kochetkov double-component, triple-component fiksirovannoj kombinacii amlodipina, A.I., Starodubova A.V. i dr. Novaya drugs, effective for treatment of patients indapamida i perindoprila, u pacientov s fiksirovannaya kombinaciya ingibitora with an arterial hypertension, according nekontroliruemoj arterial’noj gipertenziej angiotenzin-prevrashchayushchego to National clinical guideline (2018). [Amlodipine, indapamide and perindopril fermenta perindoprila i vysokoselektivnogo Conclusion. In general sales of an- fixed combination in patients with β-adrenoblokatora bisoprolola: pervaya tihypertensive combinations are char- uncontrolled hypertension] Kardiologiya sredi ravnyh [Novel combination of acterized by concentration around [Cardiology]. Moscow, 2017, 57(6), P. 29- the angiotensin converting enzyme several INN. The most realized fixed 32. DOI: 10.18565/cardio.2017.6.29-32. inhibitor perindopril and highly selective combinations in northern districts of 4. Zabolevaemost’ vsego β-adrenoblocker bisoprolol: prime among the FEFD are atenolol+сhlortalidone, naseleniya Rossii v 2016 godu. the equal] Kardiovaskulyarnaya terapiya i valsartan+amlodipine, losartan Statisticheskie materialy. CHast’ profilaktika [Cardiovascular Therapy and +hydrochlorothiazide, lisinopril I. Ministerstvo zdravoohraneniya Prevention]. Moscow, 2018, №17(3), P. +amlodipine, perindopril+amlodipine, Rossijskoj Federacii. Departament 85-95. https://doi.org/10.15829/1728- perindopril+indapamide. Leaders of monitoringa, analiza i strategicheskogo 8800-2018-3-85-95. therapeutic groups can vary consider- razvitiya zdravoohraneniya. FGBU 8. Nedogoda S.V., Chumachek ably depending on the specific regions of «Central’nyj nauchno-issledovatel’skij E.V., Ledyaeva A.A. i dr. Optimizaciya the FEFD. Despite registration and avail- institut organizacii i informatizacii kontrolya arterial’nogo davleniya, ability in drugstores of regions of modern zdravoohraneniya» Minzdrava Rossii organoprotekcii i metabolicheskih multicomponent drugs, acquisition by [Incidence of all population of Russia in narushenij s pomoshch’yu fiksirovannoj patients of medicines of a reserpine in 2016. Statistical materials. Part I, Ministry kombinacii perindopril i indapamida u 96 YAKUT MEDICAL JOURNAL

pacientov s arterial’noj gipertenziej [Op- efficacy of combined pharmacotherapy the address 08/08/2018. timization of control of blood pressure, with fixed perindopril/amlodipine metabolic disorders and target organs combination in patients with combined The authors protection with fixed perindopril and indap- cardiovascular pathology in outpatient 1. Soboleva Mariia Sergeevna - amide combination in treated patients with practice] Kardiologiya [Cardiology]. candidate of biology, associate professor arterial hypertension] Kardiologiya [Cardi- Moscow, 2018, №58(3), P. 37-42. of the department pharmacy and ology]. Moscow, 2017, №57(2), P. 5-11. DOI:10.18087/cardio.2018.3.10097. pharmacology, The Far Eastern State DOI: 10.18565/cardio.2017.2.5-11. 12. Chazova I.E., Oshchepkova Medical University, ORCID iD 0000-0002- 9. Efanov A.Yu., Vyalkina Yu.A., E.V., Zhernakova Yu.V. i dr. Rekomendacii 5452-0584, e-mail: [email protected]; Petrova Yu.A. i dr Osobennosti antigiper- po diagnostike i lecheniyu AG [Clinical phone 8-914-203-08-28 (responsible for tenzivnoj terapii u pacientov s arterial’noj guidelines for diagnostics and treatment contacts with edition), Khabarovsk, 35, gipertoniej razlichnogo kardiovaskulyar- of arterial hypertension] Kardiologicheskij Muravyev-Amursky St., 680000. nogo riska (po dannym registra bol’nyh vestnik [Cardiological messenger]. 2. Zhmerenetsky Konstantin hronicheskimi neinfekcionnymi zabol- Moscow, 2015, №1, P. 5-30. Vyacheslavovich - doctor of medical evaniyami v Tyumenskoj oblasti) [Spe- 13. Stacenko M.E., Turkina S.V., sciences, the member correspondent cifics of antihypertension therapy in Titarenko M.N. Organoprotektivnye of RAS, the rector of The Far Eastern hypertensives of various cardiovascular svojstva terapii fiksirovannoj kombinaciej State Medical University, Khabarovsk, 35, risk (by the registry of chronic non- perindoprila i amlodipina u bol’nyh Muravyev-Amursky St., 680000. communicable diseases in Tyumenskaya arterial’noj gipertenziej i saharnym 3. Voronina Natalya Vladimirovna oblast)] Kardiovaskulyarnaya terapiya i diabetom tipa 2 [Organoprotective – doctor of medical sciences, professor, profilaktika [Cardiovascular Therapy and properties of therapy by fixed combination head of department of additional profes- Prevention]. Moscow, 2018, №17(3), P. of perindoprile and amlodipine in patients sional education of Institute of continuous 4-10. https://doi.org/10.15829/1728-8800- with arterial hypertension and diabetes professional education and accreditation 2018-3-4-10. mellitus type 2] Sistemnye gipertenzii The Far Eastern State Medical Univer- 10. Ostroumova O.D. Kochetkov A.I. [Systemic Hypertension]. Moscow, 2018, sity, Khabarovsk, 35, Muravyev-Amursky Ehffektivnost’ fiksirovannoj kombinacii №15(1), P.51–55. DOI: 10.26442/2075- St., 680000; ORCID iD 0000-0002-3284- amlodipin/lizinopril u kuryashchih 082X_15.1.51-55. 8108. pacientov s arterial’noj gipertoniej 14. ACC/AHA/AAPA/ABC/ACPM/ 4. Loskutova Ekaterina Efimov- [Fixed combination of amlodipine and AGS/APhA/ASH/ASPC/NMA/PCNA na - doctor of pharmaceutical sciences, lisinopril effectiveness in hypertensive Guideline for the Prevention, Detection, professor, head of department of orga- smokers] Sistemnye gipertenzii Evaluation, and Management of High nization and economics of pharmacy of [Systemic Hypertension]. Moscow, 2018, Blood Pressure in Adults: A Report of medical faculty of Peoples’ Friendship №15(1), P. 23–31. DOI: 10.26442/2075- the American College of Cardiology/ P.K. University of Russia, Moscow, 8, Mikluho- 082X_15.1.23-3. Whelton, R.M. Carey, W.S. Aronow et al. MaklayaSt.,11719. ORCID iD 0000-0002- 11. Bezuglova E.I., Luneva Yu.V., /American Heart Association Task Force 1514-0941. Kornilov A.A. i dr. Ocenka ehffektivnosti on Clinical Practice Guidelines//J Am Coll 5. Dobryh Vyacheslav Anatol’evich kombinirovannoj farmakoterapii s Cardiol. - 2018. – Vol. 71. – P. e127-e248. - doctor of medical sciences, professor, ispol’zovaniem fiksirovannoj kombinacii DOI: 10.1016/j.jacc.2017.11.006. head of department propaedeutic of inter- perindopril/amlodipin u bol’nyh s 15. DDD. Definition and general nal diseases with a phthisiology course, sochetannoj serdechno-sosudistoj considerations. Electronic source URL: The Far Eastern State Medical University, patologiej v usloviyah obychnoj https://www.whocc.no/ddd/definition_ Khabarovsk, 35, Muravyev-Amursky St., ambulatornoj praktiki [Assessment of and_general_considera/#ddds2 Date of 680000.

S.I. Sofronova, A.N. Romanova, V.M. Nikolaev ASSOCIATION OF ACE GENE POLYMORPHISM WITH HYPERTENSION AND RISK FACTORS AMONG INDIGENOUS PEOPLE OF THE DOI 10.25789/YMJ.2018.64.29 NORTHERN TERRITORY OF YAKUTIA

ABSTRACT A study of the association of insertion-deletion (ID) polymorphism of the ACE gene with arterial hypertension and risk factors of cardiovascular diseases in the indigenous people of the northern territory of Yakutia was conducted. The obtained data show that the representatives of the indigenous population with the ID genotype of the ACE gene are associated with a level of systolic blood pressure, abdominal obesity. Carriers of this genotype of the ACE gene have the greatest chance of developing hypertension, metabolic syndrome. The heterozygous DD genotype is associated with lipid metabolic disorders both in hypertensive patients and persons without hypertension. Therefore, the research confirms influence of the D allele ACE gene polymorphism onto genetic mechanisms of cardiovascular diseases development. Keywords: polymorphism, ACE gene, arterial hypertension, indigenous people, risk factors.

Introduction. Hypertension (HTN) is the world [3, 6]. The prevalence of HTN arterial blood pressure is a multifactorial one of the main cardiovascular disease is rather high in the world: it is on the av- disease which development is defined by risk factors and the main reason for a erage by 22% among adult population, the difficult mechanism of interaction of high mortality among adult population in according to WHO data [16]. Rising of genetic and not genetic risk factors and 4’ 2018 97

influences of the environment [9, 14]. roform extraction technique [Maniatise- trol group, having and not having a mu- For today it is proved that the genetic tal. 1982]. Genotyping of ID polymorphic tant genotype. RR had a 95% confidence contribution can be considered main in marker of ACE gene was carried out by interval. The differences were considered development of HTN. In this process the means of sets (LLC NPF Litekh, Moscow) as statistically significant at p<0,05. important role belongs to the genes cod- according to the manufacturing company The research was conducted within ing the components of the renin–angio- instruction on Real-time CFX96 amplifier research projects of YSC CMP “A con- tensin system (RAS), especially to the (“BioRad”, the USA). tribution of a metabolic syndrome to angiotensin-converting enzyme (ACE) Laboratory methods of the research development of atherosclerosis of coro- [11- 13]. Previously, many researches included blood lipids test (TC, TG, HDL nary arteries in residents of Yakutia”, R confirmed the influence of D allele of the Cholesterol, LDL Cholesterol), glucose & D “Development of new technologies ACE gene on the development of an id- test. of treatment and risk prediction of hy- iopathic hypertensia, abdominal obesity When judging the incidence of dis- pertension and insult in the Republic of and the chronic coronary artery disease orders of the blood lipid profile in a Sakha (Yakutia)” (Government contract [5, 10]. There was a research where the population, we used the Russian recom- No. 1133). association of ACE gene ID polymor- mendations of the V revision of Soci- Results of researches and discus- phism with a myocardial infarction in men ety of cardiology of Russian Federation sion. In the general population distribu- (Yakuts up to 50 years) was revealed [1]. (VNOK), 2012, into account the Euro- tion of genotype frequencies is shown in The research of association of ACE gene pean recommendations, 2011. Hyper- table 1. As you see, ACE gene ID geno- polymorphism with hypertension among cholesterolemia (HCS) is the level of total type (65,2%) is the most frequent. The indigenous people of arctic territories of cholesterol (TC) ≥ 5,0 mmol/l, the high groups were created for the research: Russia is insufficiently studied and re- LDL Cholesterol level >3,0 mmol/l, the the persons having arterial hypertension mains relevant. low HDL Cholesterol level <1,0 mmol/l in (175 people), and the group of control – Research objective – studying of men; <1,2 mmol/l in women, the hyper- the persons without HTN (173 people). association of ACE gene polymorphism triglyceridemia (HTG) is the TG level is Average age of hypertensive patients with hypertension and risk factors among ≥1,7 mmol/l; a hyperglycemia on an emp- was 53,11±0,51 years, the persons with- indigenous people of the northern terri- ty stomach (a glucose in a blood plasma out HTN - 38,88±0,60 years. tory of Yakutia. on an empty stomach ≥ 6,1 mmol/l) or Results of the comparative analysis of Materials and methods of the re- glucose intolerance (a glucose in a blood distribution of allele frequencies and gen- search. The clinico-epidemiological plasma in 2 hours after glucose loading otypes in groups of hypertensive patients study of indigenous people in remote dis- within ≥7,8 and ≤11,1 mmol/l). Table 1 tricts in the North of Yakutia is conducted: The measurement of blood pressure in Kolymskoye and Andryushkino rural was carried out according to the standard РDistribution of genotype frequencies of a polymorphic site ID ACE gene localities of the Nizhnekolymsky District, procedure World Health Organization/ In- Topolinoe rural locality of the Tomponsky ternational Organization of Hypertension Genotype Frequency % District, Nelemnoye rural locality of the (1999). Hypertension is present at the Verkhnekolymsky District. 348 people 140/90 mmHg (The Russian references II 68 19,5 were examined using the continuous developed by Committee of experts of ID 227 65,2 method. Patient sample consisted of VNOK, 2004, 2009). DD 53 15,2 adult population aged from 20 up to 70 The abdominal obesity (AO) is ex- years, 225 women, and 123 men. The posed to the value of the waist measure- response made 75%. Average age of ment (WM) ≥ 80 cm on women, ≥94 cm Table 2 the respondents was 45,71±0,67 years, on men. Distribution of allele frequencies and of women 47,4±0,83б of men 42,6±1,09 The study was conducted according genotypes of a polymorphic site ID ACE years. to Ethics Committee protocol YSC CMP gene in groups of hypertensive patients Inclusion criteria: representatives of on the respondent’s informed consent to and control indigenous people of Yakutia (Evens, the processing of personal data and the Allele frequencies Patients Сontrol Chukchi, Yukaghirs, Yakuts). study. and genotypes Exclusion criteria: representatives of Statistical data processing was car- N 186 177 % 53.1 51.2 non-indigenous nationality. ried out by means of standard methods I 2 The program of the research includes of mathematical statistics, using the soft- χ (P); 0.20 (0.6536) ОР (95% ДИ) 1.08 (0.80-1.47) the following sections: the questionnaire ware package of SPSS (version 17.0). N 164 169 poll for assessment of an objective state; Data are submitted as M±m where M – % 46.9 46.8 D the informed consent of a respondent to average value of the sign size, and m – an χ2(P); 0.20 (0.6536) carrying out researches, blood donation average error of the sign size. Intergroup ОР (95% ДИ) 0.92 (0.68-1.26) (according to the Ethical Committee Pro- differences were estimated by means of N 35 33 tocol); anthropometric examination with the variance analysis or nonparametric % 20 19.1 I/I measurement of waist circumference, criteria. When comparing frequencies of χ2(P); 0.01 (0.9343) thigh size; blood sampling from basilic genotypes the standard criterion χ2 with ОР (95% ДИ) 1.06 (0.60-1.86) vein in the morning on an empty stomach Yeats’s amendment was used. The rela- N 116 111 % 66.3 64.2 with 12-hour continence from nutrition. tive risk (RR) of a disease with a certain I/D Blood drawing for the molecular genetic genotype was calculated by a standard χ2(P); 0.09 (0.6774) testing was carried out from a median formula OP=a/bxd/c where an and b – ОР (95% ДИ) 1.10 (0.69-1.75) cubital vein to a test tube with EDTA. the number of the patients having and not N 24 29 % 13.7 16.8 Genomic DNA allocated from leucocytes having a mutant genotype respectively, D/D χ2(P); 0.44 (0.5058) of a peripheral blood with phenol–chlo- and d, c – a number of people in the con- ОР (95% ДИ) 0.78 (0.42-1.47) 98 YAKUT MEDICAL JOURNAL

and control didn’t show statistically significant differences (Tab. 2). We carried out Table 3 the comparison of average concentration Mean concentrations of lipid spectrum and glucose among hypertensive patients and of fats and glucose in the carriers of this control group depending on ID genotypes of ACE gene or that genotype of ACE gene. By com- Genotype II Genotype ID Genotype DD Blood p parison of TC average values, significant parameters with HTN without with HTN without with HTN without differences between the carriers of ID HTN HTN HTN genotype and DD genotype (4,97±0,06, TC 5.05±0.14 4.68 ±0.16 5.15±0.09* 4.79±0.07* 5.13±0.16 4.71±0.16 *0.004 4,91±0,12, respectively, p=0,000) and ID LDL CS 3.24±0.13 2.88±0.13 3.32±0.08* 3.05±0.06* 3.32±0.14 3.07±0.12 *0.008 and II (4,97±0,06, 4,87±0,11, p=0,000) HDL CS 1.26±0.05 1.37±0.06 1.26±0.03 1.33±0.03 1.28±0.06 1.14±0.05 are identified. *0.000 TG 1.21±0.09# 0.92±0.07# 1.21±0.05* 0.91±0.03* 1.16±0.10 1.07±0.08 #0.023 Comparing the median concentration Glucose 4.48±0.18 4.41±0.14 5.02±0.17* 4.19±0.08* 4.48±0.27 4.25±0.14 *0.000 of LDL Cholesterol, it is taped that carriers of the genotype II had reliable differ- ferent genotypes (II – 11,8%, ID – 11,9%, riers also did not reveal the significant ences in comparison with the genotypes DD - 11,3%, p>0,05). The greatest fre- differences: TC (5,13±0,16, 4,71±0,16, ID and DD (II-3,07±0,09, ID - 3,19±0,05, quency of hyperglycemia is identified in p>0,05), LDL Cholesterol (3,32±0,14; DD - 3,18±0,09, p=0,000). Also, there ID genotype carriers - 6,6%, and, in com- 3,07±0,12, p>0,05), HDL Cholesterol were the differences in comparative parison with other genotypes, has signifi- (1,28±0,06; 1,14±0,05, p>0,05), Tg analysis of median values of HDL Cho- cant difference (II - 2,9%, p=0,035 and (1,16±0,10, 1,07±0,08; p>0,05), glucose lesterol (II - 1,31±0,04; ID - 1,29±0,02; DD - 3,8%, p=0,13). (4,48±0,27; 4,25±0,14, p>0,05). DD - 1,20±0,04, p=0,000). Statistically Furthermore, we carried out the com- We carried out the assessment of fre- significant differences in Tg median val- parison of fats and glucose median val- quency of lipid and metabolism disorders ues between the compared groups were ues among carriers of genotypes II, ID, separately among hypertensive patients among the DD genotype carriers in com- DD separately in the groups of hyperten- and persons without HTN. Hypertensive parison with two others (DD - 1,11±0,06; sive patient and control. patients have the largest frequency of hy- II - 1,07±0,06; ID - 1,07±0,03, respective- By comparison of median concentra- percholesterolemia (66,7%) (Fig. 1), ath- ly, p=0,000). By comparison of median tion of fats and carbohydrate spectrum erogenic hypercholesterolemia (70,8%) values of glucose, the significant differ- in persons with HTN and in the group of - in persons with DD genotype. The most ences isn’t identified (II - 4,45±0,11; ID - control, the significant differences were frequent hypo-alpha-cholesterolemia and 4,62±0,10; DD - 4,36±0,11, p>0,05). identified only in carriers of genotypes ID: hyperglycemia are identified in heterozy- In the general population, frequency of TC (5,15±0,09 and 4,79±0,07 respective- gous carriers, and HTG - in II homozy- hypercholesterolemia is 51,5% in carriers ly, p=0,004), LDL Cholesterol (3,32±0,08, gous carriers. Differences between them of II homozygous genotype, 42,7% in car- 3,05±0,06, p=0,008), Tg (1,21±0,05, did not reach statistically significant val- riers of ID heterozygous genotype, and 0,91±0,03; p=0,000), blood glucose ues. 49,1% in carriers of DD heterozygous (5,02±0,17; 4,19±0,08, p=0,000), ex- In the control group, the largest fre- genotype; the differences were doubtful. cept the HDL Cholesterol (1,26±0,03; quency of hypercholesterolemia is identi- Frequency of atherogenous LDL hyper- 1,33±0,03, p>0,05). The significant dif- fied in the group of II genotype carriers cholesterolemia was significantly higher ferences of TC median values were not (42,4%) (fig. 2). Atherogenic hypercho- in carriers of DD genotype (64,2%), in identified in homozygous carriers of lesterolemia was high in all persons with- comparison with carriers of genotypes genotypes II (5,05±0,14; 4,68±0,16, re- out HTN, DD homozygous carriers had II and ID (54,4 and 54,6% respectively). spectively, p>0,05), and in comparing the highest frequency of atherogenic The frequency of Hypo-alpha-cholester- LDL Cholesterol (3,24±0,13; 2,88±0,13, hypercholesterolemia (58,6%). There is olemia among the compared groups of respectively, p>0,05), HDL Cholester- the same situation with the frequency the significant differences are not identi- ol (1,26±0,05; 1,37±0,06, p>0,05), Tg of hypo-alpha-cholesterolemia (44,8%). fied (II – 33,8%, ID – 34,8%, DD - 35,8%, (1,21±0,09, 0,92±0,07; p>0,05), glucose Thus, the influence of DD genotype on p>0,05). Also, there were not the signifi- (4,48±0,18; 4,41±0,14, p p>0,05). The lipid storage disease is revealed. cant differences of TSH in carriers of dif- comparisons between groups of DD car- Also, we surveyed the association of

Fig.1. Frequency of lipid and metabolism disorders separately Fig.2. Frequency of lipid and metabolism disorders separately depending depending on the genotype ACE gene among hypertensive patients on the genotype ACE gene among persons without HTN 4’ 2018 99

ACE genotypes with the level of the sys- are compounded with references of for- Hypertens. 2018; 40(1):32-38. DOI: tolic blood pressure. The average level eign researchers [2, 5, 10]. 10.1080/10641963.2017.1291659. of systolic blood pressure in carriers of 9. Qi Y, Niu W, Zhou W, Hou S, Qiu ID heterozygous genotype (144,2±1,2 References C. Correlation between angiotensinogen mmHg) was significantly higher in com- 1. Grigor’eva L.V. Molekulyarno- gene polymorphisms and essential hy- parison with the carriers of homozygous geneticheskoe issledovanie infarkta pertension in Chinese population. J Hum genotypes II and DD (136,6±2,8 and miokarda v populyacii yakutov [Molecu- Hypertens. 2007; 22(2): 147-150. https:// 138,8±2,1 mm Hg., respectively, p=0,02). lar-genetic study of myocardial infarction www.nature.com/articles/1002282 Abdominal Obesity is independent risk in the Yakut population]: Avtoref. dis. … 10. Gender Specific Association of factor of metabolic syndrome and cardio- kand. med. nauk / L.V. Grigor’eva. – Ufa, RAS Gene Polymorphism with Essential vascular diseases. We defined associa- 2006. – 23 p. Hypertension: A Case-Control Study / tivity of genotypes to the average waist 2. Kotlovskij M.Yu., Kotlovskaya Singh K., Jajodia A., Kaur H. [et al.] // Bi- measurement (WM) and AO. By compar- O.S., Osedko O.Ya. Polimorfizm gena omed Res Int. 2014; 2014:538053. DOI: ison the average WM, we received sig- angiotenzin-prevrashchayushchego 10/1155/2014/538053 nificant differences between ID genotype fermenta u lyudej s gipertonicheskoj 11. Fox CS, Heard-Costa NL, Vasan carriers and carriers of other genotypes bolezn’yu i hronicheskoj formoj IBS [Pol- RS [et al.] Genome wide linkage analy-

(OTID=89,61±0,65, OTII=86,46±1,49, ymorphism of the gene of the angioten- sis of weight change in the Framingham

OTDD = 86,75; p<0,05). There are sta- sin-converting enzyme in people with hy- heart study // J Clin Endocrinol Metab. tistically significant differences in the pertension and chronic form of ischemic 2005; 90(60):3197-3201. DOI: 10.1210/ frequency of AO between ID carriers heart disease] Fundamental’nye issledo- jc.2004-1752. (59,9%) and II and DD carriers (55,9%, vaniya [Fundamental research]. 2011, № 12. Penesova A, Cizmarova E, Kvet- 50,9%). 11-1, p. 49-52. nansky R [et al.] Insertion/deletion poly- We compared WM separately in 3. Oganov R.G. Timofeeva morphism on ACE gene is associated groups with HTN and without HTN. T.N. Koltunov I.E. Epidemiologiya with endothelial dysfunction in young It is shown that, among persons with arterial’noj gipertonii v Rossii. Rezul’taty patients with hypertension // Horm Metab HTN, significant differences are in- car Federal’nogo monitoringa 2003-2010 gg. Res. 2006; 38(9):592-597. DOI: 10.1055/ riers of genotype ID (WM=96,23±0,89) [Epidemiology of hypertension in Rus- s-2006-951307. comparing with II homozygous carriers sia. The results of the Federal monitoring 13. Zivko M, Kusec R, Galesic K. (OT =91,43±1,99, p=0,033), DD (OT 2003-2010.] Kardiovaskulyarnaya terapi- Impact angiotensin-converting enzyme =92,63±1,27, p=0,022). Among persons ya i profilaktika. [Cardiovascular Therapy gene polymorphism on proteinuria and without HTN there are no significant dif- and Prevention]. 2011, 1: 9-13. arterial hypertension. Anthropology. ferences: ID -82,68±0,68, II - 81,18±1,85, 4. Sameera S, Syeeda N, Takc 2013; 37(3): 765-770. http://medlib.mef. DD - 81,90±1,21. In general, hyperten- S, Bashird S, Nissara S, Siddiqi M. ACE hr/id/eprint/2203 sive patients had a high frequency of AO. I/D Polymorphism in Hypertensive Pa- 14. Naber CK, Siffer W. Genetics of hu- Among genotypes the highest frequency tients of Kashmiri Population // Cardiol- man arterial hypertension. Minerva Med. of AO is in ID genotype - 84,5%. It statisti- ogy Research, 2010. Vol 1(1):1-7. doi. 2004; 5(5): 347-356. https://www.ncbi. cally differed from DD - 66,7% (p=0,001), org/10.4021/cr101e. nlm.nih.gov/pubmed/154675115. and didn’t differ from II - 71,4%. Frequen- 5. Irijanto F, Rahajeng H, Kamajaya S, 15. Bhavani BA, Padma T, Sastry cy of AO in persons without HTN among Sja’bani M, Sadewa A, Tomino Y. High D BKS, Krishna Reddy N, Nausheen K. The carriers of this or that genotype had no Allele Frequency of ACE I/D Gene Poly- Insertion I/ Deletion D polymorphism of significant differences; it varied within II – morphism in Familial Hypertension in Angiotensin- Converting Enzyme (ACE) 39,4%, ID - 34,2%, DD - 37,9%. Javanese Indonesian // Juntendo Medi- Gene Increase the Susceptibility to Hy- Conclusion. The obtained data show cal Journal, 2012. 58(3): 224-230. DOI: pertension and/or Diabetes // Int J Hum that representatives of indigenous people 10.14789/pjmj.58.224. Genet. 2017;5:247-252.https://doi.org/10 of the North of Yakutia with ID genotype 6. Appel LJ. ASH position paper: die- .1080/09723757.2005.11885934.6. of ACE gene, abdominal obesity is as- tary approaches to lower blood pressure. 16. World Health Organization. Global sociated with the level of systolic arte- J ClinHypert. 2009; 11 (7): 358-368. DOI: status report on noncommunicable dis- rial blood pressure. Thus, carriers of this 10.1111/j.1751-7176.2009.00136.x. eases 2014. Geneva, World Health Or- genotype have the highest probability of 7. Randhawa NK, Kumar A, Ma- ganization, 2014. idiopathic hypertension, metabolic syn- tharoo K, Bhanwer AJS. Association drome. It is also confirmed by the re- Study of Angiotensin-Converting En- The authors searchers conducted by some foreign zyme Ins/Del Polymorphism with Hy- Sergelyahskoe shosse 4, Yakutsk, Re- authors [4, 7, 8, 15]. The DD heterozy- pertension in Punjabi Population // Int public Sakha (Yakutia), Russia: gous genotype is connected with lipid J Hum Genet. 2006;6:317-321. DOI: 1. Sofronova Sargylana Ivanovna, storage disease, both in hypertensive pa- 10.1080/09723757.2006.11885978. PhD, researcher of YSC CMP, e-mail: tients, and persons without hypertension. 8. Sun F, He N, Zhang K, Wu N, sara2208.mail.ru; Therefore, the research confirms -in Zhao J, Qiu C. Association of ACE gene 2. Romanova Anna Nikolaevna, fluence the D allele ACE gene polymor- A2350G and I/D polymorphisms with MD, director of YSC CMP; phism onto genetic mechanisms of car- essential hypertension in the north- 3. Nikolaev Viacheslav Mikhai diovascular diseases development. Data ernmost province of China // Clin Exp lovich, PhD, researcher of YSC CMP. 100 YAKUT MEDICAL JOURNAL

SCIENTIFIC REVIEWS AND LECTURES I.V.Kononova, F.A.Zakharova, M.P.Kirillina, P.V. Nikiforov, S.N.Mamaeva, S.R.Antonov, A.N.Pavlov, N.A.Nikolaeva DIAGNOSTIC SIGNIFICANCE OF THE HUMAN PAPILLOMA VIRUS DETECTION DOI 10.25789/YMJ.2018.64.30 IN BLOOD

ABSTRACT There is still no clear understanding of the human papillomavirus infecting, as well as its eliminating process from the body. It is known that cervical cancer is caused by human papillomavirus in 99 percent of cases, but only in a small number of human papillomavirus infected women leads to develop cervical cancer. At the same time, based on cytological and histological analysis of the women cervical samples, it is currently impossible to establish criteria that would indicate the malignant progression possibility. Blood, as a unique tissue with specific and nonspecific protective adaptive mechanisms, can be a source of crucial information about the human body papillomavirus infecting. The article provides an overview of the research devoted to the human papillomavirus detection in blood and identifies unresolved issues arising from these studies. Keywords: papillomavirus, HPV, blood, viremia.

Human papillomaviruses (HPV) are considered to be sterile [12]. blood and in the cervix is different. Some small double-stranded DNA viruses that To date, the HPV genes presence in researchers found that the HPV type in infect epithelial cells. Approximately one the blood has been shown in a significant the cervix and in the blood is the same third of them have tropism to the genital number of studies. [14,9], in other studies it was shown that epithelium. These viruses can be divided Peripheral blood mononuclear cells the HPV type may not coincide [17,8]. into high-risk types (including HPV-16, (PBMCs) from women with cervical can- The results of studies on the correla- -18, -31 and -33), which are associated cer detected HPV types 16 and 18 genes tion between the HPV DNA presence in with the development of anogenital ma- [10], women with asymptomatic urogeni- the blood and the cancer starting prog- lignant neoplasms and low-risk viruses tal HPV infection - genes 6, 11, 16, 18 nosis are contradictory as well. Some (including HPV-6 and -11) that induce hy- [22], HIV-infected pediatric patients (me- studies suggest that HPV DNA detection perproliferative lesions, but they are as- dian of age 13.2 years) - HPV-16 genes in blood samples may be a useful sever- sociated with malignant neoplasms rarely [4]; men with infected HPV-16 sperm ity marker of the diseases associated [24]. Types 16 and 18 are responsible for - HPV genes of the same type [21]. PB- with HPV, metastasis, or recurrence [7, most cases of cancer caused by human MCs of healthy blood donors, it was also 6, 17, 18, 19]. However, Peedicayil et papillomaviruses [26]. possible to detect the HPV-16 genes [4]. al. showed that detection of HPV DNA In the case of cervical cancer, HPV is In Australia, from healthy blood men do- in plasma is not a prognostic marker for the causative agent in about 99 % of in- nors from PBMC, many various genes of cervical cancer recurrence [2]. cidents [20]. It is widely known that only HPV types belonging to the skin beta and Many notions remain without a clear in a small number of women infecting gamma papillomaviruses, alpha papillo- explanation, including how HPV enters HPV leads to the development of inva- mavirus mucous were identified. Here- the blood, whether viremia is a natural sive cancer. It is not yet possible to es- with high-risk HPV genes were found in stage of HPV infecting, and how blood tablish reliably the based on cytological 1.7% of cases. It is shown that HPV is at- participates in the HPV eliminating. and histological tests criteria that indicate tached to the cell surface, not inside [15]. Being the oldest human companions, the progression of pathological changes Evidence of HPV reproduction in the PB- HPV is considered by researchers as a to cervical cancer [31]. MCs is currently absent. source for exploring evolutionary sev- Until nowadays, we have not clear In the serum, HPV-16 and 18 genes eral million year history [13]. To achieve understanding the cellular immune re- were found from patients with cervical such evolutionarily successful lifestyle, sponse mechanisms that contribute to cancer [25, 3], rectal cancer, oropharyn- HPV must avoid host protection systems the HPV elimination [23]. The innate im- geal cancer [3], and squamous cell head through immune evasion [28]. munity, including macrophages, natural and neck cancer [6]. HPV-16 DNA was In other turn, the human body con- killer T-cells is thought to play a crucial found in the serum of patients with breast nected with HPV in over million years, role in the first line of defense against cancer [11, 5], as well as with benign ought to develop efficient physiological HPV infection [27]. breast neoplasms [5]. mechanisms that contribute to the virus Insufficient knowledge of the HPV- In plasma from patients with cervical removal. infecting and HPV-eliminating expands cancer, DNA of HPV 16 and 18 types Conclusion. The high potential of the field of investigations. The research [7,1,16], 45, 51, 52 types [16] was deter- blood as a unique tissue that unites the clarifying blood significance in these pro- mined. From patients with asymptomatic whole body and possessing specific cesses is of particular interest. cervix infection in the plasma, DNA of and nonspecific protective and adaptive It is supported for a long time that HPV 45, 51, 16 types was detected, and mechanisms, determines the continu- HPV does not cause viremia. Previously, HPV-16 showed the highest viral load ing considerable interest in scientific re- HPV DNA found in blood was interpreted [17]. search. as DNA from metastatic tumor cells [4]. In cord blood HPV types 6, 11, 18, 52 Over time, due to molecular biology DNA was detected [30]. References improvement, evidence has emerged of In whole heparinized blood HPV 16 1. Arias Y. Human papillomavirus the HPV presence in the blood of patients and 18 type genes were found from pa- (HPV) detected in restored plasma DNA with malignant tumors, pre-carcinogenic tients with cervical cancer [9] and lung from women diagnosed with pre-invasive changes, and in healthy people. Instead, cancer [29]. lesions and invasive cervical cancer / previously, blood in healthy people was Data on the HPV type matches in the Y.Arias, E.Carrillo, F. Aristizabal // Colom- 4’ 2018 101

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solved issues / C.B.J. Woodman, S. I. ing Research Worker – the Head of eral and Experimental Physics, 677000, Collins, L.S. Young // Nature Reviews YSC CMP Department of epidemiology Yakutsk, ulitsa Belinskogo, 58. Cancer. – 2007. – Vol. 7. – P. 11–22. of chronic non-communicable diseases 6. Antonov Stepan Romanovich Laboratory of Precancerogenesis and – Candidate of Physical and Mathemati- The authors Malignant Tumors, 677000, Yakutsk, cal sciences, the Associate Professor of 1. Kononova Irina Vasilyevna – Sergelyakhskoye shosse, 4, FGBNU North-Eastern Federal University named Candidate of Medical Sciences, the Re- “The Yakut Scientific Center of Complex after M. K. Ammosov Physics and Tech- search Worker of YSC CMP Department Medical Problems”; the Head of North- nology Institute Department of Radio of epidemiology of chronic non-communi- Eastern Federal University named after Physics and Electronics, 677000, Ya- cable diseases Laboratory of Precancer- M. K. Ammosov Medical Institute Patho- kutsk, ulitsa Belinskogo, 58. ogenesis and Malignant Tumors, e-mail: morphology, Histology and Cytology 7. Pavlov Aleksandr Nikolaevich [email protected], 677000, Yakutsk, Educational and Scientific Laboratory, – the Head of North-Eastern Federal Sergelyakhskoye shosse, 4, FGBNU Yakutsk, ulitsa Belinskogo, 58. University named after M. K. Ammosov “The Yakut Scientifc Center of Complex 4. Nikiforov Petr Vladimirovich – Physics and Technology Institute Depart- Medical Problems”; Doctor of Medicine, Oncologist, Surgeon ment of Radio Physics and Electronics 2. Zakharova Fedora Apollonovna of GBU Yakut Republican Oncology Laboratory, 677000, Yakutsk, ulitsa Be- – Doctor of Medical Sciences, Professor Center General Surgery Department, linskogo, 58. of North-Eastern Federal University 677000, Yakutsk, ulitsa Sverdlova, 3, k.2. 8. Nikolaeva Nadezhda Anatoly- named after M. K. Ammosov Medical 5. Mamaeva Sargylana Nikolae- evna – the Assistant of North-Eastern Institute Department of Normal and vna - Candidate of Physical and Math- Federal University named after M. K. Am- Pathological Physiology, 677000, ematical Sciences, the Associate Profes- mosov Physics and Technology Institute Yakutsk, ulitsa Belinskogo, 58. sor of North-Eastern Federal University Department of General and Experimental 3. Kirillina Marya Petrovna – Can- named after M. K. Ammosov Physics and Physics, 677000, Yakutsk, ulitsa Belinsk- didate of Biological Sciences, the Lead- Technology Institute Department of Gen- ogo, 58. I.T. Terentiev, M.A. Varlamova, N.I. Pavlova, A.T. Dyakonova, N.A. Solov’eva, S.K. Kononova, Kh.A. Kurtanov NECESSITY OF SCREENING PATIENTS WITH STENTING FOR ACUTE CORONARY DOI 10.25789/YMJ.2018.64.31 SYNDROME BY CYP2C19 POLYMORPHISM

ABSTRACT The relevance of this article is due to the fact that cardiovascular diseases are currently the leading cause of death and disability worldwide. The leading role in the structure of mortality from cardiovascular diseases belongs to coronary heart disease. Ischemic heart disease (IHD) is a chronic disease that develops with insufficient oxygen supply to the myocardium. The main cause (more than 90% of cases) of insufficient intake of oxygen is the formation of atherosclerotic plaques in the lumen of the coronary arteries, the arteries of the blood supplying the heart muscle (myocardium). One of the main drugs for antiplatelet therapy in cardiology is clopidogrel, the use of which can reduce the incidence of thrombotic complications. Clopidogrel is the most famous member of the thienopyridine group. Clopidogrel remains the main drug for antiplatelet therapy in patients who received stenting of the coronary vessels for acute coronary syndrome. The rationale and design of the observational study aimed at testing the hypothesis that the high frequency of the genetic polymorphism of cytochrome CYP2C19*2 is associated with coronary stent thrombosis is presented. Keywords: Clopidogrel, coronary stenting, the acute coronary syndrome, personalized therapy, clopidogrel resistance, paradoxical response, genetic polymorphisms.

The relevance of this article is due to of CHD falls more than half of all cases 2. Coronary bypass - the imposition of the fact that cardiovascular diseases are (28.9%), which in absolute terms is 385.6 shunts around the affected areas of the currently the leading cause of death and people per 100 thousand people per year. coronary arteries. As a shunt, one uses disability worldwide. The leading role in For comparison, mortality from the same his own veins (usually the subcutaneous the structure of mortality from cardiovas- cause in the European Union is 95.9 vein of the thigh) or the internal thoracic cular diseases belongs to coronary heart people per 100 thousand people a year, artery of the patient. disease. Ischemic heart disease (IHD) is which is 4 times less than in our country. Percutaneous coronary intervention a chronic disease that develops with in- The incidence of IHD increases dramati- (PCI) is one of the widely used methods sufficient oxygen supply to the myocar- cally with age: in women from 0.1-1% at for treating patients with acute coronary dium. The main cause (more than 90% of the age of 45-54 to 10-15% at the age syndrome. In the Russian Federation, cases) of insufficient intake of oxygen is of 65-74 years, and in men with 2-5% at in 2012 the number of PCI increased by the formation of atherosclerotic plaques the age of 45-54 years to 10 -20% at the 13,049 procedures or 20.9%, compared in the lumen of the coronary arteries, the age of 65-74 years. Despite the multiply to 2011, and amounted to 75,378 proce- arteries of the blood supplying the heart increased possibilities of modern con- dures. The average for Russia, indicator muscle (myocardium). servative therapy of the above pathology, of the frequency of PCI performance per According to the World Health Or- in the absence of effect, surgical meth- 1 million population in 2012 was 531 [3]. ganization (WHO), mortality from cardio- ods of treatment are performed: It is important to note that, despite the vascular disease is 31% and is the most 1. Percutaneous coronary intervention obvious success of the use of PCI, this common cause of death worldwide. In - balloon angioplasty with the installation method has certain complications. Thus, the territory of the Russian Federation, of a stent (a metal frame that preserves among patients who underwent coro- this figure is 57.1%, of which the share the restored lumen of the vessel); nary stenting, the frequency of such a 4’ 2018 103

life-threatening complication as acute or remains the first-line drug due to signifi- in the prognosis in patients with cardio- subacute stent thrombosis, according to cant differences in the availability -of in vascular pathology, especially after stent international literature, reaches 1-3% [2]. novative P2Y12 inhibitors in European placement. This applies to homozygotes In this case, the frequency of repeated in- countries. Antiplatelet therapy to optimize A/A (*2/*2), carriers of this genotype be- terventions on a stented coronary vessel the results of SCS should provide a bal- long to the group of slow metabolizers, but can reach 17% (especially when implant- ance between the minimized risk of stent patients with heterozygotes G/A (*1/*2) ing a stent without drug coating) [3]. In or- thrombosis and the risk of bleeding [17]. are also characterized by a reduced rate der to reduce the risk of developing car- At the present time, it has become evi- of clopidogrel metabolism. Currently, the diovascular disasters, the patient needs dent that the systems of conveyors and possibility of administering large doses of to use antiplatelet drugs after performing biotransformation have genetic polymor- clopidogrel to such patients is being dis- PCI and stenting of the coronary vessels. phism, characterized by the presence cussed, but no unambiguous recommen- One of the main drugs for antiplatelet of enzyme isoforms with high and low dations have yet been developed. therapy in cardiology is clopidogrel, the activity. Accordingly, there are genetic After the introduction of PCI with stent- use of which can reduce the incidence of characteristics that affect the pharmaco- ing from the 1980s, the rate of restenosis thrombotic complications. Clopidogrel is logical response in a particular patient. was 24%, then after improving the inter- the most famous member of the thieno- Depending on the status of this gene, vention procedures and introducing more pyridine group. It like ticlopidine and three groups of individuals are distin- advanced stent models, the incidence prasugrel, refers to prodrugs. The drug guished: homozygotes (without muta- of restenosis decreased to 1-2%. How- has a complex metabolism. Its absorption tions), heterozygotes (mutation in the 1st ever, according to Russian studies, in our in the intestine and entry into the blood allele), persons with a mutant genotype country this situation remains disappoint- is associated with the P-glycoprotein en- (mutations in two alleles). Based on the ing, since the recurrence of ACS due to coded by the MDR1 gene (ABCB1). 85% genotype CYP2C19, three main pheno- stent thrombosis develops on average of the dose is converted into an inactive types of the metabolizer CYP2C19 can in 8% of patients. In connection with the carboxyl derivative due to the action of be distinguished: *1/*1 - “fast” with nor- development and massive introduction of esterase plasma. The remaining 15% of mal functional activity of the enzyme, *1 these high-tech methods of treatment of the dose undergoes two-stage oxidation /*2 - “slowed” with reduced enzyme activ- cardiovascular diseases in our country under the action of cytochrome P450 iso- ity, *2/*2 - “ slow “- significantly reduced and in our region, the question of increas- forms, first turning into 2-oxo-clopidogrel, by the functional activity of the enzyme ing the number of patients with genetical- and then into the active thiol derivative. or its absence. The so-called wild type of ly determined resistance to the so-called In turn of it irreversibly inhibits the binding the CYP2C19 gene (*1st allele) is char- “standard scheme” of disaggregant of ADP to the P2Y12-receptor platelets. acterized by normal enzymatic activity of therapy: aspirin (75 mg) + clopidogrel Further, inhibition of fibrinogen binding to CYP2C19. The most common allelic vari- (75 mg) due to the polymorphism of CY- the GP IIb / IIIa receptor and reduction of ant of CYP2C19 with loss of function is P2C19, an increase in the complications aggregation occurs. Clopidogrel is used the allele *2. The frequency of genotypes in the form of restorations of implanted in patients with acute coronary syndrome according to CYP2C19, corresponding to stents. It has been demonstrated that the (ACS), including those who underwent slow metabolizers in the Russian popu- addition of clopidogrel to ASA provides coronary artery stenting (SCS) with per- lation, is 11.4%, which is comparable to additional benefit in patients with MI, es- cutaneous coronary intervention (PCI) European ethnic groups. However, in pecially with coronary artery stenting. At [4]. The standard route of administration Russian patients with ischemic heart the same time, in a number of studies, a of clopidogrel provides a loading dose of disease (IHD), CYP2C19 genotypes as- wide interindividual variability of the an- 300 mg and then a maintenance dose sociated with slow metabolism can oc- tiplatelet effect of clopidogrel has been of 75 mg daily; the increased dosage in- cur at a frequency of up to 27.3% [6]. demonstrated. Pharmacodynamic and cludes the administration of 600 mg in a Cytochrome CYP2C19 is a member of clinical studies have demonstrated that loading dose, then 150 mg for 6 days and the cytochrome P450 family of enzymes the polymorphism of the CYP2C19 gene thereafter 75 mg per day [23] or a main- and is an S-mefenitonine hydroxylase (CYP2C19*2 allele) is associated with tenance dose of 150 mg per day for 6 enzyme. Low enzyme activity is associ- a decreased antiplatelet effect of clopi- months. [25]. Double antiplatelet therapy ated with a risk of developing myocardial dogrel and an increase in the incidence is often used, involving the simultaneous infarction or ischemic stroke - in patients of severe cardiovascular complications use of clopidogrel and acetylsalicylic acid with decreased enzyme activity, the risk [8]. Evidence of a thorough analysis of preparations, both for long-term treat- of death from cardiovascular events in- the effectiveness of clopidogrel is pub- ment and for short periods (1 month after creased by 53%. The gene encoding lished in the leading cardiological jour- PCI with stenting) [25], although it has cytochrome CYP2C19 is located in 10 nals of the world, debates in European now been shown that the use of clopi- chromosomes, locus 10q24. This locus and American cardiology forums. Various dogrel without combination with aspirin is part of a large cluster containing the components of the effectiveness of clopi- is associated with a significant reduction genes CYP2C19, CYP2C18, CYP2C19, dogrel - compliance, dosages, duration in hemorrhagic complications without an CYP2C9, CYP2C8, and associated with of two-component antiplatelet therapy, increase in the frequency of thrombotic a reduced response to clopidogrel based the effect of concomitant treatment with events [26]. on the results of a full-genome assay of statins, proton pump inhibitors, and the In recent years, significant progress associations [7]. effects of other factors (smoking) are dis- has been made in the development of The allelic variant CYP2C19*2 cussed. new inhibitors of the receptor for ADP (rs4244285) refers to prothrombogenic The contribution of the polymorphism P2Y12 (prasugrel, ticagrelor) with a variants of cytochrome CYP2C19. Re- of the CYP2C19 gene to the formation of faster onset of action, more pronounced placement G

allele with an independent predictor of decreased function of CYP2C19 and an kodiruyushchikh belki gemostaza, s stent thrombosis within 30 days. A triple increased risk of cardiovascular death, parametrami perifericheskogo gemosta- increase in the risk of stent thrombosis in myocardial infarction, or cerebral stroke za i predraspolozhennost’yu k aterotrom- patients with acute coronary syndrome [11]. bozam u patsiyentov s serdechno-sos- (ACS) and the presence of the CYP2C19 A domestic study conducted in 2015 udistymi zabolevaniyami [Association of *2 allele was also shown by the TRITON- also confirmed the association between genes encoding hemostasis proteins with TIMI study [25]. A study performed on a the carriage of COR2C19*2 in patients parameters of peripheral hemostasis and Chinese population found an increased after PCI and the risk of developing re- predisposition to atherothrombosis in pa- risk of occurrence of cardiovascular com- sistance (due to high residual platelet tients with cardiovascular diseases] Kar- plications within 1 year after PCI of 3.65- activity) [5]. diovaskulyarnaya terapiya i profilaktika fold in the carrier group of at least one The accumulated knowledge served [Cardiovascular Therapy and Preven- mutant CYP2C19 allele (* 2 or *3) com- as the basis for introducing in 2010 the tion]. 2011, 4: 90-6. pared to the wild-type genotype [ 22]. A instructions on the use of original clopi- 2. Barysheva V.O. Ketova G.G. meta-analysis of nine studies, which in- dogrel information on the effect of the Analiz svyazi rezul’tatov farmakogenet- cluded 9685 patients, showed a statisti- mutant gene CYP2C19 on the effective- icheskogo testirovaniya dlya opredele- cally significantly higher risk of death for ness of therapy. The American Heart As- niya rezistentnosti k klopidogrelu i trom- cardiac and vascular reasons, as well as sociation and the American Society of boza stenta u patsiyentov [Analysis of stent thrombosis in patients who are “slow Cardiology, the European Society of Car- the relationship between the results of metabolizers” compared to individuals diology, note the need for genotyping for pharmacogenetic testing to determine who do not have alleles with a reduced CYP2C19 to detect alleles of “slow me- clopidogrel resistance and stent throm- functional activity [20]. In the PAPI (Phar- tabolizers” and recommend it for some macogenomics of Antiplatelet Interven- groups of patients at high risk of thrombosis in patients] Farmakogenetika i far- tion) study, clopidogrel was administered botic complications, mainly with ACS and makogenomika [Pharmacogenetics and within 7 days to 429 healthy individuals; planned PCI. The carrier frequency of the pharmacogenomics]. 2017.№2. P.7-8. the response was determined by the CYP2C19*2 allele in the Russian popula- 3. Bokeriya L. A. Rukovodstvo method of aggregometry. Genotyping of tion is about 13.3%, and in the IHD pa- po rentgenendovaskulyarnoy khirurgii 2C19 * 2 was performed. Data obtained tients this is slightly higher (the incidence serdtsa i sosudov [Guide to endovascular from healthy individuals were compared of genotypes with reduced metabolic ac- surgery of the heart and blood vessels] with the data of 227 patients undergo- tivity may reach 27.3%) [13]. Moskva: NTSSSKH im. A. N. Bakuleva ing stenting of the coronary arteries. We In our country, there is also growing RAMN [Moscow: NTSSSH them. A.N. studied the relationship between platelet interest in this issue, in connection with Bakulev RAMS]. 2013. T. 3. function, genotyping and cardiovascular which in various clinics, patient studies 4. Kudzoyeva Z. F. Bokeriya L. A. outcomes. It was found that the response are conducted. So in 2013, a study was Bokeriya O. L. Vliyaniye geneticheskogo to clopidogrel was highly dependent on conducted at the National Medical Sci- poliforfizma gena CYP2C19 na vybor ef- heredity (p <0.001): 13 single-nucleo- ence Centre of Cardiovascular surgery fektivnoy antiagregantnoy terapii posle tide polymorphisms in the chromosome named after A.N.Bakulev with the par- operatsii stentirovaniya koronarnykh ar- 10q24 in the CYP2C18-CYP2C19-CY- ticipation of 72 patients (50 men and 22 teriy [Influence of genetic polyphophism P2C9-CYP2C8 cluster were significantly women) who took clopidogrel after the of the CYP2C19 gene on the choice of associated with a reduced response to operation of planned myocardial revas- effective antiaggregant therapy after cor- clopidogrel. Patients with the CYP2C19*2 cularization performed a genetic study onary artery stenting] FGBU NTSSSKH allele had more MTB or fatal outcomes on the carriage of allelic variants of cy- im. A.N. Bakuleva RAMN [FSBI NTSSSH during the year (20.9% versus 10.0%, tochrome P-450 and CYP2C19*1 and *2 them. A.N. Bakulev RAMS]. risk ratio 2.42, p = 0.02) [24]. isoenzymes. As a result, it was conclud- 5. Mirzayev R.Ye. Kazakov V.V. In a meta-analysis conducted by ed that the carriage of allelic variants of Smirnov Vliyaniye metabolicheskoy M.V.Holmes, with the inclusion of 32 the CYP2C192* gene according to differ- aktivnosti izofermenta CYP3A4 i poli- studies totaling 42,000 respondents, the ent authors is found in the population with morfnykh markerov gena CYP2C19 na genotype influenced only the incidence a frequency of up to 40% (confirmed by antiagregantnyy effekt klopidogrela u of stent thrombosis, in connection with the results of the study) and is one of the bol’nykh s ostrym koronarnym sindro- other cardiovascular outcomes not dem- risk factors for low laboratory response to mom, perenesshikh chreskozhnoye onstrated [15]. clopidogrel therapy [4]. Carrying out the koronarnoye vmeshatel’stvo [Effect of At the same time, the results of a large genetic test for carriage of CYP2C19*2 metabolic activity of CYP3A4 isoenzyme randomized PLATO study revealed the to all patients before stenting can help and polymorphic markers of CYP2C19 association of various polymorphic CY- optimize the appointment of antiplatelet gene on antiplatelet effect of clopidogrel P2C19 markers with the incidence of car- therapy, which in turn could prevent the in patients with acute coronary syndrome diovascular events in patients with ACS potential complications associated with undergoing percutaneous coronary inter- only in the early stages of the disease, insufficient effectiveness of clopidogrel. vention] Ratsional’naya Farmakoterapiya after a year of observation, the differ- Summing up, there is a need for fur- ences were not significant. The results of ther larger-scale research in this area, v Kardiologii [Rational Pharmacotherapy large studies [16, 18, 20] confirmed the the purpose of which will be to develop in Cardiology] 2015. T. 11. № 4. P. 344- prognostic value of the polymorphism new clinical guidelines for the treatment 354. of the gene CYP2C19 in patients tak- of cardiovascular patients, which ulti- 6. Zelenskaya Ye. M. Slepukhina ing clopidogrel. In a meta-analysis of 9 mately aims to increase life expectancy. A.A. Kokh N.V. et all. Geneticheskiye, pharmacogenetic studies of clopidogrel patofiziologicheskiye i klinicheskiye- as that included 9685 patients, a reliable as- References pekty antiagregantnoy terapii [Genetic, sociation was found between homo- or 1. Lifshits G.I. Danilkina S.T. pathophysiological and clinical aspects heterozygotes for a mutant allele with a Gus’kova Ye.V. et al. Assotsiatsiya genov, of antiplatelet therapy] Farmakogenetika 4’ 2018 105

i farmakogenomika [Pharmacogenetics mom s pod”yemom segmenta ST, pod- with clopidogrel response variability and and pharmacogenomics]. 2015.№2. Pp. vergshikhsya pervichnoy protsedure na recurrent cardiovascular events in Chi- 12-19. koronarnoy arterii [Predictors of stent nese patients undergoing percutaneous 7. Kochergina A.M. Kashtalap V.V thrombosis in patients with acute coro- coronary intervention / Y. Liu, N Liu, W Gordeyeva L.A. Klinicheskaya znachi- nary syndrome with ST-segment eleva- Li, et al. // Pharmacology. 2013; 91 (3-4): most’ polimorfizma gena CYP2C19 u tion who underwent a primary procedure 165-72. patsiyentov s ostrym koronarnym sindro- for coronary artery] Kardiologiya [Cardiol- 23. The CURRENT-OASIS 7 In- mom s pod”yemom segmenta ST (dan- ogy]. 2011. T. 51. № 4. P. 10-15. vestigators. Dose Comparisons of Clopi- nyye registra ostrogo koronarnogo sin- 13. Solodun M.V. Farmokotera- dogrel and Aspirin in Acute Coronary droma g.Kemerevo) [Clinical significance piya pri infarkte miokarda: vklad genet- Syndromes.//N Engl J Med 2010,363(10): of the CYP2C19 gene polymorphism in icheskikh faktorov [Pharmacotherapy for 930-42. patients with acute coronary syndrome myocardial infarction: the contribution 24. The Pharmacogenomics of Anti- with ST-segment elevation (data from of genetic factors] Rossiyskiy kardio- Platelet Intervention (PAPI) Study: Varia- Kemerovo acute coronary syndrome logicheskiy zhurnal [Russian Journal of tion in Platelet Response to Clopidogrel registry)] Molekulyarnaya meditsina [Mo- Cardiology]. 2016. - № 3 (131). and Aspirin / L.M. Bozzi, B.D. Mitchell, lecular medicine] 2017.T.5.№4.P.33-36. 14. Chernov A.A. Mirzayev J.P. Lewis, et al. // Current vascular phar- 8. Kurcheva N.P. Mirzayev K.B. K.B. Sychov D.A. Pervyy meta-analiz macology. 2016; 14(1):116-124. Sychov D.A. Mnogofaktornyy algoritm otechestvennykh farmakogeneticheskikh 25. Standard High-Dose Clopido- prognozirovaniya antiagregantnogo issledovaniy klopidogrela [The first meta- grel Based on Platelet Function Test- deystviya klopidogrela, kak potentsial’nyy analysis of domestic pharmacogenetic ing After Percutaneous Coronary Inter- sposob povysheniya effektivnosti i studies of clopidogrel] Farmakogenetika vention. The GRAVITAS Randomized bezopasnosti antiagregantnoy terapii i farmakogenomika [Pharmacogenetics Trial / MJ Price, PB Berger, PS Teirst- [Multifactor algorithm for predicting the and pharmacogenomics]. 2015 №2. ein // JAMA.2011; 305(11):1097–1105. antiplatelet effect of clopidogrel, as a po- Pp.19-23 doi:10.1001/jama.2011.290. tential way to increase the effectiveness 15. Holmes M.V. Perel P. Shan T. 26. Use of clopidogrel with or with- and safety of antiplatelet therapy] Far- CYP2C19 Genotype, Clopidogrel Me- out aspirin in patients taking oralan- makogenetika i farmakogenomika [Phar- tabolism, Platelet Function, and Car- ticoagulant therapy and undergoing macogenetics and pharmacogenomics]. diovascular Events, a systematic re- percutaneous coronary intervention: 2015.№2. P. 29-32. view and meta-analysis JAMA. 2011; an open-label, randomised, con- 9. Lifshits G.I. Apartsin K.A. 306(24):2704-2714. trolled trial / W.J.M.Dewilde, T.Oirbans, Prospektivnoye mnogotsentrovoye 16. Cytochrome P450 2C19 poly- F.W.A.Verheugt, J.C.Kelder, B.J.G.L. De nablyudatel’noye issledovaniye Protokol: morphism in young patients treated with Smet, J-P. Herrman et al. // Lancet 2013, personalizirovannaya terapiya klopido- clopidogrel after myocardial infarction: a 381(9872): 1107-15. grelom pri stentirovanii popovodu ost- cohort study /J.Collet, J.Hulot, A. Pena A. rogo koronarnogo sindroma s uchetom et al. Lancet 2009. 373(9660):309-17. The authors geneticheskikh polimorfizmov [Prospec- 17. Expert position paper on the Federal State Budgetary Institution tive multicenter observational study Pro- role of platelet function testing in pa- “Yakut science center of complex medical tocol: personalized clopidogrel therapy tients undergoing percutaneous coronary problems”, 677010, Russian Federation, for stenting for acute coronary syndrome, intervention / D. Aradi, R.F. Storey,A. Republic of Sakha (Yakutia), Yakutsk, taking into account genetic polymor- Komócsi, D. Trenk, D. Gulba, R.G. Kisset Sergelyahskoe St, 4: phisms] Kachestvennaya klinicheskaya al. // Eur Heart J 2014, 35(4): 209-15. 1. Terentiev Ivan Titovich - doctor praktika [High-quality clinical practice]. 18. Genetic determinants of re- cardiologist, junior researcher of the 2015.№1.-P.78-86. sponse to clopidogrel and cardiovas- laboratory of heritable pathology. Tel.: +7 10. Martsevich S. YU. Kutishenko cular events / T. Simon, C. Verstuyft, (924) 173 15 05, E-mail: ivantit7313@ N. P. Ginzburg M. L. Antiagregantnay- M. Mary-Krause et al.. N Engl J Med mail.ru aterapiya u bol’nykh s vysokim riskom 2009.360(4):363-75. DOI:10.1056/NEJ- 2. Varlamova Marina Alekseevna razvitiya tromboticheskikh oslozhneniy: Moa0808227 –researcher of the laboratory of heritable problema effektivnosti, bezopasnosti i 19. Guidelines on myocardial re- pathology Tel.: 8 (914) 298 87 60.E-mail: priverzhennosti [Antiplatelet therapy in vascularization / W. Wijns, P. Kolh, N. [email protected]. patients with a high risk of thrombotic Danchin et al. // Eur Heart J. 2010. Vol. 3. Pavlova Nadezhda Ivanovna complications: the problem of efficacy, 31. № 20. P. 2501–2555 – cbs, temporary acting chief scientific safety and adherence] Klinitsist [Clini- 20. Mega J., Close S., Wiviott S. et officer - head of the laboratory of heritable cian]. 2001. № 2. P. 72–79. al. Cytochrome P-450 Polymorphisms pathology. Tel.: +7 (914) 289 39 36. 11. Galyavich A.S. Valeyeva D.D. and Response to Clopidogrel //N Engl J E-mail: [email protected]; Minnetdinov R.SH. Polimorfizm gena Med 2009.360(4):354-62. 4. D’yakonova Aleksandra CYP2C19 u bol’nykh infarktom mio- 21. Reduced-function CYP2C19 Timofeevna – Junior researcher of the karda, primenyayushchikh klopidogrel genotype and risk of adverse clinical out- laboratory of heritable pathology Tel.: 8 [Polymorphism of the CYP2C19 gene in comes among patients treated with clopi- (914) 238 68 93.E-mail: dyakonovaa@ patients with myocardial infarction using dogrel predominantly for PCI: a meta- bk.ru; clopidogrel] Kardiologiya [Cardiology]. analysis / J.L. Mega, Т. Simon, J.P. Collet, 5. Solov’eva Natal’ya Alekseevna 2012.№ 4. P. 20-24. J.L. Anderson, E.M. Antman, К. Bliden et – cms, temporary acting chief scientific 12. Berns S.A. Shmidt Ye.A. Kip- al. // JAMA 2010, 304(16): 1821-30. officer - head of the Laboratory of rina Ye.S. Prediktory tromboza stenta u 22. Relationship of CYP2C19*2 Population Genetics. Tel.: 8 (924) 171 34 bol’nykh s ostrym koronarnym sindro- and CYP2C19*3 gene polymorphism 89.E-mail: [email protected]; 6. Kononova Sardana Kononovna 106 YAKUT MEDICAL JOURNAL

- senior researcher of the laboratory of 7. Kurtanov Khariton Alekseevich Genetics. Tel.: +7 (914) 106 00 30. molecular genetics. Tel.: 8 (924) 166 06 – cms, Chief Scientific Officer - Head E-mail: [email protected]. 77. E-mail: [email protected] of the Department of Molecular

EXPERIENCE EXCHANGE

U.N. Mikhailova, N.A. Solovyova, M.A. Varlamova, Kh.A. Kurtanov, N.I. Pavlova HOSPITAL MORBIDITY RATES AS A FACTOR IN THE SELECTION OF PATHOLOGY TO DEVELOP PERSONALIZED PREVENTION DOI 10.25789/YMJ.2018.64.32 AND TREATMENT METHODS

ABSTRACT Indicators of the hospitalized incidence of adult population according to YSC CMP Hospital during 2015-2017 are presented in article. The characteristic of dynamics and structure of the cases demanding performing treatment in stationary conditions is given. Growth of cases of hospitalization of patients with metabolic disorders, including diabetes 2 types and diseases of cardiovascular system is established. The obtained data served as the basis for conducting research and developing molecular genetic methods of diagnosis in relation to this pathology. Keywords: hospital morbidity, structure and dynamics of incidence, methods of personalized medicine, molecular diagnostics.

Introduction. Diseases with the in- with temporary and permanent disability, the outcome of the disease, etc. from heritance of predispositions today are morbidity from the results of medical ex- which the patient has left. In cases where widespread and are determined by a fac- aminations and hospitalization activity of two or more diagnoses of diseases are tor called the genetic load. It is the high the population [3]. indicated in the map, the patient refers prevalence of polymorphic variants of As a factor in the selection of pathol- to each of these diseases in the report, genes predisposing to the development ogy by degree of importance, such an which was the main cause of hospitaliza- of multifactorial diseases that determines indicator of medical statistics as hospital- tion. This document provides the most the spectrum of somatic pathology with ized morbidity is often used, which gives rational development of information for a characteristic for a specific population an idea of the most severe pathology the preparation of the relevant sections of structure. In addition, the polymorphism requiring attention and treatment in in- the report [3,5].Thus, the purpose of this of variants of predisposing genes affects patient conditions, as a rule, in special- study is to study the dynamics and struc- not only the structure, but also the char- ized departments. This indicator is very ture of the hospitalized morbidity of the acteristics of the formation and course of informative, since it characterizes neglect adult population of the RS (Ya) according diseases, the development of complica- and severity of pathology, which in turn to the data of the YSC CMP Hospital as tions, as well as the susceptibility, resist- contributes to the formation of a chronic a factor in selecting the most significant ance and tolerance of drug therapy [4]. process and disability, which ultimately pathology for determining the priority di- Today, molecular technologies allow leads to a decrease in the patient’s qual- rections of molecular genetics research the formation of risk groups taking into ity of life [1]. in the development of diagnostic test sys- account the genetic characteristics of pa- The unit of accounting for hospitalized tems for multifactorial diseases. tients and carrying out preventive meas- morbidity is the case of hospitalization Materials and methods. The base of ures in them at the stage of preclinical of the patient in the hospital, and the ac- the study was the Yakut Science Centre manifestations of the disease in order to counting document is the “Statistical map CMP (Yakutsk), the object being the adult prevent the development of the disease of the out-of-hospital” (f. 066 / u). The population from 18 to 80 years old, hospi- itself and its complications. Personalized “statistical card of the discharged from talized in the hospital in 2015–2017. The medicine methods are highly effective the hospital” is compiled on the basis of material for analyzing the dynamics and and contribute to improving the quality the “Medical card of the inpatient patient” structure of the hospitalized morbidity and increasing the life expectancy of the (f. 003 / u) and is a statistical document was the data from the statistical reports population. In turn, the use of such ex- containing information about the disused, of the inpatient units of the Hospital of the pensive and highly specific technologies discharged from the hospital (discharged, Yakutsk Scientific Medical Center. The requires an informed approach to the dead). The card is compiled simultane- statistical data processing was carried choice of both the spectrum of diseases ously with the recording of the epicrisis out using descriptive statistics methods. and genetic markers that predispose to in the “Medical card of the inpatient” by Results and discussion. In its struc- the development of pathology. the attending physician on all those who ture, the Hospital of the YSC CMP has To determine the significance of a par- left the hospital (written out or died). The 110 beds of which 44 are therapeutic, ticular pathology helps a comprehensive card reflects the basic information: about 41 are cardiological and 25 are gyneco- assessment of public health, which is car- the duration of treatment of the patient logical. To identify current trends in the ried out using indicators of general and in the hospital, the diagnosis of the main dynamics of hospital morbidity, a pre- primary morbidity recorded by attend- and concomitant diseases, the duration, liminary analysis of the organization of ance, as well as using data on morbidity nature and effectiveness of surgical care, inpatient care was carried out. Accord- 4’ 2018 107

ing to the official statistics of the Hospital YSC CMP in 2015, the hospital incidence Table 1 rate was 2.256; in 2016 - 3.025; in 2017 The relative number of diseases that caused the hospitalization of the population in the - 2,984. Thus, over the 3-year period, the inpatient hospital of the YSC CMP Hospital for 2015-2017 by disease class hospitalization rate increased 1.3 times 2015 2016 2017 (Table 1). Class of international classification of diseases X revision According to the results of the analy- Per 1000 population sis, it was established that over the past I. Some infectious and parasitic diseases 0.005 0.037 0.024 three years there has been an increase II. Neoplasms 0.047 0.027 0.011 in cases requiring patients to be hospi- III. Diseases of the blood. blood-forming organs and certain talized with endocrine pathology, eating disorders involving the immune mechanism 0.024 0.053 0.048 disorders and metabolic disorders by 4.2 IV. Endocrine. nutritional and metabolic diseases 0.046 0.181 0.258 times, including type 2 diabetes, there is a tendency to a steady increase in the V. Mental and behavioral disorders 0.003 0 0 hospitalization of diseases of the circula- VI. Diseases of the nervous system 0.079 0.109 0.103 tory system, for three years, this figure in- IX. Diseases of the circulatory system 1.061 1.387 1.365 creased by 304 cases. At the same time, X. Respiratory diseases 0.117 0.123 0.109 for some diseases, there is a tendency to XI. Diseases of the digestive organs 0.132 0.128 0.111 reduce the level of hospitalization, so the XII. Diseases of the skin and subcutaneous tissue 0.013 0.015 0.009 number of cases requiring hospitalization XIII. Diseases of the musculoskeletal system and connective tissue 0.114 0.160 0.140 of neoplasms decreased by 3.6 times, XIV. Diseases of the genitourinary system 0.274 0.305 0.288 which may be due to timely diagnosis, treatment in the early stages of cancer XV. Pregnancy. childbirth and the postpartum period 0.361 0.500 0.518 (Table 2). The table shows that in the general Table 2 structure of the diseases, among all The overall structure of the disease hospitalized cases those admitted for the 3-year period, pain the YSC CMP Hospital for 2015-2017 tients with circulatory system diseases 2015 2016 2017 Class of international classification of diseases X revision prevailed (46.0%; 45.2%; 45.2%); sec- % ond place (15.7%; 16.4%; 17.2%) and in I. Some infectious and parasitic diseases 0.3 1.3 0.9 third place were cases related to the pa- II. Neoplasms 2.2 1.0 0.6 thology of the urogenital system (11.9%; III. Diseases of the blood. blood-forming organs and certain 10.0%; 9.6%). disorders involving the immune mechanism 1.2 1.9 1.8 Conclusion. The paper describes the characteristics of the dynamics and IV. Endocrine. nutritional and metabolic diseases 2.1 6.1 8.9 structure of the hospitalized morbidity of V. Mental and behavioral disorders 0.4 0 0 the adult population of the RS (Ya) on the VI. Diseases of the nervous system 3.5 3.7 3.1 basis of a retrospective analysis of data IX. Diseases of the circulatory system 46.0 45.2 45.2 from statistical reports of inpatient wards X. Respiratory diseases 5.3 4.2 3.7 of the YSC CMP Hospital. XI. Diseases of the digestive organs 5.8 4.3 3.9 It is established that for the period XII. Diseases of the skin and subcutaneous tissue 0.6 0.6 0.4 from 2015 to 2017 there is a tendency of a steady increase in the incidence of cas- XIII. Diseases of the musculoskeletal system and connective tissue 5.0 5.3 4.7 es requiring hospitalization for patients XIV. Diseases of the genitourinary system 11.9 10.0 9.6 with endocrine pathology, eating disor- XV. Pregnancy. childbirth and the postpartum period 15.7 16.4 17.2 ders, metabolic disorders, as well as patients with circulatory disorders. The data research is currently being conducted to prozhivayushhego v e`kologicheski obtained indicate the activation of meta- study the molecular genetics aspects of neblagopoluchny`kh rajonakh bolic disorders among the adult popula- the formation of metabolic disorders such Arkhangel`skoj oblasti [The analysis of tion of RS (Ya) receiving medical care as type 2 diabetes, obesity, and non-al- the hospitalized incidence of the work- at the YSC CMP Hospital and require a coholic fatty disease liver, hypertensive ing-age population living in ecologically more detailed analysis of the pathoge- disease. unsuccessful areas of the Arkhangelsk netics mechanisms of the formation of The research protocol was approved region] Ehkologiya cheloveka [Ecology of this group of diseases using molecular by the local committee on biomedical the person], 2005. No 7, p. 48-53. diagnostic methods, the development ethics at the YSC CMP. The work is car- 2. https://cyberleninka.ru/article/n/ and implementation of which will facilitate ried out in the framework of the research analiz-gospitalizirovannoy-zabolevae- the implementation of personalized pre- “Study of the genetic structure and bur- mosti-naseleniya-trudosposobnogo-voz- ventive and therapeutic measures that den of hereditary pathology of popula- rasta-prozhivayuschego-v-ekologiches- will reduce the risk of development and tions of the Republic of Sakha (Yakutia)”. ki-neblagopoluchnyh complications of these diseases. Taking 3. Geneticheskie issledovaniya into account the results obtained by the References narodonaseleniya Yakutii [Genetic stud- staff of the Laboratory of Hereditary and 1. Pavlova E.A., Skrebcova N.V., ies of the population of Yakutia] Pod.red. Population Genetics of the YSC CMP, to- Svetlichnaya T.G. [et al.] Analiz gos- Puzyreva V.P. [edited by V.P. Puzyrev]. gether with the doctors of the therapeutic pitalizirovannoj zabolevaemosti nas- Yakutsk: Companya Dani-Almas [Com- department of the YSC CMP Hospital, eleniya trudosposobnogo vozrasta, pany Dani-Almas], 2014, p.336. http:// 108 YAKUT MEDICAL JOURNAL

elibrary.ru/item.asp?id=23843825 dnevnoj staczionar i osobennosti - candidate of medical sciences, senior 4. Naglyadnaya mediczinskaya okazaniya gastroe`nterologicheskoj research associate of laboratory of statistika [Evident medical statistics] Pod. pomoshhi [Structure of incidence among population genetics of department red. Leonov V.P. [edited by V.P. Leonov]. the hospitalized patients in a day hospital of molecular genetics of YSC CMP, Moscow: Izdatel’skaya gruppa GEOTAR and features of rendering the features of contacts: [email protected], 8-924- media [Publ.group « GEOTAR -media»], gastroentrology care] Molodoj uchenyj 171-34-89; 2015, p. 217. http://www.biometrica. [Young scientist]. Kazan’, 2015, №17, P. 3. Pavlova Nadezhda Ivanovna - tomsk.ru 44-47. сandidate of biology sciences, the lead- 5. Novikov P.V. DNK–testirovanie: 7. https://moluch.ru/archive/97/21818/ ing researcher - the head of laboratory monogenny`e i mul`tifaktorial`ny`e of hereditary pathology of department of bolezni [DNA testing: monogenic The authors molecular genetics of YSC CMP; and multifactorial diseases] Russkij 677010, Yakutsk, Sergelyakhskoye 4. Kurtanov Khariton Alekseyevich medicinskij zhurnal [Russian medical Highway 4, FGBNU “The Yakut science - candidate of medical sciences, the chief journal]. Moscow, 2011, No. 12, p. 794. center of complex medical problems”: researcher – head of department of mo- https://www.rmj.ru/articles/genetika 1. Mihajlova Ul’yana Nikitichna - lecular genetics of YSC CMP; 6. Grishechkina I.A., Sobol junior researcher associate of laboratory 5. Varlamova Marina Alekseevna L.N., Skvorcova E.A. [et al.] of population genetics of department of - research associate of laboratory of he- Struktura zabolevaemosti sredi molecular genetics of YSC CMP; reditary pathology of department of mo- gospitalizirovanny`kh bol`ny`kh v 2. Solovyova Natalya Alekseevna lecular genetics of YSC CMP.

S.S. Shadrina, R.N. Zakharova, А.А. Donskaya, A. N. Sergeeva THE MOST FREQUENT SYMPTOMS OF JOINTS DAMAGE AMONG THE DOI 10.25789/YMJ.2018.64.33 RESIDENTS OF YAKUTIA

ABSTRACT The frequency of clinical manifestations in patients with joint damage among the indigenous people of Yakutia (n = 687) was studied. It is revealed that the damage of the joints can begin both in the early childhood (2 years) and in old age (77 years); on average, joint lesion starts at 41-43 years. The most common symptoms of joint damage are pain in the joint and crepitus in the knee joints. Among women, there are more often observed: swelling of the wrist and knee joints, restriction of mobility of the wrist joints and bilateral crepitus at the knee joints; among men, one-sided crepitus at the knee joints. With age increasing, the duration of pain and the frequency of changes in the configuration of the joints at the time of inspection increase. Keywords: joint damage, clinical symptoms, radiological signs.

Introduction. Data on the prevalence frequency of symptoms of joint damage women the damage of the joints began of diseases of the joints abroad in many among rural residents of Yakutia. at the age of 30-39 years. In other age cases are based on the results of screen- Material and methods of research. groups the beginning defeat joint dam- ing tests. The pathology of the joints in 687 patients were examined, revealed age met not more than 20% of cases. this method revealed in 10.3-35.8% of during a continuous epidemiological The most significant differences in the [5, 6]. Russian researchers have shown study rural residents of the seven vil- frequency the beginning defeat joint dam- that there are geographic variations in lages in Yakutia. Of these, 68.1% were age among both sexes were observed in the prevalence of pain in the joints. Thus, females, 31.9% - male. The median age the age group 40-49 years (χ2 = 17,46; p during a screening questionnaire in Kras- of men and women was about the same = 0,03; V = 0,16). noyarsk region did not exceed 15% [1]. - 50 and 49 years respectively. The mini- We have also studied the frequency of Yuzhno-Sakhalinsk complaints of pain mum age for both sexes was 18 years clinical signs of joint damage. The study imposed on 21% of the population in the old; the maximum age of the men was 88 revealed that the most frequent clinical joints [3], and they met in 36.5% of cas- years, women - 80. The age structure of manifestations of joint disease are pain in es [2] among the rural population of the the largest part consisted of persons in the joints (100% of patients), and crepitus Sverdlovsk region. The high prevalence age group 40-49 years - 32.9% (includ- in knee joints (54%). With a frequency of of arthralgia was established in the Re- ing women - 23.4, men - 9.5); 27.2% 10 to 30% met: change in joint configura- public of Sakha (Yakutia) - up 46.7%, that were persons aged 50-59 years (includ- tions (28.2%), one joint arthritis (25.1%) perhaps due to the influence of climatic ing women - 19.5, men - 7.7). Persons of and swelling of knee (12.5%). In 3-10% factors [4]. It was extremely high frequen- other age groups accounted for no more of patients were observed: knee limited cy of pain in the joints among industrial than 15%. Sex ratio was not significantly mobility (10%), swelling of the proximal workers Republic of Karelia, where the different in age groups (p> 0.05). interphalangeal joints (PIPhJ) brushes figure approached 65%. Moreover- ar Results and discussion. The most (6.4%), swelling of the wrist (4.6%), limit- thralgias appearance was not dependent common joint disease among both wom- ing the mobility of the hip joint (HJ) (3.9%), on the severity of physical activity, and en and men began at the age of 40-49 the wrist mobility restriction (3.6%), swell- apparently was due to other factors. years - 40.2 and 27.8%, respectively. ing of the hand metacarpophalangeal Purpose of the study - to study the Among the 23.7% of men and 23.5% joints (MCPhJ) (3.5%), arthritis of three 4’ 2018 109